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Study to Assess Steady-State Trough Concentrations, Safety, and Immunogenicity of Abatacept After Subcutaneous (SC) Administration to Subjects With Rheumatoid Arthritis (RA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00254293
First received: November 15, 2005
Last updated: March 3, 2014
Last verified: March 2014
Results First Received: August 20, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Rheumatoid Arthritis
Interventions: Drug: Abatacept or Placebo (both as IV & SC Solution)
Drug: Abatacept or Placebo (both as IV & SC solution)
Drug: Abatacept

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Short term (12 week) randomized Period: started January 2006/completed May 2007. Long term extension (LTE): started April 2006/completed July 2012. During LTE: variable dose period and fixed dose period. Patients with active Rheumatoid Arthritis (RA) and receiving disease modifying anti-rheumatic drugs (DMARDS) were eligible to participate.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Enrolled/not treated (19): prior treatment not washed out; no longer met study criteria; withdrew consent before treatment. To enter LTE, participant completed the short term period, and was assigned to a variable SC dose group (75, 125, 200 mg SC abatacept) based on body weight; completers of variable dose LTE rolled over into fixed dose LTE.

Reporting Groups
  Description
Group 1: 500 mg IV/75 mg SC Short term (ST) randomized 12 week period: Abatacept or Placebo as intravenous (IV) and subcutaneous (SC) administration: Abatacept 500 mg IV (Day 1)/Abatacept 75 mg SC (once weekly for 12 weeks); body weight < 60 kg. Long term extension (LTE) variable dosing period: 75 mg abatacept SC administered weekly following an IV loading dose (IV abatacept for participants randomized to placebo in ST period, loading dose as described in group 1 description, or IV placebo for participants randomized to abatacept in ST period) on Day 85 (IV abatacept based on their weight at screening; < 60 kg received 500 mg abatacept IV, 60 - 100 kg received 750 mg abatacept IV, > 100 kg received 1000 mg abatacept IV for participants randomized to placebo in ST period)or, IV placebo for participants randomized to abatacept in ST period). At Day 365(1-year anniversary visit), subjects were reweighed for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period
Group 2: 500 mg IV/125 mg SC Short term (ST) randomized 12 week period: Abatacept 500 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo;body weight < 60 kg. Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period; loading dose described in Group 1 description, or IV placebo for participants randomized to abatacept in ST period). Variable Long term for 125 mg SC: body weight <60 to >100 kg. Participants reweighed at 1 year anniversary for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period
Group 3 : 750 mg IV/125 mg SC Short term (ST) randomized 12 week period: Abatacept 750 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo (body weight 60-100 kg). Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, loading dose described in Group 1 description, or IV placebo for participants randomized to abatacept in ST period). Variable Long term for 125 mg SC: body weight <60 to >100 kg). Participants reweighed at 1 year anniversary for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period.
Group 4: 1000mg IV/125 mg SC Short term (ST) randomized 12 week period: Abatacept 1000 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo; Body weight > 100 kg. Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, loading dose as described in group 1 description, or IV placebo for participants randomized to abatacept in ST period); variable long term for 125 mg SC: body weight <60 to >100 kg) . Participants reweighed at 1 year anniversary for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period.
Group 5: 1000 mg IV/200 mg SC Short term (ST) randomized 12 week period: Abatacept 1000 mg IV (Day 1)/Abatacept 200 mg SC (once weekly for 12 weeks) or Placebo; body weight > 100 kg. Long term extension (LTE) variable dosing period: 200 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, loading dose based on weight as described in Group 1 description, or IV placebo for participants randomized to abatacept in ST period). Participants reweighed at 1 year anniversary for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period
Placebo Short term (ST) randomized 12 week period: Placebo IV(Day 1)/Placebo SC (once weekly for 12 weeks), by body weight. Long term extension (LTE) variable dosing period: all placebo participants rolled over to a variable dose of abatacept SC (75, 125, 200 mg) administered weekly following an IV loading dose of abatacept on Day 85. Participants reweighed at 1 year anniversary for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period
Fixed Dose 125 mg Abatacept Participants who completed the variable dose long term extension (LTE)period and received variable doses of subcutaneous (SC) abatacept (75, 125, 200 mg SC) were rolled over into the LTE with fixed dose, irrespective of body weight: SC abatacept 125 milligram (mg) in pre-filled syringes, administered Weekly.

