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) in patients with active RA who are unresponsive or intolerant to treatment with anti-TNF-alpha agents.
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 68 weeks, which includes 52 weeks of treatment. Participants who complete participation in the study will be eligible for inclusion into the long term extension 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 24, when placebo patients will cross over to one of two sirukumab dose regimens. Patient safety will be monitored throughout the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
878
Form=solution for injection, route=subcutaneous use; every 2 weeks from Week 0 through Week 22.
Form=solution for injection, route=subcutaneous use; Weeks 2, 6, and every 4 weeks through Week 52.
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 23 through Week 52.
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Response at Week 16
The ACR 20 Response is defined as greater than or equal to (\>=) 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=20 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS; 0-10 scale, 0 =no pain and 10 =worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, \[0 =no pain to 10 =worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI 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 16
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 24
The HAQ-DI is a 20-question instrument that 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 to 3 (0=no difficulty and 3=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.
Time frame: Baseline and Week 24
Percentage of Participants Achieving American College of Rheumatology (ACR) 50 Response at Week 24
The ACR 50 Response is defined as \>= 50 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=50 percent improvement in 3 of following 5 assessments: patient's assessment of pain using VAS ( 0-10 scale, 0 =no pain and 10 =worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, \[0 =no pain to 10 =worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by HAQ-DI (defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and serum C-Reactive Protein (CRP).
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Type=exact, unit=mg, number=100, form=solution for injection, route=subcutaneous use; Weeks 0, 2, and every 2 weeks through Week 52.
Type=exact, unit=mg, number=50, form=solution for injection, route=subcutaneous use; Weeks 0, 4, and every 4 weeks through Week 52.
Unnamed facility
Birmingham, Alabama, United States
Unnamed facility
Glendale, Arizona, United States
Unnamed facility
Mesa, Arizona, United States
Unnamed facility
Phoenix, Arizona, United States
Unnamed facility
Covina, California, United States
Unnamed facility
El Cajon, California, United States
Unnamed facility
Hemet, California, United States
Unnamed facility
Huntington Beach, California, United States
Unnamed facility
La Jolla, California, United States
Unnamed facility
La Palma, California, United States
...and 191 more locations
Time frame: Week 24
Percentage of Participants With Disease Activity Index Score 28 (CRP) Remission at Week 24
The Disease Activity Index Score 28 (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. DAS28 (CRP) remission is defined as a DAS28 (CRP) value of less than (\<) 2.6 at any study visit.
Time frame: Week 24