Back to resultsA Study of RoActemra/Actemra (Tocilizumab) With or Without Methotrexate in Patients With Mild to Moderate Rheumatoid Arthritis With an Inadequate Response to Methotrexate
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 3
Locations
Austria
Study Type
Interventional
Intervention
methotrexate
methotrexate
placebo
tocilizumab [RoActemra/Actemra]
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility Criteria
Inclusion Criteria:
- Adult patients, >/= 18 years of age
- Rheumatoid arthritis of >/= 1 year duration
- Mild to moderate disease activity at screening (DAS 28 </= 4.5 and >2.6)
- On methotrexate treatment for at least 12 weeks, at stable oral dose of (10)15 mg to 25 mg/week for at least 6 weeks prior to Day 1
- Body weight </= 150 kg
- Oral corticosteroids must have been at stable dose (maximum 10 mg/day) for at least 25 out of 28 days prior to baseline
Exclusion Criteria:
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months after baseline
- Rheumatic autoimmune disease other than rheumatoid arthritis
- Functional class IV American College of Rheumatology (ACR) Classification
- Prior history of or current inflammatory joint disease other than rheumatoid arthritis
- Treatment with a biologic agent at any time prior to baseline
- Treatment with traditional DMARDs other than methotrexate within 1 month (for leflunomide 3 months) prior to baseline
- Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
- Previous treatment with tocilizumab
- Pregnant or lactating women
- Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids
- Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections
- History of or currently active primary or secondary immunodeficiency
- Evidence of active malignant disease, malignancies diagnosed within the previous 5 years
- Active tuberculosis requiring treatment within the previous 3 years
- Positive for HIV infection
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
A Methotrexate
B Methotrexate Placebo
Arm Description
Outcomes
Primary Outcome Measures
Change From Week 12 (Randomization) to Week 24 in DAS28
The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis (RA). The index includes swollen joint counts (SJC) and tender joint counts (TJC), both scored 0-28 (higher scores indicate higher disease activity), as well as acute phase response (APR) determined as erythrocyte sedimentation rate (ESR), and general health (GH), both scored 1-100 (higher scores indicate higher disease activity). DAS28 was calculated according to the following formula: DAS28 equals (=) [0.56 multiplied by (*) the square root (√) of TJC] plus (+) [0.28 * √ of SJC] + (0.70 * the natural logarithm (ln) ESR in millimeters per hour (mm/h)] + [0.014 * GH in mm visual analogue assessment (VAS)]. A negative change from randomization indicated improvement.
Secondary Outcome Measures
Percentage of Participants With DAS28 Remission at Week 24
The DAS28 is a combined index for measuring disease activity in RA. The index includes SJC and TJC, both scored 0-28 (higher scores indicate higher disease activity, as well as APR determined as ESR, and GH, both scored 1-100 (higher scores indicate higher disease activity). DAS28 was calculated according to the following formula: DAS28 = 0.56 * √ of TJC + 0.28 * √ of SJC + 0.70 * ln ESR mm/hr + 0.014 * GH in mm VAS. DAS28 < 2.6 = remission.
vPercentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Week 24
The CDAI is a combined index for measuring disease activity in RA. CDAI is the sum of TJC and SJC, both scored 0-28 (higher scores indicate higher disease activity), as well as patient global assessment (PGA) and evaluator global assessment (EGA) of disease activity, both scored 0 to 10 centimeter (cm) as assessed by VAS. CDAI was calculated according to the following formula: CDAI = SJC + TJC + PGA + EGA. CDAI < 2.8 = remission.
Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission at Week 24
The SDAI is a combined index for measuring disease activity in RA. SDAI is the sum of TJC and SJC, both scored 0-28 (higher scores indicate higher disease activity), PGA and EGA of disease activity, both scored 0 to 10 cm as assessed by VAS, and C-reactive protein level (CRP) in milligrams per deciliter (mg/dL) where normal < 1 mg/dL. CDAI was calculated according to the following formula: SDAI = TJC + SJC + PGA + EGA + CRP. SDAI < 3.3 = remission.
