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

NCT ID: NCT01001832

Last Updated: 2014-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2012-10-31

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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Subcutaneous (SC) abatacept, 125 mg

Group Type: ACTIVE_COMPARATOR

Subcutaneous (SC) abatacept

Intervention Type: DRUG

Solution in prefilled syringes, SC, 125 mg, once weekly, for 169 days and then for 52 weeks

Intravenous (IV) abatacept, 125 mg

Group Type: ACTIVE_COMPARATOR

Intravenous (IV) abatacept

Intervention Type: DRUG

IV vial, 125-mg infusions on Days 1, 15, and 29, and every 28 days thereafter until Day 141.

Interventions

Intravenous (IV) abatacept

IV vial, 125-mg infusions on Days 1, 15, and 29, and every 28 days thereafter until Day 141.

Intervention Type: DRUG

Subcutaneous (SC) abatacept

Solution in prefilled syringes, SC, 125 mg, once weekly, for 169 days and then for 52 weeks

Intervention Type: DRUG

Other Intervention Names

BMS-188667; BMS-188667

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.
• 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.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Local Institution

Hannan-Shi, Osaka, Japan

Local Institution

Iruma-Gun, Saitama, Japan

Local Institution

Kawagoe-Shi, Saitama, Japan

Local Institution

Kitamoto-Shi, Saitama, Japan

Local Institution

Tokorozawa-Shi, Saitama, Japan

Local Institution

Hamamatsu, Shizuoka, Japan

Local Institution

Shizuoka, Shizuoka, Japan

Local Institution

Shimotsuke-Shi, Tochigi, Japan

Local Institution

Utsunomiya, Tochigi, Japan

Local Institution

Bunkyo-Ku, Tokyo, Japan

Local Institution

Nakano-Ku, Tokyo, Japan

Local Institution

Shinjuku-Ku, Tokyo, Japan

Local Institution

Narita-Shi, Chiba, Japan

Local Institution

Fukuoka, Fukuoka, Japan

Local Institution

Kitakyushu-Shi, Fukuoka, Japan

Local Institution

Kurume-Shi, Fukuoka, Japan

Local Institution

Maebashi, Gunma, Japan

Local Institution

Takasaki-Shi, Gunma, Japan

Local Institution

Higashi-Hiroshima-Shi, Hiroshima, Japan

Local Institution

Sapporo, Hokkaido, Japan

Local Institution

Sapporo, Hokkaido, Japan

Local Institution

Sapporo, Hokkaido, Japan

Local Institution

Sapporo, Hokkaido, Japan

Local Institution

Kanzaki-Gun, Hyōgo, Japan

Local Institution

Kato-Shi, Hyōgo, Japan

Local Institution

Kobe, Hyōgo, Japan

Local Institution

Hitachi-Shi, Ibaraki, Japan

Local Institution

Kagoshima, Kagoshima-ken, Japan

Local Institution

Sagamihara-Shi, Kanagawa, Japan

Local Institution

Yokohama, Kanagawa, Japan

Local Institution

Yokohama, Kanagawa, Japan

Local Institution

Nagano, Nagano, Japan

Local Institution

Kurashiki-Shi, Okayama-ken, Japan

Countries

Japan

References

Amano K, Matsubara T, Tanaka T, Inoue H, Iwahashi M, Kanamono T, Nakano T, Uchimura S, Izumihara T, Yamazaki A, Karyekar CS, Takeuchi T; Japan Abatacept Study Group. Long-term safety and efficacy of treatment with subcutaneous abatacept in Japanese patients with rheumatoid arthritis who are methotrexate inadequate responders. Mod Rheumatol. 2015 Sep;25(5):665-71. doi: 10.3109/14397595.2015.1012786.

Reference Type: DERIVED

PMID: 25698370 (View on PubMed)

Related Links

http://www.bms.com/clinical_trials/Pages/Investigator_Inquiry_form.aspx

Investigator Inquiry form

Other Identifiers

IM101-250

Identifier Type: -

Identifier Source: org_study_id