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

• ClinicalTrials.gov Identifier: NCT01909427
• Recruitment Status: Completed
• First Posted: July 26, 2013
• Last Update Posted: March 2, 2016
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Drug: Placebo; Drug: CNTO 6785 200 mg; Drug: CNTO 6785 100 mg; Drug: CNTO 6785 50 mg; Drug: CNTO 6785 15 mg; Drug: Methotrexate (MTX)	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 257 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: June 2013
• Actual Primary Completion Date: December 2014
• Actual Study Completion Date: May 2015

Arms and Interventions

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: 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 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: CNTO 6785 100 mg; CNTO 6785 100 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 50 mg+MTX	Drug: CNTO 6785 50 mg; CNTO 6785 50 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 15 mg+MTX	Drug: CNTO 6785 15 mg; CNTO 6785 15 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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Change from baseline in DAS28 (CRP) at Week 16 [ Time Frame: Baseline to Week 16 ]
   DAS28 (using CRP [C-reactive protein]) is a measure of tender and swollen joints and the patient's assessment of disease activity.
2. The proportion of participants who achieve ACR 50 response at Week 16 [ Time Frame: Week 16 ]
   American College of Rheumatology (ACR) 50 response is a >=50% improvement in rheumatoid arthritis (RA) symptoms.
3. The proportion of participants who achieve ACR 20 response through Week 32 [ Time Frame: Week 32 ]
4. The proportion of participants who achieve ACR 50 response through Week 32 [ Time Frame: Week 32 ]
5. The proportion of participants who achieve ACR 70 response through Week 32 [ Time Frame: Week 32 ]
   American College of Rheumatology (ACR) 70 response is a >=70% improvement in rheumatoid arthritis (RA) symptoms.
6. Change from baseline of DAS28 (CRP) through Week 32 [ Time Frame: Baseline to Week 32 ]
7. The proportion of participants with DAS28 (CRP) response through Week 32 [ Time Frame: 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.
8. The proportion of participants with DAS28 (CRP) remission at Week 16 [ Time Frame: 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.
9. The proportion of participants with DAS28 (CRP) remission at Week 32 [ Time Frame: Week 32 ]
10. Change from baseline in DAS28 (ESR) at Week 16 [ Time Frame: Baseline to Week 16 ]
    DAS28 (using erythrocyte sedimentation rate) is a measure of tender and swollen joints and the patient's assessment of disease activity.
11. Change from baseline in DAS28 (ESR) at Week 32 [ Time Frame: Baseline to Week 32 ]
12. Change from baseline in HAQ-DI score through Week 32 [ Time Frame: Baseline to 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).
13. Change from baseline in SF-36 at Week 16 [ Time Frame: Baseline to 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.
14. Change from baseline in SF-36 at Week 32 [ Time Frame: Baseline to Week 32 ]
15. Change from baseline in CDAI at Week 16 [ Time Frame: Baseline to 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.
16. Change from baseline in CDAI at Week 32 [ Time Frame: Baseline to Week 32 ]
17. Change from baseline in SDAI at Week 16 [ Time Frame: Baseline to 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.
18. Change from baseline in SDAI at Week 32 [ Time Frame: Baseline to Week 32 ]
19. The proportion of participants with SDAI-based ACR/EULAR remission at Week 16 [ Time Frame: 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.
20. The proportion of participants with SDAI-based ACR/EULAR remission at Week 32 [ Time Frame: Week 32 ]
21. The proportion of participants with Boolean-based ACR/EULAR remission at Week 16 [ Time Frame: 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.
22. The proportion of participants with Boolean-based ACR/EULAR remission at Week 32 [ Time Frame: Week 32 ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

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 5, Czech Republic

Praha, 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

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

More Information

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT01909427
• Other Study ID Numbers: CR100935; CNTO6785ARA2001 ( Other Identifier: Janssen Research & Development, LLC ); 2012-003629-40 ( EudraCT Number )
• First Posted: July 26, 2013
• Last Update Posted: March 2, 2016
• Last Verified: February 2016

Keywords provided by Janssen Research & Development, LLC:

Active rheumatoid arthritis despite methotrexate therapy; CNTO 6785; Methotrexate

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; 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