Percentage of Participants With Rheumatoid Arthritis Disease Activity Index-5 (RADAI-5) Remission at Week 24
The RADAI-5 is a combined index for measuring disease activity in RA. RADAI-5 is comprised of the following 5 questions: how active was your arthritis the last 6 months? (0 = completely inactive to 10 = extremely active); how active is your arthritis today with respect to joint tenderness and swelling? (0 = completely inactive to 10 = extremely active); how severe is your arthritis pain today? (0 = no pain to 10 = unbearable pain); how would you describe your general health today? (0 = very good to 10 = very bad); and did you experience joint (hand) stiffness on awakening yesterday morning? If yes, how long did this stiffness last? (0 = no stiffness to 10 = stiffness the whole day). RADAI was calculated according to the following formula: [question (Q) 1 + Q2 + Q3 + Q4 + Q5]/5. RADAI-5 from 0-1.4 = remission.
Change From Week 12 (Randomization) to Week 24 in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score
HAQ-DI scores were obtained by scoring participants' responses to a 20-item questionnaire. HAQ-DQ evaluated 8 domains of health: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities from a range of 0 (without any difficulty) to 3 (unable to do). The sum of scores was divided by the number of domains for a total score of 0 (best) to 3 (worst). A negative change from randomization indicated improvement.
Change From Week 12 (Randomization) to Week 24 in Short Form-36 Health Survey (SF-36) Score
SF-36 scores were obtained by scoring participants' responses to a 36-item questionnaire. SF-36 evaluated 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health from a range of 1 (better) to 5 (worst). The score for each section was an average of the individual question scores, which were scaled 0-100 (100=highest level of functioning). These 8 aspects were summarized as physical and mental component scores. A negative change from randomization indicated improvement.
Change From Week 12 (Randomization) to Week 24 in Visual Analog Scales (VAS) Scores
VAS scores were obtained by scoring participants' disease activity as assessed on a 0-100 millimeter (mm) horizontal visual scale. The left-hand extreme of the line = 0 mm (no disease activity = symptom-free and no arthritis symptoms), and the right-hand extreme of the line = 100 mm (maximum disease activity). A negative change from randomization indicated improvement.
Participant Satisfaction With Treatment as Assessed by Treatment Satisfaction Questionnaire for Medication (TSQM) Score
TSQM scores were obtained by scoring participants' responses to a 14-item questionnaire. TSQM evaluated 4 aspects of treatment satisfaction: effectiveness, side effects, convenience, and global satisfaction from a range of 0 to 100 percent (%), with 100% being the best possible result.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01587989
Brief Title
A Study of RoActemra/Actemra (Tocilizumab) With or Without Methotrexate in Patients With Mild to Moderate Rheumatoid Arthritis With an Inadequate Response to Methotrexate
Official Title
A Multi-center Study of the Safety and Effect on Disease Activity of Tocilizumab (TCZ) in Combination With Methotrexate (MTX) Versus Tocilizumab Monotherapy in Patients With Mild to Moderate Rheumatoid Arthritis, With Inadequate Response to MTX (Defined as DAS 28 < 4,5 and >2,6)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
February 2014 (Actual)
Study Completion Date
February 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
Brief Summary
This multicenter study with a randomized, double-blind, parallel-group phase will evaluate the safety and efficacy of RoActemra/Actemra (tocilizumab) in combination with methotrexate versus RoActemra/Actemra monotherapy in patients with mild to moderate rheumatoid arthritis, with an inadequate response to methotrexate. Patients will receive RoActemra/Actemra 8 mg/kg intravenously every 4 weeks plus oral methotrexate 15-25 mg weekly for 12 weeks. Patients with a good/moderate EULAR response will then be randomized to receive either RoActemra/Actemra plus methotrexate or RoActemra/Actemra plus placebo for the following 12 weeks. Anticipated time on study treatment is 6 months.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
77 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A Methotrexate
Arm Type
Active Comparator
Arm Title
B Methotrexate Placebo
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Description
15-25 mg orally weekly, Weeks 1-12
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Description
15-25 mg orally weekly, Weeks 13-24
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
methotrexate placebo orally weekly, Weeks 13-24
Intervention Type
Drug
Intervention Name(s)
tocilizumab [RoActemra/Actemra]
Intervention Description
8 mg/kg iv every 4 weeks, 24 weeks
Primary Outcome Measure Information:
Title
Change From Week 12 (Randomization) to Week 24 in DAS28
Description
The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis (RA). The index includes swollen joint counts (SJC) and tender joint counts (TJC), both scored 0-28 (higher scores indicate higher disease activity), as well as acute phase response (APR) determined as erythrocyte sedimentation rate (ESR), and general health (GH), both scored 1-100 (higher scores indicate higher disease activity). DAS28 was calculated according to the following formula: DAS28 equals (=) [0.56 multiplied by (*) the square root (√) of TJC] plus (+) [0.28 * √ of SJC] + (0.70 * the natural logarithm (ln) ESR in millimeters per hour (mm/h)] + [0.014 * GH in mm visual analogue assessment (VAS)]. A negative change from randomization indicated improvement.
