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

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

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).

Study Overview

• Status: Withdrawn
• Conditions: Active Rheumatoid Arthritis; Rheumatoid Arthritis
• Intervention / Treatment: 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)

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.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary end point is change from baseline in Disease Activity Score 28 (DAS28) (CRP) at Week 12	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in DAS28 (CRP) at Week 24	Baseline, Week 24
Change from baseline in DAS28 (ESR) at Week 12 and Week 24	Baseline, Week 12 and Week 24
DAS28 (CRP) response rates at Week 12 and Week 24	Week 12, Week 24
DAS28 (ESR) response rates at Week 12 and Week 24	Week 12, Week 24
DAS28 (CRP) remission rates at Week 12 and Week 24	Week 12, Week 24
American college of rheumatology (ACR) 20/50/70 response rates at Week 12 and Week 24	Week 12, Week 24
Hybrid ACR response at Week 12 and Week 24	Week 12, Week 24
ACR/European League Against Rheumatism (EULAR) remission rates at Week 12 and Week 24	Week 12, Week 24
Change from baseline in Simplified Disease Activity Index (SDAI) at Week 12 and Week 24	Baseline, Week 12, Week 24
Change from baseline in Clinical Disease Activity Index (CDAI) at Week 12 and Week 24	Baseline, Week 12, Week 24
Health Assessment Questionnaire - Disability Index (HAQ-DI) response at Week 12 and Week 24	Week 12, Week 24
Change from baseline in HAQ-DI score at Week 12 and Week 24	Baseline, Week 12 and Week 24
Percent change from baseline in ESR levels at Week 12 and Week 24	Baseline, Week 12 and Week 24
Percent change from baseline in ACR components at Week 12 and Week 24	Baseline, Week 12 and Week 24

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Anticipated): March 1, 2014
• Study Completion (Anticipated): March 1, 2014

Study Registration Dates

• First Submitted: November 23, 2011
• First Submitted That Met QC Criteria: November 25, 2011
• First Posted (Estimate): November 28, 2011

Study Record Updates

• Last Update Posted (Estimate): December 1, 2016
• Last Update Submitted That Met QC Criteria: November 30, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Rheumatoid arthritis; Swollen and tender joints; Dose range finding study; Concurrent treatment with methotrexate
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: CR018814; 39758979ARA2001 (Other Identifier: Janssen Research & Development, LLC); 2011-002849-36 (EudraCT Number)