Clinical trial NCT00484289: A Phase III Study of Abatacept in Japanese Subjects With Rheumatoid Arthritis
Official title: A Phase III, Multi-center, Open-label, Uncontrolled, Long-term Study to Evaluate the Safety of Abatacept (BMS-188667) in Japanese Subjects With Rheumatoid Arthritis Having Completed Clinical Studies IM101-071, IM101-034, and Also Special DMARD Failures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2007-06-08
Enrollment: 217
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to demonstrate the safety of chronic use of abatacept in Japanese Subjects with Rheumatoid Arthritis (RA) having completed clinical studies IM101-071, IM101-034, and also Disease Modifying Anti-Rheumatic Drugs (DMARDs) failures with MTX intolerance.


Eligibility criteria: Inclusion Criteria

* The participants who completed the 169 days, full study period of Phase II (IM101-071) and were not administered other biologics between completion of IM101-071 and registration of this long-term study.
* The participants of the Phase I study (IM101-034), who received abatacept, except participants who were withdrawn from the study due to safety problems related to abatacept.
* New subjects with MTX intolerance: rheumatoid arthritis (RA) patients to whom MTX cannot be administered for safety reasons and who present an inadequate response to disease-modifying antirheumatic drugs (DMARDs;excluding MTX) or biologics (new subjects with MTX intolerance: RA patients who present an inadequate response to DMARDs).

Exclusion Criteria

* Women of childbearing potential (WOCBP) who were unwilling or unable to use an acceptable method of contraception.
* Participants who have received non approved or investigational biologics (other than abatacept from previous or ongoing studies in Japan) at registration.
* Participants who have received treatment with any investigational drug within 56 days before registration or five half-lives (whichever is the longest).
* Participants currently receiving treatment with leflunomide, mycophenolate mofetil, calcineurine inhibitors such as cyclosporine and tacrolimus, D-Penicillamine, Cyclophosphamide, or immunoadsorption columns.
* The participants who completed Phase II (IM101-071) are not applicable in the following instances at time of registration: with active vasculitis, symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral disease, breast cancer, or a history of cancer within the last 5 years, evidence of active or latent bacterial , viral infections, any serious or chronic, at risk of tuberculosis (TB), with any opportunistic infections, laboratory values of hemoglobin \< 8.5 g/dL, white blood cells (WBC) \< 3,000/mm\^3, Platelets \< 100,000/mm\^3, Serum creatinine \> 2 times upper limit of normal (ULN), Serum alanine transaminase or aspartate aminotransferase \> 2 times ULN.

