A Dose Range Finding Study of JNJ-39758979 in Patients With Active Rheumatoid Arthritis Currently Treated With Methotrexate

This study has been terminated.
(Study was terminated prematurely due to 2 cases of agranulocytosis in a different clinical trial with this same drug.)
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01480388
First received: November 23, 2011
Last updated: August 16, 2013
Last verified: August 2013
  Purpose

The purpose of the study is to assess the efficacy, safety and tolerability of JNJ-39758979 at doses of 10, 30, 100, and 300 mg/day compared with placebo (inactive medical substance) in patients with active rheumatoid arthritis despite concomitant treatment with methotrexate (MTX).


Condition Intervention Phase
Active Rheumatoid Arthritis; Rheumatoid Arthritis
Drug: Placebo/JNJ-39758979 (300 mg/d)
Drug: JNJ-39758979 (10 mg)
Drug: JNJ-39758979 (30 mg)
Drug: JNJ-39758979 (100 mg)
Drug: JNJ-39758979 (300 mg)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2b Randomized, Double-blind, Multicenter, Placebo-controlled, Parallel-group, Dose Range Finding Study of JNJ-39758979 in Subjects With Active Rheumatoid Arthritis Despite Concomitant Methotrexate Therapy

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • The primary end point is change from baseline in Disease Activity Score 28 (DAS28) (CRP) at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in DAS28 (CRP) at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in DAS28 (ESR) at Week 12 and Week 24 [ Time Frame: Baseline, Week 12 and Week 24 ] [ Designated as safety issue: No ]
  • DAS28 (CRP) response rates at Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ] [ Designated as safety issue: No ]
  • DAS28 (ESR) response rates at Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ] [ Designated as safety issue: No ]
  • DAS28 (CRP) remission rates at Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ] [ Designated as safety issue: No ]
  • American college of rheumatology (ACR) 20/50/70 response rates at Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ] [ Designated as safety issue: No ]
  • Hybrid ACR response at Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ] [ Designated as safety issue: No ]
  • ACR/European League Against Rheumatism (EULAR) remission rates at Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in Simplified Disease Activity Index (SDAI) at Week 12 and Week 24 [ Time Frame: Baseline, Week 12, Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in Clinical Disease Activity Index (CDAI) at Week 12 and Week 24 [ Time Frame: Baseline, Week 12, Week 24 ] [ Designated as safety issue: No ]
  • Health Assessment Questionnaire - Disability Index (HAQ-DI) response at Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in HAQ-DI score at Week 12 and Week 24 [ Time Frame: Baseline, Week 12 and Week 24 ] [ Designated as safety issue: No ]
  • Percent change from baseline in ESR levels at Week 12 and Week 24 [ Time Frame: Baseline, Week 12 and Week 24 ] [ Designated as safety issue: No ]
  • Percent change from baseline in ACR components at Week 12 and Week 24 [ Time Frame: Baseline, Week 12 and Week 24 ] [ Designated as safety issue: No ]

Estimated Enrollment: 325
Study Start Date: November 2011
Estimated Study Completion Date: March 2014
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo/JNJ-39758979 (300 mg/d)
Form = tablet, route = oral adminstration placebo once daily from Week 0 to Week 24 followed by JNJ-39758979 300 mg once daily from Week 24 to Week 48.
Other Name: Inactive medical substance
Experimental: JNJ-39758979 (10 mg/d) Drug: JNJ-39758979 (10 mg)
Form = tablet, route = oral adminstration once daily up to 48 weeks
Experimental: JNJ-39758979 (30 mg/d) Drug: JNJ-39758979 (30 mg)
Form = tablet, route = oral adminstration once daily up to 48 weeks
Experimental: JNJ-39758979 (100 mg/d) Drug: JNJ-39758979 (100 mg)
Form = tablet, route = oral adminstration once daily up to 48 weeks
Experimental: JNJ-39758979 (300 mg/d) Drug: JNJ-39758979 (300 mg)
Form = tablet, route = oral adminstration once daily for 48 weeks

Detailed Description:

This is a double-blind (neither physician nor patient knows if the patient is receiving JNJ-39758979 or placebo), multicenter, randomized (patients are assigned to treatment by chance), placebo-controlled, dose range finding study of JNJ-39758979 in patients with stable methotrexate treatment through Week 24. The study will consist of 4 periods: a screening period, a 24-week placebo-controlled period, a 24-week extension period, and a 5-week safety follow-up period. The duration of participation in the study for an individual patient will be up to 59 weeks (including screening). All patients will be randomly assigned in a 1:1:1:1:1 ratio to receive placebo or JNJ-39758979 10 mg, 30 mg, 100 mg, or 300 mg once daily. At Week 24, all patients remaining in the placebo group will start to receive JNJ-39758979 300 mg/day. Safety assessments and evaluations to determine the efficacy of JNJ-39758979 to reduce the signs and symptoms of rheumatoid arthritis will be performed at study visits. The extension and safety follow-up periods of this study will continue through Week 53 in order to assess the safety and for maintenance of efficacy of patients.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has a diagnosis of rheumatoid arthritis (RA) for at least 6 months before screening.
  • Positive test for either anti-cyclic citrullinated peptide (anti-CCP) antibody or rheumatoid factor (RF) in serum at screening.
  • Has active RA defined as persistent disease activity with the following criteria: at least 6 swollen and 6 tender joints, and serum CRP ≥ 0.70 mg/dL at screening.
  • Has been treated with and tolerated methotrexate (MTX) treatment at dosages of 10 to 25 mg/week for a minimum of 6 months prior to screening and must be on a stable dose for a minimum of 8 weeks prior to screening
  • Must be post-menopausal or if pre-menopausal, must use an acceptable form of birth control
  • Has completed at least 5 days of daily pain diary in the 10 days prior to randomization.

Exclusion Criteria:

  • Has inflammatory diseases other than RA, such as Lupus.
  • Is currently receiving treatment for RA other than methotrexate, NSAIDS, or oral corticosteroids such as prednisone, or pain medicines.
  • Has ever received any biologic agent for a rheumatic indication.
  • Has current signs or symptoms of liver insufficiency or cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, psychiatric, or metabolic disturbances that are severe, progressive, or uncontrolled.
  • Has moderate or severe renal insufficiency
  • Has a recent (within 2 months) serious infection
  • Has had an opportunistic infection.
  • Has had cancer within the past 5 years (except certain skin or cervical conditions)
  • Has abused substances or alcohol within the past 2 years
  • Has active Hepatitis B or C infection
  • Has had active tuberculosis
  • Has had exposure to tuberculosis without preventative treatment
  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: NCT01480388

Locations
United States, Arizona
Gilbert, Arizona, United States
United States, Florida
Palm Harbor, Florida, United States
United States, New Jersey
Freehold, New Jersey, United States
United States, Pennsylvania
Wyomissing, Pennsylvania, United States
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Development, L.L.C. Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01480388     History of Changes
Other Study ID Numbers: CR018814, 39758979ARA2001, 2011-002849-36
Study First Received: November 23, 2011
Last Updated: August 16, 2013
Health Authority: United States Food and Drug Administration: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Janssen Research & Development, LLC:
Rheumatoid arthritis
Swollen and tender joints
Dose range finding study
Concurrent treatment with methotrexate

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

ClinicalTrials.gov processed this record on August 21, 2014