Clinical trial NCT00409838: A Phase III Study of Abatacept in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis, with inadequate response to methotrexate
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2006-12-11
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Key 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

Key Exclusion Criteria:

* Evidence (as assessed by the Investigator) of active or latent bacterial or viral infections at the time of potential enrollment

Primary outcomes:
measure: Percentage of Participants Meeting the Criteria of the American College of Rheumatology for 20% Improvement (ACR20)
timeFrame: At Day 169
measure: 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
timeFrame: Day 169 to up to 56 days post the last dose (Day 1485) in the LTE period
Secondary outcomes:
measure: Percentage of Participants With American College of Rheumatology (ACR) ACR50 and ACR70 Response at Day 169
timeFrame: At Day 169
measure: Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components
timeFrame: From Baseline to Day 169
measure: Change From Baseline in Disease Activity Scores (DAS) Based on C-reactive Protein (DAS 28 [CRP]) Levels or Erythrocyte Sedimentation Rate (DAS 28[ESR])
timeFrame: From Baseline to Days 169 and 1485
measure: Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score
timeFrame: From Baseline to Day 169
measure: Change From Baseline to Day 169 in Analysis of Short-Form 36 (SF-36) Health Survey Questionnaire Domains
timeFrame: From Baseline to Day 169
measure: 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
timeFrame: 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.
measure: Abatacept Pharmacokinetic (PK) Parameters: Time to Maximum Concentration (Tmax) and Half-Life of Elimination (T-Half)
timeFrame: 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
measure: Abatacept Pharmacokinetic (PK) Parameters - Maximum Concentration (Cmax)
timeFrame: 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
measure: Abatacept Pharmacokinetic (PK) Parameters - Area Under the Curve (AUC)
timeFrame: 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
measure: Abatacept Pharmacokinetic (PK) Parameters: Total Body Clearance (CLT)
timeFrame: Day 29, every 28 days until Day 141
measure: Abatacept Pharmacokinetic (PK) Parameters: Volume at Steady State (VSS)
timeFrame: 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
measure: Summary Statistics of Minimum Observed Serum Concentration (Cmin) for Abatacept
timeFrame: At the end of infusion and 2 to 4 hours after the start of the infusion on Day 85
measure: Immunogenicity of Abatacept- Number of Participants With Reactivity Toward CTLA4-IG and CTLA4-T at Day 169
timeFrame: Day 169
measure: Change From Baseline in Surrogate Marker Erythrocyte Sedimentation Rate (ESR) at Day 169
timeFrame: From Baseline to Day 169
measure: Change From Baseline in Surrogate Marker Rheumatoid Factor (RF) at Day 169
timeFrame: Baseline, Day 169
measure: LTE Period: Overall Number of Participants With Positive Results of Immunogenicity Samples
timeFrame: 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
measure: Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time
timeFrame: Days 15 through 1569
measure: Percentage of Participants With Physical Function Response as Assessed Using the Health Assessment Questionnaire Disability Index (HAQ-DI)
timeFrame: At Day 1485
measure: Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score
timeFrame: Day 1485
measure: Changes From Baseline in Short-Form 36 (SF-36) Physical and Mental Health Summaries
timeFrame: At Day 1485
measure: Percentage of Participants With European League Against Rheumatism (EULAR)-Defined Low Disease Activity Score (LDAS) and With EULAR-defined Remission
timeFrame: At Days 169 and 1485
measure: Changes From Baseline in the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) Scores
timeFrame: At Days 169 and 1569
measure: Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission
timeFrame: At Days 169, 337, 729, 1149, and 1485
measure: Change From Baseline in Levels of C-reactive Protein (CRP)
timeFrame: Days 169 to 1569
measure: Change From Baseline in Erythrocyte Sedimentation Rate
timeFrame: Days 169 to 1569
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Local Institution
state: Sungdong-Gu
city: Anyang
country: Korea, Republic of
facility: Local Institution
city: Daegu
country: Korea, Republic of
facility: Local Institution
city: Daejeon
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: