Study of Abatacept Versus Placebo to Assess the Prevention of Rheumatoid Arthritis (RA) in Adult Patients

Arthritis, Rheumatoid Clinical Trial

Official title:

A Phase II Study of Abatacept Versus Placebo to Assess the Prevention of Rheumatoid Arthritis (RA) in Adult Patients With Undifferentiated Arthritis Who Are at High Risk for the Development of RA

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00124449
• Other study ID #: IM101-046
• Status: Completed
• Phase: Phase 2
• First received: June 30, 2005
• Last updated: March 18, 2015
• Start date: February 2005
• Est. completion date: April 2008

Study information

• Verified date: March 2015
• 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 study is to assess if Abatacept given for six months will prevent rheumatoid arthritis (RA) in patients who are at risk for the development of RA in comparison to placebo. High risk patients are defined as those having a positive laboratory test for anti-cyclic citrullinated peptide (anti-CCP2).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: April 2008
• Est. primary completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Diagnosis of undifferentiated arthritis

• Clinical synovitis of two or more joints

• At least one but not more than three of the criteria for diagnosis of RA (1987).

• No prior disease modifying anti-rheumatic drugs (DMARDs)/biologics.

• Duration of disease must be 18 months or less.

• Positive for antibodies against cyclic citrullinated peptides.

Exclusion Criteria:

• Women of child bearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy.

• Active vasculitis of a major organ system.

• Severe or recurrent bacterial infection.

• History of cancer in the last five years except certain skin cancers.

• Herpes zoster that resolved less than 2 months prior to enrollment

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator)

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• Abatacept
solution, intravenous injection, monthly, 169 days weight based: <60 kg = 500 mg 60 to 100 kg = 750 mg >100 kg = 1 g
• placebo
solution, intravenous injection, 0 mg, monthly, 169 days

Locations

Country	Name	City	State
Australia	Local Institution	Cairns	Queensland
Australia	Local Institution	Clayton	Victoria
Australia	Local Institution	Malvern	Victoria
Australia	Local Institution	Shenton Park	Western Australia
Belgium	Local Institution	Bruxelles
Belgium	Local Institution	Leuven
France	Local Institution	Paris
France	Local Institution	Strasbourg Cedex
Germany	Local Institution	Berlin
Germany	Local Institution	Dresden
Germany	Local Institution	Hamburg
Germany	Local Institution	Hannover
Germany	Local Institution	Heidelberg
Italy	Local Institution	Bari
Italy	Local Institution	Ferrara
Italy	Local Institution	Milano
Mexico	Local Institution	Guadalajara	Distrito Federal
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Leon	Guanajuato
Mexico	Local Institution	Morelia	Michioacan
Puerto Rico	Local Institution	Ponce
Spain	Local Institution	A Coruna
Spain	Local Institution	Barcelona
Spain	Local Institution	Madrid
Spain	Local Institution	Oviedo
Spain	Local Institution	Sevilla
United Kingdom	Local Institution	Leeds	North Yorkshire
United Kingdom	Local Institution	Liverpool	Merseyside
United States	Local Institution	Arlington	Virginia
United States	Local Institution	Austin	Texas
United States	Local Institution	Boulder	Colorado
United States	Local Institution	Charleston	South Carolina
United States	Local Institution	Chicago	Illinois
United States	Local Institution	Colorado Springs	Colorado
United States	Local Institution	Cumberland	Maryland
United States	Local Institution	Duluth	Minnesota
United States	Local Institution	Durham	North Carolina
United States	Local Institution	Evansville	Indiana
United States	Local Institution	Ft. Lauderdale	Florida
United States	Local Institution	Hagerstown	Maryland
United States	Local Institution	Huntington Beach	California
United States	Local Institution	Huntsville	Alabama
United States	Local Institution	Los Angeles	California
United States	Local Institution	Mobile	Alabama
United States	Local Institution	New Orleans	Louisiana
United States	Local Institution	Oklahoma City	Oklahoma
United States	Local Institution	Willow Grove	Pennsylvania
United States	Local Institution	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Germany,  Italy,  Mexico,  Puerto Rico,  Spain,  United Kingdom, 

References & Publications (1)

