Back to resultsA Study of CNTO 136 (Sirukumab), Administered Subcutaneously, in Patients With Active Rheumatoid Arthritis Despite Disease-Modifying Antirheumatic Drug (DMARD) Therapy (SIRROUND-D)
Primary Purpose
Arthritis, Rheumatoid
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Placebo
Placebo
Sirukumab
Sirukumab
Sirukumab
Sponsored by
About this trial
This is an interventional treatment trial for Arthritis, Rheumatoid focused on measuring Active rheumatoid arthritis despite disease-modifying antirheumatic drug therapy, Sirukumab, Human Anti-IL-6 monoclonal antibody
Eligibility Criteria
Inclusion Criteria:
- Have a diagnosis of rheumatoid arthritis (RA) for at least 3 months before screening
- Have moderately to severely active RA with at least 6 of 68 tender joints and 6 of 66 swollen joints, at screening and at baseline
- Have been unresponsive to single-agent or combination disease-modifying antirheumatic drugs (DMARD) therapy that includes methotrexate (MTX) or sulfasalazine (SSZ) due to lack of benefit after at least 12 weeks of DMARD, as assessed by the treating physician
- If using oral corticosteroids, must be on a stable dose equivalent to less than or equal to 10 mg/day of prednisone for at least 2 weeks prior to the first administration of study agent. If currently not using corticosteroids, must not have received oral corticosteroids for at least 2 weeks prior to the first administration of study agent
- If using non nonsteroidal anti-inflammatory drug (NSAIDs) or other analgesics for RA, must be on a stable dose for at least 2 weeks prior to the first administration of study agent
- If using non-biologic DMARD such as MTX, SSZ, hydroxychloroquine, chloroquine, or bucillamine, must be on a stable dose for at least 4 weeks prior to the first administration of study agent and should have no serious toxic side effects attributable to the DMARD
Exclusion Criteria:
- Has a history of intolerance to at least 2 or inadequate response to at least 1 anti-tumor necrosis factor alpha agent after 3 months of therapy
- Has received infliximab, golimumab, adalimumab, or certolizumab pegol within 3 months of the first study agent administration
- Has received etanercept or yisaipu within 6 weeks of the first study agent administration
- Has a history of intolerance to tocilizumab that precluded further treatment with it, or inadequate response to 3 months of tocilizumab (anti-IL-6 receptor) therapy
- Has used B-cell-depleting therapy (eg, rituximab) within 7 months of first study agent administration or have evidence during screening of abnormally low B cell level caused by previous B-cell depletion therapy
- Has used anakinra within 4 weeks of first study agent administration
- Has used any other biologic therapy for the treatment of RA within 3 months of the first study agent administration
- Has received intra-articular (IA), intramuscular (IM), or intravenous (IV) corticosteroids for RA, including adrenocorticotrophic hormone during the 4 weeks prior to first study agent administration-
- Has received leflunomide within 24 months before the first study agent administration and have not undergone a drug elimination procedure, unless the M1 metabolite is measured and is undetectable. If a drug elimination procedure is performed during screening, the M1 metabolite should be measured and found to be undetectable
- Has a history of cyclophosphamide or cytotoxic agent use
- Has received cyclosporine A, azathioprine, tacrolimus, mycophenolate mofetil, oral or parenteral gold, or D-penicillamine within 4 weeks of the first study agent administration
- Has received an investigational drug (including investigational vaccines) or used an investigational medical device within 3 months or 5 half lives, whichever is longer, before the first study agent administration
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Placebo then Sirukumab 50 mg or Sirukumab 100 mg
Sirukumab 100 mg
Sirukumab 50 mg + Placebo
Arm Description
Outcomes
Primary Outcome Measures
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Week 16
ACR 20 response is greater than or equal to (>=) 20 percent (%) improvement in both tender joint count (68) and swollen joint count (66) and >= 20% improvement in 3 of following 5 assessments:Participant's assessment of pain using visual analog scale (VAS) (0-10 scale, 0=no pain and 10=worst possible pain),Participant's global assessment of disease activity by using VAS (scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician's global assessment of disease activity using VAS (scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), Participant's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) (scale ranges from 0= no difficulty to 3= inability to perform a task in that area), and Serum C-reactive protein (CRP). Participants were analyzed according to randomized treatment groups they were assigned, regardless of treatments they actually received. Here, TF= treatment failure.
Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Score at Week 52
The van der Heijde-modified Sharpe (vdH-S) score is defined as a measurement of progression in structural damage. It is the sum of joint erosion (32 joints of the hands and 12 joints of the feet) score and joint space narrowing (JSN) (30 joints of the hands and 12 joints of the feet) score. The joint erosion assessment is scored according to the surface area involved, from 0 to 5, with 0 indicating no erosion and 5 indicating complete collapse of bone whereas the JSN assessment including subluxation, is scored from 0 (normal) to 4 (bony ankylosis or complete luxation). The total score ranges from 0 (best) to 448 (worst) with higher scores indicating more joint damage. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received. Here, EE= early escape.
Secondary Outcome Measures
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24
The Health Assessment Questionnaire-Disability Index (HAQ-DI) score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24
An American College of Rheumatology (ACR) 50 response is defined as >= 50 % improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and >= 50% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area), and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Percentage of Participants With Disease Activity Index Score 28 (DAS28) (C-reactive Protein (CRP) Remission at Week 24
The DAS28 based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. The Disease Activity Index Score 28 (DAS28) C-reactive protein (CRP) remission is defined as a DAS28 (CRP) value of less than 2.6 at a visit. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Percentage of Participants With Major Clinical Response (MCR) at Week 52
MCR- participant achieving ACR 70 response for 6 continuous months (24 weeks) in the study period (i.e., through Week 52). An ACR 70 response is defined as >= 70% improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and >= 70% improvement in 3 of the following 5 assessments Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician's global assessment of disease activity using VAS (scale ranges from 0 to 10, [0=no arthritis to 10=extremely active arthritis]), Participant's assessment of physical function as measured by HAQ-DI (scale ranges from 0= no difficulty, to 3= inability to perform a task in that area) and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response Through Week 52
An ACR 20 response is defined as >= 20 % improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and >= 20% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area), and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Percentage of Participants With an American College of Rheumatology (ACR) 50 Response
An ACR 50 response is defined as >= 50 % improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and >= 50% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Percentage of Participants With an American College of Rheumatology (ACR) 70 Response Through Week 52
An ACR 70 response is defined as >= 70 % improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and >= 70% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Percentage of Participants With an American College of Rheumatology (ACR) 90 Response Through Week 52
An ACR 90 response is defined as >= 90 percent (%) improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and >= 90% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Percentage of Participants With Disease Activity Index Score 28 (DAS28) C-reactive Protein (CRP) Response Through Week 52
DAS28 based on C-Reactive Protein (CRP), a statistically derived index combining tender joints (28), swollen joints (28), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both upper right extremity and upper left extremity as well as knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. Good responders: improvement from baseline greater than (>) 1.2 with DAS28 less than or equal to (<=) 3.2; moderate responders: improvement from baseline >1.2 with DAS28 >3.2 to <=5.1 or improvement from baseline >0.6 to <=1.2 with DAS28 <=5.1; non-responders: improvement from baseline <=0.6 or improvement from baseline >0.6 and <=1.2 with DAS28 >5.1. Participants were analyzed according to randomized treatment groups they were assigned to, regardless of treatments they actually received.
Change From Baseline in Disease Activity Index Score 28 (DAS28) C-reactive Protein (CRP) Through Week 52
The DAS28 based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. A negative change from baseline in DAS28 (CRP) (that is, a decrease from baseline) indicates improvement from baseline. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Percentage of Participants With Disease Activity Index Score 28 (DAS28) (C-reactive Protein (CRP) Remission Through Week 52
The DAS28 based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. The Disease Activity Index Score 28 (DAS28) C-reactive protein (CRP) remission is defined as a DAS28 (CRP) value of less than 2.6 at a visit. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Change From Baseline in Simplified Disease Activity Index (SDAI) Score Through Week 52
The SDAI score is a derived score combining tender joints (28 joints), swollen joints (28 joints), patient's global assessment of disease activity, physician's global assessments of disease activity, and CRP. The total score range is from 0 to 86 with a lower score indicating less disease activity. A negative change from baseline indicates an improvement and a positive change from baseline indicates a worsening. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Change From Baseline in Clinical Disease Activity Index (CDAI) Score Through Week 52
The CDAI score is a derived score of 4 components: tender joints (28 joints), swollen joints (28 joints), patient's global assessment of disease activity, and physician's global assessments of disease activity. The total score ranges from 0 to 76 with a lower score indicating less disease activity. A negative change in CDAI score indicates an improvement in disease activity and a positive change in score indicates a worsening of disease activity. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Percentage of Participants With Simplified Disease Activity Index Based (SDAI-based) American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) Remission Through Week 52
Participant having SDAI-based ACR/EULAR remission at a visit if SDAI score is of <= 3.3. SDAI derived by combining 5 disease assessments: tender joint (28), swollen joint (28) counts, participants global assessment of disease activity using VAS (scale ranges from 0 to 10 [0 =very well to 10 = very poor]), physicians global assessment of disease activity using VAS (scale ranges from 0 to 10 [0=no arthritis to 10=extremely active arthritis]) and CRP. 28 joints evaluated for swelling and tenderness are same set of 28 joints used in DAS28 includes shoulder, elbow, wrist, MCP1, MCP2, MCP3, MCP4, MCP5, PIP1, PIP2, PIP3, PIP4, PIP5 joints of upper right and left extremities and knee joints of lower right and left extremities. Change from baseline in SDAI score measures change in disease activity, where negative change= improvement and positive change= worsening. Participants were analyzed according to randomized treatment groups they were assigned regardless of treatments actually received.
Percentage of Participants With Boolean-based American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) Remission Through Week 52
A participant was considered as having achieved the Boolean-based American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) remission at a visit if all of the following 4 criteria were met at that visit: Tender joint count (68 joints) less than or equal to (<=) 1; Swollen joint count (66 joints) <=1; CRP <=1 milligram per deciliter (mg/dL); Patient's Global Assessment of Disease Activity <=1 on a 0 (very well) to 10 (very poor) VAS. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Through Week 52
The Health Assessment Questionnaire-Disability Index (HAQ-DI) score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Negative change reflects an improvement and a positive change reflects a worsening. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Area Under the Curve (AUC) of Change From Baseline in HAQ-DI Score From Week 0 Through Week 24 and From Week 0 Through Week 52
HAQ-DI has 20-question in 8 functional areas: dressing, arising, eating, walking, hygiene, reaching, gripping, and daily living activities, scored from 0=no difficulty to 3=inability to perform task in that area. Overall score computed as sum of domain score divided by number of domains answered. Total possible score range 0= least difficulty to 3= extreme difficulty. AUC of change from baseline in HAQ-DI score is AUC of change from baseline in HAQ-DI score versus time. AUC was calculated based on measurement (observed HAQ-DI score change from baseline) at scheduled visits using trapezoidal rule.Functional status was determined as cumulative measure of HAQ-DI over 1 year by using AUC of change from baseline in HAQ-DI score through week 52. Decreases in AUC of change from baseline in HAQ-DI means greater average improvement in physical function over time. Participants analyzed according to randomized treatment groups they were assigned, regardless of treatments they actually received.
