A Study of CNTO 136 (Sirukumab) Administered Subcutaneously in Japanese Patients With Active Rheumatoid Arthritis Unresponsive to Methotrexate or Sulfasalazine

NCT ID: NCT01689532

Last Updated: 2016-10-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 122 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2015-03-31

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of sirukumab as a single therapy in Japanese patients with moderately to severely active rheumatoid arthritis (RA) who have not responded to treatment with methotrexate (MTX) or sulfasalazine (SSZ).

Detailed Description

This is a randomized (patients will be assigned to treatment by chance), double-blind (study personnel and patients will not know what treatments are being given), multicenter study. The expected duration of the study is 68 weeks. This will include 52 weeks of treatment with study agent with dosing every 2 weeks and 16 weeks of safety follow-up after the last dose. Disease-modifying antirheumatic drugs (DMARDs), including MTX and SSZ, are not permitted from 4 weeks before the first dosing with study agent until Week 24. The use of DMARDs is discouraged at or any time after Week 24; however, patients who have less than 20% improvement from baseline in both swollen and tender joint counts at Week 24 will be allowed to take DMARDs. At or any time after Week 16, the initiation and/or adjustment of oral corticosteroids will be allowed for patients who have less than 20% improvement from baseline in both swollen and tender joint counts at Week 16.

Conditions

Arthritis, Rheumatoid

Keywords

Active Rheumatoid Arthritis Unresponsive to Methotrexate or Sulfasalazine; Sirukumab; Human Anti-IL-6 Monoclonal Antibody

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Sirukumab 100 mg

Group Type: EXPERIMENTAL

Sirukumab 100 mg

Intervention Type: DRUG

Sirukumab 100 mg subcutaneous (SC) injection, at Weeks 0, 2, and every 2 weeks through Week 52.

Sirukumab 50 mg and Placebo

Group Type: EXPERIMENTAL

Sirukumab 50 mg

Intervention Type: DRUG

Sirukumab 50 mg SC at Weeks 0, 4, and every 4 weeks through Week 52.

Placebo

Intervention Type: DRUG

Between sirukumab injections, placebo SC at Weeks 2, 6, and every 4 weeks through Week 52.

Interventions

Sirukumab 100 mg

Sirukumab 100 mg subcutaneous (SC) injection, at Weeks 0, 2, and every 2 weeks through Week 52.

Intervention Type: DRUG

Sirukumab 50 mg

Sirukumab 50 mg SC at Weeks 0, 4, and every 4 weeks through Week 52.

Intervention Type: DRUG

Placebo

Between sirukumab injections, placebo SC at Weeks 2, 6, and every 4 weeks through Week 52.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Be a Japanese man or woman with a diagnosis of rheumatoid arthritis (RA), according to the revised 1987 criteria of the American Rheumatism Association, for at least 3 months before screening
• Has moderately to severely active RA with at least 6 of 68 tender joints and 6 of 66 swollen joints, at screening and at baseline
• Has been unresponsive to adequate treatment with methotrexate (MTX), sulfasalazine (SSZ), or combination of MTX or SSZ with other disease-modifying antirheumatic drugs (DMARDs) at screening due to lack of benefit after at least 12 weeks of marketed dose of MTX or SSZ, as assessed by the treating physician. Documented lack of benefit may include inadequate improvement in joint counts, physical function, or overall disease activity
• If using oral corticosteroids, must be on a stable dose equivalent to <=10 mg/day of prednisolone for at least 2 weeks prior to first dosing with study agent. If currently not using corticosteroids, the patient must not have received oral corticosteroids (by mouth) for at least 2 weeks prior to first dosing with study agent
• If using nonsteroidal anti-inflammatory drugs (NSAIDs) or other analgesics (pain relievers) for RA, must be on a stable dose for at least 2 weeks prior to first dosing with study agent

Exclusion Criteria

• Has a history of intolerance to at least 2 or inadequate response to at least one anti-tumor necrosis factor-alpha (anti-TNF-alpha) agent after 3 months of therapy; has received anti-TNF-alpha (eg, infliximab, golimumab, adalimumab, or etanercept) within 3 months of first study agent dosing
• Has a history of intolerance to tocilizumab that precluded further treatment with it, or inadequate response to 3 months of tocilizumab (anti-IL-6 receptor) therapy; has used B-cell-depleting therapy (eg, rituximab) within 7 months of first study agent dosing or has evidence during screening of abnormally low B-cell level caused by previous B-cell depletion therapy; has used any other biologic therapy for the treatment of RA within 3 months of first study agent dosing; has a history of sirukumab use
• Has received intra-articular (IA), intramuscular (IM), or intravenous (IV) corticosteroids for RA, including adrenocorticotrophic hormone during the 4 weeks prior to first study agent dosing
• Has received leflunomide within 24 months before first study agent dosing and has not undergone a drug elimination procedure, unless the M1 metabolite is measured and is undetectable. Drug elimination procedure must be completed prior to obtaining informed consent
• Has a history of cyclophosphamide or cytotoxic agent use; has received cyclosporine A, azathioprine, tacrolimus, mycophenolate mofetil, oral or parenteral gold, or D-penicillamine within 4 weeks of first study agent dosing; has received an investigational drug (including investigational vaccines) or used an investigational medical device within 3 months or 5 half-lives, whichever is longer, before first study agent dosing

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Janssen Pharmaceutical K.K.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Pharmaceutical K.K., Japan Clinical Trial

Role: STUDY_DIRECTOR

Janssen Pharmaceutical K.K.

Locations

Asahikawa, , Japan

Fukuoka, , Japan

Hiroshima, , Japan

Hitachi-Naka, , Japan

Kagoshima, , Japan

Kirishima, , Japan

Kitakyushu, , Japan

Kobe, , Japan

Kumamoto, , Japan

Matsumoto, , Japan

Miyagi, , Japan

Ōita, , Japan

Sapporo, , Japan

Sendai, , Japan

Shizuoka, , Japan

Tokyo, , Japan

Yokohama, , Japan

Countries

Japan

References

Takeuchi T, Yamanaka H, Harigai M, Tamamura R, Kato Y, Ukyo Y, Nakano T, Hsu B, Tanaka Y. Sirukumab in rheumatoid arthritis refractory to sulfasalazine or methotrexate: a randomized phase 3 safety and efficacy study in Japanese patients. Arthritis Res Ther. 2018 Mar 7;20(1):42. doi: 10.1186/s13075-018-1536-9.

Reference Type: DERIVED

PMID: 29514712 (View on PubMed)

Other Identifiers

CNTO136ARA3001

Identifier Type: OTHER

Identifier Source: secondary_id

CR100876

Identifier Type: -

Identifier Source: org_study_id