Participant Flow for 3 periods

Period 1:   Short Term (12 Week) Randomized Dosing
    Group 1: 500 mg IV/75 mg SC     Group 2: 500 mg IV/125 mg SC     Group 3 : 750 mg IV/125 mg SC     Group 4: 1000mg IV/125 mg SC     Group 5: 1000 mg IV/200 mg SC     Placebo     Fixed Dose 125 mg Abatacept  
STARTED     7     4     29     6     5     17 [1]   0  
COMPLETED     7     3     26     5     5     17     0  
NOT COMPLETED     0     1     3     1     0     0     0  
Adverse Event                 0                 1                 0                 1                 0                 0                 0  
Lost to Follow-up                 0                 0                 1                 0                 0                 0                 0  
poor/non-compliance by participant                 0                 0                 2                 0                 0                 0                 0  
[1] 2, 2, 9, 2, and 2 were randomized to placebo in body weight Groups 1, 2, 3, 4, 5, respectively.

Period 2:   LTE Open Label Variable SC Dosing
    Group 1: 500 mg IV/75 mg SC     Group 2: 500 mg IV/125 mg SC     Group 3 : 750 mg IV/125 mg SC     Group 4: 1000mg IV/125 mg SC     Group 5: 1000 mg IV/200 mg SC     Placebo     Fixed Dose 125 mg Abatacept  
STARTED     11 [1]   0 [2]   42 [3]   0 [2]   10 [4]   0 [5]   0 [6]
COMPLETED     8     0     32     0     8     0     0  
NOT COMPLETED     3     0     10     0     2     0     0  
Death                 0                 0                 1                 0                 0                 0                 0  
Adverse Event                 1                 0                 2                 0                 1                 0                 0  
Lack of Efficacy                 2                 0                 2                 0                 1                 0                 0  
Lost to Follow-up                 0                 0                 1                 0                 0                 0                 0  
Withdrawal by Subject                 0                 0                 1                 0                 0                 0                 0  
Poor or non-compliance                 0                 0                 1                 0                 0                 0                 0  
not specified                 0                 0                 2                 0                 0                 0                 0  
[1] Participants who received ST placebo rolled over to 75mg SC dose group (by body weight, <60kg).
[2] Participants rolled over to 125mg dose group summarized as one group (body weight <60 to >100 kg).
[3] Variable SC dose group: 125 mg Weekly, body weight <60 to >100kg (Groups 2, 3, 4 in ST Period).
[4] Participants who received ST placebo rolled over to variable SC dose group (by body weight, >100kg).
[5] Participants rolled over to a variable SC dose group of 75, 125 or 200 mg Weekly by body weight.
[6] Participant rolled over from LTE (Variable Dose Period) to LTE (Fixed Dose Period).

Period 3:   LTE Open Label Fixed Dosing
    Group 1: 500 mg IV/75 mg SC     Group 2: 500 mg IV/125 mg SC     Group 3 : 750 mg IV/125 mg SC     Group 4: 1000mg IV/125 mg SC     Group 5: 1000 mg IV/200 mg SC     Placebo     Fixed Dose 125 mg Abatacept  
STARTED     0     0     0     0     0     0     48  
COMPLETED     0     0     0     0     0     0     35  
NOT COMPLETED     0     0     0     0     0     0     13  
Death                 0                 0                 0                 0                 0                 0                 3  
Adverse Event                 0                 0                 0                 0                 0                 0                 1  
Lack of Efficacy                 0                 0                 0                 0                 0                 0                 3  
Lost to Follow-up                 0                 0                 0                 0                 0                 0                 1  
Withdrawal by Subject                 0                 0                 0                 0                 0                 0                 3  
Poor or non-compliance                 0                 0                 0                 0                 0                 0                 1  
not specified                 0                 0                 0                 0                 0                 0                 1  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Baseline includes all participants enrolled and treated. Baseline parameters are presented for each arm but the total value for baseline mean age and standard deviation (SD) includes all participants in LTE. Data are presented by treatment the participant actually received, not to what they were randomized to receive.

