Rheumatoid ArthritisPhase 3NCT00484289
A Phase III Study of Abatacept in Japanese Subjects With Rheumatoid Arthritis
A Phase 3 study testing Abatacept in people with Rheumatoid Arthritis, run by Bristol-Myers Squibb at 39 sites in Japan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Abatacept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 217 participants
- Where
- 39 sitesJapan
- Study dates
- Dec 2006to Dec 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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- The participants of the Phase I study (IM101-034), who received abatacept, except participants who were withdrawn from the study due to safety problems related to abatacept.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).
Who cannot join
- 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.
Trial locations and contacts
39 sites in 1 country.
39 sites in 1 country
Japan39 sites
Local Institution
Arakawa-Ku, Tokyo, 116-0011
Local Institution
Bunkyo-Ku, Tokyo, 113-0022
Local Institution
Bunkyo-Ku, Tokyo, 113-8519
Local Institution
Chiba, Chiba
Local Institution
Chiba, 260-0801
Local Institution
Fukui-shi, Fukui, 910-0041
Local Institution
Fukui-shi, Fukui, 9100067
Local Institution
Fukui-shi, Fukui, 9103133
Local Institution
Fukuoka, Fukuoka, 810-0065
Local Institution
Fukuoka, Fukuoka, 812-0025
Local Institution
Goshogawara-Shi, Aomori, 037-0053
Local Institution
Hamamatsu, Shizuoka, 430-0906
Local Institution
Higashi-Hiroshima-Shi, Hiroshima, 739-0002
Local Institution
Hitachi-Shi, Ibaraki, 316-0035
Local Institution
Iruma-Gun, Saitama, 350-0495
Local Institution
Kanzaki-Gun, Hyōgo, 679-2414
Local Institution
Kato-Gun, Hyōgo, 673-1462
Local Institution
Kawachigun, Tochigi, 329-1104
Local Institution
Kawachinagano-Shi, Osaka, 86-0008
Local Institution
Kawagoe-Shi, Saitama, 350-8550
Local Institution
Kitakyushu-Shi, Fukuoka, 807-8555
Local Institution
Kitamoto-Shi, Saitama, 364-0026
Local Institution
Nagano, Nagano, 380-8582
Local Institution
Nagoya, Aichi-ken, 460-0001
Local Institution
Nagoya, Aichi-ken, 466-8550
Local Institution
Sagamihara-Shi, Kanagawa, 228-8522
Local Institution
Sapporo, Hokkaido, 060-0001
Local Institution
Sapporo, Hokkaido, 060-8604
Local Institution
Sapporo, Hokkaido, 060-8648
Local Institution
Sendai, Miyagi, 981-0911
Local Institution
Sendai, Miyagi, 982-0032
Local Institution
Sendai, Miyagi
Local Institution
Setagaya-Ku, Tokyo, 155-0032
Local Institution
Shimotsuke-Shi, Tochigi, 3290498
Local Institution
Shinjuku-Ku, Tokyo, 162-0054
Local Institution
Takaoka-Shi, Toyama, 933-8525
Local Institution
Tsukuba, Ibaraki, 305-0005
Local Institution
Tsukubo-Gun, Okayama-ken, 701-0304
Local Institution
Ureshino-Shi, Saga-ken, 843-0301
About this study
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
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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Abatacept
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AbataceptDrug
Also called Orencia®, BMS-188667
Vials (250 mg/vial), Intravenous, Weight-tiered dose of abatacept (equivalent to 10 mg/kg) based on their body weight at the enrollment visit; 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1,000 mg for participants > 100 kg, administered over a period of approximately 30 minutes at week 0, 2, 4 and every 4 weeks thereafter, until approved in Japan and was continued as a post-marketing study until the completion of the shift to a commercially available product.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Participants from Phase I study (IM101-034) | Experimental | Not described Receives: Drug: Abatacept |
| Arm 2: Participants from Phase II study (IM101-071) | Experimental | Not described Receives: Drug: Abatacept |
| Arm 3: New Participants with Methotrexate (MTX) Intolerance | Experimental | Not described Receives: Drug: Abatacept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to AEs
AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is 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 cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event. Both subjective and objective AEs and SAEs are included.
Measured: 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).
Number of Participants With Abnormal Laboratory Changes (ALC)
The laboratory tests were analyses included enzyme, gastrointestinal, hematology, hepatobiliary, lipid, metabolic, nutritional, blood gas, microbiology, serology, protein, chemistry, renal, urinary tract, urinalyses, water, electrolyte and mineral investigations.
Measured: 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).
Number of Participants With Vital Signs, Physical Examinations, and Electrocardiogram Findings That Were Considered to be AEs by the Investigator
Measured: 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 (22)
Percentage of Participants With American College of Rheumatology (ACR 20) Response Over Time
ACR 20 response requires a participant to have a 20% reduction in the number of swollen and tender joints, and a reduction of 20% in three of the following five parameters: physician global assessment of disease activity, participant global assessment of disease activity, participant global assessment of pain, C-reactive protein, and degree of disability in Health Assessment Questionnaire score.
Measured: At weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192.
Percentage of Participants With ACR 50 Response Over Time
ACR 50 response requires a participant to have a 50% reduction in the number of swollen and tender joints, and a reduction of 50% in three of the following five parameters: physician global assessment of disease activity, participant global assessment of disease activity, participant global assessment of pain, C-reactive protein, and degree of disability in Health Assessment Questionnaire score.
Measured: At weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192.
Percentage of Participants With ACR 70 Response Over Time
ACR 70 response requires a participant to have a 70% reduction in the number of swollen and tender joints, and a reduction of 70% in three of the following five parameters: physician global assessment of disease activity, participant global assessment of disease activity, participant global assessment of pain, C-reactive protein, and degree of disability in Health Assessment Questionnaire score.
Measured: At weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192.
Baseline (BL) and Postbaseline (PBL) Disease Activity Scores (DAS 28)
The DAS 28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, CRP levels, and participant assessment of disease activity measure on a visual analogue scale of 100 mm. The DAS28 has numeric thresholds that define high disease activity (change of > 5.1), low disease activity (change of ≤ 3.2) and remission (< 2.6). Please see outcome 8 for change from BL data.
Measured: At BL (week 0), week 24, 48, 96, 144, and 192.
Change From Baseline in DAS 28 Scores at Week 24, 48, 96, 144, and 192
The DAS 28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, CRP levels, and participant assessment of disease activity measure on a visual analogue scale of 100 mm. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (≤ 3.2) and remission (< 2.6). Please refer to outcome 7 for BL and PBL values.
Measured: At BL (week 0), weeks 24, 48, 96, 144, and 192.
Number of Participants With DAS 28 Score Change ≥ 1.2 From Baseline at Weeks 24, 48, 96, 144, and 192
The DAS 28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, CRP levels, and participant assessment of disease activity measure on a visual analogue scale.
Participants with DAS 28 score change ≥ 1.2 from BL were considered to have improvement.
Measured: At BL (week 0), weeks 24, 48, 96, 144, and 192.
Number of Participants With Low Disease Activity Score (DAS 28 Score ≤ 3.2) at Weeks 24, 48, 96, 144, 192
The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, CRP levels, and participant assessment of disease activity measure on a visual analogue scale. Participants with DAS 28 score ≤ 3.2 were considered to have low disease activity.
Measured: At weeks 24, 48, 96, 144, and 192.
Number of Participants in Remission (DAS 28 Score < 2.6) at Weeks 24, 48, 96, 144, 192
The DAS 28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, CRP levels, and participant assessment of disease activity measure on a visual analogue scale.
Participants with DAS 28 score < 2.6 were considered to be in remission.
Measured: At weeks 24, 48, 96, 144, and 192.
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
The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from BL in HAQ.
Measured: At BL (week 0), weeks 24, 48, 96, 144, and 192.
Baseline and Postbaseline Physical Component Summary (PCS) of Health-Related Quality of Life (SF-36) Scores
The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role functioning [physical], bodily pain, and general health) and 4 mental subscales (vitality, social function, role emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from 0 to 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.Please see outcome 14 for change from BL data.
Measured: At BL (week 0), weeks 24, 48, 96, 144, and 192.
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
The SF-36 covers 8 health dimensions including 4 physical (physical function, role functioning [physical], bodily pain, and general health) and 4 mental subscales (vitality, social function, role emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from a minimum of 0 to a maximum of 100, higher score indicating better quality of life. Improvements of >3 points were considered clinically meaningful. Please see outcome 13 for BL and PBL values.
Measured: At baseline (week 0), weeks 24, 48, 96, 144, and 192.
Baseline and Postbaseline Mental Component Summary (MCS) of Health-Related Quality of Life (SF-36) Scores
The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role functioning [physical], bodily pain, and general health) and 4 mental subscales (vitality, social function, role emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from 0 to 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful. Please see outcome 14 for change from BL data.
Measured: At BL (week 0), weeks 24, 48, 96, 144, and 192.
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
The SF-36 covers 8 health dimensions including 4 physical (physical function, role functioning [physical], bodily pain, and general health) and 4 mental subscales (vitality, social function, role emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from a minimum of 0 to a maximum of 100, higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.Please see outcome 15 for BL and PBL values.
Measured: At BL (Week 0), weeks 24, 48, 96, 144, and 192.
Baseline and Postbaseline C-reactive Protein (CRP) Levels
CRP is an acute phase reactant protein that is a clinical marker for Rheumatoid Arthritis (RA) and is a core component of the ACR scoring system. CRP was evaluated from serum samples. Increasing levels indicate increasing level of disease. Please see outcome 18 for change from BL data.
