A Study of Effectiveness and Safety of CNTO 136 in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy

NCT ID: NCT00718718

Last Updated: 2018-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 187 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-08-11
• Study Completion Date: 2011-03-03

Brief Summary

The purpose of this study is to evaluate the effectiveness and safety of subcutaneous (under the skin) administration of anti-interleukin-6 monoclonal antibody (CNTO 136) in reducing signs and symptoms of participants with active rheumatoid arthritis (RA) with methotrexate (MTX) therapy.

Detailed Description

This is a multicenter, double-blind (neither physician nor participants knows the treatment that the participant receives), randomized (study medication is assigned by chance), placebo-controlled (an inactive substance is compared with a medication to test whether the medication has a real effect in a clinical study) study. This study will be conducted in 2 parts (Part A and Part B). Each part consists of 3 phases: screening (approximately 1 month prior to the start of study medication), treatment phase (Part A: 22 weeks and Part B: 24 weeks), and follow-up phase (approximately 4 months after the last administration of study medication). In Part A, participants will be randomly assigned to 2 groups to receive CNTO 136 100 mg and placebo for 22 weeks. All participants in Part A, will be crossed over at Week 12 from placebo to CNTO 136 (for Group 1) and from CNTO 136 to placebo (for Group 2). In Part B, participants will be randomly assigned to 5 groups to receive placebo and/or 1 of 3 doses of CNTO 136 (100mg, 50mg or 25mg) for 24 weeks. Participants in Part B, Group 1 will be crossed over at Week 12 from placebo to CNTO 136. All participants should be maintained on a stable dose of MTX for at least 6 weeks prior to the start of study medication through Week 24. Safety will be evaluated by the assessment of adverse events, vital signs, clinical findings, 12-lead electrocardiogram, and clinical laboratory tests which will be monitored throughout the study. The total duration of study participation for a participant will be approximately 42 weeks.

Conditions

Arthritis, Rheumatoid

Study Design

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

Study Groups

Part A, Group 1

Participants will receive placebo (Week 0 to Week 10) and later CNTO 136 100 mg (Week 12 to Week 22) every 2 weeks. Stable dose of methotrexate will be maintained through Week 24.

Group Type: EXPERIMENTAL

CNTO 136 100 mg

Intervention Type: DRUG

CNTO 136 100 mg will be administered subcutaneously (under the skin) every 2 or 4 weeks as per the appropriate randomized arm.

Placebo

Intervention Type: DRUG

Placebo will be adminstered subcutaneously as per the appropriate randomized arm.

Methotrexate

Intervention Type: DRUG

Stable dose of methotrexate will be maintained through Week 24.

Part A, Group 2

Participants will receive CNTO 136 100 mg (Week 0 to Week 10) and later placebo (Week 12 to Week 22) every 2 weeks. Stable dose of methotrexate will be maintained through Week 24.

Group Type: EXPERIMENTAL

CNTO 136 100 mg

Intervention Type: DRUG

CNTO 136 100 mg will be administered subcutaneously (under the skin) every 2 or 4 weeks as per the appropriate randomized arm.

Placebo

Intervention Type: DRUG

Placebo will be adminstered subcutaneously as per the appropriate randomized arm.

Methotrexate

Intervention Type: DRUG

Stable dose of methotrexate will be maintained through Week 24.

Part B, Group 1

Participants will receive placebo (Week 0 to Week 10) and later CNTO 136 100 mg (Week 12 to Week 24) every 2 weeks. Stable dose of methotrexate will be maintained through Week 24.

Group Type: EXPERIMENTAL

CNTO 136 100 mg

Intervention Type: DRUG

CNTO 136 100 mg will be administered subcutaneously (under the skin) every 2 or 4 weeks as per the appropriate randomized arm.

Placebo

Intervention Type: DRUG

Placebo will be adminstered subcutaneously as per the appropriate randomized arm.

Methotrexate

Intervention Type: DRUG

Stable dose of methotrexate will be maintained through Week 24.

Part B, Group 2

Participants will receive CNTO 136 100 mg (Week 0 to Week 24) every 2 weeks. Stable dose of methotrexate will be maintained through Week 24.

Group Type: EXPERIMENTAL

CNTO 136 100 mg

Intervention Type: DRUG

CNTO 136 100 mg will be administered subcutaneously (under the skin) every 2 or 4 weeks as per the appropriate randomized arm.

Methotrexate

Intervention Type: DRUG

Stable dose of methotrexate will be maintained through Week 24.

Part B, Group 3

Participants will receive CNTO 136 100 mg (Week 0 to Week 24) every 4 weeks and placebo at interim visits (Weeks 2, 6, 10, 14, 18, and 22). Stable dose of methotrexate will be maintained through Week 24.

Group Type: EXPERIMENTAL

CNTO 136 100 mg

Intervention Type: DRUG

CNTO 136 100 mg will be administered subcutaneously (under the skin) every 2 or 4 weeks as per the appropriate randomized arm.

Placebo

Intervention Type: DRUG

Placebo will be adminstered subcutaneously as per the appropriate randomized arm.

Methotrexate

Intervention Type: DRUG

Stable dose of methotrexate will be maintained through Week 24.

Part B, Group 4

Participants will receive CNTO 136 50 mg (Week 0 to Week 24) every 4 weeks and placebo at interim visits (Weeks 2, 6,10, 14, 18, and 22). Stable dose of methotrexate will be maintained through Week 24.

