Substudy - Low Dose of Abatacept in Subjects With Rheumatoid Arthritis

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00989235
First received: October 2, 2009
Last updated: June 18, 2011
Last verified: June 2011
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Abatacept
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Time to Disease Relapse Through Month 12 (Kaplan-Meier Cumulative Percentage of Events of Disease Relapse) [ Time Frame: Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Number of Participants Experiencing Disease Relapse [ Time Frame: After 12 Months of treatment ] [ Designated as safety issue: No ]
    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.

  • Mean Time-Matched Baseline DAS28 CRP Scores [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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).

  • Adjusted Mean Change From Baseline in DAS28 CRP During Double-Blind Treatment [ Time Frame: Baseline, Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365 ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With 2 Consecutive DAS 28 CRP Scores ≥ 3.2 (Loss of Low Disease Activity Status) [ Time Frame: After 12 months of treatment ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants Given Additional DMARD Therapy During Double-Blind Treatment [ Time Frame: After 12 months of treatment ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who at Any Time During Double-Blind Treatment Were Given 2 or More Courses of High-Dose Steroids [ Time Frame: After 12 months of treatment ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants Given Rescue Medication Therapy During Double-Blind Treatment [ Time Frame: After 12 months of treatment ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Modified Therapy During Double-Blind Treatment [ Time Frame: After 12 months of treatment ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Lost Remission Status [ Time Frame: After 12 months of treatment ] [ Designated as safety issue: No ]
    Loss of remission is defined as DAS 28 CRP >=2.6.

  • Steady-state Trough Serum Concentration (Cmin) of Abatacept During Double-Blind Treatment [ Time Frame: Day 701 of the main study; sub-study Days 1, 85, 169, 253 ] [ Designated as safety issue: No ]
  • Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations During Double-Blind Treatment [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants With Infection and Infestation AEs Reported During Double-Blind Treatment [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants With Malignant Neoplasms Reported During Double-Blind Treatment [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
    All neoplasms were assessed by medical review as to whether or not the event was malignant.

  • Percentage of Participants With Prespecified Acute Infusional Adverse Events (AIAEs) During Double-Blind Treatment, by Intensity [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants With Prespecified Peri-Infusional Adverse Events (PAIAEs) During Double-Blind Treatment, by Intensity [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants With Pre-specified Autoimmune Disorders (ADs) Reported During Double-Blind Treatment, by Intensity [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
    A total of 127 autoimmune disorders were prespecified in the protocol. MCTD=Musculoskeletal and Connective Tissue Disorders

  • Percentage of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During Double-Blind Treatment [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
    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.

  • Clinically Significant Changes in Vital Signs and Physical Findings [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
    Clinical significance was determined by investigator. Parameters include blood pressure, heart rate, respiration rate, and temperature.

  • Participants With Positive Antibody Responses to Abatacept (Electrochemiluminescence [ECL] Method) During Double-Blind Treatment [ Time Frame: After 12 months of treatment ] [ Designated as safety issue: Yes ]
    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'


Enrollment: 108
Study Start Date: April 2007
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Abatacept (10 mg/Kg) Drug: Abatacept
IV solution, IV, 10 mg/Kg, Once monthly, 1 year
Other Name: BMS-188667
Active Comparator: Abatacept (5 mg/Kg) Drug: Abatacept
IV solution, IV, 5 mg/Kg, Once monthly, 1 year
Other Name: BMS-188667

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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:

  • None
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00989235

Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00989235     History of Changes
Other Study ID Numbers: IM101-023 LT (Sub study), Eudrac # 2002-000784-26
Study First Received: October 2, 2009
Results First Received: May 12, 2011
Last Updated: June 18, 2011
Health Authority: Korea: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Poland: National Institute of Medicines
Russia: Ministry of Health of the Russian Federation
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Brazil: National Committee of Ethics in Research
Canada: Health Canada, Biologics and General Therapies Directorate, Regulatory Affairs Division Office of Clinical Trials Therapeutic Products Directorate
Mexico: Federal Commission for Sanitary Risks Protection
United States: Food and Drug Administration
Spain: Spanish Agency of Medicines

Keywords provided by Bristol-Myers Squibb:
NOS

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Abatacept
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 30, 2014