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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Centocor, Inc.
ClinicalTrials.gov Identifier:
NCT00718718
First received: July 17, 2008
Last updated: December 16, 2013
Last verified: December 2013

July 17, 2008
December 16, 2013
August 2008
March 2011   (final data collection date for primary outcome measure)
Part B: Number of participants who achieved American College of Rheumatology (ACR) 50 response at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
An ACR 50 response is defined as a greater than or equal to 50 percent improvement from baseline in swollen (66 joints) and tender (68 joints) joint counts and greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: 1) Participant's assessment of pain by Visual Analog Scale (VAS) (0-10 cm), 2) Participant's global assessment of disease activity by VAS (0-10 cm), 3) Physician's global assessment of disease activity by VAS (0-10 cm) 4) Participant's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) and 5) C reactive protein.
The primary outcomes in Part A are the safety and the effectiveness of CNTO 136 as measured by the Disease Activity Score (DAS) 28 response at Week 12. The primary outcome in Part B is the American College of Rheumatology (ACR) 50 response at Week 12
Complete list of historical versions of study NCT00718718 on ClinicalTrials.gov Archive Site
  • Part A and Part B: Change from baseline in Disease Activity Score 28 (DAS28) using C-reactive protein (CRP) at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    DAS28 using CRP is an index to measure the disease activity in participants with rheumatoid arthritis combining tender joints (28 joints), swollen joints (28 joints), CRP, and participant's global assessment of disease activity. The DAS28 score ranges from 0 (best) to 10 (worst). DAS28 score above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Higher scores indicate worsening.
  • Part A: Number of participants who achieved American College of Rheumatology (ACR) 50 response at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    An ACR 50 response is defined as a greater than or equal to 50 percent improvement from baseline in swollen (66 joints) and tender (68 joints) joint counts and greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: 1) Participant's assessment of pain by Visual Analog Scale (VAS) (0-10 cm), 2) Participant's global assessment of disease activity by VAS (0-10 cm), 3) Physician's global assessment of disease activity by VAS (0-10 cm) 4) Participant's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) and 5) C reactive protein.
  • Part A: Serum CNTO 136 concentrations [ Time Frame: Screening, Week 0, Day 2, Day 5, Day 8, Day 11, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, and Week 38 ] [ Designated as safety issue: No ]
  • Part B: Serum CNTO 136 concentrations [ Time Frame: Screening, Week 0, Day 5, Day 8, Day 11, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 30, and Week 38 ] [ Designated as safety issue: No ]
  • Part A and Part B: Percent change from baseline in serum C reactive protein at Week 2 [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
  • Part A and Part B: Number of participants with adverse events [ Time Frame: Up to 42 weeks ] [ Designated as safety issue: Yes ]
Secondary outcomes include change from baseline in Disease Activity Score (DAS) 28 response at Week 12, serum CNTO 136 concentrations, and percent change from baseline in serum C-reactive protein at Week 2.
Not Provided
Not Provided
 
A Study of Effectiveness and Safety of CNTO 136 in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy
A Phase 2, 2-Part, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled, Proof-of-concept, Dose-finding Study Evaluating the Efficacy and Safety of CNTO 136 Administered Subcutaneously in Subjects With Active Rheumatoid Arthritis Despite Methotrexate Therapy

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Arthritis, Rheumatoid
  • Drug: 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.
  • Drug: CNTO 136 50 mg
    CNTO 136 50 mg will be administered subcutaneously every 4 weeks from Week 0 to Week 24.
  • Drug: CNTO 136 25 mg
    CNTO 136 25 mg will be administered subcutaneously every 4 weeks from Week 0 to Week 24.
  • Drug: Placebo
    Placebo will be adminstered subcutaneously as per the appropriate randomized arm.
  • Drug: Methotrexate
    Stable dose of methotrexate will be maintained through Week 24.
  • Experimental: 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.
    Interventions:
    • Drug: CNTO 136 100 mg
    • Drug: Placebo
    • Drug: Methotrexate
  • Experimental: 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.
    Interventions:
    • Drug: CNTO 136 100 mg
    • Drug: Placebo
    • Drug: Methotrexate
  • Experimental: 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.
    Interventions:
    • Drug: CNTO 136 100 mg
    • Drug: Placebo
    • Drug: Methotrexate
  • Experimental: 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.
    Interventions:
    • Drug: CNTO 136 100 mg
    • Drug: Methotrexate
  • Experimental: 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.
    Interventions:
    • Drug: CNTO 136 100 mg
    • Drug: Placebo
    • Drug: Methotrexate
  • Experimental: 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.
    Interventions:
    • Drug: CNTO 136 50 mg
    • Drug: Placebo
    • Drug: Methotrexate
  • Experimental: 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.
    Interventions:
    • Drug: CNTO 136 25 mg
    • Drug: Placebo
    • Drug: Methotrexate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
187
March 2011
March 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Hungary,   Japan,   Korea, Republic of,   Mexico,   Poland,   Russian Federation
 
NCT00718718
CR015214, C1377T04, 2007-006603-20
Yes
Centocor, Inc.
Centocor, Inc.
Not Provided
Study Director: Centocor Clinical Trial Centocor, Inc.
Centocor, Inc.
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP