Back to resultsA Study of Effectiveness and Safety of CNTO 136 in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy
Primary Purpose
Arthritis, Rheumatoid
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
CNTO 136 100 mg
CNTO 136 50 mg
CNTO 136 25 mg
Placebo
Methotrexate
Sponsored by
About this trial
This is an interventional treatment trial for Arthritis, Rheumatoid focused on measuring Arthritis, Rheumatoid, Rheumatoid Arthritis, Active Rheumatoid Arthritis, CNTO 136, Interleukin-6, Anti-interleukin-6 monoclonal antibody, Methotrexate, Placebo
Eligibility Criteria
Inclusion Criteria:
- Diagnosed with rheumatoid arthritis (RA) for at least 4 months prior to screening
- Have been treated and having an inadequate response with the tolerated dose of methotrexate (MTX) (at least 15mg/week) for at least 4 months prior to screening. MTX doses of 10 or 12.5 mg/week are allowed if participant had intolerance of 15 mg/week
- MTX route of administration and dose (not to exceed 25 mg/week) should be stable for at least 6 weeks prior to the start of the study medication
- Have active RA as defined by persistent disease activity with at least 6 swollen and 6 tender joints, at the time of screening and baseline, and either anti-cyclic citrullinated peptide antibody-positive or rheumatoid factor positive at screening
- C-reactive protein greater than or equal to 1.0 mg/dL (10 mg/L)
- Agree to use one of the contraception methods defined in the protocol
Exclusion Criteria:
- Have inflammatory diseases other than RA that might confound the evaluation of the benefit of CNTO 136 therapy in arthritis
- Family history of/ have long QT syndrome; or a history of second or third-degree heart block
- Received systemic immunosuppressives or disease modifying antirheumatic drug other than MTX, sulfasalazine, hydroxychloroquine or chloroquine within 4 weeks prior to the start of study medication
- Received intra articular (into joints), intramuscular, or intravenous corticosteroids within 4 weeks prior to the start of study medication
- Positive human immunodeficiency virus test, hepatitis B or hepatitis C
- History of / have chronic or recurrent infectious disease, history of / active tuberculosis
- Have serious infection within 2 months prior to start of study medication
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Part A, Group 1
Part A, Group 2
Part B, Group 1
Part B, Group 2
Part B, Group 3
Part B, Group 4
Part B, Group 5
Arm Description
Participants will receive placebo (Week 0 to Week 10) and later CNTO 136 100 mg (Week 12 to Week 22) every 2 weeks. Stable dose of methotrexate will be maintained through Week 24.
Participants will receive CNTO 136 100 mg (Week 0 to Week 10) and later placebo (Week 12 to Week 22) every 2 weeks. Stable dose of methotrexate will be maintained through Week 24.
Participants will receive placebo (Week 0 to Week 10) and later CNTO 136 100 mg (Week 12 to Week 24) every 2 weeks. Stable dose of methotrexate will be maintained through Week 24.
Participants will receive CNTO 136 100 mg (Week 0 to Week 24) every 2 weeks. Stable dose of methotrexate will be maintained through Week 24.
Participants will receive CNTO 136 100 mg (Week 0 to Week 24) every 4 weeks and placebo at interim visits (Weeks 2, 6, 10, 14, 18, and 22). Stable dose of methotrexate will be maintained through Week 24.
Participants will receive CNTO 136 50 mg (Week 0 to Week 24) every 4 weeks and placebo at interim visits (Weeks 2, 6,10, 14, 18, and 22). Stable dose of methotrexate will be maintained through Week 24.
Participants will receive CNTO 136 25 mg (Week 0 to Week 24) every 4 weeks and placebo at interim visits (Weeks 2, 6,10, 14, 18, and 22). Stable dose of methotrexate will be maintained through Week 24.