Percentage of Participants With Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Through Week 52
HAQ-DI response was defined as change of less than -0.22 from baseline in HAQ-DI score. The HAQ-DI score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Percentage of Participants With Health Assessment Questionnaire-Disability Index (HAQ-DI) Score of Less Than or Equal to 0.5
HAQ-DI score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Score at Week 24
vdH-S score is defined as a measurement of progression in structural damage. It is the sum of joint erosion (32 joints of the hands and 12 joints of the feet) score and joint space narrowing (JSN) (30 joints of the hands and 12 joints of the feet) score. The joint erosion assessment is scored according to the surface area involved, from 0 to 5, with 0 indicating no erosion and 5 indicating complete collapse of bone whereas the JSN assessment including subluxation, is scored from 0 (normal) to 4 (bony ankylosis or complete luxation). The total score ranges from 0 (best) to 448 (worst) with higher scores indicating more joint damage. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Sub-score by Type of Damage (Erosion or JSN) at Week 24 and 52
vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S).JE is summary of erosion severity in 32 of hands(H) and 12 of feet(F) joints, scored as per surface area- from 0 (no erosion) to 5 (complete(CM) collapse of bone). Maximum (MAX) JES for H-160 (32*5) and MAX JES for F- 120 (12*10 [5*2 sides of foot]). MAX JES is 280 whereas JSN is summary of severity of 30 of H and 12 of F joints, scored to subluxation from 0(normal) to 4(bony ankylosis or CM luxation). MAX JSNS for H-120(30*4), and MAX JSS for F-48(12*4). MAX JSNS is 168.Thus MAX JES-280 combined with MAX JSNS-168 gives worst possible vdH-SS (i.e., JE score + JSN score) of 448. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Sub-score by Region Hand or Feet and Type Erosion or JSN at Week 24 and 52
vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S).JE is summary of erosion severity in 32 of hands(H) and 12 of feet(F) joints, scored as per surface area- from 0 (no erosion) to 5 (complete(CM) collapse of bone). Maximum (MAX) JES for H-160 (32*5) and MAX JES for F- 120 (12*10 [5*2 sides of foot]). MAX JES is 280 whereas JSN is summary of severity of 30 of H and 12 of F joints, scored to subluxation from 0(normal) to 4(bony ankylosis or CM luxation). MAX JSNS for H-120(30*4), and MAX JSS for F-48(12*4). MAX JSNS is 168.Thus MAX JES-280 combined with MAX JSNS-168 gives worst possible vdH-SS (i.e., erosion score + JSN score) of 448. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Percentage of Participants With Change From Baseline in Van Der Heijde Modified Sharpe Score (vdH-S Score) Greater Than Smallest Detectable Change (SDC) at Weeks 24 and 52
vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S). JE is summary of erosion severity in 32 of hand and 12 of feet joints, scored according to the surface area, from 0 (no erosion) to 5 (complete collapse of bone) whereas the JSN is summary of severity of 30 of hand and 12 of feet joints, scored according to the subluxation from 0 (normal) to 4 (bony ankylosis or complete luxation). The SDC is smallest change in score that is considered to be assessed correctly based on limits of agreement (that is., above the measurement error). The SDC for change from baseline in vdH-S Score is determined as: SDC=1.96 * SD / (root 2 * root k), where SD is the standard deviation of the difference between 2 readers in change from baseline in vdH-S score; k is the number of readers. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Percentage of Participants With a Change of Less Than or Equal to 0 From Baseline in Van Der Heijde Modified Sharpe (vdH-S) Score at Weeks 24 and 52
vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S).JE is summary of erosion severity in 32 of hands(H) and 12 of feet(F) joints, scored as per surface area- from 0 (no erosion) to 5 (complete(CM) collapse of bone). Maximum (MAX) JES for H-160 (32*5) and MAX JES for F- 120 (12*10 [5*2 sides of foot]). MAX JES is 280 whereas JSN is summary of severity of 30 of H and 12 of F joints, scored to subluxation from 0(normal) to 4(bony ankylosis or CM luxation). MAX JSNS for H-120(30*4), and MAX JSS for F-48(12*4). MAX JSNS is 168.Thus MAX JES-280 combined with MAX JSNS-168 gives worst possible vdH-SS of (i.e., erosion score + JSN score) 448. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Change From Baseline in Van Der Heijde Modified Sharpe Score (vdH-S Score) by Reader at Weeks 24 and 52
vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S).JE is summary of erosion severity in 32 of hands(H) and 12 of feet(F) joints, scored as per surface area- from 0 (no erosion) to 5 (complete(CM) collapse of bone). Maximum (MAX) JES for H-160 (32*5) and MAX JES for F- 120 (12*10 [5*2 sides of foot]). MAX JES is 280 whereas JSN is summary of severity of 30 of H and 12 of F joints, scored to subluxation from 0(normal) to 4(bony ankylosis or CM luxation). MAX JSNS for H-120(30*4), and MAX JSS for F-48(12*4). MAX JSNS is 168.Thus MAX JES-280 combined with MAX JSNS-168 gives worst possible vdH-SS (i.e., JE score + JSN score) of 448. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Change From Baseline in Serum C-reactive Protein (CRP) Levels Through Week 52
Serum CRP is a marker of systemic inflammation. A negative change from baseline in CRP represents improvement. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Change From Baseline in the Duration of Morning Stiffness Through Week 52
Duration of morning stiffness was defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness in minutes (If none was present = 0; If morning stiffness was continuing at the time of assessment or was unusual compared to the recent past, average of duration of stiffness over the past 3 days was reported; If stiffness persisted the entire day, 1440 minutes was recorded). Negative values for this outcome measure represent improvement, i.e. shortening of duration of morning stiffness. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Change From Baseline in Physical and Mental Component Summary Scores of 36-Item Short Form Health Survey (SF-36) at Weeks 24 and 52
SF-36 questionnaire is health related quality of life (QOL) instrument with 36 questions with 8 multi-item scales (evaluated limitations in): physical functioning due to health problems; usual role activities due to physical health problems; Bodily pain; General mental health (psychological distress and well-being); usual role activities due to personal or emotional problems; social functioning due to physical or mental health problems; Vitality (energy and fatigue); General health perception. Each 8 scales scored from 0 to 100 with higher scores= better health. Based on scale scores, summary scores, physical component score (PCS) and mental component score (MCS) will be derived. Scoring is derived based on algorithm developed in software provided by developer. Summary MCS and PCS score is also scaled from 0 to 100 with higher scores= better health. Participants were analyzed according to randomized treatment groups they were assigned regardless of treatments they actually received.
Percentage of Participants With Greater Than or Equal to 4-Point Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 8, 16, 24, 36 and 52
The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) is a questionnaire that assesses self-reported tiredness, weakness, and difficulty conducting usual activities due to fatigue. The questionnaire consists of 13 questions that assess a participant's level of fatigue and tiredness over the last 7 days. Each question is graded on a 5-point scale (0 - 4); and accordingly, the total FACIT-Fatigue scores can range from 0 to 52, with lower score reflecting more fatigue and higher scores reflecting less fatigue. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Change From Baseline in Total Scores of Work Limitations Questionnaire (WLQ) Week 8, 16, 24, 36 and 52
The Work Limitations Questionnaire (WLQ) was used to measure the impairment in work-related productivity, with reference to the previous two weeks. Each work-related question is scored from 0 to 4 and the total score ranges from 0-100, with lower scores signifying fewer limitations at work. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Change From Baseline in EuroQol Health State Visual Analogue Scale (EQ VAS)
The EuroQol Health State Visual Analogue Scale (EQ VAS) records the respondent's self-rated health on a vertical line, VAS where the endpoints are labeled as 0= 'Worst imaginable health state' and 100= 'Best imaginable health state'. The EQ VAS can be used as a quantitative measure of health outcome as judged by the individual respondents. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Change From Baseline in EuroQol EQ-5D-3L Descriptive System
The EQ-5D-3L Descriptive System comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, with 1.00 indicating "full health" and 0 representing dead. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Full Information
NCT ID
NCT01604343
First Posted
May 21, 2012
Last Updated
December 8, 2017
Sponsor
Janssen Research & Development, LLC
Collaborators
GlaxoSmithKline
1. Study Identification
Unique Protocol Identification Number
NCT01604343
Brief Title
A Study of CNTO 136 (Sirukumab), Administered Subcutaneously, in Patients With Active Rheumatoid Arthritis Despite Disease-Modifying Antirheumatic Drug (DMARD) Therapy (SIRROUND-D)
Official Title
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Study of CNTO 136 (Sirukumab), a Human Anti-IL-6 Monoclonal Antibody, Administered Subcutaneously, in Subjects With Active Rheumatoid Arthritis Despite DMARD Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
August 15, 2012 (Actual)
Primary Completion Date
September 2, 2015 (Actual)
Study Completion Date
December 6, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
Collaborators
GlaxoSmithKline
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to assess the efficacy of sirukumab as measured by the reduction of the signs and symptoms of rheumatoid arthritis (RA) and inhibition of radiographic progression in patients with active RA who are unresponsive to treatment with disease-modifying antirheumatic drugs (DMARD).
Detailed Description
Patients will be randomly assigned to treatment groups, and they and study personnel will not know the identity of the treatments given. Some patients will receive a placebo, which resembles a medication, but does not contain an active substance. This helps to determine if the study agent is effective. Patients will receive placebo or sirukumab by injection under the skin. The expected duration of the study is 120 weeks, which includes 104 weeks of treatment. Participants who complete participation in the study will be eligible for inclusion into the long-term safety and efficacy study, if enrollment at a participating site is available to them. If they do not participate in the long-term study, they will continue into the safety follow-up for approximately 16 weeks. The placebo-controlled portion of the study is through Week 52, when placebo patients will cross over to one of two sirukumab dose regimens. Patient safety will be monitored throughout the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arthritis, Rheumatoid
Keywords
Active rheumatoid arthritis despite disease-modifying antirheumatic drug therapy, Sirukumab, Human Anti-IL-6 monoclonal antibody
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
1670 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo then Sirukumab 50 mg or Sirukumab 100 mg
Arm Type
Experimental
Arm Title
Sirukumab 100 mg
Arm Type
Experimental
Arm Title
Sirukumab 50 mg + Placebo
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Form=solution for injection, route=subcutaneous use; every 2 weeks from Week 0 through Week 50.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Form=solution for injection, route=subcutaneous use; Weeks 2, 6, and every 4 weeks through Week 104.
Intervention Type
Drug
Intervention Name(s)
Sirukumab
Intervention Description
Type=exact, unit=mg, number=50 or 100, form=solution for injection, route=subcutaneous use; every 2 weeks for 100 mg and every 4 weeks for 50 mg, Week 52 through Week 104.
Intervention Type
Drug
Intervention Name(s)
Sirukumab
Intervention Description
Type=exact, unit=mg, number=100, form=solution for injection, route=subcutaneous use; Weeks 0, 2, and every 2 weeks through Week 104.
Intervention Type
Drug
Intervention Name(s)
Sirukumab
Intervention Description
Type=exact, unit=mg, number=50, form=solution for injection, route=subcutaneous use; Weeks 0, 4, and every 4 weeks through Week 104.
Primary Outcome Measure Information:
Title
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Week 16
Description
ACR 20 response is greater than or equal to (>=) 20 percent (%) improvement in both tender joint count (68) and swollen joint count (66) and >= 20% improvement in 3 of following 5 assessments:Participant's assessment of pain using visual analog scale (VAS) (0-10 scale, 0=no pain and 10=worst possible pain),Participant's global assessment of disease activity by using VAS (scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician's global assessment of disease activity using VAS (scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), Participant's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) (scale ranges from 0= no difficulty to 3= inability to perform a task in that area), and Serum C-reactive protein (CRP). Participants were analyzed according to randomized treatment groups they were assigned, regardless of treatments they actually received. Here, TF= treatment failure.
Time Frame
Week 16
Title
Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Score at Week 52
Description
The van der Heijde-modified Sharpe (vdH-S) score is defined as a measurement of progression in structural damage. It is the sum of joint erosion (32 joints of the hands and 12 joints of the feet) score and joint space narrowing (JSN) (30 joints of the hands and 12 joints of the feet) score. The joint erosion assessment is scored according to the surface area involved, from 0 to 5, with 0 indicating no erosion and 5 indicating complete collapse of bone whereas the JSN assessment including subluxation, is scored from 0 (normal) to 4 (bony ankylosis or complete luxation). The total score ranges from 0 (best) to 448 (worst) with higher scores indicating more joint damage. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received. Here, EE= early escape.
