Substudy - Low Dose of Abatacept in Subjects With Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

Official title:

A Phase 3B, Multi-Center, Randomized, Double-blind Study to Evaluate Remission and Joint Damage Progression in Methotrexate-naïve Early Erosive Rheumatoid Arthritis Subjects Treated With Abatacept Plus Methotrexate Compared With Methotrexate - Low Dose Sub-Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00989235
• Other study ID #: IM101-023 LT (Sub study)
• Secondary ID: Eudrac # 2002-00
• Status: Completed
• Phase: Phase 3
• First received: October 2, 2009
• Last updated: June 18, 2011
• Start date: April 2007
• Est. completion date: October 2009

Study information

• Verified date: June 2011
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical DevicesPoland: National Institute of MedicinesRussia: Ministry of Health of the Russian FederationFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentBrazil: National Committee of Ethics in ResearchCanada: Health Canada, Biologics and General Therapies Directorate, Regulatory Affairs Division Office of Clinical Trials Therapeutic Products DirectorateMexico: Federal Commission for Sanitary Risks ProtectionUnited States: Food and Drug AdministrationSpain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial Summary

The purpose of this exploratory sub-study was to evaluate from a clinical perspective the impact on disease activity of lowering the dose of abatacept from 10 mg/kg to 5 mg/kg in subjects who had achieved remission (Disease Activity Score 28 [DAS 28]-erythrocyte sedimentation rate [ESR] < 2.6) at Day 701 of study IM101023.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• 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:

• Subjects who have completed the main study, are willing to participate and have a DAS 28 ESR score of < 2.6 on Day 701 of the main study

Exclusion Criteria:

Study Design

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Abatacept
IV solution, IV, 10 mg/Kg, Once monthly, 1 year
• Abatacept
IV solution, IV, 5 mg/Kg, Once monthly, 1 year

