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

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

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

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: CC-292; Drug: Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Achieve Clinical Research LLC
  • Arizona
    • Phoenix, Arizona, United States, 85023
      • Arizona Arthritis and Rheumatology Research, PLLC
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Generations Medical Research
  • California
    • Los Angeles, California, United States, 90095
      • UCLA
  • Connecticut
    • Bridgeport, Connecticut, United States, 6606
      • Joao Nascimento, MD
  • Florida
    • Gainesville, Florida, United States, 32607
      • Southeastern Integrated Medical
    • Jupiter, Florida, United States, 33458
      • Family Arthritis Center
    • Ocala, Florida, United States, 34474
      • Ocala Rheumatology Research Center
    • Plantation, Florida, United States, 33324
      • Integral Rheumatology And Immunology Specialists
  • Maryland
    • Columbia, Maryland, United States, 21045
      • Columbia Medical Practice
  • Massachusetts
    • Worcester, Massachusetts, United States, 01610
      • Clinical Pharmacology Study Group
  • Michigan
    • Kalamazoo, Michigan, United States, 49048
      • Borgess Research Institute
  • New Jersey
    • Freehold, New Jersey, United States, 07728
      • Arthritis and Osteoporosis Associates
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinic
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • DJL Clinical Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Instiute
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center For Clinical Research
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Med Univ of South Carolina
    • Rock Hill, South Carolina, United States, 29732
      • PMG Research of Charlotte LLC
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • West Tennessee Research Institute
    • Memphis, Tennessee, United States, 38119
      • Ramesh C Gupta MD
  • Texas
    • Austin, Texas, United States, 78731
      • Austin Regional Clinic
    • Houston, Texas, United States, 77070
      • DM Clinical Research
  • West Virginia
    • Clarksburg, West Virginia, United States, 26301
      • Mountain State Clinical Research
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226-3522
      • Froedtert Hospital BMT Medical College of Wisconsin
    • Onalaska, Wisconsin, United States, 54650
      • Gundersen Clinic Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Control	Drug: Placebo; Twice daily for 28 days
EXPERIMENTAL: CC-292 375mg; Treatment	Drug: CC-292; 375 mg PO daily (250 mg in the AM and 125 mg in the PM for 28 days)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Douglas Hough, MD, MBA, Celgene Corporation

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (ACTUAL): January 1, 2016
• Study Completion (ACTUAL): February 1, 2016

Study Registration Dates

• First Submitted: October 29, 2013
• First Submitted That Met QC Criteria: October 29, 2013
• First Posted (ESTIMATE): November 3, 2013

Study Record Updates

• Last Update Posted (ACTUAL): July 31, 2017
• Last Update Submitted That Met QC Criteria: July 27, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Arthritis, Rheumatoid, Autoimmune, Inflammatory, Synovial, Bruton's tyrosine kinase (Btk), CC-292, Joint Disease
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Spebrutinib
• Other Study ID Numbers: CC-292-RA-001