Time Frame
Baseline, Week 52
Secondary Outcome Measure Information:
Title
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24
Description
The Health Assessment Questionnaire-Disability Index (HAQ-DI) score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Baseline, Week 24
Title
Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24
Description
An American College of Rheumatology (ACR) 50 response is defined as >= 50 % improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and >= 50% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area), and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Week 24
Title
Percentage of Participants With Disease Activity Index Score 28 (DAS28) (C-reactive Protein (CRP) Remission at Week 24
Description
The DAS28 based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. The Disease Activity Index Score 28 (DAS28) C-reactive protein (CRP) remission is defined as a DAS28 (CRP) value of less than 2.6 at a visit. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Week 24
Title
Percentage of Participants With Major Clinical Response (MCR) at Week 52
Description
MCR- participant achieving ACR 70 response for 6 continuous months (24 weeks) in the study period (i.e., through Week 52). An ACR 70 response is defined as >= 70% improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and >= 70% improvement in 3 of the following 5 assessments Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician's global assessment of disease activity using VAS (scale ranges from 0 to 10, [0=no arthritis to 10=extremely active arthritis]), Participant's assessment of physical function as measured by HAQ-DI (scale ranges from 0= no difficulty, to 3= inability to perform a task in that area) and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Week 52
Title
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response Through Week 52
Description
An ACR 20 response is defined as >= 20 % improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and >= 20% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area), and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Week 2, 4, 6, 8, 12, 18, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
Percentage of Participants With an American College of Rheumatology (ACR) 50 Response
Description
An ACR 50 response is defined as >= 50 % improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and >= 50% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Week 2, 4, 6, 8, 12, 16, 18, 20, 28, 32, 36, 40, 44, 48 and 52
Title
Percentage of Participants With an American College of Rheumatology (ACR) 70 Response Through Week 52
Description
An ACR 70 response is defined as >= 70 % improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and >= 70% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Title
Percentage of Participants With an American College of Rheumatology (ACR) 90 Response Through Week 52
Description
An ACR 90 response is defined as >= 90 percent (%) improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and >= 90% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Title
Percentage of Participants With Disease Activity Index Score 28 (DAS28) C-reactive Protein (CRP) Response Through Week 52
Description
DAS28 based on C-Reactive Protein (CRP), a statistically derived index combining tender joints (28), swollen joints (28), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both upper right extremity and upper left extremity as well as knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. Good responders: improvement from baseline greater than (>) 1.2 with DAS28 less than or equal to (<=) 3.2; moderate responders: improvement from baseline >1.2 with DAS28 >3.2 to <=5.1 or improvement from baseline >0.6 to <=1.2 with DAS28 <=5.1; non-responders: improvement from baseline <=0.6 or improvement from baseline >0.6 and <=1.2 with DAS28 >5.1. Participants were analyzed according to randomized treatment groups they were assigned to, regardless of treatments they actually received.
Time Frame
Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Title
Change From Baseline in Disease Activity Index Score 28 (DAS28) C-reactive Protein (CRP) Through Week 52
Description
The DAS28 based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. A negative change from baseline in DAS28 (CRP) (that is, a decrease from baseline) indicates improvement from baseline. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Title
Percentage of Participants With Disease Activity Index Score 28 (DAS28) (C-reactive Protein (CRP) Remission Through Week 52
Description
The DAS28 based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. The Disease Activity Index Score 28 (DAS28) C-reactive protein (CRP) remission is defined as a DAS28 (CRP) value of less than 2.6 at a visit. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Week 2, 4, 6, 8, 12, 16, 18, 20, 28, 32, 36, 40, 44, 48 and 52
Title
Change From Baseline in Simplified Disease Activity Index (SDAI) Score Through Week 52
Description
The SDAI score is a derived score combining tender joints (28 joints), swollen joints (28 joints), patient's global assessment of disease activity, physician's global assessments of disease activity, and CRP. The total score range is from 0 to 86 with a lower score indicating less disease activity. A negative change from baseline indicates an improvement and a positive change from baseline indicates a worsening. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Title
Change From Baseline in Clinical Disease Activity Index (CDAI) Score Through Week 52
Description
The CDAI score is a derived score of 4 components: tender joints (28 joints), swollen joints (28 joints), patient's global assessment of disease activity, and physician's global assessments of disease activity. The total score ranges from 0 to 76 with a lower score indicating less disease activity. A negative change in CDAI score indicates an improvement in disease activity and a positive change in score indicates a worsening of disease activity. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Title
Percentage of Participants With Simplified Disease Activity Index Based (SDAI-based) American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) Remission Through Week 52
Description
Participant having SDAI-based ACR/EULAR remission at a visit if SDAI score is of <= 3.3. SDAI derived by combining 5 disease assessments: tender joint (28), swollen joint (28) counts, participants global assessment of disease activity using VAS (scale ranges from 0 to 10 [0 =very well to 10 = very poor]), physicians global assessment of disease activity using VAS (scale ranges from 0 to 10 [0=no arthritis to 10=extremely active arthritis]) and CRP. 28 joints evaluated for swelling and tenderness are same set of 28 joints used in DAS28 includes shoulder, elbow, wrist, MCP1, MCP2, MCP3, MCP4, MCP5, PIP1, PIP2, PIP3, PIP4, PIP5 joints of upper right and left extremities and knee joints of lower right and left extremities. Change from baseline in SDAI score measures change in disease activity, where negative change= improvement and positive change= worsening. Participants were analyzed according to randomized treatment groups they were assigned regardless of treatments actually received.
Time Frame
Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Title
Percentage of Participants With Boolean-based American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) Remission Through Week 52
Description
A participant was considered as having achieved the Boolean-based American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) remission at a visit if all of the following 4 criteria were met at that visit: Tender joint count (68 joints) less than or equal to (<=) 1; Swollen joint count (66 joints) <=1; CRP <=1 milligram per deciliter (mg/dL); Patient's Global Assessment of Disease Activity <=1 on a 0 (very well) to 10 (very poor) VAS. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Title
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Through Week 52
Description
The Health Assessment Questionnaire-Disability Index (HAQ-DI) score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Negative change reflects an improvement and a positive change reflects a worsening. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 28, 32, 36, 40, 44, 48 and 52
Title
Area Under the Curve (AUC) of Change From Baseline in HAQ-DI Score From Week 0 Through Week 24 and From Week 0 Through Week 52
Description
HAQ-DI has 20-question in 8 functional areas: dressing, arising, eating, walking, hygiene, reaching, gripping, and daily living activities, scored from 0=no difficulty to 3=inability to perform task in that area. Overall score computed as sum of domain score divided by number of domains answered. Total possible score range 0= least difficulty to 3= extreme difficulty. AUC of change from baseline in HAQ-DI score is AUC of change from baseline in HAQ-DI score versus time. AUC was calculated based on measurement (observed HAQ-DI score change from baseline) at scheduled visits using trapezoidal rule.Functional status was determined as cumulative measure of HAQ-DI over 1 year by using AUC of change from baseline in HAQ-DI score through week 52. Decreases in AUC of change from baseline in HAQ-DI means greater average improvement in physical function over time. Participants analyzed according to randomized treatment groups they were assigned, regardless of treatments they actually received.
