Back to resultsEfficacy and Safety Study of CC-292 Versus Placebo as Co-therapy With Methotrexate in Active Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CC-292
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Arthritis, Rheumatoid, Autoimmune, Inflammatory, Synovial, Bruton's tyrosine kinase (Btk), CC-292, Joint Disease
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.
Sites / Locations
- Achieve Clinical Research LLC
- Arizona Arthritis and Rheumatology Research, PLLC
- Generations Medical Research
- UCLA
- Joao Nascimento, MD
- Southeastern Integrated Medical
- Family Arthritis Center
- Ocala Rheumatology Research Center
- Integral Rheumatology and Immunology specialists
- Columbia Medical Practice
- Clinical Pharmacology Study Group
- Borgess Research Institute
- Arthritis and Osteoporosis Associates
- Albuquerque Clinic
- NYU Langone Medical Center
- DJL Clinical Research
- Lynn Health Science Instiute
- Altoona Center for Clinical Research
- Med Univ of South Carolina
- PMG Research of Charlotte LLC
- West Tennessee Research Institute
- Ramesh C Gupta MD
- Austin Regional Clinic
- DM Clinical Research
- Mountain State Clinical Research
- Froedtert Hospital BMT Medical College of Wisconsin
- Gundersen Clinic Ltd
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
CC-292 375mg
Placebo
Arm Description
Treatment
Control
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01975610
Brief Title
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
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
October 2013 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
February 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Arthritis, Rheumatoid, Autoimmune, Inflammatory, Synovial, Bruton's tyrosine kinase (Btk), CC-292, Joint Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
47 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CC-292 375mg
Arm Type
Experimental
Arm Description
Treatment
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Control
Intervention Type
Drug
Intervention Name(s)
CC-292
Intervention Description
375 mg PO daily (250 mg in the AM and 125 mg in the PM for 28 days)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Twice daily for 28 days
Primary Outcome Measure Information:
Title
American College of Rheumatology Criteria for a 20% improvement (ACR 20)
Description
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
Time Frame
Week 4
Secondary Outcome Measure Information:
Title
Number of participants with adverse events
Description
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.
Time Frame
Up to 8 Weeks
Title
American College of Rheumatology Criteria for a 50% improvement (ACR 50)
Description
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.
Time Frame
Week 4
Title
American College of Rheumatology Criteria for a 70% improvement (ACR 70)
Description
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.
Time Frame
Week 4
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Douglas Hough, MD, MBA
Organizational Affiliation
Celgene Corporation
Official's Role
Study Director
Facility Information:
Facility Name
Achieve Clinical Research LLC
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35216
Country
United States
Facility Name
Arizona Arthritis and Rheumatology Research, PLLC
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85023
Country
United States
Facility Name
Generations Medical Research
City
Hot Springs
State/Province
Arkansas
ZIP/Postal Code
71913
Country
United States
Facility Name
UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Joao Nascimento, MD
City
Bridgeport
State/Province
Connecticut
ZIP/Postal Code
6606
Country
United States
Facility Name
Southeastern Integrated Medical
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32607
Country
United States
Facility Name
Family Arthritis Center
City
Jupiter
State/Province
Florida
ZIP/Postal Code
33458
Country
United States
Facility Name
Ocala Rheumatology Research Center
City
Ocala
State/Province
Florida
ZIP/Postal Code
34474
Country
United States
Facility Name
Integral Rheumatology and Immunology specialists
City
Plantation
State/Province
Florida
ZIP/Postal Code
33324
Country
United States
Facility Name
Columbia Medical Practice
City
Columbia
State/Province
Maryland
ZIP/Postal Code
21045
Country
United States
Facility Name
Clinical Pharmacology Study Group
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01610
Country
United States
Facility Name
Borgess Research Institute
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49048
Country
United States
Facility Name
Arthritis and Osteoporosis Associates
City
Freehold
State/Province
New Jersey
ZIP/Postal Code
07728
Country
United States
Facility Name
Albuquerque Clinic
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87102
Country
United States
Facility Name
NYU Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
DJL Clinical Research
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28210
Country
United States
Facility Name
Lynn Health Science Instiute
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
Altoona Center for Clinical Research
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
Facility Name
Med Univ of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
PMG Research of Charlotte LLC
City
Rock Hill
State/Province
South Carolina
ZIP/Postal Code
29732
Country
United States
Facility Name
West Tennessee Research Institute
City
Jackson
State/Province
Tennessee
ZIP/Postal Code
38305
Country
United States
Facility Name
Ramesh C Gupta MD
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38119
Country
United States
Facility Name
Austin Regional Clinic
City
Austin
State/Province
Texas
ZIP/Postal Code
78731
Country
United States
Facility Name
DM Clinical Research
City
Houston
State/Province
Texas
ZIP/Postal Code
77070
Country
United States
Facility Name
Mountain State Clinical Research
City
Clarksburg
State/Province
West Virginia
ZIP/Postal Code
26301
Country
United States
Facility Name
Froedtert Hospital BMT Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226-3522
Country
United States
Facility Name
Gundersen Clinic Ltd
City
Onalaska
State/Province
Wisconsin
ZIP/Postal Code
54650
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
31721017
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.
Results Reference
derived
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Efficacy and Safety Study of CC-292 Versus Placebo as Co-therapy With Methotrexate in Active Rheumatoid Arthritis
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