Clinical trial NCT01689532: A Study of CNTO 136 (Sirukumab) Administered Subcutaneously in Japanese Patients With Active Rheumatoid Arthritis Unresponsive to Methotrexate or Sulfasalazine
Official title: A Multicenter, Randomized, Double-blind, Parallel Group Study of CNTO 136 (Sirukumab), a Human Anti-IL-6 Monoclonal Antibody, Administered Subcutaneously as Monotherapy, in Japanese Subjects With Active Rheumatoid Arthritis Unresponsive to Methotrexate or Sulfasalazine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arthritis, Rheumatoid
Keywords: Active Rheumatoid Arthritis Unresponsive to Methotrexate or Sulfasalazine
Sirukumab
Human Anti-IL-6 Monoclonal Antibody
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2012-09-21
Enrollment: 122
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAE)
timeFrame: Baseline upto Week 68
Secondary outcomes:
measure: Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Response
timeFrame: At Weeks 16 and 24
measure: Percentage of Participants Achieving American College of Rheumatology (ACR) 50 Response
timeFrame: At Weeks 16 and 24
measure: Percentage of Participants Achieving American College of Rheumatology (ACR) 70 Response
timeFrame: At Weeks 16 and 24
measure: Percentage of Participants Achieving American College of Rheumatology (ACR) 90 Response
timeFrame: At Weeks 16 and 24
measure: Percent Change From Baseline in Number of Swollen Joints at Weeks 16 and 24
timeFrame: Baseline, Weeks 16 and 24
measure: Percent Change From Baseline in Number of Tender Joints at Weeks 16 and 24
timeFrame: Baseline, Weeks 16 and 24
measure: Percent Change From Baseline in Patient's Assessment of Pain at Weeks 16 and 24
timeFrame: Baseline, Weeks 16 and 24
measure: Percent Change From Baseline in Patient's Global Assessment of Disease Activity at Weeks 16 and 24
timeFrame: Baseline, Weeks 16 and 24
measure: Percent Change From Baseline in Physician's Global Assessment of Disease Activity at Weeks 16 and 24
timeFrame: Baseline, Weeks 16 and 24
measure: Percent Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Weeks 16 and 24
timeFrame: Baseline, Weeks 16 and 24
measure: Percent Change From Baseline in C-Reactive Protein (CRP) at Weeks 16 and 24
timeFrame: Baseline, Weeks 16 and 24
measure: Percentage of Participants Who Achieved Major Clinical Response at Week 52
timeFrame: Week 52
measure: Percentage of Participants With Disease Activity Index Score 28 (CRP) Response at Weeks 16 and 24
timeFrame: At Weeks 16 and 24
measure: Percentage of Participants Achieving DAS28 (CRP) Remission at Week 24
timeFrame: At Week 24
measure: Change From Baseline in DAS28 (CRP) Score at Weeks 16 and 24
timeFrame: Baseline, Weeks 16 and 24
measure: Percentage of Participants With Simplified Disease Activity Index (SDAI) Based ACR/European League Against Rheumatism (EULAR) Remission at Weeks 16, 24 and 52
timeFrame: At Weeks 16, 24 and 52
measure: Percentage of Participants With Boolean Based ACR/EULAR Remission at Weeks 16, 24 and 52
timeFrame: At Weeks 16, 24 and 52
measure: Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Weeks 16 and 24
timeFrame: Baseline, Weeks 16 and 24
measure: Change From Baseline in Simplified Disease Activity Index (SDAI) Score at Weeks 16 and 24
timeFrame: Baseline, Weeks 16 and 24
measure: Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 16 and 24
timeFrame: Baseline, at Week 16 and 24
measure: Percentage of Participants Achieving HAQ-DI Response at Weeks 16 and 24
timeFrame: At Weeks 16 and 24
measure: Percentage of Participants Maintaining HAQ-DI Response
timeFrame: Baseline upto Week 52
measure: Area Under Curve (AUC) of Change From Baseline in HAQ-DI Score From Week 0 Through Week 24 and From Week 0 Through Week 52
timeFrame: Baseline, Weeks 24 and 52
measure: Change From Baseline in Duration of Morning Stiffness at Weeks 16 and 24
timeFrame: Baseline, Weeks 16 and 24
measure: Change From Baseline in Mental Component Scores of 36-Item Short Form Health Survey (SF-36) at Weeks 16, 24 and 52
timeFrame: Baseline, Weeks 16, 24 and 52
measure: Change From Baseline in Physical Component Scores of 36-Item Short Form Health Survey (SF-36) at Weeks 16, 24 and 52
timeFrame: Baseline, Weeks 16, 24 and 52
measure: Change From Baseline in EuroQol 5-Dimensional Questionnaire (EQ-5D) Visual Analog Scale (VAS) Score at Weeks 16, 24 and 52
timeFrame: Baseline, Weeks 16, 24 and 52
measure: Change From Baseline in EuroQol 5-Dimensional Questionnaire (EQ-5D) Index Score at Weeks 16, 24 and 52
timeFrame: Baseline, Weeks 16, 24 and 52
Other outcomes:
Locations:
city: Asahikawa
country: Japan
city: Fukuoka
country: Japan
city: Hiroshima
country: Japan
city: Hitachinaka
country: Japan
city: Kagoshima
country: Japan
city: Kirishima
country: Japan
city: Kitakyushu
country: Japan
city: Kobe
country: Japan
city: Kumamoto
country: Japan
city: Matsumoto
country: Japan
city: Miyagi
country: Japan
city: Oita
country: Japan
city: Sapporo
country: Japan
city: Sendai
country: Japan
city: Shizuoka
country: Japan
city: Tokyo
country: Japan
city: Yokohama
country: Japan
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K., Japan Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.