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Substudy - Low Dose of Abatacept in Subjects With Rheumatoid Arthritis

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ClinicalTrials.gov Identifier: NCT00989235
Recruitment Status : Completed
First Posted : October 5, 2009
Results First Posted : June 3, 2011
Last Update Posted : June 21, 2011
Sponsor:
Information provided by:
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE October 2, 2009
First Posted Date  ICMJE October 5, 2009
Results First Submitted Date  ICMJE May 12, 2011
Results First Posted Date  ICMJE June 3, 2011
Last Update Posted Date June 21, 2011
Study Start Date  ICMJE April 2007
Actual Primary Completion Date October 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 18, 2011)
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 ]
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).
Original Primary Outcome Measures  ICMJE
 (submitted: October 2, 2009)
The primary objective is to assess the time to disease relapse for the abatacept 10 mg/kg and 5 mg/kg doses in subjects with early RA in remission (DAS 28 ESR < 2.6) who have received treatment with abatacept 10 mg/kg for at least one year [ Time Frame: After 12 months of Treatment ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 18, 2011)
  • Number of Participants Experiencing Disease Relapse [ Time Frame: After 12 Months of treatment ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
  • 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) ]
    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) ]
    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) ]
    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) ]
    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) ]
    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) ]
    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) ]
    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) ]
    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 ]
    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'
Original Secondary Outcome Measures  ICMJE
 (submitted: October 2, 2009)
  • Assess disease activity as measured by DAS28 CRP score monthly [ Time Frame: After 12 months of treatment ]
  • Assess proportion of subjects who in the 1st year modify therapy and/or have 2 consecutive DAS 28 CRP scores ≥ 3.2 for Additional DMARD therapy given; Two or more course of high dose steroids given; Return to abatacept 10 mg/kg (rescue medication given) [ Time Frame: After 12 months of treatment ]
  • Assess the proportion of subjects who at any time in the 1st year lose remission status [ Time Frame: After 12 months of treatment ]
  • Assess the steady-state trough serum concentration of abatacept in the two dose groups [ Time Frame: After 12 months of treatment ]
  • Determine the safety and tolerability of abatacept in this subject population [ Time Frame: After 12 months of treatment ]
  • Evaluation of immunogenicity of abatacept [ Time Frame: After 12 months of treatment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Substudy - Low Dose of Abatacept in Subjects With Rheumatoid Arthritis
Official Title  ICMJE 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
Brief 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • Drug: Abatacept
    IV solution, IV, 10 mg/Kg, Once monthly, 1 year
    Other Name: BMS-188667
  • Drug: Abatacept
    IV solution, IV, 5 mg/Kg, Once monthly, 1 year
    Other Name: BMS-188667
Study Arms  ICMJE
  • Active Comparator: Abatacept (10 mg/Kg)
    Intervention: Drug: Abatacept
  • Active Comparator: Abatacept (5 mg/Kg)
    Intervention: Drug: Abatacept
Publications * Westhovens R, Robles M, Ximenes AC, Wollenhaupt J, Durez P, Gomez-Reino J, Grassi W, Haraoui B, Shergy W, Park SH, Genant H, Peterfy C, Becker JC, Murthy B. Maintenance of remission following 2 years of standard treatment then dose reduction with abatacept in patients with early rheumatoid arthritis and poor prognosis. Ann Rheum Dis. 2015 Mar;74(3):564-8. doi: 10.1136/annrheumdis-2014-206149. Epub 2014 Dec 30.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 12, 2011)
108
Original Actual Enrollment  ICMJE
 (submitted: October 2, 2009)
124
Actual Study Completion Date  ICMJE October 2009
Actual Primary Completion Date October 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00989235
Other Study ID Numbers  ICMJE IM101-023 LT (Sub study)
Eudrac # 2002-000784-26
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Study Director, Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date June 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP