Abatacept Versus Adalimumab Head-to-Head

Rheumatoid Arthritis Clinical Trial

Official title:

A Randomized, Head-to-Head, Single-Blind Study to Compare the Efficacy and Safety of Subcutaneous Abatacept Versus Subcutaneous Adalimumab, Both With Background Methotrexate, in Biologic-Naive Subjects With Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00929864
• Other study ID #: IM101-235
• Status: Completed
• Phase: Phase 3
• First received: June 29, 2009
• Last updated: January 3, 2014
• Start date: October 2009
• Est. completion date: November 2012

Study information

• Verified date: January 2014
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Minesterio de SaludCanada: Health CanadaChile: Instituto de Salud Pública de ChileColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosPeru: Instituto Nacional de Salud
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is demonstrate that subcutaneous abatacept is non-inferior (no worse than) to subcutaneous adalimumab in the treatment of subjects with rheumatoid arthritis who are biologic naive

Recruitment information / eligibility

• Status: Completed
• Enrollment: 869
• Est. completion date: November 2012
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Moderate to severe Rheumatoid arthritis (RA) according to American College of Rheumatology (ACR) criteria

• Methotrexate failure

• Naive to RA biologics

• =5 years duration of disease

• Disease Activity Score-28 C-reactive protein (DAS28 CRP) = 3.2

• Willingness to self-inject subcutaneous (SC) drug

Exclusion Criteria:

• Previous or current medical conditions that are warnings against the use of tumor necrosis factor (TNF)-blocking agents

• History of active or chronic hepatitis

• Cancer in the last 5 years

• History of severe chronic or recurrent bacterial or viral infections

• Risk of tuberculosis

• Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, Gastro-intestinal, pulmonary, cardiac, neurologic, or cerebral disease

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Abatacept
Syringes, Subcutaneous, 125 mg/syringe for Subcutaneous, Weekly Subcutaneous injections, 24 months (729 days)
• Adalimumab
Syringes, Subcutaneous, 40 mg, Biweekly Subcutaneous injections, 24 months (729 days)

