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Efficacy and Safety Study of CC-292 Versus Placebo as Co-therapy With Methotrexate in Active Rheumatoid Arthritis

Phase 2
Completed
Conditions
Rheumatoid Arthritis
Interventions
Drug: Placebo
Registration Number
NCT01975610
Lead Sponsor
Celgene
Brief Summary

CC-292 is an oral agent that is under clinical development for the treatment of rheumatoid arthritis an autoimmune inflammatory disorder.

This study will test the clinical effectiveness and safety of an orally (PO) administered dose of CC-292 compared to placebo in US female patients currently on background Methotrexate (MTX) with active Rheumatoid Arthritis (RA

Detailed Description

This is a Phase 2a, multicenter, randomized, double-blind, placebo-controlled, proof-of-concept study to determine the efficacy and safety of CC-292 (375 mg PO daily) on a stable background of MTX therapy in female subjects with active RA.

Approximately 80 female subjects with active RA will be randomized 1:1 into two dose groups: active CC-292 (375 mg PO daily) or identically-appearing placebo capsules for 4 weeks

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
47
Inclusion Criteria
  • Female between 18 and 80 years of age (inclusive) at the time of signing the informed consent.
  • Must meet the 2010 ACR/EULAR Classification Criteria for RA (Appendix A), have RA for at least 6 months and must continue to have active RA at the time of randomization despite at least 3 months of treatment with stable doses of MTX (7.5 to 25 mg/week oral or parenteral) for at least 4 weeks prior to randomization.
  • Must have been treated with MTX for at least 3 months prior to randomization, and must be on a stable dose between 7.5 and 25 mg/week (PO or parenteral, not both) for at least 4 weeks prior to randomization. Subjects will be required to maintain their stable dose through Day 28/Week 4 of the study. Oral folate supplementation is required with a minimum dose of 5 mg/week (ie, folic acid) while the subject is taking MTX. Leucovorin may be used instead of folic acid and may be dosed up to 10 mg/week orally.
  • Sulfasalazine is allowed as a concomitant medication, however, subject must be on a stable dose for at least 4 weeks prior to randomization and through Day 28/Week 4 of the study.
  • Hydroxychloroquine or chloroquine is allowed as concomitant medications, however, subject must be on a stable dose for at least 4 weeks prior to randomization and through Day 28/Week 4 of the study.
  • Modification of Diet in Renal Disease formula (MDRD) estimated glomerular filtration rate (MDRD eGFR) ≥ 60 mL/min/1.73m2+
Exclusion Criteria
  • Male subjects
  • Any condition that could affect CC-292 absorption, including gastric restrictions, bariatric surgery, such as gastric bypass, and clinical conditions that are associated with decreased intragastric acid production such as acid pernicious anemia.
  • Currently using treatment with DMARDs (other than sulfasalazine, hydroxychloroquine or chloroquine and MTX), including biologics. Previous use is only allowed after adequate washout (4 weeks or 5 half-lives, whichever is longer) prior to randomization.
  • Previous treatment with any cell depleting therapies, including investigational agents (eg, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20) within 6 months of screening.
  • Treatment with intravenous gamma globulin, plasmapheresis or Prosorba® column within 2 weeks prior to randomization.
  • Intra-articular or parenteral corticosteroids are not allowed within 2 weeks prior to randomization.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CC-292 375mgCC-292Treatment
PlaceboPlaceboControl
Primary Outcome Measures
NameTimeMethod
American College of Rheumatology Criteria for a 20% improvement (ACR 20)Week 4

Percentage of participants with an American College of Rheumatology ≥20% (ACR20) response. A participant is a responder if the following 3 criteria for improvement from Baseline are met: • ≥ 20% improvement in 68 tender joint count; • ≥ 20% improvement in 66 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: o Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); o Patient's global assessment of disease activity (measured on a 100 mm VAS); o Physician's global assessment of disease activity (measured on a 100 mm VAS); o Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); o C-Reactive Protein

Secondary Outcome Measures
NameTimeMethod
American College of Rheumatology Criteria for a 70% improvement (ACR 70)Week 4

Percentage of participants with an American College of Rheumatology ≥70% (ACR70) response. A participant is a responder if the following 3 criteria for improvement from Baseline are met:

* ≥ 70% improvement in 68 tender joint count;

* ≥ 70% improvement in 66 swollen joint count; and

* ≥ 70% improvement in at least 3 of the 5 following parameters:

* Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]);

* Patient's global assessment of disease activity (measured on a 100 mm VAS);

* Physician's global assessment of disease activity (measured on a 100 mm VAS);

* Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI));

* C-Reactive Protein.

American College of Rheumatology Criteria for a 50% improvement (ACR 50)Week 4

Percentage of participants with an American College of Rheumatology ≥50% (ACR50) response. A participant is a responder if the following 3 criteria for improvement from Baseline are met:

* ≥ 50% improvement in 68 tender joint count;

* ≥ 50% improvement in 66 swollen joint count; and

* ≥ 50% improvement in at least 3 of the 5 following parameters:

* Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]);

* Patient's global assessment of disease activity (measured on a 100 mm VAS);

* Physician's global assessment of disease activity (measured on a 100 mm VAS);

* Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI));

* C-Reactive Protein.

Number of participants with adverse eventsUp to 8 Weeks

Safety and tolerability of CC-292 compared with placebo in subjects on a background of stable MTX therapy. An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values (as specified by the criteria below), regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.

Trial Locations

Locations (27)

NYU Langone Medical Center

🇺🇸

New York, New York, United States

UCLA

🇺🇸

Los Angeles, California, United States

Family Arthritis Center

🇺🇸

Jupiter, Florida, United States

Ocala Rheumatology Research Center

🇺🇸

Ocala, Florida, United States

Albuquerque Clinic

🇺🇸

Albuquerque, New Mexico, United States

DJL Clinical Research

🇺🇸

Charlotte, North Carolina, United States

Altoona Center for Clinical Research

🇺🇸

Duncansville, Pennsylvania, United States

Ramesh C Gupta MD

🇺🇸

Memphis, Tennessee, United States

Austin Regional Clinic

🇺🇸

Austin, Texas, United States

Mountain State Clinical Research

🇺🇸

Clarksburg, West Virginia, United States

Southeastern Integrated Medical

🇺🇸

Gainesville, Florida, United States

Columbia Medical Practice

🇺🇸

Columbia, Maryland, United States

Generations Medical Research

🇺🇸

Hot Springs, Arkansas, United States

PMG Research of Charlotte LLC

🇺🇸

Rock Hill, South Carolina, United States

Joao Nascimento, MD

🇺🇸

Bridgeport, Connecticut, United States

Arthritis and Osteoporosis Associates

🇺🇸

Freehold, New Jersey, United States

West Tennessee Research Institute

🇺🇸

Jackson, Tennessee, United States

Froedtert Hospital BMT Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

Gundersen Clinic Ltd

🇺🇸

Onalaska, Wisconsin, United States

Integral Rheumatology and Immunology specialists

🇺🇸

Plantation, Florida, United States

Clinical Pharmacology Study Group

🇺🇸

Worcester, Massachusetts, United States

Borgess Research Institute

🇺🇸

Kalamazoo, Michigan, United States

Med Univ of South Carolina

🇺🇸

Charleston, South Carolina, United States

Achieve Clinical Research LLC

🇺🇸

Birmingham, Alabama, United States

Arizona Arthritis and Rheumatology Research, PLLC

🇺🇸

Phoenix, Arizona, United States

Lynn Health Science Instiute

🇺🇸

Oklahoma City, Oklahoma, United States

DM Clinical Research

🇺🇸

Houston, Texas, United States

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