A Dose Range Finding Study of JNJ-38518168 in Patients With Active Rheumatoid Arthritis in Spite of Treatment With Methotrexate

This study has been terminated.
(The decision was made to prematurely discontinue this trial due to lack of efficacy.)
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01679951
First received: September 3, 2012
Last updated: July 1, 2014
Last verified: July 2014
  Purpose

The purpose of this dose range finding study is to assess the effectiveness, safety and tolerability of JNJ-38518168 at doses of 3, 10, and 30 mg/d compared with placebo in patients with active rheumatoid arthritis (RA) despite concomitant methotrexate (MTX) therapy.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Placebo
Drug: JNJ-38518168 (3 mg)
Drug: JNJ-38518168 (10 mg)
Drug: JNJ-38518168 (30 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-38518168 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:
  • Disease Activity Score 28 (DAS28) (C-reactive protein [CRP]) at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The DAS28 using CRP is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP, and Patient's Global Assessment of Disease Activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst.


Secondary Outcome Measures:
  • Change from baseline in DAS28 (CRP) at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in DAS28 (erythrocyte sedimentation rate [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 and Week 24 ] [ Designated as safety issue: No ]
  • DAS28 (ESR) response rates at Week 12 and Week 24 [ Time Frame: Week 12 and Week 24 ] [ Designated as safety issue: No ]
  • DAS28 (CRP) remission rates at Week 12 and Week 24 [ Time Frame: Week 12 and Week 24 ] [ Designated as safety issue: No ]
  • DAS28 (ESR) remission rates at Week 12 and Week 24 [ Time Frame: Week 12 and 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 and Week 24 ] [ Designated as safety issue: No ]
    An ACR 20/50/70 response is defined as a greater than or equal to 20/50/70 percentage improvement from baseline in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) 2. greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: a. Patient's assessment of pain (VAS) (0-10 cm) b.Patient's Global Assessment of Disease activity (VAS) (0-10 cm) c. Physician's Global Assessment of Disease Activity (VAS) (0-10 cm) d. Patient's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein (CRP).

  • Hybrid ACR response at Week 12 and Week 24 [ Time Frame: Week 12 and Week 24 ] [ Designated as safety issue: No ]
    The hybrid ACR response is a continuous variable that is limited to an overall score of -100 (maximal worsening) to +100 (maximal improvement).

  • ACR/European League Against Rheumatism (EULAR) remission rates at Week 12 and Week 24 [ Time Frame: Week 12 and Week 24 ] [ Designated as safety issue: No ]

    According to the ACR/EULAR provisional definition, a patients RA can be defined as being in remission based on either of 2 definitions:

    when scores on the tender joint count, swollen joint count, CRP (in mg/dL), and patient global assessment (0-10 scale) are all less than or equal to 1 OR when the score on the simplified disease activity index (SDAI) is less than or equal to 3.3 Analyses based on each definition will be performed.


  • Change from baseline in Simplified Disease Activity Index (SDAI) at Week 12 and Week 24 [ Time Frame: Baseline, Week 12 and Week 24 ] [ Designated as safety issue: No ]
    The SDAI is the numerical sum of 5 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) based on a 28‐joint assessment, patient global assessment of disease activity (PGA VAS in cm), physician global assessment of disease activity (MDGA VAS in cm) and C‐reactive protein (CRP in mg/dL).

  • Change from baseline in Clinical Disease Activity Index (CDAI) at Week 12 and Week 24 [ Time Frame: Baseline, Week 12 and Week 24 ] [ Designated as safety issue: No ]
    The CDAI is the numerical sum of 5 outcome parameters: TJC and SJC based on a 28‐joint assessment, PGA, and MDGA.

  • Health Assessment Questionnaire - Disability Index (HAQ-DI) response at Week 12 and Week 24 [ Time Frame: Week 12 and Week 24 ] [ Designated as safety issue: No ]
    The HAQ-DI is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0 (no difficulty), to 3 (inability to perform a task in that area).

  • 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 ]
  • Number of patients with adverse events [ Time Frame: Up to Week 28 ] [ Designated as safety issue: Yes ]

Enrollment: 272
Study Start Date: October 2012
Estimated Study Completion Date: July 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Form=tablet, route=oral. Placebo will be administered once daily from week 0 to week 24.
Experimental: JNJ-38518168 (3 mg/d) Drug: JNJ-38518168 (3 mg)
Type=exact number, unit=mg, number=3, form=tablet, route=oral. JNJ-38518168 will be administered once daily up to 24 weeks.
Experimental: JNJ-38518168 (10 mg/d) Drug: JNJ-38518168 (10 mg)
Type=exact number, unit=mg, number=10, form=tablet, route=oral. JNJ-38518168 will be administered once daily up to 24 weeks.
Experimental: JNJ-38518168 (30 mg/d) Drug: JNJ-38518168 (30 mg)
Type=exact number, unit=mg, number=30, form=tablet, route=oral. JNJ-38518168 will be administered once daily up to 24 weeks.

Detailed Description:

This is a randomized (the study medication is assigned by chance), double-blind (neither physician nor patient knows the treatment that the patient receives), multicenter, placebo-controlled (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), parallel-group (each group of patients will be treated at the same time), dose range finding study of JNJ-38518168 in patients with active RA despite concomitant MTX therapy. The study will consist a screening period, a 24-week placebo-controlled period and a 4-week follow-up period between the last dose and the last visit. The duration of participation in the study for an individual patient will be up to 34 weeks (including screening). The patients will be assigned to 1 of 4 treatment groups in a 1:1:1:1 ratio to placebo and JNJ-38518168 (3 mg or 10 mg or 30 mg). Safety assessments and evaluations to determine the efficacy of JNJ-38518168 to reduce the signs and symptoms of RA will be performed at study visits. Safety will be monitored throughout the study.

  Eligibility

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

Inclusion Criteria:

  • Has had rheumatoid arthritis for at least 6 months prior to the date of signing the informed consent at screening
  • Must be positive for either anti-cyclic citrullinated peptide antibody or rheumatoid factor in serum at screening
  • Must have active rheumatoid arthritis (at least 6 swollen and 6 tender joints using a 66/68 joint count at the time of screening and at baseline and Serum C reactive protein greater than or equal to 0.80 mg/dL at the time of screening
  • Has been treated with and tolerated methotrexate treatment at dosages from 10 to 25 mg/week inclusive, for a minimum of 6 months with stable dose for at least 8 weeks prior to the date of signing the informed consent at screening

Exclusion Criteria:

  • Has inflammatory diseases other than rheumatoid arthritis, including but not limited to adult onset Still's disease, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, and Lyme disease that might confound the evaluation of the benefit of study agent therapy
  • Has current signs or symptoms of liver or renal insufficiency or cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, psychiatric, or metabolic disturbances that are severe, progressive or uncontrolled
  • Has ever received any approved or investigational biologic agent for a rheumatoid indication
  • Has been treated with any nonbiologic disease modifying antirheumatic drugs within 4 weeks prior to the first administration of study agent
  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: NCT01679951

  Show 89 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research and Development, LLC Clinical Trial Janssen Research and Development LLC
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01679951     History of Changes
Other Study ID Numbers: CR100734, 38518168ARA2002, 2011-002840-29
Study First Received: September 3, 2012
Last Updated: July 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Janssen Research & Development, LLC:
Rheumatoid arthritis
Swollen and tender joints
Methotrexate
Immunology
Dose range finding study

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
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 September 16, 2014