An Efficacy And Safety Study of CNTO 6785 In Participants With Active Rheumatoid Arthritis Despite Methotrexate Therapy

A Randomized, Placebo-controlled Double-blind, Multicenter, Phase 2 Dose Ranging Study To Assess The Efficacy And Safety of CNTO 6785 In Subjects With Active Rheumatoid Arthritis Despite Methotrexate Therapy

The purpose of this study is to assess the efficacy and safety of CNTO6785 in participants with active rheumatoid arthritis (RA) despite methotrexate (MTX) therapy.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Placebo; Drug: CNTO 6785 200 mg; Drug: CNTO 6785 200 mg; Drug: Methotrexate (MTX); Drug: CNTO 6785 100 mg; Drug: CNTO 6785 50 mg; Drug: CNTO 6785 15 mg

Detailed Description

This is a randomized (participants are assigned to treatment by chance), double-blind (participants and study personnel will not know which treatments are being given), placebo-controlled (a placebo appears identical to a study drug but has no active ingredients), multicenter study. The study will consist of 3 phases: a screening phase, a treatment phase, and a follow-up phase. Approximately 250 participants with active RA despite MTX therapy will be randomly assigned to receive placebo or CNTO 6785 during the double-blind treatment phase. The maximum period of active treatment will be 28 weeks. The maximum duration of study participation will be 44 weeks. Participant safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 257
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
  • Ciudad Autonoma Buenos Aires, Argentina
  • Cordoba, Argentina
  • La Capital, Argentina
  • San Juan, Argentina
• Colombia
  • Barranquilla, Colombia
  • Bogota, Colombia
  • Medellín, Colombia
• Czech Republic
  • Jihlava, Czech Republic
  • Praha, Czech Republic
  • Praha 5, Czech Republic
• Philippines
  • Cebu, Philippines
  • Iloilo City, Philippines
  • Lipa City, Philippines
  • Quezon City, Philippines
• Poland
  • Bydgoszcz, Poland
  • Grodzisk Mazowiecki, Poland
  • Lodz, Poland
  • Lublin, Poland
  • Poznan, Poland
  • Warszawa, Poland
  • Wroclaw, Poland
• Russian Federation
  • Barnaul, Russian Federation
  • Ekaterinburg, Russian Federation
  • Kemerovo, Russian Federation
  • Kursk, Russian Federation
  • Moscow, Russian Federation
  • Novosibirsk, Russian Federation
  • Petrozavodsk, Russian Federation
  • Saint-Petersburg, Russian Federation
  • St. Petersburg, Russian Federation
  • Yaroslavl, Russian Federation
• Thailand
  • Bangkok, Thailand
  • Chiang Mai, Thailand

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:

• Have a diagnosis of rheumatoid arthritis (RA) (according to the revised 1987 criteria of the American Rheumatism Association) and have had RA for at least 6 months prior to the date of signing the informed consent at screening
• Have active RA defined study as persistent disease activity with both of the following criteria: 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 (CRP) ≥ 0.8 mg/dL at screening or erythrocyte sedimentation rate (ESR) ≥ 28 mm in the first hour at screening or baseline
• Have been treated with and tolerated methotrexate (MTX) treatment at dosages from 7.5 to 25 mg/week, inclusive, for a minimum of 6 months prior to screening and must have a stable MTX dose for a minimum of 6 weeks prior to the first dosing with study agent

Exclusion Criteria:

• Has inflammatory diseases other than RA, that might confound the evaluation of the benefit of study agent therapy
• Has a diagnosis of fibromyalgia
• Has a recent history (within 12 months prior to screening) of uncontrolled, chronic disease including, but not limited to, pulmonary, psychiatric, and metabolic disturbances, cardiovascular, endocrine, neurological, hepatic, gastrointestinal, renal, hematological, or urological diseases that the investigator believes are clinically significant
• At screening, the results of laboratory tests must meet protocol-specified criteria
• Has ever received any approved or investigational biologic agent for a rheumatic indication

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo/CNTO 6785 200 mg+Methotrexate (MTX)	Drug: Placebo; Placebo subcutaneous injections (SC) every 4 weeks through Week 12; Drug: CNTO 6785 200 mg; CNTO 6785 200 mg SC every 4 weeks from Week 16 through Week 28; Drug: CNTO 6785 200 mg; CNTO 6785 200 mg SC every 4 weeks through Week 28; Drug: Methotrexate (MTX); MTX at the same stable dose through Week 32, that participants were receiving prior to screening.
Experimental: CNTO 6785 200 mg+MTX	Drug: CNTO 6785 200 mg; CNTO 6785 200 mg SC every 4 weeks from Week 16 through Week 28; Drug: CNTO 6785 200 mg; CNTO 6785 200 mg SC every 4 weeks through Week 28; Drug: Methotrexate (MTX); MTX at the same stable dose through Week 32, that participants were receiving prior to screening.
Experimental: CNTO 6785 100 mg+MTX	Drug: Methotrexate (MTX); MTX at the same stable dose through Week 32, that participants were receiving prior to screening.; Drug: CNTO 6785 100 mg; CNTO 6785 100 mg SC every 4 weeks through Week 28
Experimental: CNTO 6785 50 mg+MTX	Drug: Methotrexate (MTX); MTX at the same stable dose through Week 32, that participants were receiving prior to screening.; Drug: CNTO 6785 50 mg; CNTO 6785 50 mg SC every 4 weeks through Week 28
Experimental: CNTO 6785 15 mg+MTX	Drug: Methotrexate (MTX); MTX at the same stable dose through Week 32, that participants were receiving prior to screening.; Drug: CNTO 6785 15 mg; CNTO 6785 15 mg SC every 4 weeks through Week 28

