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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
  Purpose

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.


Condition Intervention Phase
Arthritis, Rheumatoid
Drug: CNTO 136 100 mg
Drug: CNTO 136 50 mg
Drug: CNTO 136 25 mg
Drug: Placebo
Drug: Methotrexate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Centocor, Inc.:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 187
Study Start Date: August 2008
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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: 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 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.
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: 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 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.
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: 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 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.
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: Methotrexate
Stable dose of methotrexate will be maintained through Week 24.
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.
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: 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 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.
Drug: CNTO 136 50 mg
CNTO 136 50 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 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.
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00718718

  Show 38 Study Locations
Sponsors and Collaborators
Centocor, Inc.
Investigators
Study Director: Centocor Clinical Trial Centocor, Inc.
  More Information

No publications provided

Responsible Party: Centocor, Inc.
ClinicalTrials.gov Identifier: NCT00718718     History of Changes
Other Study ID Numbers: CR015214, C1377T04, 2007-006603-20
Study First Received: July 17, 2008
Last Updated: December 16, 2013
Health Authority: United States: Food and Drug Administration
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
United States: Federal Government

Keywords provided by Centocor, Inc.:
Arthritis, Rheumatoid
Rheumatoid Arthritis
Active Rheumatoid Arthritis
CNTO 136
Interleukin-6
Anti-interleukin-6 monoclonal antibody
Methotrexate
Placebo

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

ClinicalTrials.gov processed this record on November 25, 2014