Time Frame
Week 0 Through Week 24 and 52
Title
Percentage of Participants With Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Through Week 52
Description
HAQ-DI response was defined as change of less than -0.22 from baseline in HAQ-DI score. The HAQ-DI score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Title
Percentage of Participants With Health Assessment Questionnaire-Disability Index (HAQ-DI) Score of Less Than or Equal to 0.5
Description
HAQ-DI score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Title
Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Score at Week 24
Description
vdH-S score is defined as a measurement of progression in structural damage. It is the sum of joint erosion (32 joints of the hands and 12 joints of the feet) score and joint space narrowing (JSN) (30 joints of the hands and 12 joints of the feet) score. The joint erosion assessment is scored according to the surface area involved, from 0 to 5, with 0 indicating no erosion and 5 indicating complete collapse of bone whereas the JSN assessment including subluxation, is scored from 0 (normal) to 4 (bony ankylosis or complete luxation). The total score ranges from 0 (best) to 448 (worst) with higher scores indicating more joint damage. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Baseline, Week 24
Title
Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Sub-score by Type of Damage (Erosion or JSN) at Week 24 and 52
Description
vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S).JE is summary of erosion severity in 32 of hands(H) and 12 of feet(F) joints, scored as per surface area- from 0 (no erosion) to 5 (complete(CM) collapse of bone). Maximum (MAX) JES for H-160 (32*5) and MAX JES for F- 120 (12*10 [5*2 sides of foot]). MAX JES is 280 whereas JSN is summary of severity of 30 of H and 12 of F joints, scored to subluxation from 0(normal) to 4(bony ankylosis or CM luxation). MAX JSNS for H-120(30*4), and MAX JSS for F-48(12*4). MAX JSNS is 168.Thus MAX JES-280 combined with MAX JSNS-168 gives worst possible vdH-SS (i.e., JE score + JSN score) of 448. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Baseline, Week 24 and 52
Title
Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Sub-score by Region Hand or Feet and Type Erosion or JSN at Week 24 and 52
Description
vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S).JE is summary of erosion severity in 32 of hands(H) and 12 of feet(F) joints, scored as per surface area- from 0 (no erosion) to 5 (complete(CM) collapse of bone). Maximum (MAX) JES for H-160 (32*5) and MAX JES for F- 120 (12*10 [5*2 sides of foot]). MAX JES is 280 whereas JSN is summary of severity of 30 of H and 12 of F joints, scored to subluxation from 0(normal) to 4(bony ankylosis or CM luxation). MAX JSNS for H-120(30*4), and MAX JSS for F-48(12*4). MAX JSNS is 168.Thus MAX JES-280 combined with MAX JSNS-168 gives worst possible vdH-SS (i.e., erosion score + JSN score) of 448. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Baseline, Week 24 and 52
Title
Percentage of Participants With Change From Baseline in Van Der Heijde Modified Sharpe Score (vdH-S Score) Greater Than Smallest Detectable Change (SDC) at Weeks 24 and 52
Description
vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S). JE is summary of erosion severity in 32 of hand and 12 of feet joints, scored according to the surface area, from 0 (no erosion) to 5 (complete collapse of bone) whereas the JSN is summary of severity of 30 of hand and 12 of feet joints, scored according to the subluxation from 0 (normal) to 4 (bony ankylosis or complete luxation). The SDC is smallest change in score that is considered to be assessed correctly based on limits of agreement (that is., above the measurement error). The SDC for change from baseline in vdH-S Score is determined as: SDC=1.96 * SD / (root 2 * root k), where SD is the standard deviation of the difference between 2 readers in change from baseline in vdH-S score; k is the number of readers. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Weeks 24 and 52
Title
Percentage of Participants With a Change of Less Than or Equal to 0 From Baseline in Van Der Heijde Modified Sharpe (vdH-S) Score at Weeks 24 and 52
Description
vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S).JE is summary of erosion severity in 32 of hands(H) and 12 of feet(F) joints, scored as per surface area- from 0 (no erosion) to 5 (complete(CM) collapse of bone). Maximum (MAX) JES for H-160 (32*5) and MAX JES for F- 120 (12*10 [5*2 sides of foot]). MAX JES is 280 whereas JSN is summary of severity of 30 of H and 12 of F joints, scored to subluxation from 0(normal) to 4(bony ankylosis or CM luxation). MAX JSNS for H-120(30*4), and MAX JSS for F-48(12*4). MAX JSNS is 168.Thus MAX JES-280 combined with MAX JSNS-168 gives worst possible vdH-SS of (i.e., erosion score + JSN score) 448. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Week 24 and 52
Title
Change From Baseline in Van Der Heijde Modified Sharpe Score (vdH-S Score) by Reader at Weeks 24 and 52
Description
vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S).JE is summary of erosion severity in 32 of hands(H) and 12 of feet(F) joints, scored as per surface area- from 0 (no erosion) to 5 (complete(CM) collapse of bone). Maximum (MAX) JES for H-160 (32*5) and MAX JES for F- 120 (12*10 [5*2 sides of foot]). MAX JES is 280 whereas JSN is summary of severity of 30 of H and 12 of F joints, scored to subluxation from 0(normal) to 4(bony ankylosis or CM luxation). MAX JSNS for H-120(30*4), and MAX JSS for F-48(12*4). MAX JSNS is 168.Thus MAX JES-280 combined with MAX JSNS-168 gives worst possible vdH-SS (i.e., JE score + JSN score) of 448. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Baseline, Weeks 24 and 52
Title
Change From Baseline in Serum C-reactive Protein (CRP) Levels Through Week 52
Description
Serum CRP is a marker of systemic inflammation. A negative change from baseline in CRP represents improvement. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Title
Change From Baseline in the Duration of Morning Stiffness Through Week 52
Description
Duration of morning stiffness was defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness in minutes (If none was present = 0; If morning stiffness was continuing at the time of assessment or was unusual compared to the recent past, average of duration of stiffness over the past 3 days was reported; If stiffness persisted the entire day, 1440 minutes was recorded). Negative values for this outcome measure represent improvement, i.e. shortening of duration of morning stiffness. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Title
Change From Baseline in Physical and Mental Component Summary Scores of 36-Item Short Form Health Survey (SF-36) at Weeks 24 and 52
Description
SF-36 questionnaire is health related quality of life (QOL) instrument with 36 questions with 8 multi-item scales (evaluated limitations in): physical functioning due to health problems; usual role activities due to physical health problems; Bodily pain; General mental health (psychological distress and well-being); usual role activities due to personal or emotional problems; social functioning due to physical or mental health problems; Vitality (energy and fatigue); General health perception. Each 8 scales scored from 0 to 100 with higher scores= better health. Based on scale scores, summary scores, physical component score (PCS) and mental component score (MCS) will be derived. Scoring is derived based on algorithm developed in software provided by developer. Summary MCS and PCS score is also scaled from 0 to 100 with higher scores= better health. Participants were analyzed according to randomized treatment groups they were assigned regardless of treatments they actually received.
