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

Rheumatoid Arthritis Clinical Trial

Official title:

A Phase 2a, 4-Week Double-Blind, Proof-of-Concept Efficacy and Safety Study of CC-292 Versus Placebo as Co-therapy With Methotrexate in Active Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01975610
• Other study ID #: CC-292-RA-001
• Status: Completed
• Phase: Phase 2
• First received: October 29, 2013
• Last updated: July 27, 2017
• Start date: October 2013
• Est. completion date: February 2016

Study information

• Verified date: July 2017
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: February 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• CC-292
375 mg PO daily (250 mg in the AM and 125 mg in the PM for 28 days)
• Placebo
Twice daily for 28 days

Locations

Country	Name	City	State
United States	Albuquerque Clinic	Albuquerque	New Mexico
United States	Austin Regional Clinic	Austin	Texas
United States	Achieve Clinical Research LLC	Birmingham	Alabama
United States	Joao Nascimento, MD	Bridgeport	Connecticut
United States	Med Univ of South Carolina	Charleston	South Carolina
United States	DJL Clinical Research	Charlotte	North Carolina
United States	Mountain State Clinical Research	Clarksburg	West Virginia
United States	Columbia Medical Practice	Columbia	Maryland
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Arthritis and Osteoporosis Associates	Freehold	New Jersey
United States	Southeastern Integrated Medical	Gainesville	Florida
United States	Generations Medical Research	Hot Springs	Arkansas
United States	DM Clinical Research	Houston	Texas
United States	West Tennessee Research Institute	Jackson	Tennessee
United States	Family Arthritis Center	Jupiter	Florida
United States	Borgess Research Institute	Kalamazoo	Michigan
United States	UCLA	Los Angeles	California
United States	Ramesh C Gupta MD	Memphis	Tennessee
United States	Froedtert Hospital BMT Medical College of Wisconsin	Milwaukee	Wisconsin
United States	NYU Langone Medical Center	New York	New York
United States	Ocala Rheumatology Research Center	Ocala	Florida
United States	Lynn Health Science Instiute	Oklahoma City	Oklahoma
United States	Gundersen Clinic Ltd	Onalaska	Wisconsin
United States	Arizona Arthritis and Rheumatology Research, PLLC	Phoenix	Arizona
United States	Integral Rheumatology and Immunology specialists	Plantation	Florida
United States	PMG Research of Charlotte LLC	Rock Hill	South Carolina
United States	Clinical Pharmacology Study Group	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	American College of Rheumatology Criteria for a 20% improvement (ACR 20)	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	Week 4
Secondary	Number of participants with adverse events	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.	Up to 8 Weeks
Secondary	American College of Rheumatology Criteria for a 50% improvement (ACR 50)	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.	Week 4
Secondary	American College of Rheumatology Criteria for a 70% improvement (ACR 70)	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.	Week 4