Time Frame
Weeks 12 and 24
Secondary Outcome Measure Information:
Title
Percentage of Participants With DAS28 Remission at Week 24
Description
The DAS28 is a combined index for measuring disease activity in RA. The index includes SJC and TJC, both scored 0-28 (higher scores indicate higher disease activity, as well as APR determined as ESR, and GH, both scored 1-100 (higher scores indicate higher disease activity). DAS28 was calculated according to the following formula: DAS28 = 0.56 * √ of TJC + 0.28 * √ of SJC + 0.70 * ln ESR mm/hr + 0.014 * GH in mm VAS. DAS28 < 2.6 = remission.
Time Frame
Week 24
Title
vPercentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Week 24
Description
The CDAI is a combined index for measuring disease activity in RA. CDAI is the sum of TJC and SJC, both scored 0-28 (higher scores indicate higher disease activity), as well as patient global assessment (PGA) and evaluator global assessment (EGA) of disease activity, both scored 0 to 10 centimeter (cm) as assessed by VAS. CDAI was calculated according to the following formula: CDAI = SJC + TJC + PGA + EGA. CDAI < 2.8 = remission.
Time Frame
Week 24
Title
Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission at Week 24
Description
The SDAI is a combined index for measuring disease activity in RA. SDAI is the sum of TJC and SJC, both scored 0-28 (higher scores indicate higher disease activity), PGA and EGA of disease activity, both scored 0 to 10 cm as assessed by VAS, and C-reactive protein level (CRP) in milligrams per deciliter (mg/dL) where normal < 1 mg/dL. CDAI was calculated according to the following formula: SDAI = TJC + SJC + PGA + EGA + CRP. SDAI < 3.3 = remission.
Time Frame
Week 24
Title
Percentage of Participants With Rheumatoid Arthritis Disease Activity Index-5 (RADAI-5) Remission at Week 24
Description
The RADAI-5 is a combined index for measuring disease activity in RA. RADAI-5 is comprised of the following 5 questions: how active was your arthritis the last 6 months? (0 = completely inactive to 10 = extremely active); how active is your arthritis today with respect to joint tenderness and swelling? (0 = completely inactive to 10 = extremely active); how severe is your arthritis pain today? (0 = no pain to 10 = unbearable pain); how would you describe your general health today? (0 = very good to 10 = very bad); and did you experience joint (hand) stiffness on awakening yesterday morning? If yes, how long did this stiffness last? (0 = no stiffness to 10 = stiffness the whole day). RADAI was calculated according to the following formula: [question (Q) 1 + Q2 + Q3 + Q4 + Q5]/5. RADAI-5 from 0-1.4 = remission.
Time Frame
Week 24
Title
Change From Week 12 (Randomization) to Week 24 in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score
Description
HAQ-DI scores were obtained by scoring participants' responses to a 20-item questionnaire. HAQ-DQ evaluated 8 domains of health: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities from a range of 0 (without any difficulty) to 3 (unable to do). The sum of scores was divided by the number of domains for a total score of 0 (best) to 3 (worst). A negative change from randomization indicated improvement.
Time Frame
Weeks 12 and 24
Title
Change From Week 12 (Randomization) to Week 24 in Short Form-36 Health Survey (SF-36) Score
Description
SF-36 scores were obtained by scoring participants' responses to a 36-item questionnaire. SF-36 evaluated 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health from a range of 1 (better) to 5 (worst). The score for each section was an average of the individual question scores, which were scaled 0-100 (100=highest level of functioning). These 8 aspects were summarized as physical and mental component scores. A negative change from randomization indicated improvement.
Time Frame
Weeks 12 and 24
Title
Change From Week 12 (Randomization) to Week 24 in Visual Analog Scales (VAS) Scores
Description
VAS scores were obtained by scoring participants' disease activity as assessed on a 0-100 millimeter (mm) horizontal visual scale. The left-hand extreme of the line = 0 mm (no disease activity = symptom-free and no arthritis symptoms), and the right-hand extreme of the line = 100 mm (maximum disease activity). A negative change from randomization indicated improvement.
Time Frame
Weeks 12 and 24
Title
Participant Satisfaction With Treatment as Assessed by Treatment Satisfaction Questionnaire for Medication (TSQM) Score
Description
TSQM scores were obtained by scoring participants' responses to a 14-item questionnaire. TSQM evaluated 4 aspects of treatment satisfaction: effectiveness, side effects, convenience, and global satisfaction from a range of 0 to 100 percent (%), with 100% being the best possible result.
Time Frame
Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult patients, >/= 18 years of age
Rheumatoid arthritis of >/= 1 year duration
Mild to moderate disease activity at screening (DAS 28 </= 4.5 and >2.6)
On methotrexate treatment for at least 12 weeks, at stable oral dose of (10)15 mg to 25 mg/week for at least 6 weeks prior to Day 1
Body weight </= 150 kg
Oral corticosteroids must have been at stable dose (maximum 10 mg/day) for at least 25 out of 28 days prior to baseline
Exclusion Criteria:
Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months after baseline
Rheumatic autoimmune disease other than rheumatoid arthritis
Functional class IV American College of Rheumatology (ACR) Classification
Prior history of or current inflammatory joint disease other than rheumatoid arthritis
Treatment with a biologic agent at any time prior to baseline
Treatment with traditional DMARDs other than methotrexate within 1 month (for leflunomide 3 months) prior to baseline
Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
Previous treatment with tocilizumab
Pregnant or lactating women
Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids
Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections
History of or currently active primary or secondary immunodeficiency
Evidence of active malignant disease, malignancies diagnosed within the previous 5 years
Active tuberculosis requiring treatment within the previous 3 years
Positive for HIV infection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Graz-Eggenberg
ZIP/Postal Code
8020
Country
Austria
City
Graz
ZIP/Postal Code
8036
Country
Austria
City
Hollabrunn
ZIP/Postal Code
2020
Country
Austria
City
Innsbruck
ZIP/Postal Code
6020
Country
Austria
City
Linz
ZIP/Postal Code
4020
Country
Austria
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
City
Stockerau
ZIP/Postal Code
2000
Country
Austria
City
Wels
ZIP/Postal Code
4600
Country
Austria
City
Wien
ZIP/Postal Code
1090
Country
Austria
City
Wien
ZIP/Postal Code
1100
Country
Austria
City
Wien
ZIP/Postal Code
1130
Country
Austria
City
Wien
ZIP/Postal Code
1140
Country
Austria
City
Wien
ZIP/Postal Code
1160
Country
Austria
12. IPD Sharing Statement
Learn more about this trial
A Study of RoActemra/Actemra (Tocilizumab) With or Without Methotrexate in Patients With Mild to Moderate Rheumatoid Arthritis With an Inadequate Response to Methotrexate
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