A Phase IIb, Randomized, Multi-Center, Double-Blind, Dose-Ranging Study to Evaluate the Efficacy and Safety of Clazakizumab in Subjects With Moderate to Severe Active Rheumatoid Arthritis Who Have Experienced an Inadequate Response to TNF Inhibitors
Overview
- Phase
- Phase 2
- Intervention
- Clazakizumab
- Conditions
- Rheumatoid Arthritis
- Sponsor
- CSL Behring
- Enrollment
- 143
- Locations
- 25
- Primary Endpoint
- Change From Baseline in Disease Activity Score in 28 Joints - C-reactive Protein (DAS28-CRP) at Week 12
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The primary purpose of this study is to identify an appropriate dose of study medication.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •Active serious infection
- •History of or active tuberculosis (TB)
- •Elevated liver function tests (LFTs)
Arms & Interventions
Arm 1: Clazakizumab (Dose # A) (Double-Blind)
Clazakizumab Dose # A injection by subcutaneous for 12 weeks + background Methotrexate
Intervention: Clazakizumab
Arm 2: Clazakizumab (Dose # B) (Double-Blind)
Clazakizumab Dose # B injection by subcutaneous for 12 weeks + background Methotrexate
Intervention: Clazakizumab
Arm 3: Clazakizumab (Dose # C) (Double-Blind)
Clazakizumab Dose # C injection by subcutaneous for 12 weeks + background Methotrexate
Intervention: Clazakizumab
Arm 4: Placebo matching with Clazakizumab (Double-Blind)
Clazakizumab Dose # D injection by subcutaneous for 12 weeks + background Methotrexate
Intervention: Placebo (Matching with Clazakizumab)
Outcomes
Primary Outcomes
Change From Baseline in Disease Activity Score in 28 Joints - C-reactive Protein (DAS28-CRP) at Week 12
Time Frame: 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 Outcomes
- Percent of Participants With a DAS28-Erythrocyte Sedimentation Rate (ESR) <2.6(At week 12)
- American College of Rheumatology (ACR) 20/50/70 Response Rates(At week 12)
- Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12(Baseline and week 12)
- Percent of Participants With a DAS28-C Reactive Protein (CRP) <2.6(At week 12)
- Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Week 12(Baseline and week 12)
- Boolean Remission at Week 12(At week 12)
- Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 12(Baseline and Week 12)