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of participants who achieve an ACR 20 response at Week 16	American College of Rheumatology (ACR) 20 response is a >=20% improvement in rheumatoid arthritis (RA) symptoms.	Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in DAS28 (CRP) at Week 16	DAS28 (using CRP [C-reactive protein]) is a measure of tender and swollen joints and the patient's assessment of disease activity.	Baseline to Week 16
The proportion of participants who achieve ACR 50 response at Week 16	American College of Rheumatology (ACR) 50 response is a >=50% improvement in rheumatoid arthritis (RA) symptoms.	Week 16
The proportion of participants who achieve ACR 20 response through Week 32		Week 32
The proportion of participants who achieve ACR 50 response through Week 32		Week 32
The proportion of participants who achieve ACR 70 response through Week 32	American College of Rheumatology (ACR) 70 response is a >=70% improvement in rheumatoid arthritis (RA) symptoms.	Week 32
Change from baseline of DAS28 (CRP) through Week 32		Baseline to Week 32
The proportion of participants with DAS28 (CRP) response through Week 32	DAS28 (using CRP [C-reactive protein]) response is improvement from baseline, with >1.2 indicating a good or moderate response and <=0.6 indicating no response.	Week 32
The proportion of participants with DAS28 (CRP) remission at Week 16	DAS28 (using CRP [C-reactive protein]) remission is defined as a value of <2.6 on the Disease Activity Index, a measure of tender and swollen joints and the patient's assessment of disease activity.	Week 16
The proportion of participants with DAS28 (CRP) remission at Week 32		Week 32
Change from baseline in DAS28 (ESR) at Week 16	DAS28 (using erythrocyte sedimentation rate) is a measure of tender and swollen joints and the patient's assessment of disease activity.	Baseline to Week 16
Change from baseline in DAS28 (ESR) at Week 32		Baseline to Week 32
Change from baseline in HAQ-DI score through Week 32	The Health Assessment Questionnaire-Disability Index (HAQ-DI) assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas, each scored from 0 (no difficulty) to 3 (inability to perform a task).	Baseline to Week 32
Change from baseline in SF-36 at Week 16	The SF-36 is a medical outcome study health measure and consists of 8 multi-item scales that are scored from 0 to 100, with higher scores indicating better health.	Baseline to Week 16
Change from baseline in SF-36 at Week 32		Baseline to Week 32
Change from baseline in CDAI at Week 16	Clinical Disease Activity Index (CDAI) score is a derived score combining tender joints (28 joints), swollen joints (28 joints), Patient's Global Assessment of Disease Activity, and Physician's Global Assessments of Disease Activity.	Baseline to Week 16
Change from baseline in CDAI at Week 32		Baseline to Week 32
Change from baseline in SDAI at Week 16	The Simplified Disease Activity Index (SDAI) score is a derived score combining tender joints (28 joints), swollen joints (28 joints), Patient's Global Assessment of Disease Activity, Physician's Global Assessments of Disease Activity, and CRP.	Baseline to Week 16
Change from baseline in SDAI at Week 32		Baseline to Week 32
The proportion of participants with SDAI-based ACR/EULAR remission at Week 16	The Simplified Disease Activity Index (SDAI)-based ACR/EULAR (European League Against Rheumatism) remission is defined as a SDAI value of <=3.3 at a visit.	Week 16
The proportion of participants with SDAI-based ACR/EULAR remission at Week 32		Week 32
The proportion of participants with Boolean-based ACR/EULAR remission at Week 16	Boolean-based ACR/EULAR remission is achieved if all of the following 4 criteria at that visit are met: tender joint count (68 joints) <=1; swollen joint count (66 joints) <=1; CRP <=1 mg/dL; and Patient's Global Assessment of Disease Activity on VAS <=1 on a 0 to 10 scale.	Week 16
The proportion of participants with Boolean-based ACR/EULAR remission at Week 32		Week 32

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: July 10, 2013
• First Submitted That Met QC Criteria: July 23, 2013
• First Posted (Estimate): July 26, 2013

Study Record Updates

• Last Update Posted (Estimate): March 2, 2016
• Last Update Submitted That Met QC Criteria: February 3, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Methotrexate; Active rheumatoid arthritis despite methotrexate therapy; CNTO 6785
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: CR100935; CNTO6785ARA2001 (Other Identifier: Janssen Research & Development, LLC); 2012-003629-40 (EudraCT Number)