Group Type: EXPERIMENTAL

CNTO 136 50 mg

Intervention Type: DRUG

CNTO 136 50 mg will be administered subcutaneously every 4 weeks from Week 0 to Week 24.

Placebo

Intervention Type: DRUG

Placebo will be adminstered subcutaneously as per the appropriate randomized arm.

Methotrexate

Intervention Type: DRUG

Stable dose of methotrexate will be maintained through Week 24.

Part B, Group 5

Participants will receive CNTO 136 25 mg (Week 0 to Week 24) every 4 weeks and placebo at interim visits (Weeks 2, 6,10, 14, 18, and 22). Stable dose of methotrexate will be maintained through Week 24.

Group Type: EXPERIMENTAL

CNTO 136 25 mg

Intervention Type: DRUG

CNTO 136 25 mg will be administered subcutaneously every 4 weeks from Week 0 to Week 24.

Placebo

Intervention Type: DRUG

Placebo will be adminstered subcutaneously as per the appropriate randomized arm.

Methotrexate

Intervention Type: DRUG

Stable dose of methotrexate will be maintained through Week 24.

Interventions

CNTO 136 100 mg

CNTO 136 100 mg will be administered subcutaneously (under the skin) every 2 or 4 weeks as per the appropriate randomized arm.

Intervention Type: DRUG

CNTO 136 50 mg

CNTO 136 50 mg will be administered subcutaneously every 4 weeks from Week 0 to Week 24.

Intervention Type: DRUG

CNTO 136 25 mg

CNTO 136 25 mg will be administered subcutaneously every 4 weeks from Week 0 to Week 24.

Intervention Type: DRUG

Placebo

Placebo will be adminstered subcutaneously as per the appropriate randomized arm.

Intervention Type: DRUG

Methotrexate

Stable dose of methotrexate will be maintained through Week 24.

Intervention Type: DRUG

Other Intervention Names

Sirukumab; Sirukumab; Sirukumab

Eligibility Criteria

Inclusion Criteria

• Diagnosed with rheumatoid arthritis (RA) for at least 4 months prior to screening
• Have been treated and having an inadequate response with the tolerated dose of methotrexate (MTX) (at least 15mg/week) for at least 4 months prior to screening. MTX doses of 10 or 12.5 mg/week are allowed if participant had intolerance of 15 mg/week
• MTX route of administration and dose (not to exceed 25 mg/week) should be stable for at least 6 weeks prior to the start of the study medication
• Have active RA as defined by persistent disease activity with at least 6 swollen and 6 tender joints, at the time of screening and baseline, and either anti-cyclic citrullinated peptide antibody-positive or rheumatoid factor positive at screening
• C-reactive protein greater than or equal to 1.0 mg/dL (10 mg/L)
• Agree to use one of the contraception methods defined in the protocol

Exclusion Criteria

• Have inflammatory diseases other than RA that might confound the evaluation of the benefit of CNTO 136 therapy in arthritis
• Family history of/ have long QT syndrome; or a history of second or third-degree heart block
• Received systemic immunosuppressives or disease modifying antirheumatic drug other than MTX, sulfasalazine, hydroxychloroquine or chloroquine within 4 weeks prior to the start of study medication
• Received intra articular (into joints), intramuscular, or intravenous corticosteroids within 4 weeks prior to the start of study medication
• Positive human immunodeficiency virus test, hepatitis B or hepatitis C
• History of / have chronic or recurrent infectious disease, history of / active tuberculosis
• Have serious infection within 2 months prior to start of study medication

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centocor, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Centocor Clinical Trial

Role: STUDY_DIRECTOR

Centocor, Inc.

Locations

Aventura, Florida, United States

Lexington, Kentucky, United States

Frederick, Maryland, United States

Kalamazoo, Michigan, United States

Charlotte, North Carolina, United States

Winston-Salem, North Carolina, United States

Duncansville, Pennsylvania, United States

Anderson, South Carolina, United States

Budapest, , Hungary

Győr, , Hungary

Kecskemét, , Hungary

Goshogawara, , Japan

Hitachi, , Japan

Kawagoe, , Japan

Kitakyushu, , Japan

Miyazaki, , Japan

Sasebo, , Japan

Shinjuku-Ku, , Japan

Tomigusuku, , Japan

Guadalajara, , Mexico

Mexico City, , Mexico

México, , Mexico

Bialystok, , Poland

Bydgoszcz, , Poland

Elblag, , Poland

Gdynia, , Poland

Krakow, , Poland

Lublin, , Poland

Poznan, , Poland

Warsaw, , Poland

Kemerovo, , Russia

Moscow, , Russia

Novosibirsk, , Russia

Saint Petersburg, , Russia

Busan, , South Korea

Daegu, , South Korea

Daejeon, , South Korea

Seoul, , South Korea

Countries

United States; Hungary; Japan; Mexico; Poland; Russia; South Korea

References

Smolen JS, Weinblatt ME, Sheng S, Zhuang Y, Hsu B. Sirukumab, a human anti-interleukin-6 monoclonal antibody: a randomised, 2-part (proof-of-concept and dose-finding), phase II study in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis. 2014 Sep;73(9):1616-25. doi: 10.1136/annrheumdis-2013-205137. Epub 2014 Apr 3.

Reference Type: DERIVED

PMID: 24699939 (View on PubMed)

Other Identifiers

C1377T04

Identifier Type: OTHER

Identifier Source: secondary_id

2007-006603-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR015214

Identifier Type: -

Identifier Source: org_study_id