A Phase III Study of BMS-188667 in Subjects With Active Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00048932
• Other study ID #: IM101-031
• Status: Completed
• Phase: Phase 3
• First received: November 11, 2002
• Last updated: November 15, 2011
• Start date: December 2002
• Est. completion date: October 2009

Study information

• Verified date: November 2011
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1795
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Double-blind Abatacept
Concentrate and diluted in a solution, IV, 500 mg (body weight < 60 Kg); 750 mg (body weight 60-100 Kg); 1000 mg (body weight > 100 Kg), Once daily, Day 1, 15, and 29.
• Double-blind Placebo
Concentrate and diluted in a solution, IV, 0 mg, Once daily, Day 1, 15, and 29.
• Open-label Abatacept
Concentrate and diluted in a solution, IV, 500 mg (body weight < 60 Kg); 750 mg (body weight 60-100 Kg); 1000 mg (body weight > 100 Kg), Once daily, Every 28 days.

Locations

Country	Name	City	State
United States	Local Institution	Baltimore	Maryland
United States	Local Institution	Blairsville	Georgia
United States	Local Institution	Boston	Massachusetts
United States	Local Institution	Canton	Ohio
United States	Local Institution	Chicago	Illinois
United States	Local Institution	Cleveland	Ohio
United States	Local Institution	Columbia	South Carolina
United States	Local Institution	Columbus	Ohio
United States	Local Institution	Cumberland	Maryland
United States	Local Institution	Decatur	Alabama
United States	Local Institution	Ducktown	Tennessee
United States	Local Institution	Durham	North Carolina
United States	Local Institution	Edmonds	Washington
United States	Local Institution	Elyria	Ohio
United States	Local Institution	Evansville	Indiana
United States	Local Institution	Grand Rapids	Michigan
United States	Local Institution	Hamden	Connecticut
United States	Local Institution	Hickory	North Carolina
United States	Local Institution	Indianapolis	Indiana
United States	Local Institution	Lake Worth	Florida
United States	Local Institution	Largo	Florida
United States	Local Institution	Los Alamos	New Mexico
United States	Local Institution	Louisville	Kentucky
United States	Local Institution	Loveland	Colorado
United States	Local Institution	Menomonee Falls	Wisconsin
United States	Local Institution	Milwaukee	Wisconsin
United States	Local Institution	Nashville	Tennessee
United States	Local Institution	New Orleans	Louisiana
United States	Local Institution	New York	New York
United States	Local Institution	Oklahoma City	Oklahoma
United States	Local Institution	Olympia	Washington
United States	Local Institution	Paradise	Arizona
United States	Local Institution	Phoenix	Arizona
United States	Local Institution	Richmond	Virginia
United States	Local Institution	Royal Oak	Michigan
United States	Local Institution	San Francisco	California
United States	Local Institution	Sioux Falls	South Dakota
United States	Local Institution	Tacoma	Washington
United States	Local Institution	Toms River	New Jersey
United States	Local Institution	Tucson	Arizona
United States	Local Institution	Westminster	Maryland
United States	Local Institution	Wichita	Kansas
United States	Local Institution	Wyomissing	Pennsylvania
United States	Local Institution	Youngstown	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=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 congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Related SAE/AE = possibly, probably, or certainly related to study drug	Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication	Yes
Primary	DB; Number of Participants With AEs of Special Interest	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, and opportunistic infections; autoimmune disorders; neoplasms; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion).	Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication	Yes
Primary	DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria	Upper Normal Limit (ULN), Lower Normal Limit (LLN), Baseline (BL). Marked abnormality criteria are: Hemoglobin (HGB): >3 g/dL decrease from BL; Hematocrit: <0.75 * BL; Erythrocytes: <0.75 * BL; Platelets (PLT): <0.67 * LLN/>1.5 * ULN, or if BL < LLN then use <0.5 * BL and <100,000 mm^3; Leukocytes: <0.75 * LLN/ >1.25 * ULN, or if BL	Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication	Yes
Primary	DB; Number of Participants With Blood Chemistry Laboratories Meeting Marked Abnormality (MA) Criteria	ULN=upper level of normal; BL=baseline.Marked abnormality criteria: High alkaline phosphatase (ALP): >2* ULN, or if BL>ULN then use >3* BL; high aspartate aminotransferase (AST): >3* ULN (80 U/L), or if BL>ULN then use >4* BL; high alanine aminotransferase (ALT): >3* ULN (34-47 U/L), or if BL>ULN then use >4* BL; high G-Glutamyl transferase (GGT): >2* ULN, or if BL>ULN then use >3* BL; high bilirubin: >2* ULN, or if BL>ULN then use >4* BL; high blood urea nitrogen (BUN): >2* BL; high creatinine: >1.5* BL (ULN 14.6 pg/mg. AST ULN=80 U/L; ALT ULN=34-47 U/L;creatinine ULN=14.6 pg/mg.	Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication	Yes
Primary	DB; Number of Participants With Clinically Significant Physical Examination or Vital Signs Abnormalities	Physical examinations were performed at the discretion of the investigator and included breast examinations for female participants. Vital sign measurements were performed for participants before and after infusion of study medication at each visit and included seated systolic blood pressure, seated diastolic blood pressure, temperature, and heart rate. Abnormalities were determined to be clinically significant by the investigator.	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.	Yes
Primary	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	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=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 congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Related SAE/AE = possibly, probably, or certainly related to study drug	Day 365 to Day 1,821	Yes
Primary	OL; Number of Participants With AEs of Special Interest	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, and opportunistic infections; autoimmune disorders; neoplasms; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion).	Day 365 to Day 1821	Yes
Primary	OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria	Upper Normal Limit (ULN), Lower Normal Limit (LLN), Baseline (BL). Marked abnormality criteria are: Hemoglobin (HGB): >3 g/dL decrease from BL; Hematocrit: <0.75 * BL; Erythrocytes: <0.75 * BL; Platelets (PLT): <0.67 * LLN/>1.5 * ULN, or if BL < LLN then use <0.5 * BL and <100,000 mm^3; Leukocytes: <0.75 * LLN/ >1.25 * ULN, or if BL	Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication	Yes
Primary	OL; Number of Participants With Liver Function Laboratories Meeting Marked Abnormality Criteria	Marked abnormality criteria: Alkaline phosphatase (ALP): >2* ULN, or if BL>ULN then use >3* BL; aspartate aminotransferase (AST): >3* ULN, or if BL>ULN then use >4* BL; alanine aminotransferase (ALT): >3* ULN, or if BL>ULN then use >4* BL; G-Glutamyl transferase (GGT): >2* ULN, or if BL>ULN then use >3* BL; Bilirubin: >2* ULN, or if BL>ULN then use >4* BL; blood urea nitrogen (BUN): >2* BL; creatinine: >1.5* BL	Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication	Yes
Primary	OL; Number of Participants With Electrolyte Laboratories Meeting Marked Abnormality Criteria	Marked abnormality criteria: Sodium (Na): <0.95*LLN/ >1.05*ULN, or if BL	Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication	Yes
Primary	OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria	MA criteria: serum glucose (Glu): <65 mg/dL/>220 mg/dL;fasting serum Glu: <0.8* LLN/>1.5*ULN,or if BL	Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication	Yes
Primary	OL; Number of Participants With Clinically Significant Physical Examination or Vital Signs Abnormalities	Physical examinations were performed at the discretion of the investigator and included breast examinations for female participants. Vital sign measurements were performed for participants before and after infusion of study medication at each visit and included seated systolic blood pressure, seated diastolic blood pressure, temperature, and heart rate. Abnormalities were determined to be clinically significant by the investigator.	Days 365 to Day 1821	Yes
Secondary	DB; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by Enzyme-Linked Immunosorbant Assay (ELISA)	Serum samples from all treated adult participants with active rheumatoid arthritis (RA) were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.	Days 1, 29, 57, 85, 113,169, 281, 365	Yes
Secondary	DB; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by ELISA	Serum samples from all treated adult participants with active rheumatoid arthritis were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.	Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm