Clinical trial NCT00048932: A Phase III Study of BMS-188667 in Subjects With Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2002-11-13
Enrollment: 1795
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this clinical research study is to learn if abatacept is safe when co-administered with other approved rheumatoid arthritis medications.

Detailed description: This was a multinational, multicenter, randomized, double-blind, 2-arm, parallel-dosing designed study. The treatment period was 12 months. Eligible participants were randomized to 1 of 2 treatment groups: abatacept fixed dose approximating 10 mg/kg (based on participant's body weight; 500 mg for participants weighing \< 60kg; 750 mg for participants weighing 60 to 100 kg; and 1 gram for participants weighing \> 100 kg, monthly) or placebo intravenous (IV) infusion. All participants continued their background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period. Double-blind study medication (abatacept or placebo) was administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses.

All participants who completed the 12-month double-blind study period (Day 1 through Day 365), were eligible to continue into the open-label period. All eligible participants (active or placebo) were re-allocated to receive abatacept at a weight-tiered dose that approximated 10 mg/kg, based on their Day 365 body weight. Participants continued to receive infusions every 28 days.

Eligibility criteria: Inclusion Criteria:

* Meet criteria of American Rheumatism Association for the diagnosis of rheumatoid arthritis and the American College of Rheumatology functional classes I, II III or IV
* Participants must be taking 1 or more DMARDs and/or biologic approved for rheumatoid arthritis (RA) for at least 3 months and be on a stable dose for 28 days prior to Day 1.

Exclusion:

* Other auto-immune disease as a main diagnosis (e.g. Systemic Lupus Erythematosus \[SLE\], Scleroderma)
* Active tuberculosis (TB) requiring treatment within last 3 years

Primary outcomes:
measure: Double Blind Period (DB); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation
timeFrame: Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication
measure: DB; Number of Participants With AEs of Special Interest
timeFrame: Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication
measure: DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
timeFrame: Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication
measure: DB; Number of Participants With Blood Chemistry Laboratories Meeting Marked Abnormality (MA) Criteria
timeFrame: Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication
measure: DB; Number of Participants With Clinically Significant Physical Examination or Vital Signs Abnormalities
timeFrame: Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337. Vital signs were measured at these visits before and after study medication infusion.
measure: Open Label Period (OL); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation
timeFrame: Day 365 to Day 1,821
measure: OL; Number of Participants With AEs of Special Interest
timeFrame: Day 365 to Day 1821
measure: OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
timeFrame: Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication
measure: OL; Number of Participants With Liver Function Laboratories Meeting Marked Abnormality Criteria
timeFrame: Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication
measure: OL; Number of Participants With Electrolyte Laboratories Meeting Marked Abnormality Criteria
timeFrame: Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication
measure: OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria
timeFrame: Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication
measure: OL; Number of Participants With Clinically Significant Physical Examination or Vital Signs Abnormalities
timeFrame: Days 365 to Day 1821
Secondary outcomes:
measure: DB; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by Enzyme-Linked Immunosorbant Assay (ELISA)
timeFrame: Days 1, 29, 57, 85, 113,169, 281, 365
measure: DB; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by ELISA
timeFrame: Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337
Other outcomes:
Locations:
city: Decatur
country: United States
facility: Local Institution
state: Alabama
city: Paradise
country: United States
facility: Local Institution
state: Arizona
city: Phoenix
country: United States
facility: Local Institution
state: Arizona
city: Tucson
country: United States
facility: Local Institution
state: Arizona
city: San Francisco
country: United States
facility: Local Institution
state: California
city: Loveland
country: United States
facility: Local Institution
state: Colorado
city: Hamden
country: United States
facility: Local Institution
state: Connecticut
city: Lake Worth
country: United States
facility: Local Institution
state: Florida
city: Largo
country: United States
facility: Local Institution
state: Florida
city: Blairsville
country: United States
facility: Local Institution
state: Georgia
city: Chicago
country: United States
facility: Local Institution
state: Illinois
city: Evansville
country: United States
facility: Local Institution
state: Indiana
city: Indianapolis
country: United States
facility: Local Institution
state: Indiana
city: Wichita
country: United States
facility: Local Institution
state: Kansas
city: Louisville
country: United States
facility: Local Institution
state: Kentucky
city: New Orleans
country: United States
facility: Local Institution
state: Louisiana
city: Baltimore
country: United States
facility: Local Institution
state: Maryland
city: Cumberland
country: United States
facility: Local Institution
state: Maryland
city: Westminster
country: United States
facility: Local Institution
state: Maryland
city: Boston
country: United States
facility: Local Institution
state: Massachusetts
city: Grand Rapids
country: United States
facility: Local Institution
state: Michigan
city: Royal Oak
country: United States
facility: Local Institution
state: Michigan
city: Toms River
country: United States
facility: Local Institution
state: New Jersey
city: Los Alamos
country: United States
facility: Local Institution
state: New Mexico
city: New York
country: United States
facility: Local Institution
state: New York
city: Durham
country: United States
facility: Local Institution
state: North Carolina
city: Hickory
country: United States
facility: Local Institution
state: North Carolina
city: Canton
country: United States
facility: Local Institution
state: Ohio
city: Cleveland
country: United States
facility: Local Institution
state: Ohio
city: Columbus
country: United States
facility: Local Institution
state: Ohio
city: Elyria
country: United States
facility: Local Institution
state: Ohio
city: Youngstown
country: United States
facility: Local Institution
state: Ohio
city: Oklahoma City
country: United States
facility: Local Institution
state: Oklahoma
city: Wyomissing
country: United States
facility: Local Institution
state: Pennsylvania
city: Columbia
country: United States
facility: Local Institution
state: South Carolina
city: Sioux Falls
country: United States
facility: Local Institution
state: South Dakota
city: Ducktown
country: United States
facility: Local Institution
state: Tennessee
city: Nashville
country: United States
facility: Local Institution
state: Tennessee
city: Richmond
country: United States
facility: Local Institution
state: Virginia
city: Edmonds
country: United States
facility: Local Institution
state: Washington
city: Olympia
country: United States
facility: Local Institution
state: Washington
city: Tacoma
country: United States
facility: Local Institution
state: Washington
city: Menomonee Falls
country: United States
facility: Local Institution
state: Wisconsin
city: Milwaukee
country: United States
facility: Local Institution
state: Wisconsin
Study officials:
References:
citation: Alten R, Burkhardt H, Feist E, Kruger K, Rech J, Rubbert-Roth A, Voll RE, Elbez Y, Rauch C. Abatacept used in combination with non-methotrexate disease-modifying antirheumatic drugs: a descriptive analysis of data from interventional trials and the real-world setting. Arthritis Res Ther. 2018 Jan 2;20(1):1. doi: 10.1186/s13075-017-1488-5.