Clinical trial NCT01975610: Efficacy and Safety Study of CC-292 Versus Placebo as Co-therapy With Methotrexate in Active Rheumatoid Arthritis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Arthritis, Rheumatoid, Autoimmune, Inflammatory, Synovial, Bruton's tyrosine kinase (Btk), CC-292, Joint Disease
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2013-11-03
Enrollment: 47
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: American College of Rheumatology Criteria for a 20% improvement (ACR 20)
timeFrame: Week 4
Secondary outcomes:
measure: Number of participants with adverse events
timeFrame: Up to 8 Weeks
measure: American College of Rheumatology Criteria for a 50% improvement (ACR 50)
timeFrame: Week 4
measure: American College of Rheumatology Criteria for a 70% improvement (ACR 70)
timeFrame: Week 4
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Achieve Clinical Research LLC
state: Alabama
city: Phoenix
country: United States
facility: Arizona Arthritis and Rheumatology Research, PLLC
state: Arizona
city: Hot Springs
country: United States
facility: Generations Medical Research
state: Arkansas
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Bridgeport
country: United States
facility: Joao Nascimento, MD
state: Connecticut
city: Gainesville
country: United States
facility: Southeastern Integrated Medical
state: Florida
city: Jupiter
country: United States
facility: Family Arthritis Center
state: Florida
city: Ocala
country: United States
facility: Ocala Rheumatology Research Center
state: Florida
city: Plantation
country: United States
facility: Integral Rheumatology and Immunology specialists
state: Florida
city: Columbia
country: United States
facility: Columbia Medical Practice
state: Maryland
city: Worcester
country: United States
facility: Clinical Pharmacology Study Group
state: Massachusetts
city: Kalamazoo
country: United States
facility: Borgess Research Institute
state: Michigan
city: Freehold
country: United States
facility: Arthritis and Osteoporosis Associates
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Clinic
state: New Mexico
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: Charlotte
country: United States
facility: DJL Clinical Research
state: North Carolina
city: Oklahoma City
country: United States
facility: Lynn Health Science Instiute
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Charleston
country: United States
facility: Med Univ of South Carolina
state: South Carolina
city: Rock Hill
country: United States
facility: PMG Research of Charlotte LLC
state: South Carolina
city: Jackson
country: United States
facility: West Tennessee Research Institute
state: Tennessee
city: Memphis
country: United States
facility: Ramesh C Gupta MD
state: Tennessee
city: Austin
country: United States
facility: Austin Regional Clinic
state: Texas
city: Houston
country: United States
facility: DM Clinical Research
state: Texas
city: Clarksburg
country: United States
facility: Mountain State Clinical Research
state: West Virginia
city: Milwaukee
country: United States
facility: Froedtert Hospital BMT Medical College of Wisconsin
state: Wisconsin
city: Onalaska
country: United States
facility: Gundersen Clinic Ltd
state: Wisconsin
Study officials:
affiliation: Celgene Corporation
name: Douglas Hough, MD, MBA
role: STUDY_DIRECTOR
References:
citation: Schafer PH, Kivitz AJ, Ma J, Korish S, Sutherland D, Li L, Azaryan A, Kosek J, Adams M, Capone L, Hur EM, Hough DR, Ringheim GE. Spebrutinib (CC-292) Affects Markers of B Cell Activation, Chemotaxis, and Osteoclasts in Patients with Rheumatoid Arthritis: Results from a Mechanistic Study. Rheumatol Ther. 2020 Mar;7(1):101-119. doi: 10.1007/s40744-019-00182-7. Epub 2019 Nov 13.