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

NCT00718718 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: CR015214C1377T042007-006603-20
• Study Type: interventional
• Target: 187
• Locations: 7 countries
• Sites: 38

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.

Conditions

Arthritis, Rheumatoid

Keywords

Arthritis, Rheumatoid; Rheumatoid Arthritis; Active Rheumatoid Arthritis; CNTO 136; Interleukin-6; Anti-interleukin-6 monoclonal antibody; Methotrexate; Placebo

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Week 12 (Part B)

  An American College of Rheumatology (ACR) 50 response is defined as greater than or equal to (\>=) 50 percent (%) improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and \>= 50% improvement in 3 of the following 5 assessments: participant's assessment of pain using Visual Analogue Scale (Score) VAS (0-10 scale, 0=no pain and 10=worst possible pain), participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, \[0 = very well to 10 = very poor\]), physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, \[0=no arthritis activity to 10=extremely active arthritis\]), participant's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area), and serum C-reactive protein (CRP).

  Week 12

Secondary Outcomes (5)

• Change From Baseline in Disease Activity Index Score 28 (DAS28) Based on C-reactive Protein (CRP) at Week 12 (Part A and Part B)

  Baseline, Week 12

• Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 12 (Part A)

  Week 12

• Serum Sirukumab Concentrations Through Week 38 (Part A)

  Week 0, Day 2, Day 5, Day 8, Day 11, Week 2, Week 4, Week 8, Week 10, Week 10 Day 4, Week 10 Day 7, Week 12, Week 14, Week 18, Week 22, Week 24, and Week 38

• Serum Sirukumab Concentrations Through Week 38 (Part B)

  Week 0, Day 5, Day 8, Day 11, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 24 Day4, Week 24 Day7, Week 26, Week 28, Week 30, Week 34 and Week 38

• Percent Improvement From Baseline in Serum C-Reactive Protein (CRP) At Week 2 (Part A and Part B)

  Baseline, Week 2

Study Arms (7)

Part A, Group 1

EXPERIMENTAL

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.

Drug: CNTO 136 100 mg; Drug: Placebo; Drug: Methotrexate

Part A, Group 2

EXPERIMENTAL

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.

Drug: CNTO 136 100 mg; Drug: Placebo; Drug: Methotrexate

Part B, Group 1

EXPERIMENTAL

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.

Drug: CNTO 136 100 mg; Drug: Placebo; Drug: Methotrexate

Part B, Group 2

EXPERIMENTAL

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.

Drug: CNTO 136 100 mg; Drug: Methotrexate

Part B, Group 3

EXPERIMENTAL

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.

Drug: CNTO 136 100 mg; Drug: Placebo; Drug: Methotrexate

Part B, Group 4

EXPERIMENTAL

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.

Drug: CNTO 136 50 mg; Drug: Placebo; Drug: Methotrexate

Part B, Group 5

EXPERIMENTAL

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.

Drug: CNTO 136 25 mg; Drug: Placebo; Drug: Methotrexate

Interventions

CNTO 136 100 mg DRUG

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

Also known as: Sirukumab

Part A, Group 1; Part A, Group 2; Part B, Group 1; Part B, Group 2; Part B, Group 3

CNTO 136 50 mg DRUG

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

Also known as: Sirukumab

Part B, Group 4

CNTO 136 25 mg DRUG

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

Also known as: Sirukumab

Part B, Group 5

Placebo DRUG

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

Part A, Group 1; Part A, Group 2; Part B, Group 1; Part B, Group 3; Part B, Group 4; Part B, Group 5

Methotrexate DRUG

Stable dose of methotrexate will be maintained through Week 24.

Part A, Group 1; Part A, Group 2; Part B, Group 1; Part B, Group 2; Part B, Group 3; Part B, Group 4; Part B, Group 5

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centocor, Inc.: lead

Study Sites (38)

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Aventura, Florida, United States

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Lexington, Kentucky, United States

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Frederick, Maryland, United States

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Kalamazoo, Michigan, United States

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Charlotte, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Duncansville, Pennsylvania, United States

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Anderson, South Carolina, United States

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Budapest, Hungary

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Győr, Hungary

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Kecskemét, Hungary

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Goshogawara, Japan

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Hitachi, Japan

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Kawagoe, Japan

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Kitakyushu, Japan

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Miyazaki, Japan

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Sasebo, Japan

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Shinjuku-Ku, Japan

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Tomigusuku, Japan

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Guadalajara, Mexico

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Mexico City, Mexico

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México, Mexico

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Bialystok, Poland

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Bydgoszcz, Poland

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Elblag, Poland

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Gdynia, Poland

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Krakow, Poland

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Lublin, Poland

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Poznan, Poland

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Warsaw, Poland

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Kemerovo, Russia

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Moscow, Russia

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Novosibirsk, Russia

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Saint Petersburg, Russia

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Busan, South Korea

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Daegu, South Korea

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Daejeon, South Korea

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Seoul, South Korea

Location

Related Publications (1)

• 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.

  PMID: 24699939 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

sirukumab; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Associate Director
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

Study Officials

• Centocor Clinical Trial

  Centocor, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2008
• First Posted: July 21, 2008
• Study Start: August 11, 2008
• Primary Completion: March 3, 2011
• Study Completion: March 3, 2011
• Last Updated: January 23, 2018
• Results First Posted: December 4, 2017

Record last verified: 2017-12

Locations

PL (8); HU (3); ME (3); RU (4); US (8); KR (4); JP (8)