A Phase III, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Abatacept Administered Intravenously in Korean Subjects With Active Rheumatoid Arthritis While Receiving Methotrexate
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 113
- Locations
- 1
- Primary Endpoint
- Percentage of Participants Meeting the Criteria of the American College of Rheumatology for 20% Improvement (ACR20)
Study Overview
Brief Summary
The purpose of the study is to demonstrate the clinical efficacy of abatacept (body-weight tiered dose approximating 10 mg/kg) compared with placebo on a background of methotrexate after 6 months (Day 169) of treatment in Korean patients with active rheumatoid arthritis and an inadequate clinical response to methotrexate
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Rheumatoid arthritis (RA) for longer than 1 year from the time of the initial diagnosis of RA
- •Patients must have been taking methotrexate for at least 3 months with at least a weekly dose of 15 mg, and a stable dose for 28 days prior to treatment (Day 1)
- •Methotrexate weekly dose as low as 10 mg is permitted for patients who cannot tolerate higher doses
Exclusion Criteria
- •Evidence (as assessed by the Investigator) of active or latent bacterial or viral infections at the time of potential enrollment
Arms & Interventions
Abatacept and Methotrexate
Intervention: Abatacept (Drug)
Abatacept and Methotrexate
Intervention: Methotrexate (Drug)
Placebo and Methotrexate
(standard of care)
Intervention: Methotrexate (Drug)
Placebo and Methotrexate
(standard of care)
Intervention: Placebo (Drug)
Abatacept - Open Label
Open-label extension phase
Intervention: Abatacept (Drug)
Abatacept - Open Label
Open-label extension phase
Intervention: Methotrexate (Drug)
Outcomes
Primary Outcomes
Percentage of Participants Meeting the Criteria of the American College of Rheumatology for 20% Improvement (ACR20)
Time Frame: At Day 169
The ACR 20 is based on 20% improvement (compared with baseline values) in tender and swollen joint counts and on 20% improvement in 3 of the remaining 5 core set measures (participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function) and 1 acute phase reactant value.
Long-term Extension (LTE) (Open-Label) Period: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuatons Due to SAEs, Adverse Events (AEs), Related AEs, and Discontinuations Due to AEs
Time Frame: Day 169 to up to 56 days post the last dose (Day 1485) in the LTE period
AE=any new untoward medical occurrence or worsening of a preexisting medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Secondary Outcomes
- Percentage of Participants With American College of Rheumatology (ACR) ACR50 and ACR70 Response at Day 169(At Day 169)
- Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components(From Baseline to Day 169)
- Change From Baseline in Disease Activity Scores (DAS) Based on C-reactive Protein (DAS 28 [CRP]) Levels or Erythrocyte Sedimentation Rate (DAS 28[ESR])(From Baseline to Days 169 and 1485)
- Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score(From Baseline to Day 169)
- Change From Baseline to Day 169 in Analysis of Short-Form 36 (SF-36) Health Survey Questionnaire Domains(From Baseline to Day 169)
- Percentage of Participants Experiencing Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), Related SAEs and AEs, and Discontinuations Due to SAEs and AEs During the Double-Blind Period(Throughout double-blind study period (up to Day 169); table includes data up to 56 days past double-blind period or start of the open-label period, whichever occurred first.)
- Abatacept Pharmacokinetic (PK) Parameters: Time to Maximum Concentration (Tmax) and Half-Life of Elimination (T-Half)(At the end of infusion and 2 to 4 hours after the start of infusion on Day 85, at anytime between Day 92 and 96, and pre-dose on Day 113)
- Abatacept Pharmacokinetic (PK) Parameters - Maximum Concentration (Cmax)(At the end of infusion and 2 to 4 hours after the start of the infusion on Day 85, at anytime between Day 92 and 96, and pre-dose on Day 113)
- Abatacept Pharmacokinetic (PK) Parameters - Area Under the Curve (AUC)(At the end of infusion, 2 to 4 hours after the start of infusion on Day 85, anytime between Day 92 and 96, and predose on Day 113)
- Abatacept Pharmacokinetic (PK) Parameters: Total Body Clearance (CLT)(Day 29, every 28 days until Day 141)
- Abatacept Pharmacokinetic (PK) Parameters: Volume at Steady State (VSS)(At the end of infusion, 2 to 4 hours after the start of infusion on Day 85, anytime between Day 92 and 96, and predose on Day 113)
- Summary Statistics of Minimum Observed Serum Concentration (Cmin) for Abatacept(At the end of infusion and 2 to 4 hours after the start of the infusion on Day 85)
- Immunogenicity of Abatacept- Number of Participants With Reactivity Toward CTLA4-IG and CTLA4-T at Day 169(Day 169)
- Change From Baseline in Surrogate Marker Erythrocyte Sedimentation Rate (ESR) at Day 169(From Baseline to Day 169)
- Change From Baseline in Surrogate Marker Rheumatoid Factor (RF) at Day 169(Baseline, Day 169)
- LTE Period: Overall Number of Participants With Positive Results of Immunogenicity Samples(Days 169, at 6-month intervals on-treatment, and at Days 28, 56, and 85 after the last infusion of study medication in the LTE period)
- Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time(Days 15 through 1569)
- Percentage of Participants With Physical Function Response as Assessed Using the Health Assessment Questionnaire Disability Index (HAQ-DI)(At Day 1485)
- Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score(Day 1485)
- Changes From Baseline in Short-Form 36 (SF-36) Physical and Mental Health Summaries(At Day 1485)
- Percentage of Participants With European League Against Rheumatism (EULAR)-Defined Low Disease Activity Score (LDAS) and With EULAR-defined Remission(At Days 169 and 1485)
- Changes From Baseline in the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) Scores(At Days 169 and 1569)
- Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission(At Days 169, 337, 729, 1149, and 1485)
- Change From Baseline in Levels of C-reactive Protein (CRP)(Days 169 to 1569)
- Change From Baseline in Erythrocyte Sedimentation Rate(Days 169 to 1569)