Efficacy and Safety of Olokizumab With Rheumatoid Arthritis With Previously Failed to Anti-tumor Necrosis Factor (Anti-TNF) Therapy

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the efficacy and safety of CDP6038 administered subcutaneous (sc) at various doses compared to placebo.

Official Title
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A Randomized, Double-blind, Placebo Controlled, Dose Ranging Study to Evaluate the Efficacy and Safety of CDP6038 Administered Subcutaneously for 12 Weeks to Asian Subjects With Active Rheumatoid Arthritis Having Previously Failed TNF Blocker Therapy

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: Placebo
* Biological: Olokizumab 60 mg
* Biological: Olokizumab 120 mg
* Biological: Olokizumab 240 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of adult-onset RA of at least 6 months' (24 weeks) duration as defined by the 1987 ACR classification criteria or a score of ≥6 as defined by the ACR/European League Against Rheumatism Classification and Diagnostic Criteria for RA Must have moderately to severely active RA disease as defined by ≥6 tender joints (68-joint count) at Screening and Baseline, ≥6 swollen joints (66-joint count) at Screening and Baseline, CRP ≥1.2 times the upper limit of normal (ULN) or ESR >28mm/hour Must be on an MTX dose of 6 to 16mg/week in Japan or 7.5 to 20mg/week in Korea and Taiwan, which has been stable for at least 6 weeks prior to Screening with a stable route of administration Must have had intolerance or inadequate response to treatment with 1 or more TNF-blocker therapies within 2 years of Screening Female subjects must be either postmenopausal for at least 1 year, surgically incapable of childbearing, or effectively practicing 2 acceptable methods of contraception Exclusion Criteria: Have a diagnosis of any other inflammatory arthritis Female subjects who are breast-feeding, pregnant, or plan to become pregnant during the study or within 24 weeks Disease modifying antirheumatic drug (DMARDs) other than methotrexate (MTX) Subjects with known concurrent acute or chronic viral hepatitis B or C infection Subject has known tuberculosis (TB) disease, high risk of acquiring TB infection, or latent TB infection Subjects with known history of or current clinically active infection Subjects at high risk of infection Subjects with known human immunodeficiency virus (HIV) or human T cell lymphotropic virus type 1 (HTLV 1) infection Have received vaccinations within 8 weeks prior to Screening or plan to receive vaccines during the study (with the exception of injectable influenza and pneumococcal vaccinations which are permitted) Concurrent malignancy or a history of malignancy (with the exception of successfully treated carcinoma of the cervix more than 5 years prior to Screening or no more than 2 successfully treated basal cell carcinomas within 2 years prior to Screening

Ages Eligible for Study
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Minimum Age: 20 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo every 2 weeks<br>Injections administered at week 0, 2, 4, 6, 8 and 10 | Biological: Placebo<br>* Placebo solution for injection, administered as subcutaneous injections<br>|
| Experimental: Olokizumab 60 mg every 2 weeks<br>Olokizumab 60 mg injections administered at week 0, 2, 4, 6, 8 and 10 | Biological: Olokizumab 60 mg<br>* Olokizumab 60 mg solution for injection, administered as subcutaneous injections<br>* Other names: CDP6038;|
| Experimental: Olokizumab 60 mg every 4 weeks<br>Olokizumab 60 mg injection administered at week 0, 4, and 8 and Placebo injection administered at week 2, 6, and 10 | Biological: Placebo<br>* Placebo solution for injection, administered as subcutaneous injections<br>Biological: Olokizumab 60 mg<br>* Olokizumab 60 mg solution for injection, administered as subcutaneous injections<br>* Other names: CDP6038;|
| Experimental: Olokizumab 120 mg every 2 weeks<br>Olokizumab 120 mg injections administered at week 0, 2, 4, 6, 8 and 10 | Biological: Olokizumab 120 mg<br>* Olokizumab 120 mg solution for injection, administered as subcutaneous injections<br>* Other names: CDP6038;|
| Experimental: Olokizumab 120 mg every 4 weeks<br>Olokizumab 120 mg injections administered at week 0, 4 and 8 and Placebo injections at week 2, 6 and 10 | Biological: Placebo<br>* Placebo solution for injection, administered as subcutaneous injections<br>Biological: Olokizumab 120 mg<br>* Olokizumab 120 mg solution for injection, administered as subcutaneous injections<br>* Other names: CDP6038;|
| Experimental: Olokizumab 240 mg very 4 weeks<br>Olokizumab 240 mg injections administered at week 0, 4 and 8 and Placebo injections at week 2, 6 and 10 | Biological: Placebo<br>* Placebo solution for injection, administered as subcutaneous injections<br>Biological: Olokizumab 240 mg<br>* Olokizumab 240 mg solution for injection, administered as subcutaneous injections<br>* Other names: CDP6038;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in the Disease Activity Score 28-joint count (C-reactive protein) (DAS28[CRP]) at Week 12 |  | From Week 0 (Baseline) to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of responders in American College of Rheumatology 20% Response Criteria (ACR20) at Week 12 | Number of subjects who achieve ACR 20 will be calculated at week 12. The calculation is based on the improvement from the baseline in the number of tender joints and in the number of swollen joints each; and the improvement based on assessments from the patient and the physician drawn according to defined standards. | From Week 0 (Baseline) to Week 12 | 
| Number of responders in American College of Rheumatology 50% Response Criteria (ACR50) at Week 12 | Number of subjects who achieve ACR 50 will be calculated at week 12. The calculation is based on the improvement from the baseline in the number of tender joints and in the number of swollen joints each; and the improvement based on assessments from the patient and the physician drawn according to defined standards. | From Week 0 (Baseline) to Week 12 | 
| Number of responders in American College of Rheumatology 70% Response Criteria (ACR70) at Week 12 | Number of subjects who achieve ACR 70 will be calculated at week 12. The calculations is based on the improvement from the baseline in the number of tender joints and in the number of swollen joints each; and the improvement based on assessments from the patient and the physician drawn according to defined standards. | From Week 0 (Baseline) to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, Monoclonal Antibody, Interleukin-6, Olokizumab, CDP6038