Locations

Country	Name	City	State
Argentina	Local Institution	Ciudad Autonoma	Buenos Aires
Argentina	Local Institution	Ciudad Autonoma De Beunos Aire	Buenos Aires
Argentina	Local Institution	Ciudad Autonoma De Buenos Aire	Buenos Aires
Argentina	Local Institution	Ciudad Autonoma De Buenos Aire	Buenos Aires
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Cordoba, Crd	Cordoba
Argentina	Local Institution	Quilmes	Buenos Aires
Argentina	Local Institution	Rosario	Santa Fe
Argentina	Local Institution	San Juan
Argentina	Local Institution	San Miguel De Tucuman	Tucuman
Argentina	Local Institution	Tucuman
Canada	Local Institution	Hamilton	Ontario
Canada	Local Institution	Quebec
Canada	Local Institution	Trois-Rivieres	Quebec
Canada	Local Institution	Winnipeg	Manitoba
Chile	Local Institution	Santiago	Providencia
Peru	Local Institution	Bellavista	Callao 2
Peru	Local Institution	Lima
Peru	Local Institution	Lima
Peru	Local Institution	Lima
Peru	Local Institution	Lima
United States	Asheville Rheumatology & Osteoporosis Research Asso P. A.	Asheville	North Carolina
United States	Arthritis & Rheumatology Of Georgia	Atlanta	Georgia
United States	Laureate Clinical Research Group	Atlanta	Georgia
United States	Lovelace Scientific Resources, Inc.	Austin	Texas
United States	Arthritis And Rheumatic Disease Specialties	Aventura	Florida
United States	Associated Internal Medicine Specialists	Battle Creek	Michigan
United States	East Penn Rheumatology Associates, P.C.	Bethlehem	Pennsylvania
United States	Rheumatology Associates, Pc	Birmingham	Alabama
United States	University Of Alabama At Birmingham	Birmingham	Alabama
United States	St. Luke'S Clinic - Rheumatology	Boise	Idaho
United States	Brigham And Women'S Hospital	Boston	Massachusetts
United States	Physicians Clinic Of Iowa	Cedar Rapids	Iowa
United States	Low Country Rheumatology, Pa	Charleston	South Carolina
United States	Center For Arthritis & Rheumatic Diseases, Pc	Chesapeake	Virginia
United States	Mountain State Clinical Research	Clarksburg	West Virginia
United States	Coeur D'Alene Arthrit Clin	Coeur D Alene	Idaho
United States	Columbia Arthritis Center, P.A.	Columbia	South Carolina
United States	Klein And Associates, M.D., Pa	Cumberland	Maryland
United States	Arthritis Centers Of Texas	Dallas	Texas
United States	Seacoast Arthritis And Osteoporosis Center	Dover	New Hampshire
United States	Altoona Center For Clinical Research	Duncansville	Pennsylvania
United States	Center For Arthritis And Osteoporosis	Elizabethtown	Kentucky
United States	Arthritis Center Of North Georgia	Gainesville	Georgia
United States	University Of Florida College Of Medicine At Jacksonville	Gainesville	Florida
United States	Rheumatic Disease Center	Glendale	Wisconsin
United States	Mercy Clinic Hot Springs Communities	Hot Springs	Arkansas
United States	Rheumatic Disease Clinical Research Center, Llc	Houston	Texas
United States	Talbert Medical Group	Huntington Beach	California
United States	Arthritis Associates Of Mississippi	Jackson	Mississippi
United States	Rheumatology Pc	Kalamazoo	Michigan
United States	Allergy & Rheumatology Medical Clinic, Inc.	La Jolla	California
United States	North Shore Lij Health System	Lake Success	New York
United States	Arthritis And Osteoporosis Associates Of New Mexico	Las Cruces	New Mexico
United States	Bluegrass Community Research, Inc.	Lexington	Kentucky
United States	Valerius Med Group & Res Ctr Of Greater Long Beach, Inc.	Long Beach	California
United States	Mansfield Health Center	Mansfield	Massachusetts
United States	Center For Arthritis And Rheumatic Diseases	Miami	Florida
United States	Winthrop University Hospital	Mineola	New York
United States	Nashua Rheumatology	Nashua	New Hampshire
United States	Health Research Institute	Oklahoma City	Oklahoma
United States	Health Research Of Oklahoma	Oklahoma City	Oklahoma
United States	Lynn Health Sciences Institute	Oklahoma City	Oklahoma
United States	Arthritis Research Of Florida, Inc.	Palm Harbor	Florida
United States	Irene Y. Tong	Pasadena	California
United States	Sun Valley Arthritis Center, Ltd.	Peoria	Arizona
United States	Quincy Medical Group	Quincy	Illinois
United States	Arthritis Center Of Reno	Reno	Nevada
United States	Rockford Orthopedic Associates, Ltd.	Rockford	Illinois
United States	San Diego Arthritis Medical Clinic	San Diego	California
United States	Sarasota Arthritis Research Center	Sarasota	Florida
United States	Rheumatology Associates Of Long Island	Smithtown	New York
United States	Miami Research Associates	South Miami	Florida
United States	Rockwood Research Center	Spokane	Washington
United States	Physician Groups, Lc Dba	St.Louis	Missouri
United States	Carolina Pharmaceutical Research	Statesville	North Carolina
United States	West Broward Rheumatology Associates	Tamarac	Florida
United States	Drs. Goldin, Nies, Klashman & Eng	Torrance	California
United States	Healthcare Partners Medical Group	Torrance	California
United States	Clinical And Translational Research Center Of Alabama, Pc	Tuscaloosa	Alabama
United States	Inland Rheumatology & Osteoporosis Medical Group	Upland	California
United States	Lovelace Scientific Resources, Inc	Venice	Florida
United States	The Center For Rheumatology And Bone Research	Wheaton	Maryland