Emery P, Durez P, Dougados M, Legerton CW, Becker JC, Vratsanos G, Genant HK, Peterfy C, Mitra P, Overfield S, Qi K, Westhovens R. Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial). Ann Rheum Dis. 2010 Mar;69(3):510-6. doi: 10.1136/ard.2009.119016. Epub 2009 Nov 23. Erratum in: Ann Rheum Dis. 2011 Aug;70(8):1519. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With a Diagnosis of Rheumatoid Arthritis (RA) by American Rheumatism Association (ARA) Criteria and/or Discontinued Due to Lack of Efficacy	ARA criteria is a 7-item tool for RA classification purposes; a patient is said to have RA (meeting endpoint) if he or she has satisfied at least 4 of the 7 criteria. If a participant discontinued due to lack of efficacy, he/she was regarded as meeting primary endpoint also.	12 months	No
Secondary	Number of Participants With a Diagnosis of RA by 1987 ARA Criteria and/or Discontinued Due to Lack of Efficacy	ARA criteria is a 7-item tool for classification purposes; a patient is said to have RA (meeting endpoint) if he or she has satisfied at least 4 of the 7 criteria. If a participant discontinued due to lack of efficacy, he/she was regarded as meeting endpoint also.	24 months	No
Secondary	Number of Participants With Undifferentiated Inflammatory Arthritis (UA) Who Develop Another Rheumatic Disease	Clinical diagnosis of other rheumatic diseases at 12 and 24 months. If a participant discontinued due to lack of efficacy, he/she was regarded as meeting endpoint also.	12 months, 24 months	No
Secondary	Change From Baseline in Radiographic Erosion and Joint Space Narrowing Score at 6 Months, 12 Months, and 24 Months	Mean change from baseline using the Genant-Modified Sharp Score. Erosion score=assessment of 14 sites in each hand and wrist + 6 joints in each foot, using an 8-point scale from 0 (no erosions) to 3.5 (erosions of 100% or articular surfaces). Joint score= assessment of 13 sites in each wrist and hand + 6 sites in each foot using a 9-point scale from 0 (normal) to 4.0 (definite ankylosis). As-observed data. Change from Baseline=postbaseline score at timepoint (6 or 12 or 24 months) minus baseline score; a lower value signifies improvement.	Baseline, 6 months, 12 months, 24 months	No
Secondary	Change From Baseline in Total Erosion, Edema, Synovitis Scores at 6 Months, 12 Months, and 24 Months	Mean change from baseline. Degree of synovitis and structural joint damage (erosion, edema) of the carpal and metacarpophalangeal joints, as measured by magnetic resonance imaging (MRI) scores using the European League Against Rheumatism (EULAR)-Outcome Measures in Rheumatology Clinical Trials (OMERACT) assessment. Edema scale=0 (no bone involved) to 3 (67% to 100% of bone involved). Synovitis scale=0 (normal) and 1-3 (mild, moderate, severe. Bone erosion scale=0 (0% of bone involved) to 10 (91% to 100% of bone involved). Change from baseline=postbaseline score at timepoint - baseline score.	Baseline, 6 months, 12 months, 24 months	No
Secondary	Number of Participants With Persistent Symptomatic Clinical Synovitis	Synovitis, assessed by clinical signs and symptoms	6, 12, and 24 months	No
Secondary	Short Form-36 (SF-36) Physical and Mental Component Summary (PCS and MCS) Scores - Mean Change From Baseline	SF-36, a 36-item instrument that covers 8 quality of life domains, which were used to derive the physical and mental component summary scores, which ranged from 0 to 100, with higher scores indicating a better quality of life. Change from baseline=postbaseline - baseline value; a higher value signifies improvement.	6 months, 12 months, 24 months	No
Secondary	Change From Baseline in Cytokine Levels and Second Generation Anti-cyclic Citrullinated Peptide (Anti-CCP2) Antibodies at 6 Months, 12 Months, and 24 Months	To assess pharmacodynamic effect of abatacept on serum levels of autoantibodies, mean change from baseline in cytokines (interleukin-6 [IL-6], interleukin-1B [IL-1B], tumor necrosis factor Alpha [TNF-Alpha], Matrix Metalloproteinase 3T [MMP3T], and anti-CCP2), as measured by standard laboratory investigations, were assessed. Change from baseline=postbaseline value at timepoint (6 or 12 or 24 months) minus baseline value; a lower value signifies improvement.	Baseline, 6 Months, 12 months, 24 months	No
Secondary	Number of Participants With Anti-CCP2 Positive and/or Rheumatoid Factor (RF) Positive Over Time	To assess the pharmacodynamic effect of abatacept on serum levels of autoantibodies, number of participants with Anti-CCP2 Positive of Rheumatoid Factor (RF) positive	Day 1, 6 months, 12 months, 24 months	No
Secondary	Frequency of Human Leukocyte Antigen (HLA) Typing	To assess the pharmacodynamic effect of abatacept on serum levels of autoantibodies, a blood sample was obtained for HLA typing to determine the presence or absence of alleles associated with RA susceptibility and severity (shared epitope alleles HLA-DRB10401 and HLA-DRB10404).	Day 1	No
Secondary	DAS 28 C Reactive Protein (CRP) Score - Mean Change From Baseline	The DAS 28 (CRP) is a composite of 4 variables: 28 tender joint count, 28 swollen joint count, CRP, and subject assessment of disease activity measure on a VAS of 100 mm. Change from Baseline=postbaseline score-baseline score; a lower value signifies improvement.	6 months, 12 months, 24 months	No
Secondary	Number of Participants With a DAS 28 (CRP) Score of =3.2 (Low Disease Activity) or <2.6 (in Remission)	The DAS 28 (CRP) is a composite of 4 variables: tender joint count, swollen joint count, CRP, and subject assessment of disease activity measure on a VAS of 100 mm. Scores for disease activity are defined as low (= 3.2) and in remission (< 2.6).	6 months, 12 months, 24 months	No
Secondary	Number of Subjects With Health Assessment Questionnaire (HAQ) Disability Index Response	This questionnaire includes 20 questions assessing physical function in 8 domains. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty and 3=unable to do. Higher scores indicate greater dysfunction. HAQ response =improvement of at least 0.3 units from baseline.	6 months, 12 months, 24 months	No
Secondary	Overall Safety - Adverse Events (AEs), Serious AEs, and Deaths	AEs were monitored at all scheduled visits of the study drug treatment and observation periods and at the follow-up visits performed 28, 56, and 85 days after the last infusion of study medication for participants who were withdrawn prematurely	Throughout the treatment period (6 months)	Yes
Secondary	Number of Participants With Positive Responses for Serum Levels of Abatacept-specific Antibodies	Immunogenicity, as measured by the number of positive repsonses for serum levels of abatacept-specific antibodies measured by enzyme-linked immunosorbent assays (ELISA). Postive response for whole molecule assessment was a value of > 400 and for tip assessment was =25.	Up to 12 months	No

External Links

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