Primary outcomes:
measure: Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to AEs
timeFrame: From initiation of the study drug (31 Mar 2008) to data cutoff (27 Dec 2010). The overall mean duration of exposure to the study drug was approximately 3 years (34.3 ± 10.7 months).
measure: Number of Participants With Abnormal Laboratory Changes (ALC)
timeFrame: From initiation of the study drug (31 Mar 2008) to data cutoff (27 Dec 2010). The overall mean duration of exposure to the study drug was approximately 3 years (34.3 ± 10.7 months).
measure: Number of Participants With Vital Signs, Physical Examinations, and Electrocardiogram Findings That Were Considered to be AEs by the Investigator
timeFrame: At week 0, 2, 4; then once every 4 weeks up to 48 months; then once in every 3 months or 12 weeks to end of study (27 Dec 2010). The overall mean duration of exposure to the study drug was approximately 3 years (34.3 ± 10.7 months).
Secondary outcomes:
measure: Percentage of Participants With American College of Rheumatology (ACR 20) Response Over Time
timeFrame: At weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192.
measure: Percentage of Participants With ACR 50 Response Over Time
timeFrame: At weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192.
measure: Percentage of Participants With ACR 70 Response Over Time
timeFrame: At weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192.
measure: Baseline (BL) and Postbaseline (PBL) Disease Activity Scores (DAS 28)
timeFrame: At BL (week 0), week 24, 48, 96, 144, and 192.
measure: Change From Baseline in DAS 28 Scores at Week 24, 48, 96, 144, and 192
timeFrame: At BL (week 0), weeks 24, 48, 96, 144, and 192.
measure: Number of Participants With DAS 28 Score Change ≥ 1.2 From Baseline at Weeks 24, 48, 96, 144, and 192
timeFrame: At BL (week 0), weeks 24, 48, 96, 144, and 192.
measure: Number of Participants With Low Disease Activity Score (DAS 28 Score ≤ 3.2) at Weeks 24, 48, 96, 144, 192
timeFrame: At weeks 24, 48, 96, 144, and 192.
measure: Number of Participants in Remission (DAS 28 Score < 2.6) at Weeks 24, 48, 96, 144, 192
timeFrame: At weeks 24, 48, 96, 144, and 192.
measure: Percentage of Participants Who Achieved a Reduction of At Least 0.3 Units From Baseline in Health Assessment Questionnaire (HAQ) at Weeks 24, 48, 96, 144, 192
timeFrame: At BL (week 0), weeks 24, 48, 96, 144, and 192.
measure: Baseline and Postbaseline Physical Component Summary (PCS) of Health-Related Quality of Life (SF-36) Scores
timeFrame: At BL (week 0), weeks 24, 48, 96, 144, and 192.
measure: Change From Baseline in Physical Component Summary (PCS) of Health-Related Quality of Life (SF-36) Score at Weeks 24, 48, 96, 144, and 192
timeFrame: At baseline (week 0), weeks 24, 48, 96, 144, and 192.
measure: Baseline and Postbaseline Mental Component Summary (MCS) of Health-Related Quality of Life (SF-36) Scores
timeFrame: At BL (week 0), weeks 24, 48, 96, 144, and 192.
measure: Change From Baseline in Mental Component Summary (MCS) of Health-Related Quality of Life (SF-36) Score at Weeks 24, 48, 96, 144, and 192
timeFrame: At BL (Week 0), weeks 24, 48, 96, 144, and 192.
measure: Baseline and Postbaseline C-reactive Protein (CRP) Levels
timeFrame: At BL (week 0), weeks 24, 48, 96, 144, and 192.
measure: Percentage Decrease in C-reactive Protein Levels From Baseline at Weeks 24, 48, 96, 144, and 192
timeFrame: At BL (week 0), weeks 24, 48, 96, 144, and 192.
measure: Baseline and Postbaseline Rheumatoid Factor Levels
timeFrame: At BL (week 0), weeks 24, 48, 96, 144, and 192.
measure: Change From Baseline in Rheumatoid Factor Levels at Weeks 24, 48, 96, 144, and 192
timeFrame: At BL (week 0), weeks 24, 48, 96, 144, and 192.
measure: Number of Participants Who Were Positive for Anti-abatacept and Anti-CTLA4-T Antibodies
timeFrame: At BL (week 0), weeks 24, 48, 72, 96, 120, 144, 168, and 192.
measure: Abatacept PK Parameter: Total Body Clearance
timeFrame: Samples were collected predose at week 8, 12, 16, 24; end of infusion at week 12; and at week 13-15 visits.
measure: Abatacept PK Parameter: Area Under the Serum Concentration-time Curve at Steady State
timeFrame: Samples were collected predose at week 8, 12, 16, 24; end of infusion at week 12; and at week 13-15 visits.
measure: Abatacept PK Parameter: Maximum Serum Concentration at Steady State
timeFrame: Samples were collected predose at week 8, 12, 16, 24; end of infusion at week 12; and at week 13-15 visits.
measure: Abatacept PK Parameter: Minimum Plasma Concentration at Steady State
timeFrame: Samples were collected predose at week 8, 12, 16, 24; end of infusion at week 12; and at week 13-15 visits.
Other outcomes:
Locations:
city: Nagoya-Shi
country: Japan
facility: Local Institution
state: Aichi
city: Nagoya
country: Japan
facility: Local Institution
state: Aichi
city: Goshogawara-Shi
country: Japan
facility: Local Institution
state: Aomori
city: Chiba-Shi
country: Japan
facility: Local Institution
state: Chiba
city: Fukui-Shi
country: Japan
facility: Local Institution
state: Fukui
city: Fukui-Shi
country: Japan
facility: Local Institution
state: Fukui
city: Fukui-Shi
country: Japan
facility: Local Institution
state: Fukui
city: Fukuoka-Shi
country: Japan
facility: Local Institution
state: Fukuoka
city: Fukuoka-Shi
country: Japan
facility: Local Institution
state: Fukuoka
city: Kitakyushu-Shi
country: Japan
facility: Local Institution
state: Fukuoka
city: Higashi-Hiroshima-Shi
country: Japan
facility: Local Institution
state: Hiroshima
city: Sapporo City
country: Japan
facility: Local Institution
state: Hokkaido
city: Sapporo-City
country: Japan
facility: Local Institution
state: Hokkaido
city: Sapporo-City
country: Japan
facility: Local Institution
state: Hokkaido
city: Kanzaki-Gun
country: Japan
facility: Local Institution
state: Hyogo
city: Kato-Gun
country: Japan
facility: Local Institution
state: Hyogo
city: Hitachi-Shi
country: Japan
facility: Local Institution
state: Ibaraki
city: Tsukuba-Shi
country: Japan
facility: Local Institution
state: Ibaraki
city: Sagamihara-Shi
country: Japan
facility: Local Institution
state: Kanagawa
city: Sendai-Shi
country: Japan
facility: Local Institution
state: Miyagi
city: Sendai-Shi
country: Japan
facility: Local Institution
state: Miyagi
city: Sendai
country: Japan
facility: Local Institution
state: Miyagi
city: Nagano-Shi
country: Japan
facility: Local Institution
state: Nagano
city: Tsukubo-Gun
country: Japan
facility: Local Institution
state: Okayama
city: Kawachinagano-Shi
country: Japan
facility: Local Institution
state: Osaka
city: Ureshino-Shi
country: Japan
facility: Local Institution
state: Saga
city: Iruma-Gun
country: Japan
facility: Local Institution
state: Saitama
city: Kawagoe-Shi
country: Japan
facility: Local Institution
state: Saitama
city: Kitamoto-Shi
country: Japan
facility: Local Institution
state: Saitama
city: Hamamatsu-Shi
country: Japan
facility: Local Institution
state: Shizuoka
city: Kawachigun
country: Japan
facility: Local Institution
state: Tochigi
city: Shimotsuke-Shi
country: Japan
facility: Local Institution
state: Tochigi
city: Arakawa-Ku
country: Japan
facility: Local Institution
state: Tokyo
city: Bunkyo-Ku
country: Japan
facility: Local Institution
state: Tokyo
city: Bunkyo-Ku
country: Japan
facility: Local Institution
state: Tokyo
city: Setagaya-Ku
country: Japan
facility: Local Institution
state: Tokyo
city: Shinjuku-Ku
country: Japan
facility: Local Institution
state: Tokyo
city: Takaoka-Shi
country: Japan
facility: Local Institution
state: Toyama
city: Chiba-Shi
country: Japan
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Takeuchi T, Matsubara T, Urata Y, Suematsu E, Ohta S, Honjo S, Abe T, Yamamoto A, Miyasaka N; Japan Abatacept Study Group. Phase III, multicenter, open-label, long-term study of the safety of abatacept in Japanese patients with rheumatoid arthritis and an inadequate response to conventional or biologic disease-modifying antirheumatic drugs. Mod Rheumatol. 2014 Sep;24(5):744-53. doi: 10.3109/14397595.2014.899179. Epub 2014 Apr 23.