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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
GlaxoSmithKline, PLC
Information provided by (Responsible Party):
Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier:
NCT01689532
First received: September 18, 2012
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

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).


Condition Intervention Phase
Arthritis, Rheumatoid
Drug: Sirukumab 100 mg
Drug: Sirukumab 50 mg
Drug: Placebo
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Janssen Pharmaceutical K.K.:

Primary Outcome Measures:
  • The number of patients with adverse events [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
  • Neutrophil count [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
  • Platelet count [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
  • Hepatobiliary laboratory abnormalities [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
  • Lipid parameter abnormalities [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The number of patients who achieve ACR 20 response [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
    American College of Rheumatology (ACR) 20 response is at least a 20% improvement in rheumatoid arthritis (RA) symptoms.

  • The number of patients who achieve ACR 50 response [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
    ACR 50 response is at least a 50% improvement in RA symptoms.

  • The number of patients who achieve ACR 70 response [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
    ACR 70 response is at least a 70% improvement in RA symptoms.

  • The number of patients who achieve ACR 90 response [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
    ACR 90 response is at least a 90% improvement in RA symptoms.

  • Major clinical response [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
    Major clinical response is achieving ACR 70 for 6 continuous months.

  • Percent improvement from baseline in ACR components [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
  • The number of patients with DAS28 (CRP) response [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
    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.

  • The number of patients with DAS28 (CRP) remission [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
    DAS28 (CRP) remission is defined as a value of <2.6 at a visit.

  • Change from baseline in DAS28 (CRP) [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
  • The number of patients with SDAI-based ACR/EULAR remission [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
    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.

  • The number of patients with Boolean-based ACR/EULAR remission [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
    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.

  • Change from baseline in SDAI [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in CDAI [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
    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).

  • Change from baseline in HAQ-DI score [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
    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.

  • AUC of change from baseline in HAQ-DI score from Week 0 through Week 24 and from Week 0 through Week 52 [ Time Frame: Up to 52 weeks ] [ Designated as safety issue: No ]
    AUC is "area under the curve," an assessment of blood concentration of study agent over time.

  • Proportion of HAQ-DI responders (ie, those who have a change from baseline of > 0.22 in HAQ-DI score) [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
  • Proportion of HAQ-DI responders in sirukumab treatment groups who maintain a change from baseline of > 0.22 in HAQ-DI score [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in duration of morning stiffness [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in physical and mental component scores and in domain scores of SF-36 [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
    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.

  • Change from baseline in EQ VAS [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
    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).

  • Change from baseline in EQ-5D index [ Time Frame: Up to 68 weeks ] [ Designated as safety issue: No ]
    The EQ-5D is a standardized measure of health status with 3 levels: 1=no problems, 2=some problems, and 3=extreme problems.


Enrollment: 122
Study Start Date: November 2012
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sirukumab 100 mg Drug: Sirukumab 100 mg
Sirukumab 100 mg subcutaneous (SC) injection, at Weeks 0, 2, and every 2 weeks through Week 52.
Experimental: Sirukumab 50 mg and Placebo Drug: Sirukumab 50 mg
Sirukumab 50 mg SC at Weeks 0, 4, and every 4 weeks through Week 52.
Drug: Placebo
Between sirukumab injections, placebo SC at Weeks 2, 6, and every 4 weeks through Week 52.

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

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01689532

Locations
Japan
Asahikawa, Japan
Fukuoka, Japan
Hiroshima, Japan
Hitachinaka, Japan
Kagoshima, Japan
Kirishima, Japan
Kitakyushu, Japan
Kobe, Japan
Kumamoto, Japan
Matsumoto, Japan
Miyagi, Japan
Oita, Japan
Sapporo, Japan
Sendai, Japan
Shinjuku, Japan
Shizuoka, Japan
Yokohama, Japan
Sponsors and Collaborators
Janssen Pharmaceutical K.K.
GlaxoSmithKline, PLC
Investigators
Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial Janssen Pharmaceutical K.K.
  More Information

No publications provided

Responsible Party: Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier: NCT01689532     History of Changes
Other Study ID Numbers: CR100876, CNTO136ARA3001
Study First Received: September 18, 2012
Last Updated: June 30, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Janssen Pharmaceutical K.K.:
Active Rheumatoid Arthritis Unresponsive to Methotrexate or Sulfasalazine
Sirukumab
Human Anti-IL-6 Monoclonal Antibody

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antibodies, Monoclonal
Methotrexate
Sulfasalazine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Infective Agents
Anti-Inflammatory Agents, Non-Steroidal

ClinicalTrials.gov processed this record on August 28, 2014