Measured: At BL (week 0), weeks 24, 48, 96, 144, and 192.
Percentage Decrease in C-reactive Protein Levels From Baseline at Weeks 24, 48, 96, 144, and 192
CRP is an acute phase reactant protein that is a clinical marker for Rheumatoid Arthritis (RA) and is a core component of the ACR scoring system. CRP was evaluated from serum samples. Increasing levels indicate increasing level of disease, negative values indicate improvement. Percentage improvement from BL = (BL - PBL value) / BL value * 100. Please refer to outcome 17 for BL and PBL values.
Measured: At BL (week 0), weeks 24, 48, 96, 144, and 192.
Baseline and Postbaseline Rheumatoid Factor Levels
Rheumatoid factor (RF or RhF) is an autoantibody (antibody directed against an organism's own tissues) most relevant in rheumatoid arthritis. It is an antibody against the Fc portion of Immunoglobulin (Ig)G, which is itself an antibody. RF and IgG join to form immune complexes which contribute to the disease process. RF levels are considered positive if value is >20 and considered negative if value is <20. Please see outcome 20 for change from BL data.
Measured: At BL (week 0), weeks 24, 48, 96, 144, and 192.
Change From Baseline in Rheumatoid Factor Levels at Weeks 24, 48, 96, 144, and 192
RF is an autoantibody (antibody directed against an organism's own tissues) most relevant in rheumatoid arthritis. It is an antibody against the Fc portion of Immunoglobulin (Ig)G, which is itself an antibody. RF and IgG join to form immune complexes which contribute to the disease process. RF levels are considered positive if value is >20 and considered negative if value is <20. Please refer to outcome 19 for BL and PBL values.
Measured: At BL (week 0), weeks 24, 48, 96, 144, and 192.
Number of Participants Who Were Positive for Anti-abatacept and Anti-CTLA4-T Antibodies
Validated enzyme-linked immunoassay (ELISA) method was used to measure anti-abatacept and anti-CTLA4-T antibody levels. For anti-abatacept antibody ELISA, a sample was considered seropositive if it had a titer of 400 or greater and if immunodepletion was observed. The responses that were negative in initial screen were reported as seronegative with a value of < 400. A sample was considered positive in CTLA4-T antibody ELISA if it had a titer of 25 or greater and if immunodepletion was observed.
Measured: At BL (week 0), weeks 24, 48, 72, 96, 120, 144, 168, and 192.
Abatacept PK Parameter: Total Body Clearance
Total body clearance is the rate and extent at which the drug is eliminated from the body. The clearance of a drug is used to understand the processes involved in drug elimination, distribution and metabolism.
Measured: Samples were collected predose at week 8, 12, 16, 24; end of infusion at week 12; and at week 13-15 visits.
Abatacept PK Parameter: Area Under the Serum Concentration-time Curve at Steady State
Area under the plasma concentration-time curve (AUCss) at steady state for each dosing interval was determined using the linear trapezoidal rule.
Measured: Samples were collected predose at week 8, 12, 16, 24; end of infusion at week 12; and at week 13-15 visits.
Abatacept PK Parameter: Maximum Serum Concentration at Steady State
Maximum plasma concentration is the maximum observed serum drug concentration at steady state (Css max).
Measured: Samples were collected predose at week 8, 12, 16, 24; end of infusion at week 12; and at week 13-15 visits.
Abatacept PK Parameter: Minimum Plasma Concentration at Steady State
Minimum Plasma Concentration (Cmin) is the minimum observed serum drug concentration at steady state.
Measured: Samples were collected predose at week 8, 12, 16, 24; end of infusion at week 12; and at week 13-15 visits.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2007 (estimated)
- Study startDec 2006
- Primary completionDec 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 217 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00484289
- Sponsor's protocol ID
- IM101-129
- Status last verified
- Jun 2013
- First submitted
- 7 Jun 2007
- Last updated
- 24 Jun 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 24754273
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00484289
- Acronym / sponsor ID
- IM101-129
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 217 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Dec 2006
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 8 Jun 2007 (estimated)
- Results
- Posted 9 Aug 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Participants from Phase I study (IM101-034) | Experimental | Drug: Abatacept |
| Arm 2: Participants from Phase II study (IM101-071) | Experimental | Drug: Abatacept |
| Arm 3: New Participants with Methotrexate (MTX) Intolerance | Experimental | Drug: Abatacept |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AbataceptAlso: Orencia®, BMS-188667Vials (250 mg/vial), Intravenous, Weight-tiered dose of abatacept (equivalent to 10 mg/kg) based on their body weight at the enrollment visit; 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1,000 mg for participants > 100 kg, administered over a period of approximately 30 minutes at week 0, 2, 4 and every 4 weeks thereafter, until approved in Japan and was continued as a post-marketing study until the completion of the shift to a commercially available product. | Drug | Arm 1: Participants from Phase I study (IM101-034), Arm 2: Participants from Phase II study (IM101-071), Arm 3: New Participants with Methotrexate (MTX) Intolerance |
Primary outcome
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to AEs
Time frame: 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).
AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is 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 cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event. Both subjective and objective AEs and SAEs are included.
Number of Participants With Abnormal Laboratory Changes (ALC)
Time frame: 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).
The laboratory tests were analyses included enzyme, gastrointestinal, hematology, hepatobiliary, lipid, metabolic, nutritional, blood gas, microbiology, serology, protein, chemistry, renal, urinary tract, urinalyses, water, electrolyte and mineral investigations.
Number of Participants With Vital Signs, Physical Examinations, and Electrocardiogram Findings That Were Considered to be AEs by the Investigator
Time frame: 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).
22 secondary outcomes
Percentage of Participants With American College of Rheumatology (ACR 20) Response Over Time
Time frame: At weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192.
Percentage of Participants With ACR 50 Response Over Time
Time frame: At weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192.
Percentage of Participants With ACR 70 Response Over Time
Time frame: At weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192.
Baseline (BL) and Postbaseline (PBL) Disease Activity Scores (DAS 28)
Time frame: At BL (week 0), week 24, 48, 96, 144, and 192.
Change From Baseline in DAS 28 Scores at Week 24, 48, 96, 144, and 192
Time frame: At BL (week 0), weeks 24, 48, 96, 144, and 192.
Number of Participants With DAS 28 Score Change ≥ 1.2 From Baseline at Weeks 24, 48, 96, 144, and 192
Time frame: At BL (week 0), weeks 24, 48, 96, 144, and 192.
Number of Participants With Low Disease Activity Score (DAS 28 Score ≤ 3.2) at Weeks 24, 48, 96, 144, 192
Time frame: At weeks 24, 48, 96, 144, and 192.
Number of Participants in Remission (DAS 28 Score < 2.6) at Weeks 24, 48, 96, 144, 192
Time frame: At weeks 24, 48, 96, 144, and 192.
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
Time frame: At BL (week 0), weeks 24, 48, 96, 144, and 192.
Baseline and Postbaseline Physical Component Summary (PCS) of Health-Related Quality of Life (SF-36) Scores
Time frame: At BL (week 0), weeks 24, 48, 96, 144, and 192.
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
Time frame: At baseline (week 0), weeks 24, 48, 96, 144, and 192.
Baseline and Postbaseline Mental Component Summary (MCS) of Health-Related Quality of Life (SF-36) Scores
Time frame: At BL (week 0), weeks 24, 48, 96, 144, and 192.
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
Time frame: At BL (Week 0), weeks 24, 48, 96, 144, and 192.
Baseline and Postbaseline C-reactive Protein (CRP) Levels
Time frame: At BL (week 0), weeks 24, 48, 96, 144, and 192.
Percentage Decrease in C-reactive Protein Levels From Baseline at Weeks 24, 48, 96, 144, and 192
Time frame: At BL (week 0), weeks 24, 48, 96, 144, and 192.
Baseline and Postbaseline Rheumatoid Factor Levels
Time frame: At BL (week 0), weeks 24, 48, 96, 144, and 192.
Change From Baseline in Rheumatoid Factor Levels at Weeks 24, 48, 96, 144, and 192
Time frame: At BL (week 0), weeks 24, 48, 96, 144, and 192.
Number of Participants Who Were Positive for Anti-abatacept and Anti-CTLA4-T Antibodies
Time frame: At BL (week 0), weeks 24, 48, 72, 96, 120, 144, 168, and 192.
Abatacept PK Parameter: Total Body Clearance
Time frame: Samples were collected predose at week 8, 12, 16, 24; end of infusion at week 12; and at week 13-15 visits.
Abatacept PK Parameter: Area Under the Serum Concentration-time Curve at Steady State
Time frame: Samples were collected predose at week 8, 12, 16, 24; end of infusion at week 12; and at week 13-15 visits.
Abatacept PK Parameter: Maximum Serum Concentration at Steady State
Time frame: Samples were collected predose at week 8, 12, 16, 24; end of infusion at week 12; and at week 13-15 visits.
Abatacept PK Parameter: Minimum Plasma Concentration at Steady State
Time frame: Samples were collected predose at week 8, 12, 16, 24; end of infusion at week 12; and at week 13-15 visits.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24754273Takeuchi 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
39 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Abatacept in people with Rheumatoid Arthritis, run by Bristol-Myers Squibb at 39 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Aug 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to AEs (time frame: 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).). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00484289, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2013.