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Efficacy, Pharmacokinetics, Safety, and Immunogenicity Study of Abatacept Administered Subcutaneously to Treat Rheumatoid Arthritis in Japanese Patients

Information source: Bristol-Myers Squibb
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Rheumatoid Arthritis

Intervention: Intravenous (IV) abatacept (Drug); Subcutaneous (SC) abatacept (Drug)

Phase: Phase 2/Phase 3

Status: Completed

Sponsored by: Bristol-Myers Squibb

Official(s) and/or principal investigator(s):
Bristol-Myers Squibb, Study Director, Affiliation: Bristol-Myers Squibb

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.

Clinical Details

Official title: 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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Day 169 in 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

Mean Change From Baseline in HAQ-DI Score at Day 533 in Long Term Period

Percentage of Participants With Health Assessment Questionnaire (HAQ) Response at Day 533 in Long Term Period

Mean Change in DAS28-CRP From Baseline at Day 533 in Long Term Period

Secondary outcome:

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

Mean Change From Baseline in HAQ-DI Score at Day 169 in Short Term Period

Percentage of Participants With HAQ Response at Day 169 in the Short Term Period

Mean Change From Baseline at Six Months in DAS28-CRP - All Treated Participants

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

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

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

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

Short-term Period: Number of Participants With Hematology Laboratory Values Meeting the Criteria for Marked Abnormality

Long-term Period: Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria

Short-term Period: Number of Participants With Liver and Kidney Function Laboratory Values Meeting the Criteria for Marked Abnormality

Short-term Period: Number of Participants With Electrolyte Laboratory Values Meeting the Criteria for Marked Abnormality

Long-term Period: Number of Participants With Liver and Kidney Function Laboratory Values Meeting the Criteria for Marked Abnormality

Long-term Period: Number of Participants With Electrolyte Laboratory Values Meeting the Criteria for Marked Abnormality

Eligibility

Minimum age: 20 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Key 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. Key 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.

- Physical examination and laboratory test findings: Hepatitis B surface

antigen-positive status; hepatitis C antibody-positive status. Any of the following laboratory values: Hemoglobin concentration: <.5 g/dL; white blood cell count: <3,000/μL (3*10^9/L); platelet count: <100,000/mm^3(100*10^9/L); serum creatinine: >2 times upper limit of normal (ULN); serum alanine aminotransferase: >2 ULN; serum aspartate aminotransferase: >2 ULN.

- Prohibited treatments and/or therapies: Prior exposure to abatacept (CTLA4-Ig);

prior RA treatment with any biologics, such as anti-tumor necrosis factor therapy; prior exposure to any investigational biologic not currently approved in Japan; exposure to any study medication in any other previous study within 4 weeks or 5 half-lives, whichever was longer; receipt of any live vaccines within 3 months of administration of study medication or scheduled to receive live vaccines.

Locations and Contacts

Local Institution, Narita-Shi, Chiba 2868523, Japan

Local Institution, Fukuoka-Shi, Fukuoka 8108563, Japan

Local Institution, Kitakyushu-Shi, Fukuoka 8078555, Japan

Local Institution, Kurume-Shi, Fukuoka 8308543, Japan

Local Institution, Maebashi-Shi, Gunma 3718511, Japan

Local Institution, Takasaki-Shi, Gunma 3700053, Japan

Local Institution, Higashi-Hiroshima-Shi, Hiroshima 7390002, Japan

Local Institution, Sapporo-Shi, Hokkaido 0630811, Japan

Local Institution, Sapporo-Shi, Hokkaido 0608648, Japan

Local Institution, Sapporo-Shi, Hokkaido 0608604, Japan

Local Institution, Sapporo, Hokkaido 0630005, Japan

Local Institution, Kanzaki-Gun, Hyogo 6792414, Japan

Local Institution, Kato-Shi, Hyogo 6731462, Japan

Local Institution, Kobe-Shi, Hyogo 6500001, Japan

Local Institution, Hitachi-Shi, Ibaraki 3160035, Japan

Local Institution, Kagoshima-Shi, Kagoshima 8900067, Japan

Local Institution, Sagamihara-Shi, Kanagawa 2520392, Japan

Local Institution, Yokohama-Shi, Kanagawa 2220036, Japan

Local Institution, Yokohama-Shi, Kanagawa 2360037, Japan

Local Institution, Nagano-Shi, Nagano 3808582, Japan

Local Institution, Kurashiki-Shi, Okayama 7128044, Japan

Local Institution, Hannan-Shi, Osaka 5990212, Japan

Local Institution, Iruma-Gun, Saitama 3500495, Japan

Local Institution, Kawagoe-Shi, Saitama 3508550, Japan

Local Institution, Kitamoto-Shi, Saitama 3640026, Japan

Local Institution, Tokorozawa-Shi, Saitama 3591111, Japan

Local Institution, Hamamatsu-Shi, Shizuoka 4308558, Japan

Local Institution, Shizuoka-Shi, Shizuoka 4208623, Japan

Local Institution, Shimotsuke-Shi, Tochigi 3290498, Japan

Local Institution, Utsunomiya-Shi, Tochigi 3291193, Japan

Local Institution, Bunkyo-Ku, Tokyo 1138519, Japan

Local Institution, Nakano-Ku, Tokyo 1648541, Japan

Local Institution, Shinjuku-Ku, Tokyo 1608582, Japan

Additional Information

BMS Clinical Trials Disclosure

Investigator Inquiry form

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm

Starting date: December 2009
Last updated: January 2, 2014

Page last updated: August 23, 2015

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