Time Frame
Baseline, Week 24 and 52
Title
Percentage of Participants With Greater Than or Equal to 4-Point Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 8, 16, 24, 36 and 52
Description
The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) is a questionnaire that assesses self-reported tiredness, weakness, and difficulty conducting usual activities due to fatigue. The questionnaire consists of 13 questions that assess a participant's level of fatigue and tiredness over the last 7 days. Each question is graded on a 5-point scale (0 - 4); and accordingly, the total FACIT-Fatigue scores can range from 0 to 52, with lower score reflecting more fatigue and higher scores reflecting less fatigue. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Week 8, 16, 24, 36 and 52
Title
Change From Baseline in Total Scores of Work Limitations Questionnaire (WLQ) Week 8, 16, 24, 36 and 52
Description
The Work Limitations Questionnaire (WLQ) was used to measure the impairment in work-related productivity, with reference to the previous two weeks. Each work-related question is scored from 0 to 4 and the total score ranges from 0-100, with lower scores signifying fewer limitations at work. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Baseline, Week 8, 16, 24, 36 and 52
Title
Change From Baseline in EuroQol Health State Visual Analogue Scale (EQ VAS)
Description
The EuroQol Health State Visual Analogue Scale (EQ VAS) records the respondent's self-rated health on a vertical line, VAS where the endpoints are labeled as 0= 'Worst imaginable health state' and 100= 'Best imaginable health state'. The EQ VAS can be used as a quantitative measure of health outcome as judged by the individual respondents. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
Baseline, Week 8, 16, 24, 36 and 52
Title
Change From Baseline in EuroQol EQ-5D-3L Descriptive System
Description
The EQ-5D-3L Descriptive System comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, with 1.00 indicating "full health" and 0 representing dead. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame
at Week 8, 16, 24, and 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have a diagnosis of rheumatoid arthritis (RA) for at least 3 months before screening
Have moderately to severely active RA with at least 6 of 68 tender joints and 6 of 66 swollen joints, at screening and at baseline
Have been unresponsive to single-agent or combination disease-modifying antirheumatic drugs (DMARD) therapy that includes methotrexate (MTX) or sulfasalazine (SSZ) due to lack of benefit after at least 12 weeks of DMARD, as assessed by the treating physician
If using oral corticosteroids, must be on a stable dose equivalent to less than or equal to 10 mg/day of prednisone for at least 2 weeks prior to the first administration of study agent. If currently not using corticosteroids, must not have received oral corticosteroids for at least 2 weeks prior to the first administration of study agent
If using non nonsteroidal anti-inflammatory drug (NSAIDs) or other analgesics for RA, must be on a stable dose for at least 2 weeks prior to the first administration of study agent
If using non-biologic DMARD such as MTX, SSZ, hydroxychloroquine, chloroquine, or bucillamine, must be on a stable dose for at least 4 weeks prior to the first administration of study agent and should have no serious toxic side effects attributable to the DMARD
Exclusion Criteria:
Has a history of intolerance to at least 2 or inadequate response to at least 1 anti-tumor necrosis factor alpha agent after 3 months of therapy
Has received infliximab, golimumab, adalimumab, or certolizumab pegol within 3 months of the first study agent administration
Has received etanercept or yisaipu within 6 weeks of the first study agent administration
Has a history of intolerance to tocilizumab that precluded further treatment with it, or inadequate response to 3 months of tocilizumab (anti-IL-6 receptor) therapy
Has used B-cell-depleting therapy (eg, rituximab) within 7 months of first study agent administration or have evidence during screening of abnormally low B cell level caused by previous B-cell depletion therapy
Has used anakinra within 4 weeks of first study agent administration
Has used any other biologic therapy for the treatment of RA within 3 months of the first study agent administration
Has received intra-articular (IA), intramuscular (IM), or intravenous (IV) corticosteroids for RA, including adrenocorticotrophic hormone during the 4 weeks prior to first study agent administration-
Has received leflunomide within 24 months before the first study agent administration and have not undergone a drug elimination procedure, unless the M1 metabolite is measured and is undetectable. If a drug elimination procedure is performed during screening, the M1 metabolite should be measured and found to be undetectable
Has a history of cyclophosphamide or cytotoxic agent use
Has received cyclosporine A, azathioprine, tacrolimus, mycophenolate mofetil, oral or parenteral gold, or D-penicillamine within 4 weeks of the first study agent administration
Has received an investigational drug (including investigational vaccines) or used an investigational medical device within 3 months or 5 half lives, whichever is longer, before the first study agent administration
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Glendale
State/Province
Arizona
Country
United States
City
Mesa
State/Province
Arizona
Country
United States
City
Peoria
State/Province
Arizona
Country
United States
City
Phoenix
State/Province
Arizona
Country
United States
City
Covina
State/Province
California
Country
United States
City
El Cajon
State/Province
California
Country
United States
City
Glendale
State/Province
California
Country
United States
City
Hemet
State/Province
California
Country
United States
City
Huntington Beach
State/Province
California
Country
United States
City
La Jolla
State/Province
California
Country
United States
City
La Palma
State/Province
California
Country
United States
City
Whittier
State/Province
California
Country
United States
City
Aventura
State/Province
Florida
Country
United States
City
Brandon
State/Province
Florida
Country
United States
City
Daytona Beach
