A Study of the Effectiveness and Safety of Ustekinumab (STELARA) and CNTO 1959 Administered Under the Skin of Patients With Active Rheumatoid Arthritis, Despite Existing Methotrexate Therapy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of ustekinumab and CNTO 1959 in reducing the signs and symptoms of disease in patients with active rheumatoid arthritis (RA) despite concomitant methotrexate (MTX) therapy and to evaluate the safety of ustekinumab and CNTO 1959 in this population.

Detailed Description
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This is a randomized (patients assigned to treatment by chance), double-blind (study personnel and patients will not know what treatment is being assigned to patients), multicenter, placebo-controlled (a placebo is a treatment identical in appearance to the study agent, but containing no active ingredient), dose-ranging study. Approximately 250 patients will be randomly assigned to 1 of 5 treatment groups. The maximum length of study participation is 54 weeks, including a 6-week screening period. The end of the study will be the last follow-up visit of the last patient. Study visits and evaluations will occur, and patient safety will be monitored throughout the study.

Official Title
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A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Study Evaluating the Efficacy and Safety of Ustekinumab (STELARA®) and CNTO 1959 Administered Subcutaneously in Subjects With Active Rheumatoid Arthritis Despite Concomitant Methotrexate Therapy

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Drug: Placebo + methotrexate (MTX) (Group 1)
* Drug: Ustekinumab + MTX (Group 2)
* Drug: Ustekinumab + MTX (Group 3)
* Drug: CNTO 1959 + MTX (Group 4)
* Drug: CNTO 1959 + MTX (Group 5)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have had RA for at least 6 months prior to screening Have a diagnosis of RA according to the revised 1987 criteria of the American Rheumatism Association - Be positive for either anti-cyclic citrullinated peptide antibody or rheumatoid factor in serum at screening Have been treated with and tolerated MTX for at least 6 months prior to screening, and have a MTX dose of >= 10 mg and <= 25 mg per week and stable for at least 12 weeks prior to first administration of study agent Have active RA, defined as persistent disease activity with both of the following criteria: at least 6 swollen and 6 tender joints at the time of screening and baseline; serum C-reactive protein (CRP) >= 0.80 mg/dL at screening. The investigator may consider the patient eligible if the CRP value is at least 0.80 mg/dL in a single repeat testing during the screening period If using oral corticosteroids, must be on a stable dose of <= 10 mg/day of prednisone or an equipotent dose of another oral corticosteroid for at least 2 weeks prior to the first administration of study agent. If not using corticosteroids at Week 0, the patient must not have received oral corticosteroids for at least 2 weeks prior to the first administration of study agent If using nonsteroidal anti-inflammatory drugs (NSAIDs) or other analgesics regularly for RA, the patient must have been on a stable dose for at least 2 weeks prior to the first administration of study agent. If not using NSAIDs or other analgesics for RA at Week 0, the patient must have not received NSAIDs or other analgesics for RA for at least 2 weeks prior to the first administration of study agent Exclusion Criteria: Has other inflammatory diseases, including but not limited to psoriatic arthritis, ankylosing spondylitis (AS), systemic lupus erythematosus, or Lyme disease, that might confound the evaluation of the benefit of study agent therapy Has current signs or symptoms of liver insufficiency or cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, psychiatric, or metabolic disturbances that are severe, progressive, or uncontrolled Has any known malignancy or history of malignancy (with the exception of basal cell carcinoma, squamous cell carcinoma in situ of the skin, or cervical carcinoma in situ that has been treated with no evidence of recurrence, or squamous cell carcinoma of the skin that has been treated with no evidence of recurrence within 5 years prior to the first administration of study agent) Has a history of lymphoproliferative disease, including lymphoma, or signs suggestive of possible lymphoproliferative disease such as lymphadenopathy of unusual size or location, or clinically significant splenomegaly Has known allergies, hypersensitivity, or intolerance to ustekinumab or CNTO 1959 or its inactive ingredients Has ever received any approved or investigational biologic agent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group 1<br> | Drug: Placebo + methotrexate (MTX) (Group 1)<br>* Placebo: form = solution for injection, route = subcutaneous use, at Weeks 0, 4, then every 8 weeks (Weeks 12, 20, and 28) + MTX (pre-study dose)<br>|
| Experimental: Group 2<br> | Drug: Ustekinumab + MTX (Group 2)<br>* Ustekinumab: type = exact number, unit = mg, number = 90, form = solution for injection, route = subcutaneous use, at Weeks 0, 4, then every 8 weeks (Weeks 12, 20, and 28) + MTX (pre-study dose)<br>|
| Experimental: Group 3<br> | Drug: Ustekinumab + MTX (Group 3)<br>* Ustekinumab: type = exact number, unit = mg, number = 90, form = solution for injection, route = subcutaneous use, at Weeks 0, 4, then every 12 weeks (Weeks 16 and 28) + MTX (pre-study dose)<br>|
| Experimental: Group 4<br> | Drug: CNTO 1959 + MTX (Group 4)<br>* CNTO 1959: type = exact number, unit = mg, number = 200, form = powder for solution for injection, route = subcutaneous use, at Weeks 0, 4, then every 8 weeks (Weeks 12, 20, and 28) + MTX (pre-study dose)<br>|
| Experimental: Group 5<br> | Drug: CNTO 1959 + MTX (Group 5)<br>* CNTO 1959: type = exact number, unit = mg, number = 50, form = powder for solution for injection, route = subcutaneous use, at Weeks 0, 4, then every 8 weeks (Weeks 12, 20, and 28)+ MTX (pre-study dose)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With American College of Rheumatology 20 (ACR 20) Response at Week 28 | The ACR 20 responders are participants with at least 20 percent (%) improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) patient's assessment of arthritis pain-visual analog scale, 2) patient's global assessment of disease activity-visual analog scale, 3) physician's global assessment of disease activity-visual analog scale, 4) patient's assessment of physical function as measured by health assessment questionnaire-disability index (HAQ-Di), 5) C-reactive protein (CRP). | Week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Disease Activity Index Score 28 (DAS28; Using C-reactive Protein [CRP]) Score at Week 28 | The DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, CRP (mG/L) and patient's global assessment (PGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 <=3.2 = low disease activity, DAS28 >3.2 to 5.1 = moderate to high disease activity. | From Baseline to Week 28 | 
| Percentage of Participants With American College of Rheumatology 20 (ACR 20) Response at Week 12 | The ACR 20 responders are participants with at least 20 percent (%) improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Patient's Assessment of Arthritis Pain-Visual Analog Scale, 2) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 3) Physician's Global Assessment of Disease Activity-Visual Analog Scale, 4) Patient's Assessment of Physical Function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI), 5) C-reactive Protein (CRP). | Week 12 | 
| Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 28 | The Health Assessment Questionnaire-Disability Index (HAQ-DI): participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. 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. | Baseline and Week 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Active rheumatoid arthritis, Ustekinumab, STELARA, CNTO 1959