Phase IIB Dose Ranging Study in Subjects With Moderate to Severe Rheumatoid Arthritis
- Conditions
- Rheumatoid Arthritis
- Interventions
- Drug: Placebo (Matching with Clazakizumab)
- Registration Number
- NCT02015520
- Lead Sponsor
- CSL Behring
- Brief Summary
The primary purpose of this study is to identify an appropriate dose of study medication.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 143
- Diagnosis of active Rheumatoid Arthritis (RA) by standard criteria (American Rheumatism association (ARA) [1987] or American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) [2010]) at least 16 weeks prior to screening
- ACR global functional status class of 1 to 3
- Documented evidence of inadequate response tumor necrosis factor (TNF) inhibitors
- All subjects must have been receiving treatment with a minimum dose of 15 mg per week of Methotrexate for at least 12 weeks and at a stable dose for 28 days prior to screening. A dose as low as 10 mg Methotrexate is permitted if 15 mg could not be reached, due to toxicity. In Japan, Korea and Taiwan, a minimum dose of 7.5 mg per week is permitted. Additional treatment with Hydroxychloroquine or Chloroquine is permitted, if it is at a dose approved for the treatment of RA and the dose has been stable for at least 28 days prior to screening
- Minimum of 6 swollen and 6 tender joints on a 66/68 joint count at screening and at baseline (Day 1)
- Elevated High-sensitivity (hs) CRP and/or ESR
- Active serious infection
- History of or active tuberculosis (TB)
- Elevated liver function tests (LFTs)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 3: Clazakizumab (Dose # C) (Double-Blind) Clazakizumab Clazakizumab Dose # C injection by subcutaneous for 12 weeks + background Methotrexate Arm 4: Placebo matching with Clazakizumab (Double-Blind) Placebo (Matching with Clazakizumab) Clazakizumab Dose # D injection by subcutaneous for 12 weeks + background Methotrexate Arm 2: Clazakizumab (Dose # B) (Double-Blind) Clazakizumab Clazakizumab Dose # B injection by subcutaneous for 12 weeks + background Methotrexate Arm 1: Clazakizumab (Dose # A) (Double-Blind) Clazakizumab Clazakizumab Dose # A injection by subcutaneous for 12 weeks + background Methotrexate
- Primary Outcome Measures
Name Time Method Change From Baseline in Disease Activity Score in 28 Joints - C-reactive Protein (DAS28-CRP) at Week 12 Baseline and Week 12 DAS28-CRP describes severity of rheumatoid arthritis. The components of the joint count assessment are shoulder, elbow, wrist, metacarpophalangeal joints 1 through 5, proximal interphalangeal joints 1 through 5, and the knee joints on the right and left sides, whereby the number of affected joints, tender and swollen, respectively, are counted. The formula used to calculate the score is: DAS28-CRP=0.56 \\times \\sqrt{TEN28} + 0.28 \\times \\sqrt{SW28} + 0.36 \\times \\ln(CRP+1) + 0.014 \\times SA+0.96 with:
TEN28: number of joints with tenderness upon touching SW28: number of swollen joints CRP: C-reactive Protein SA: subjective assessment of disease activity by the patient during the preceding 7 days on a scale between 0 and 100 ("0":no activity, "100": highest activity possible).
DAS-CRP score range is 0.49 to 9.07 A DAS-CRP value \>5.1 corresponds to a high disease activity A DAS-28 reduction by 0.6 represents a moderate improvement. A reduction \>1.2 represents a major improvement
- Secondary Outcome Measures
Name Time Method American College of Rheumatology (ACR) 20/50/70 Response Rates At week 12 The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure \[most often Health Assessment Questionnaire (HAQ)\], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).
Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12 Baseline and week 12 SDAI is a composite index for assessing disease activity. CDAI is based on the simple summation of the count of swollen joint count (0-28) and tender joint count (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity and C-reactive protein (0-10). The SDAI has a range from 0 to 86.
