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

Arthritis, Rheumatoid Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01689532
• Other study ID #: CR100876
• Secondary ID: CNTO136ARA3001
• Status: Completed
• Phase: Phase 3
• First received: September 18, 2012
• Last updated: February 16, 2016
• Start date: November 2012
• Est. completion date: March 2015

Study information

• Verified date: February 2016
• Source: Janssen Pharmaceutical K.K.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• Sirukumab 100 mg
Sirukumab 100 mg subcutaneous (SC) injection, at Weeks 0, 2, and every 2 weeks through Week 52.
• Sirukumab 50 mg
Sirukumab 50 mg SC at Weeks 0, 4, and every 4 weeks through Week 52.
• Placebo
Between sirukumab injections, placebo SC at Weeks 2, 6, and every 4 weeks through Week 52.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Janssen Pharmaceutical K.K.	GlaxoSmithKline

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of patients with adverse events		Up to 68 weeks	No
Primary	Neutrophil count		Up to 68 weeks	No
Primary	Platelet count		Up to 68 weeks	No
Primary	Hepatobiliary laboratory abnormalities		Up to 68 weeks	No
Primary	Lipid parameter abnormalities		Up to 68 weeks	No
Secondary	The number of patients who achieve ACR 20 response	American College of Rheumatology (ACR) 20 response is at least a 20% improvement in rheumatoid arthritis (RA) symptoms.	Up to 68 weeks	No
Secondary	The number of patients who achieve ACR 50 response	ACR 50 response is at least a 50% improvement in RA symptoms.	Up to 68 weeks	No
Secondary	The number of patients who achieve ACR 70 response	ACR 70 response is at least a 70% improvement in RA symptoms.	Up to 68 weeks	No
Secondary	The number of patients who achieve ACR 90 response	ACR 90 response is at least a 90% improvement in RA symptoms.	Up to 68 weeks	No
Secondary	Major clinical response	Major clinical response is achieving ACR 70 for 6 continuous months.	Up to 68 weeks	No
Secondary	Percent improvement from baseline in ACR components		Up to 68 weeks	No
Secondary	The number of patients with DAS28 (CRP) response	The Disease Activity Index (DAS28, using CRP [C-reactive protein]) is a measure of tender and swollen joints (28 joints each) and the patient's assessments of disease activity. A score of higher than 5.1 indicates high disease activity, and a score below 3.2 indicates low disease activity.	Up to 68 weeks	No
Secondary	The number of patients with DAS28 (CRP) remission	DAS28 (CRP) remission is defined as a value of <2.6 at a visit.	Up to 68 weeks	No
Secondary	Change from baseline in DAS28 (CRP)		Up to 68 weeks	No
Secondary	The number of patients with SDAI-based ACR/EULAR remission	The Simplified Disease Activity Index (SDAI) is a derived score combining tender joints (28 joints), swollen joints (28 joints), Patient's Global Assessment of Disease Activity (GH), Physician's global assessments of disease activity (PGH), and CRP. SDAI-based ACR/EULAR remission is defined as a SDAI value of = 3.3 at the visit.	Up to 68 weeks	No
Secondary	The number of patients with Boolean-based ACR/EULAR remission	Boolean-based ACR/EULAR remission is defined as meeting all of the following 4 criteria at a visit: Tender joint count (68 joints) = 1; Swollen joint count (68 joints) = 1; CRP = 1 mg/dL; Patient's Global Assessment of Disease Activity on VAS = 1 on a 0 to 10 scale.	Up to 68 weeks	No
Secondary	Change from baseline in SDAI		Up to 68 weeks	No
Secondary	Change from baseline in CDAI	The Clinical Disease Activity Index (CDAI) score is a derived score combining tender joints (28 joints), swollen joints (28 joints), GH, and PGH. Scores range from 0 (remission) to 76 (high activity).	Up to 68 weeks	No
Secondary	Change from baseline in HAQ-DI score	The Health Assessment Questionnaire - Disability Index (HAQ-DI) 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, indicating no difficulty, to 3, indicating inability to perform a task in that area.	Up to 68 weeks	No
Secondary	AUC of change from baseline in HAQ-DI score from Week 0 through Week 24 and from Week 0 through Week 52	AUC is "area under the curve," an assessment of blood concentration of study agent over time.	Up to 52 weeks	No
Secondary	Proportion of HAQ-DI responders (ie, those who have a change from baseline of > 0.22 in HAQ-DI score)		Up to 68 weeks	No
Secondary	Proportion of HAQ-DI responders in sirukumab treatment groups who maintain a change from baseline of > 0.22 in HAQ-DI score		Up to 68 weeks	No
Secondary	Change from baseline in duration of morning stiffness		Up to 68 weeks	No
Secondary	Change from baseline in physical and mental component scores and in domain scores of SF-36	36-Item Short Form Questionnaire (SF-36) is 8 multi-item scales that are scored from 0 to 100 with higher scores indicating better health.	Up to 68 weeks	No
Secondary	Change from baseline in EQ VAS	The EuroQoL Group visual analogue scale (EQ VAS) is a self-rated health assessment. Scores range from 0 (worst health imaginable) to 100 (best health imaginable).	Up to 68 weeks	No
Secondary	Change from baseline in EQ-5D index	The EQ-5D is a standardized measure of health status with 3 levels: 1=no problems, 2=some problems, and 3=extreme problems.	Up to 68 weeks	No