United States	Clinical Research Center Of Reading, Llp	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Chile,  Peru, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Proportion of Participants Meeting the American College of Rheumatology (ACR) Criteria of 20% Improvement (ACR20) After 12 Months of Treatment - Intent to Treat Population	Proportion(%)=number of participants meeting criteria (n) divided by number of participants who received drug (N). The ACR score indicates degree of improvement in a patient's rheumatoid arthritis (RA), based on guidelines set forth by the ACR and represents a percentage. To qualify a ACR20 score, patient must have >=20% fewer tender joints and >=20% fewer swollen joints and show 20% improvement from baseline 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 (CRP) test (to assess inflammation). Baseline was Day 1. Randomization was stratified using screening Disease Activity Score-28 (DAS28) CRP, a composite of 4 variables: number of tender joints/28, number of swollen joints/28, CRP in mg/L and participant assessment of disease activity with visual analogue scale.	Day 1 to Day 365	No
Secondary	Proportion of Participants With Local Injection Site Reactions Adverse Events (Pre-specified) Reported During 12 Month Period - ITT Population	n=number of participants with a pre-specified local injection site reaction event, N=number of participants at risk. Proportion (%) = n/N. 12 Months includes data up to 56 days post last dose of the first 12 months Period or start of the first dose of second 12 months period.	Day 1 to 12 Months	Yes
Secondary	Incidence Rate of Local Injection Site Reactions (Pre-specified) Reported During 24 Month Period - ITT Population	Incidence Rate: (incidence/100 person-years) = number of participants with event * 100 /exposure (person-years) Exposure (person-years) = the sum over all participants of the exposure per participant in the 24 months (censored at the time of first occurrence of AE) expressed in days, divided by 365.25. The 24 Month Period includes data up to 56 days post the last dose in the 24 month period. Poisson distribution used to construct the 95% CIs.	Day 1 to Day 729	Yes
Secondary	Proportion of Participants Without Radiographic Progression in Total Score Less Than or Equal to the Smallest Detectable Change (SDC) From Baseline to Months 12 and 24 Using Modified Van Der Heijde Total Sharp Score (mSvdHS) - ITT Population	Plain radiographs of hands and feet taken at baseline (BL), Day 365, and Day 729. BL and Day 365 radiographs were re-read concurrent with Day 729 films by readers blinded to sequence and treatment (a second pre-specified reading campaign). SDC defined as amount of change for which anything smaller could not be reliably distinguished from random error in measurement of simultaneously read films. Non-progression defined: change from BL (Day 1, prior to dosing) in total score less than, equal to (<=) SDC(2.2). Proportion n/m (%)=number meeting criteria (n); number analyzed (m). SDC calculated as SD/sqrt(2)*1.96/sqrt(2)with standard deviation (SD) of paired differences of change from BL in total score between 2 readers; squared root(sqrt). mSvdHS=summary of erosion severity in 32 hand and 12 foot joints. Hand joints scored 0 to 5; foot joints 0 to 10 with 0=no erosion and higher numbers indicating greater erosion severity. BL: radiographic data within 14 days or less of first dose.	Baseline to Day 729	No
Secondary	Incidence Rate of Serious Adverse Events (SAEs), Serious Infections, Pre-specified Opportunistic Infections, and Discontinuation for Any Cause at 12 Months of Treatment - ITT Population	Pre-specified opportunistic infections include: pneumonia, tuberculosis, herpes zoster, combined opportunistic infections, all hospitalized infections. Incidence Rate: incidence/100 person-years: numerator was number of unique events within this period (up to 56 days post-last dose of first 12 months or start of first dose of second 12 months); denominator was overall total exposure (person-years) within this period, calculated as sum over all participants of exposure (in days) divided by 365.25. The resulting incidence rate was multiplied by 100 to express rate per 100 person-years. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE is a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.	Day 1 to Day 365	Yes
Secondary	Incidence Rate of Serious Adverse Events (SAEs), Serious Infections, Pre-specified Opportunistic Infections, and Discontinuation for Any Cause at 24 Months of Treatment - ITT Population	Pre-specified opportunistic infections include: pneumonia, tuberculosis, herpes zoster, combined opportunistic infections, and all hospitalized infections. Incidence Rate: incidence/100 person-years: numerator was number of unique events within this period (up to 56 days post the last dose of the 24 Months period); denominator was overall total exposure (person-years) within this period, which was calculated as the sum over all participants of exposure (in days) divided by 365.25. The resulting incidence rate was multiplied by 100 to express the rate per 100 person-years. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE is a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.	Day 1 to Day 729	Yes
Secondary	Proportion of Participants With Induction of Autoantibodies During the 12 Months and 24 Months Periods - ITT Population	The induction of autoantibodies was defined as participant's antinuclear antibodies (ANA) or anti-double stranded deoxyribonucleic acid (dsDNA) converting from a negative status at baseline to a positive status at a post-baseline measurement time point (Day 365 or Day 729). Proportion (%) = n/m, where n=number of participants with positive ANA or dsDNA at a time point and m=number of participants who had negative ANA or dsDNA at baseline. Blood samples were first tested for ANA by indirect fluorescent assay using HEp-2 Cell Line Substrate, and when positive, samples were further tested for anti-dsDNA by indirect fluorescent assay using Crithidia Luciliae Substrate.	Day 1 to Day 729	Yes

External Links

•   BMS clinical trial educational resource
•   BMS Clinical Trial Information
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form