0.0 - 3.3 = Remission 3.4 - 11.0 = Low Activity 11.1 - 26.0 = Moderate Activity 26.1 - 86.0 = High ActivityPercent of Participants With a DAS28-Erythrocyte Sedimentation Rate (ESR) <2.6 At week 12 DAS28- ESR = Disease Activity Scores 28 based on erythrocyte sedimentation rate. A DAS28-ESR below 2.6 is interpreted as remission.
Percent of Participants With a DAS28-C Reactive Protein (CRP) <2.6 At week 12 DAS28-CRP = Disease Activity Scores 28 based on C Reactive Protein. A DAS28-CRP below 2.6 is interpreted as remission.
Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Week 12 Baseline and week 12 CDAI is a composite index for assessing disease activity. CDAI is based on the simple summation of the count of swollen joint count (SCJ) (0-28) and tender joint count (TJC) (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity. The CDAI has a range from 0 to 76.
CDAI \<= 2.8 = Remission CDAI \> 2.8 and \<= 10 = Low Disease Activity CDAI \> 10 and \<= 22 = Moderate Disease Activity CDAI \> 22 = High Disease ActivityBoolean Remission at Week 12 At week 12 Boolean-based definition:
At any time point, a patient must satisfy all of the following:
TJC ≤1 (0-28) SJC ≤1 (0-28) CRP ≤1 mg/dl Patient Global Assessment ≤1 (on a 0-10 scale)Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 12 Baseline and Week 12 Patients report the amount of difficulty they have in performing 8 categories. Each category is scored on a scale ranging from 0 (performed without any difficulty) to 3 (cannot be done at all). The HAQ-DI is then calculated by summing the scores and dividing by the number of categories answered. Total score is between 0-3.0. Increasing scores indicate worse functioning with 0 indicating no functional impairment and 3 indicating complete impairment. The HAQ-DI cannot be calculated if the subject does not have scores for at least 6 categories. A response was defined as a subject with a reduction from baseline in HAQ-DI of at least 0.22.
Trial Locations
- Locations (25)
Cincinnati Rheumatic Disease Study Group
🇺🇸Cincinnati, Ohio, United States
Seattle Rheumatology Associates
🇺🇸Seattle, Washington, United States
Center For Inflammatory Disease
🇺🇸Nashville, Tennessee, United States
Arthritis & Rheumatology Center Of Oklahoma Pllc
🇺🇸Oklahoma City, Oklahoma, United States
Health Research Of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Rheumatology Associates Of North Alabama, P.C.
🇺🇸Huntsville, Alabama, United States
Valerius Med Group & Res Ctr Of Greater Long Beach, Inc.
🇺🇸Long Beach, California, United States
Desert Medical Advances
🇺🇸Palm Desert, California, United States
Sarasota Arthritis Research Center
🇺🇸Sarasota, Florida, United States
Mercy Clinic Hot Springs Communities
🇺🇸Hot Springs, Arkansas, United States
Clinical Pharmacology Study Group
🇺🇸Worcester, Massachusetts, United States
Credit Valley Rheumatology
🇨🇦Mississauga, Ontario, Canada
Paramount Medical Research & Consulting, Llc
🇺🇸Middleburg Heights, Ohio, United States
Low Country Rheumatology
🇺🇸Charleston, South Carolina, United States
Cividino Medicine Professional Corporation
🇨🇦Hamilton, Ontario, Canada
Albuquerque Center For Rheumatology
🇺🇸Albuquerque, New Mexico, United States
Physicians East, Pa
🇺🇸Greenville, North Carolina, United States
Albuquerque Clinical Trials
🇺🇸Albuquerque, New Mexico, United States
Physician Research Collaboration, Llc
🇺🇸Lincoln, Nebraska, United States
Healthcare Research Consultants
🇺🇸Tulsa, Oklahoma, United States
Joint And Muscle Medical Care And Research Institute (Jmmcri)
🇺🇸Charlotte, North Carolina, United States
Rheumatology Consultants Pllc
🇺🇸Knoxville, Tennessee, United States
Local Institution
🇿🇦Stellenbosch, Western Cape, South Africa
Dr. Latha Naik Medical Professional Corporation
🇨🇦Saskatoon, Saskatchewan, Canada
St. Paul Rheumatology, P.A.
🇺🇸Eagan, Minnesota, United States