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Disease Relapse Through Month 12 (Kaplan-Meier Cumulative Percentage of Events of Disease Relapse)	An event of disease relapse was defined as additional Disease-modifying antirheumatic drug (DMARD) therapy given, or 2 or more courses of high steroids given, or return to abatacept 10 mg/kg (rescue medication given), or DAS28 C-reactive protein (CRP) score >=3.2 at 2 consecutive visits. Time to disease relapse was evaluated using life tables (Kaplan-Meier Cumulative Percentage of Events of Disease Relapse).	Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12	No
Secondary	Number of Participants Experiencing Disease Relapse	Disease relapse is defined as additional DMARD therapy given, or 2 or more courses of high steroids given, or return to abatacept 10 mg/kg (rescue medication given), or DAS28 CRP score >= 3.2 at 2 consecutive visits.	After 12 Months of treatment	No
Secondary	Mean Time-Matched Baseline DAS28 CRP Scores	Mean baseline DAS28 CRP values for the cohort of participants with serum samples available at that timepoint. DAS 28 is a continuous variable which is a composite of 4 variables: number of tender joints out of 28, number of swollen joints out of 28 joints, CRP in mg/L and subject assessment of disease activity measure on a visual analogue scale (VAS) of 100 mm. The DAS28 provides a score on a scale from 0 to 10 indicating the current activity of the rheumatoid arthritis (>5.1=high disease activity; <3.2=low disease activity; <2.6=remission).	Baseline	No
Secondary	Adjusted Mean Change From Baseline in DAS28 CRP During Double-Blind Treatment	Mean baseline DAS28 CRP values for the cohort of participants with serum samples available at that timepoint. DAS 28 is a continuous variable which is a composite of 4 variables: number of tender joints out of 28, number of swollen joints out of 28 joints, CRP in mg/L and subject assessment of disease activity measure on a VAS of 100 mm. The DAS28 provides a score on a scale from 0 to 10 indicating the current activity of the rheumatoid arthritis (>5.1=high disease activity; <3.2=low disease activity; <2.6=remission).	Baseline, Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365	No
Secondary	Percentage of Participants With 2 Consecutive DAS 28 CRP Scores = 3.2 (Loss of Low Disease Activity Status)	DAS 28 is a continuous variable which is a composite of 4 variables: number of tender joints out of 28, number of swollen joints out of 28 joints, CRP in mg/L and subject assessment of disease activity measure on a VAS of 100 mm. The DAS28 provides a score on a scale from 0 to 10 indicating the current activity of the rheumatoid arthritis (>5.1=high disease activity; <3.2=low disease activity; <2.6=remission).	After 12 months of treatment	No
Secondary	Percentage of Participants Given Additional DMARD Therapy During Double-Blind Treatment	Additional DMARD therapy is defined as a re-introduction of methotrexate (MTX), an increase of at least 2.5 mg of MTX, or the addition of at least 1 DMARD.	After 12 months of treatment	No
Secondary	Percentage of Participants Who at Any Time During Double-Blind Treatment Were Given 2 or More Courses of High-Dose Steroids	A course of high dose steroids is defined as a course of intramuscular, intravenous, or high dose oral corticosteroids (use of > 10 mg/day equivalent of prednisone for a minimum of 3 consecutive days or for those subjects who had continued use for long durations of time, each course was determined by 28 day intervals).	After 12 months of treatment	No
Secondary	Percentage of Participants Given Rescue Medication Therapy During Double-Blind Treatment	All subjects in the sub-study randomized to receive double-blind abatacept 5 mg/kg or 10 mg/kg. Subjects rescued to open-label treatment received abatacept 10 mg/kg.	After 12 months of treatment	No
Secondary	Percentage of Participants Who Modified Therapy During Double-Blind Treatment	Modified therapy=additional DMARD therapy, 2 or more courses of high dose steroids or rescue medication. Additional DMARD therapy=re-introduction of methotrexate (MTX), an increase of at least 2.5 mg of MTX, or the addition of at least 1 DMARD. A course of high dose steroids=a course of intramuscular, intravenous, or high dose oral corticosteroids (use of > 10 mg/day equivalent of prednisone for a minimum of 3 consecutive days or for those subjects who had continued use for long durations of time, each course was determined by 28 day intervals). Rescue medication=abatacept 10 mg/kg.	After 12 months of treatment	No
Secondary	Percentage of Participants Who Lost Remission Status	Loss of remission is defined as DAS 28 CRP >=2.6.	After 12 months of treatment	No
Secondary	Steady-state Trough Serum Concentration (Cmin) of Abatacept During Double-Blind Treatment		Day 701 of the main study; sub-study Days 1, 85, 169, 253	No
Secondary	Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations During Double-Blind Treatment	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Related AE/SAE=Certain, Probable, Possible, or Missing. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.	From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)	Yes
Secondary	Percentage of Participants With Infection and Infestation AEs Reported During Double-Blind Treatment	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Infection and Infestation AEs = any AE within the System Organ Class Infection and Infestation.	From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)	Yes
Secondary	Percentage of Participants With Malignant Neoplasms Reported During Double-Blind Treatment	All neoplasms were assessed by medical review as to whether or not the event was malignant.	From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)	Yes
Secondary	Percentage of Participants With Prespecified Acute Infusional Adverse Events (AIAEs) During Double-Blind Treatment, by Intensity	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Acute Infusional AE= a subset of the peri-infusional AEs with onset during the first hour after the start of the study drug infusion. A total of 105 infusional events were prespecified in the protocol.	From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)	Yes
Secondary	Percentage of Participants With Prespecified Peri-Infusional Adverse Events (PAIAEs) During Double-Blind Treatment, by Intensity	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Peri-infusional AE=a pre-specified infusional AE occuring during the first 24 hours after the start of study drug infusion.A total of 105 infusional events were prespecified in the protocol. GDASC=General Disorders and Administration Site Conditions, RTMD=Respiratory, Thoracic and Mediastinal Disorders.	From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)	Yes
Secondary	Percentage of Participants With Pre-specified Autoimmune Disorders (ADs) Reported During Double-Blind Treatment, by Intensity	A total of 127 autoimmune disorders were prespecified in the protocol. MCTD=Musculoskeletal and Connective Tissue Disorders	From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)	Yes
Secondary	Percentage of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During Double-Blind Treatment	Not evaluated: high hemoglobin,high hematocrit,high erythrocytes,high neutrophils+bands(N+B),low monocytes,low basophils,low eosinophils,low alkaline phosphatase(ALP),low aspartate aminotransferase(AST),low alanine aminotransferase(ALT),low G-Glutamyl transferase(GGT),low total bilirubin,low blood urea nitrogen,low creatinine,high albumin,low uric acid,low urine protein,low urine glucose,low urine blood,low urine leukocyte esterase,low urine white blood cells,low red blood cells.Pre Rx=pretreatment,(*)Lymphocytes(c/uL):Low<.750x10^3,High>7.50x10^3.(*)Eosinophils:>.750x10^3 c/uL.	From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)	Yes
Secondary	Clinically Significant Changes in Vital Signs and Physical Findings	Clinical significance was determined by investigator. Parameters include blood pressure, heart rate, respiration rate, and temperature.	From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)	Yes
Secondary	Participants With Positive Antibody Responses to Abatacept (Electrochemiluminescence [ECL] Method) During Double-Blind Treatment	A positive antibody response to Abatacept (measured by the ECL assay) is further classified as a positive response for either Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Possibly immunoglobulin (Ig)' or 'Ig and/or Junction Region'	After 12 months of treatment	Yes

External Links

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