Outcomes
Primary Outcome Measures
Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Week 12 (Part B)
An American College of Rheumatology (ACR) 50 response is defined as greater than or equal to (>=) 50 percent (%) 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 Visual Analogue Scale (Score) 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 Health Assessment Questionnaire-Disability Index (HAQ-DI, the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area), and serum C-reactive protein (CRP).
Secondary Outcome Measures
Change From Baseline in Disease Activity Index Score 28 (DAS28) Based on C-reactive Protein (CRP) at Week 12 (Part A and Part B)
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.
Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 12 (Part A)
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.
Serum Sirukumab Concentrations Through Week 38 (Part A)
Sirukumab Concentrations in serum were measured.
Serum Sirukumab Concentrations Through Week 38 (Part B)
Sirukumab Concentrations in serum were measured.
Percent Improvement From Baseline in Serum C-Reactive Protein (CRP) At Week 2 (Part A and Part B)
Serum CRP is a marker of systemic inflammation. A negative change from baseline in CRP represents improvement.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00718718
Brief Title
A Study of Effectiveness and Safety of CNTO 136 in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy
Official Title
A Phase 2, 2-Part, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled, Proof-of-concept, Dose-finding Study Evaluating the Efficacy and Safety of CNTO 136 Administered Subcutaneously in Subjects With Active Rheumatoid Arthritis Despite Methotrexate Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
August 11, 2008 (Actual)
Primary Completion Date
March 3, 2011 (Actual)
Study Completion Date
March 3, 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centocor, Inc.
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 evaluate the effectiveness and safety of subcutaneous (under the skin) administration of anti-interleukin-6 monoclonal antibody (CNTO 136) in reducing signs and symptoms of participants with active rheumatoid arthritis (RA) with methotrexate (MTX) therapy.
Detailed Description
This is a multicenter, double-blind (neither physician nor participants knows the treatment that the participant receives), randomized (study medication is assigned by chance), placebo-controlled (an inactive substance is compared with a medication to test whether the medication has a real effect in a clinical study) study. This study will be conducted in 2 parts (Part A and Part B). Each part consists of 3 phases: screening (approximately 1 month prior to the start of study medication), treatment phase (Part A: 22 weeks and Part B: 24 weeks), and follow-up phase (approximately 4 months after the last administration of study medication). In Part A, participants will be randomly assigned to 2 groups to receive CNTO 136 100 mg and placebo for 22 weeks. All participants in Part A, will be crossed over at Week 12 from placebo to CNTO 136 (for Group 1) and from CNTO 136 to placebo (for Group 2). In Part B, participants will be randomly assigned to 5 groups to receive placebo and/or 1 of 3 doses of CNTO 136 (100mg, 50mg or 25mg) for 24 weeks. Participants in Part B, Group 1 will be crossed over at Week 12 from placebo to CNTO 136. All participants should be maintained on a stable dose of MTX for at least 6 weeks prior to the start of study medication through Week 24. Safety will be evaluated by the assessment of adverse events, vital signs, clinical findings, 12-lead electrocardiogram, and clinical laboratory tests which will be monitored throughout the study. The total duration of study participation for a participant will be approximately 42 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arthritis, Rheumatoid
Keywords
Arthritis, Rheumatoid, Rheumatoid Arthritis, Active Rheumatoid Arthritis, CNTO 136, Interleukin-6, Anti-interleukin-6 monoclonal antibody, Methotrexate, Placebo
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
187 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part A, Group 1
Arm Type
Experimental
Arm Description
Participants will receive placebo (Week 0 to Week 10) and later CNTO 136 100 mg (Week 12 to Week 22) every 2 weeks. Stable dose of methotrexate will be maintained through Week 24.
Arm Title
Part A, Group 2
Arm Type
Experimental
Arm Description
Participants will receive CNTO 136 100 mg (Week 0 to Week 10) and later placebo (Week 12 to Week 22) every 2 weeks. Stable dose of methotrexate will be maintained through Week 24.
