A Phase II/III, Multicenter, Randomized, Double-Blind, Double-Dummy Study to Assess Similarity of the Efficacy, Pharmacokinetics, Safety and Immunogenicity of Abatacept Administered Subcutaneously or Intravenously in Japanese Subjects With Rheumatoid Arthritis, Receiving Background Methotrexate, and Experiencing an Inadequate Response to Methotrexate
Overview
- Phase
- Phase 2
- Intervention
- Subcutaneous (SC) abatacept
- Conditions
- Rheumatoid Arthritis
- Sponsor
- Bristol-Myers Squibb
- Enrollment
- 118
- Locations
- 1
- Primary Endpoint
- Percentage of Participants With Health Assessment Questionnaire (HAQ) Response at Day 533 in Long Term Period
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
The purpose of this study is to assess the efficacy, pharmacokinetics, safety, and immunogenicity of abatacept after subcutaneous and intravenous administration in Japanese participants with active rheumatoid arthritis and inadequate response to methotrexate.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Meeting criteria of the American Rheumatism Association for the diagnosis of rheumatoid arthritis (RA) and the American College of Rheumatology functional Classes I, II, or III.
- •Inadequate response (as deemed by investigator) to methotrexate taken for at least 3 months (12 weeks) at a stable dose (6 to 8 mg/week) for 28 days prior to randomization (Day 1).
- •Stabilization requirements for concomitant therapy: Oral corticosteroid treatment reduced to the equivalent of ≤10 mg prednisolone daily for 28 days and stabilized for at least 25 of 28 days prior to treatment (Day 1). No intra-articular, intravenous, or intramuscular injections of corticosteroids were permitted within 28 days prior to randomization (Day 1.)
- •Washout requirements: Participants receiving combination RA therapy had to discontinue the following therapies at least 28 days prior to treatment (Day 1):
- •disease-modifying antirheumatic drugs (DMARDs), such as gold (auranofin and aurothiomalate sodium), actarit, bucillamine, azathioprine, salazosulfapyridine, lobenzarit disodium, D-penicillamine, cyclophosphamide, mycophenolate mofetil, mizoribine; cyclosporin, tacrolimus, and other calcineurin inhibitors; and immunoadsorption columns.
- •Disease Activity Requirements: At randomization (Day 1), participants had to meet the following disease activity criteria: Swollen joint count: 10 or more swollen joints (66 joint count); tender joint count: 12 or more tender joints (68 joint count); C reactive protein (CRP): ≥0.8 mg/dL (result from screening visit).
- •For participants receiving methotrexate plus other DMARDs(washout of a combination therapy required): At screening visit, participants had to meet the following disease activity criteria: Swollen joint count: 6 or more swollen joints (66 joint count); tender joint count: 8 or more tender joints (68 joint count); CRP: no restriction on CRP (not applicable).
- •After washout, at randomization (Day 1), participants must meet the following disease activity criteria: Swollen joint count-10 or more swollen joints (66 joint count) and tender joint count-12 or more tender joints (68 joint count) and CRP: ≥0.8 mg/dL (result from screening visit). For those whose screening period were longer than 4 weeks, CRP test needed to be performed on Day
- •28 to Day -3 (prior to treatment Day 1) to verify eligibility.
Exclusion Criteria
- •Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, pulmonary, cardiac, neurologic, or cerebral disease. Concomitant medical conditions that, in the opinion of the investigator, might place the participant at unacceptable risk for participation in this study.
- •Female participants who had undergone breast cancer screening that was suspicious for malignancy, and in whom the possibility of malignancy could not be reasonably excluded following additional clinical, laboratory, or other diagnostic evaluations.
- •History of cancer within the last 5 years (other than nonmelanoma skin cell cancers cured by local resection)
- •Existing nonmelanoma skin cell cancers had been removed prior to the first administration. Participants with carcinoma in situ, treated with definitive surgical intervention prior to study entry were allowed to participate.
- •Clinically significant drug or alcohol abuse
- •Any serious acute bacterial infection (such as pneumonia or pyelonephritis unless treated and completely resolved with antibiotics)
- •Serious, chronic, or recurrent bacterial infections (such as recurrent pneumonia, chronic bronchiectasis)
- •Those at risk for tuberculosis (TB). Specifically, those with current clinical, radiographic, or laboratory evidence suggestive of active TB; history of active TB within the last 3 years, even if treated; history of active TB more than 3 years ago unless there was documentation that the prior anti-TB treatment was appropriate in type and duration; latent TB that was not successfully treated. Participants with a positive result on TB screening test indicative of latent TB were not eligible for the study unless active TB infection had been ruled out and treatment for latent TB with isoniazid had been initiated for at least 4 weeks prior to administration of the study drug and the participant had a negative finding for TB on a chest X-ray film at enrollment.
- •Herpes zoster resolving less than 2 months prior to enrollment
- •Current evidence (as assessed by the investigator) suggestive of active or latent bacterial or viral infections, including human immunodeficiency virus infection.