State/Province
Florida
Country
United States
City
Lake Mary
State/Province
Florida
Country
United States
City
Naples
State/Province
Florida
Country
United States
City
Palm Harbor
State/Province
Florida
Country
United States
City
Tampa
State/Province
Florida
Country
United States
City
Zephyrhills
State/Province
Florida
Country
United States
City
Indianapolis
State/Province
Indiana
Country
United States
City
Cedar Rapids
State/Province
Iowa
Country
United States
City
Bowling Green
State/Province
Kentucky
Country
United States
City
Monroe
State/Province
Louisiana
Country
United States
City
Wheaton
State/Province
Maryland
Country
United States
City
Eagan
State/Province
Minnesota
Country
United States
City
Saint Louis
State/Province
Missouri
Country
United States
City
Springfield
State/Province
Missouri
Country
United States
City
Omaha
State/Province
Nebraska
Country
United States
City
Albuquerque
State/Province
New Mexico
Country
United States
City
Brooklyn
State/Province
New York
Country
United States
City
Plainview
State/Province
New York
Country
United States
City
Charlotte
State/Province
North Carolina
Country
United States
City
Cincinnati
State/Province
Ohio
Country
United States
City
Middleburg Heights
State/Province
Ohio
Country
United States
City
Edmond
State/Province
Oklahoma
Country
United States
City
Tulsa
State/Province
Oklahoma
Country
United States
City
Duncansville
State/Province
Pennsylvania
Country
United States
City
Wyomissing
State/Province
Pennsylvania
Country
United States
City
Carrollton
State/Province
Texas
Country
United States
City
Corpus Christi
State/Province
Texas
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Houston
State/Province
Texas
Country
United States
City
Lubbock
State/Province
Texas
Country
United States
City
Mesquite
State/Province
Texas
Country
United States
City
Kennewick
State/Province
Washington
Country
United States
City
Beckley
State/Province
West Virginia
Country
United States
City
Clarksburg
State/Province
West Virginia
Country
United States
City
Plovdiv
Country
Bulgaria
City
Sofia
Country
Bulgaria
City
Victoria
State/Province
British Columbia
Country
Canada
City
Winnipeg
State/Province
Manitoba
Country
Canada
City
Ottawa
State/Province
Ontario
Country
Canada
City
Burlington
Country
Canada
City
Edmonton
Country
Canada
City
Rancagua
Country
Chile
City
Santiago
Country
Chile
City
Valdivia
Country
Chile
City
Bogotá
Country
Colombia
City
Chia
Country
Colombia
City
Medellín
Country
Colombia
City
Osijek
Country
Croatia
City
Rijeka
Country
Croatia
City
Zagreb
Country
Croatia
City
Ayauta-Gun
Country
Japan
City
Bunkyo-Ku
Country
Japan
City
Fukuoka
Country
Japan
City
Higashihiroshima
Country
Japan
City
Izumo
Country
Japan
City
Kagoshima
Country
Japan
City
Kato
Country
Japan
City
Kawagoe
Country
Japan
City
Kita-Gun
Country
Japan
City
Kumamoto
Country
Japan
City
Kurume
Country
Japan
City
Miyazaki
Country
Japan
City
Nagano
Country
Japan
City
Nagasaki
Country
Japan
City
Nagoya
Country
Japan
City
Osaka
Country
Japan
City
Sapporo
Country
Japan
City
Sasebo
Country
Japan
City
Shimonoseki
Country
Japan
City
Shimotsuke
Country
Japan
City
Shinjuku-Ku
Country
Japan
City
Sumida-Ku
Country
Japan
City
Takaoka,Toyama
Country
Japan
City
Takasaki
Country
Japan
City
Tokorozawa
Country
Japan
City
Tokushima
Country
Japan
City
Tomishiro
Country
Japan
City
Tsu
Country
Japan
City
Ureshino
Country
Japan
City
Yokohama
Country
Japan
City
Busan
Country
Korea, Republic of
City
Daegu
Country
Korea, Republic of
City
Daejeon
Country
Korea, Republic of
City
Gwangju
Country
Korea, Republic of
City
Incheon
Country
Korea, Republic of
City
Jeonju-Si
Country
Korea, Republic of
City
Namdong-Gu
Country
Korea, Republic of
City
Seongnam-Si
Country
Korea, Republic of
City
Seoul
Country
Korea, Republic of
City
Suwon
Country
Korea, Republic of
City
Alytus
Country
Lithuania
City
Kaunas
Country
Lithuania
City
Klaipeda
Country
Lithuania
City
Siauliai
Country
Lithuania
City
Kuala Lumpur
Country
Malaysia
City
Kuching
Country
Malaysia
City
Cuernavaca
Country
Mexico
City
Guadalajara
Country
Mexico
City
Juarez
Country
Mexico
City
Merida
Country
Mexico
City
Mexicali
Country
Mexico
City
Mexico Df
Country
Mexico
City
Morelia
Country
Mexico
City
México
Country
Mexico
City
San Luis De Potosi
Country
Mexico
City
Bialystok
Country
Poland
City
Bydgoszcz
Country
Poland
City
Elblag
Country
Poland
City
Lublin
Country
Poland
City
Poznan
Country
Poland
City
Ustron
Country
Poland
City
Warszawa N/A
Country
Poland
City
Warszawa
Country
Poland
City
Bucharest
Country
Romania
City
Bucuresti
Country
Romania
City
Cluj-Napoca
Country
Romania
City
Iasi
Country
Romania
City
Kemerovo
Country
Russian Federation
City
Moscow
Country
Russian Federation
City
Novosibirsk
Country
Russian Federation
City
Orenburg
Country
Russian Federation
City
Ryazan
Country
Russian Federation
City
Saint Petersburg
Country
Russian Federation
City
Saratov
Country
Russian Federation
City
Smolensk
Country
Russian Federation
City
St Petersburg
Country
Russian Federation
City
Ulyanovsk
Country
Russian Federation
City
Yaroslavl
Country
Russian Federation
City
Belgrade
Country
Serbia
City
Kragujevac
Country
Serbia
City
Niska Banja
Country
Serbia
City
Cape Town
Country
South Africa
City
Port Elizabeth
Country
South Africa
City
Pretoria
Country
South Africa
City
Kaohsiung
Country
Taiwan
City
Taichung City
Country
Taiwan
City
Taichung
Country
Taiwan
City
Taipei
Country
Taiwan
City
Donetsk
Country
Ukraine
City
Kharkiv
Country
Ukraine
City
Kiev
Country
Ukraine
City
Kyiv
Country
Ukraine
City
Odesa
Country
Ukraine
City
Sympheropol
Country
Ukraine
City
Vinnytsia
Country
Ukraine
City
Zaporizhzhia
Country
Ukraine
12. IPD Sharing Statement
Citations:
PubMed Identifier
28855173
Citation
Takeuchi T, Thorne C, Karpouzas G, Sheng S, Xu W, Rao R, Fei K, Hsu B, Tak PP. Sirukumab for rheumatoid arthritis: the phase III SIRROUND-D study. Ann Rheum Dis. 2017 Dec;76(12):2001-2008. doi: 10.1136/annrheumdis-2017-211328. Epub 2017 Aug 30.
Results Reference
derived
Learn more about this trial
A Study of CNTO 136 (Sirukumab), Administered Subcutaneously, in Patients With Active Rheumatoid Arthritis Despite Disease-Modifying Antirheumatic Drug (DMARD) Therapy (SIRROUND-D)
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