Arm Title
Part B, Group 1
Arm Type
Experimental
Arm Description
Participants will receive placebo (Week 0 to Week 10) and later CNTO 136 100 mg (Week 12 to Week 24) every 2 weeks. Stable dose of methotrexate will be maintained through Week 24.
Arm Title
Part B, Group 2
Arm Type
Experimental
Arm Description
Participants will receive CNTO 136 100 mg (Week 0 to Week 24) every 2 weeks. Stable dose of methotrexate will be maintained through Week 24.
Arm Title
Part B, Group 3
Arm Type
Experimental
Arm Description
Participants will receive CNTO 136 100 mg (Week 0 to Week 24) every 4 weeks and placebo at interim visits (Weeks 2, 6, 10, 14, 18, and 22). Stable dose of methotrexate will be maintained through Week 24.
Arm Title
Part B, Group 4
Arm Type
Experimental
Arm Description
Participants will receive CNTO 136 50 mg (Week 0 to Week 24) every 4 weeks and placebo at interim visits (Weeks 2, 6,10, 14, 18, and 22). Stable dose of methotrexate will be maintained through Week 24.
Arm Title
Part B, Group 5
Arm Type
Experimental
Arm Description
Participants will receive CNTO 136 25 mg (Week 0 to Week 24) every 4 weeks and placebo at interim visits (Weeks 2, 6,10, 14, 18, and 22). Stable dose of methotrexate will be maintained through Week 24.
Intervention Type
Drug
Intervention Name(s)
CNTO 136 100 mg
Other Intervention Name(s)
Sirukumab
Intervention Description
CNTO 136 100 mg will be administered subcutaneously (under the skin) every 2 or 4 weeks as per the appropriate randomized arm.
Intervention Type
Drug
Intervention Name(s)
CNTO 136 50 mg
Other Intervention Name(s)
Sirukumab
Intervention Description
CNTO 136 50 mg will be administered subcutaneously every 4 weeks from Week 0 to Week 24.
Intervention Type
Drug
Intervention Name(s)
CNTO 136 25 mg
Other Intervention Name(s)
Sirukumab
Intervention Description
CNTO 136 25 mg will be administered subcutaneously every 4 weeks from Week 0 to Week 24.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo will be adminstered subcutaneously as per the appropriate randomized arm.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
Stable dose of methotrexate will be maintained through Week 24.
Primary Outcome Measure Information:
Title
Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Week 12 (Part B)
Description
An American College of Rheumatology (ACR) 50 response is defined as greater than or equal to (>=) 50 percent (%) 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 Visual Analogue Scale (Score) 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 Health Assessment Questionnaire-Disability Index (HAQ-DI, the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area), and serum C-reactive protein (CRP).
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Change From Baseline in Disease Activity Index Score 28 (DAS28) Based on C-reactive Protein (CRP) at Week 12 (Part A and Part B)
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.
Time Frame
Baseline, Week 12
Title
Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 12 (Part A)
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.
Time Frame
Week 12
Title
Serum Sirukumab Concentrations Through Week 38 (Part A)
Description
Sirukumab Concentrations in serum were measured.
Time Frame
Week 0, Day 2, Day 5, Day 8, Day 11, Week 2, Week 4, Week 8, Week 10, Week 10 Day 4, Week 10 Day 7, Week 12, Week 14, Week 18, Week 22, Week 24, and Week 38
Title
Serum Sirukumab Concentrations Through Week 38 (Part B)
Description
Sirukumab Concentrations in serum were measured.
Time Frame
Week 0, Day 5, Day 8, Day 11, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 24 Day4, Week 24 Day7, Week 26, Week 28, Week 30, Week 34 and Week 38
Title
Percent Improvement From Baseline in Serum C-Reactive Protein (CRP) At Week 2 (Part A and Part B)
Description
Serum CRP is a marker of systemic inflammation. A negative change from baseline in CRP represents improvement.
Time Frame
Baseline, Week 2
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosed with rheumatoid arthritis (RA) for at least 4 months prior to screening
Have been treated and having an inadequate response with the tolerated dose of methotrexate (MTX) (at least 15mg/week) for at least 4 months prior to screening. MTX doses of 10 or 12.5 mg/week are allowed if participant had intolerance of 15 mg/week
MTX route of administration and dose (not to exceed 25 mg/week) should be stable for at least 6 weeks prior to the start of the study medication
Have active RA as defined by persistent disease activity with at least 6 swollen and 6 tender joints, at the time of screening and baseline, and either anti-cyclic citrullinated peptide antibody-positive or rheumatoid factor positive at screening
C-reactive protein greater than or equal to 1.0 mg/dL (10 mg/L)
Agree to use one of the contraception methods defined in the protocol
Exclusion Criteria:
Have inflammatory diseases other than RA that might confound the evaluation of the benefit of CNTO 136 therapy in arthritis
Family history of/ have long QT syndrome; or a history of second or third-degree heart block
Received systemic immunosuppressives or disease modifying antirheumatic drug other than MTX, sulfasalazine, hydroxychloroquine or chloroquine within 4 weeks prior to the start of study medication
Received intra articular (into joints), intramuscular, or intravenous corticosteroids within 4 weeks prior to the start of study medication
Positive human immunodeficiency virus test, hepatitis B or hepatitis C
History of / have chronic or recurrent infectious disease, history of / active tuberculosis
Have serious infection within 2 months prior to start of study medication
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Centocor Clinical Trial
Organizational Affiliation
Centocor, Inc.
Official's Role
Study Director
Facility Information:
City
Aventura
State/Province
Florida
Country
United States
City
Lexington
State/Province
Kentucky
Country
United States
City
Frederick
State/Province
Maryland
Country
United States
City
Kalamazoo
State/Province
Michigan
Country
United States
City
Charlotte
State/Province
North Carolina
Country
United States
City
Winston-Salem
State/Province
North Carolina
Country
United States
City
Duncansville
State/Province
Pennsylvania
Country
United States
City
Anderson
State/Province
South Carolina
Country
United States
City
Budapest
Country
Hungary
City
Győr
Country
Hungary
City
Kecskemét
Country
Hungary
City
Goshogawara
Country
Japan
City
Hitachi
Country
Japan
City
Kawagoe
Country
Japan
City
Kitakyushu
Country
Japan
City
Miyazaki
Country
Japan
City
Sasebo
Country
Japan
City
Shinjuku-Ku
Country
Japan
City
Tomigusuku
Country
Japan
City
Busan
Country
Korea, Republic of
City
Dae-Gu
Country
Korea, Republic of
City
Daejeon
Country
Korea, Republic of
City
Seoul
Country
Korea, Republic of
City
Ciudad De Mexico
Country
Mexico
City
Guadalajara
Country
Mexico
City
Mexico
Country
Mexico
City
Bialystok
Country
Poland
City
Bydgoszcz N/A
Country
Poland
City
Elblag
Country
Poland
City
Gdynia
Country
Poland
City
Krakow
Country
Poland
City
Lublin
Country
Poland
City
Poznan
Country
Poland
City
Warszawa
Country
Poland
City
Kemerovo
Country
Russian Federation
City
Moscow
Country
Russian Federation
City
Novosibirsk
Country
Russian Federation
City
St Petersburg
Country
Russian Federation
12. IPD Sharing Statement
Citations:
PubMed Identifier
24699939
Citation
Smolen JS, Weinblatt ME, Sheng S, Zhuang Y, Hsu B. Sirukumab, a human anti-interleukin-6 monoclonal antibody: a randomised, 2-part (proof-of-concept and dose-finding), phase II study in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis. 2014 Sep;73(9):1616-25. doi: 10.1136/annrheumdis-2013-205137. Epub 2014 Apr 3.
Results Reference
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A Study of Effectiveness and Safety of CNTO 136 in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy
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