Arms & Interventions
Subcutaneous (SC) abatacept, 125 mg
Intervention: Subcutaneous (SC) abatacept
Intravenous (IV) abatacept, 125 mg
Intervention: Intravenous (IV) abatacept
Outcomes
Primary Outcomes
Percentage of Participants With Health Assessment Questionnaire (HAQ) Response at Day 533 in Long Term Period
Time Frame: Day 533
The Health Assessment Questionnaire (HAQ) disability index assesses patients' functional ability by rating their abilities over the previous week. At least 2 questions are asked from each of 8 categories: dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities. Patients rate difficulty performing specific tasks: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The higher the number the worse the outcome. The sum of the categories score (the highest scored item in the category) is divided by the number of categories answered, yielding a score from 0-3. HAQ response=reduction of at least 0.30 units in HAQ score from baseline. The percentage of participants with a reduction of at least 0.30 units in their HAQ score from baseline is presented. Baseline is Day 1 of the study or last non-missing pre-treatment value. Treatment groups represent treatment received in the short term period.
Percentage of Participants With Sustained American College of Rheumatology (ACR) Response at Day 533 in Long Term Period - All Randomized and Treated Participants During the Long Term Period
Time Frame: Day 533
The ACR score indicates the degree of improvement in a patient's rheumatoid arthritis (RA), based on ACR guidelines. The ACR score= a percentage. To qualify for a score of 20, 50 or 70 (ACR20, ACR50 or ACR70), the patient must have \>=20%, \>=50% or \>=70%, respectively, fewer tender joints and \>=20%, \>=50% or \>=70%, respectively, fewer swollen joints and show 20%, 50% or 70%, respectively, improvement in at least 3 of the following: patient overall assessment of his/her RA, physician global assessment of the patient's RA, patient self-assessment of pain, patient self-assessment of physical functioning, and results of an erythrocyte sedimentation rate or C-reactive protein test (to assess inflammation). Treatment groups represent treatment received in the short term period. Percentage calculated as n/m with n=number of paticipants with sustained ACR response at Day 533; m= long term participants who received at least one dose of drug and were ACR responders in the short term period.
Mean Change From Baseline in HAQ-DI Score at Day 533 in Long Term Period
Time Frame: Baseline to Day 533
Adjusted mean. The Health Assessment Questionnaire Disability Index (HAQ-DI) assesses patients' functional ability by rating their abilities over the previous week. At least 2 questions are asked from each of 8 categories: dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities. Patients rate difficulty performing specific tasks: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The sum of the categories score (the highest scored item in the category) is divided by the number of categories answered, yielding a score from 0-3. Treatment groups represent treatment received in the short term period. Baseline is Day 1 of the study or last non-missing pre-treatment value.
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Day 169 in Short Term Period
Time Frame: Day 169
The ACR score of 20 indicates the degree of improvement in a patient's rheumatoid arthritis (RA), based on ACR guidelines (ACR20). The ACR score represents a percentage. To qualify for an ACR20 score, the patient must have \>=20% fewer tender joints and \>=20% fewer swollen joints and show 20% improvement in at least 3 of: patient overall assessment of his/her RA, physician global assessment of the patient's RA, patient self-assessment of pain, patient self-assessment of physical functioning, and results of an erythrocyte sedimentation rate or C-reactive protein test (to assess inflammation). Percentage is calculated n/N with n=number of participants with ACR score of 20 and N= all randomized participants who received at least one dose of study drug.
Mean Change in DAS28-CRP From Baseline at Day 533 in Long Term Period
Time Frame: Baseline to Day 533
The Disease Activity Score 28 using C-Reactive Protein (DAS28-CRP) is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). An overall DAS \>5.1 implies active disease; \<3.2, well controlled disease; and \<2.6, remission.). Treatment groups represent treatment received in the short term period. Baseline is Day 1 of the study or last non-missing pre-treatment value.
Secondary Outcomes
- Mean Change From Baseline at Six Months in DAS28-CRP - All Treated Participants(Baseline to 6 Months)
- Percentage of Participants With European League Against Rheumatism (EULAR)-Defined Low Disease Activity Score (LDAS) and EULAR-defined Remission (REM) at Day 533 in Long Term Period(Day 533)
- Percentage of Participants With European League Against Rheumatism (EULAR)-Defined Low Disease Activity Score (LDAS) and EULAR-defined Remission (REM) at Day 169 in Short Term Period(Day 169)
- Long-term Period: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, and Discontinuations Due to AEs(Baseline to Day 533 and up to 56 days following last dose in Long-Term period)
- Percentage of Participants With American College of Rheumatology 50 (ACR50) and American College of Rheumatology 70 (ACR70) Responses at Day 169 in Short Term Period(Day 169)
- Mean Change From Baseline in HAQ-DI Score at Day 169 in Short Term Period(Baseline to Day 169)
- Percentage of Participants With HAQ Response at Day 169 in the Short Term Period(Day 169)
- Short-term Period: Number of Participants With Hematology Laboratory Values Meeting the Criteria for Marked Abnormality(Baseline to Day 169)
- Long-term Period: Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria(Baseline to Day 533)
- Short-term Period: Number of Participants With Liver and Kidney Function Laboratory Values Meeting the Criteria for Marked Abnormality(Baseline to Day 169)
- Short-term Period: Number of Participants With Electrolyte Laboratory Values Meeting the Criteria for Marked Abnormality(Baseline to Day 169)
- Long-term Period: Number of Participants With Liver and Kidney Function Laboratory Values Meeting the Criteria for Marked Abnormality(Baseline to Day 533)
- Long-term Period: Number of Participants With Electrolyte Laboratory Values Meeting the Criteria for Marked Abnormality(Baseline to Day 533)
- Short-term Period: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, and Discontinuations Due to AEs(Baseline to Day 169)