Reporting Groups
  Description
Group 1: 500 mg IV/75 mg SC (Body Weight < 60 kg) Short term (ST) randomized 12 week period: Abatacept or Placebo as intravenous (IV) and subcutaneous (SC) administration: Abatacept 500 mg IV (Day 1)/Abatacept 75 mg SC (once weekly for 12 weeks); Long term extension (LTE) variable dosing period: 75 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, IV placebo for participants randomized to abatacept in ST period).
Group 2: 500 mg IV/125 mg SC (Body Weight < 60 kg) Short term (ST) randomized 12 week period: Abatacept 500 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo. Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, IV placebo for participants randomized to abatacept in ST period).
Group 3 : 750 mg IV/125 mg SC (Body Weight 60-100 kg) Short term (ST) randomized 12 week period: Abatacept 750 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo. Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 ((IV abatacept for participants randomized to placebo in ST period, IV placebo for participants randomized to abatacept in ST period). Participants from Group 3 in ST period were rolled into Group 2 for LTE variable dosing period (125 mg SC abatacept).
Group 4: 1000mg IV/125 mg SC (Body Weight > 100 kg) Short term (ST) randomized 12 week period: Abatacept 1000 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo. Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, IV placebo for participants randomized to abatacept in ST period). Participants from Group 4 in ST period were rolled into Group 2 for LTE variable dosing period (125 mg SC abatacept).
Group 5: 1000 mg IV/200 mg SC (Body Weight > 100 kg) Short term (ST) randomized 12 week period: Abatacept 1000 mg IV (Day 1)/Abatacept 200 mg SC (once weekly for 12 weeks) or Placebo. Long term extension (LTE) variable dosing period: 200 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, IV placebo for participants randomized to abatacept in ST period).
Placebo Short term (ST) randomized 12 week period: Placebo IV(Day 1)/Placebo SC (once weekly for 12 weeks). Long term extension (LTE) variable dosing period: all placebo participants were rolled over to a variable dose of abatacept SC administered weekly following an IV loading dose of abatacept on Day 85.
Total Total of all reporting groups

Baseline Measures
    Group 1: 500 mg IV/75 mg SC (Body Weight < 60 kg)     Group 2: 500 mg IV/125 mg SC (Body Weight < 60 kg)     Group 3 : 750 mg IV/125 mg SC (Body Weight 60-100 kg)     Group 4: 1000mg IV/125 mg SC (Body Weight > 100 kg)     Group 5: 1000 mg IV/200 mg SC (Body Weight > 100 kg)     Placebo     Total  
Number of Participants  
[units: participants]
  7     4     29     6     5     17     68  
Age  
[units: years]
Mean ± Standard Deviation
  72  ± 5     64  ± 10     59  ± 12     51  ± 9     55  ± 9     59  ± 11     60  ± 11  
Gender  
[units: participants]
             
Female     7     3     26     5     4     12     57  
Male     0     1     3     1     1     5     11  
Region of Enrollment  
[units: participants]
             
United States     7     4     29     6     5     17     68  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Short Term Period: Steady-state Trough Serum Concentration (Cmin) of Abatacept Following Weekly Subcutaneous Dosing in Participants With Active Rheumatoid Arthritis Receiving Disease Modifying Anti-rheumatic Drugs (DMARDS)   [ Time Frame: Days 71 to 85 ]

2.  Primary:   Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Discontinuations Due to Adverse Events Reported During the Variable Dosing Phase of the Long Term Period (LTE)   [ Time Frame: Day 85 to 56 days post last dose ]

3.  Primary:   Number of Participants With Pre-specified AEs of Special Interest in the Variable Dosing Phase of Long Term Extension (LTE)   [ Time Frame: Day 85 to Day 533 ]

4.  Primary:   Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Discontinuations Due to Adverse Events Summarized Over the Entire Long Term Extension (LTE) Period (Both Variable and Fixed Dosing)   [ Time Frame: Day 533 to 56 Days Post last dose ]

5.  Secondary:   Short Term Period: Peak Serum Concentration (Cmax) of Abatacept at Steady State in Participants With Rheumatoid Arthritis Receiving DMARDS   [ Time Frame: Day 71 to Day 78 ]

6.  Secondary:   Short Term Period: Area Under the Curve (AUC) in Time Interval of 7 Days [AUC(TAU)] of Abatacept in Participants With Rheumatoid Arthritis Receiving DMARDS   [ Time Frame: Day 71 to Day 78 ]

7.  Secondary:   Short Term Period: Summary of Adverse Events (AEs), Serious AEs, Deaths, and Discontinuations Due to AEs During 12 Weeks of Treatment With Either Abatacept or Placebo   [ Time Frame: Day 1 to Day 85 (or early termination) ]

8.  Secondary:   Short Term Period: Number of Participants With Pre-specified Adverse Events (AEs) of Special Interest After Administration of Abatacept or Placebo Over 12 Weeks   [ Time Frame: Day 1 to Day 85 (or early termination) ]

9.  Secondary:   Short Term Period: Mean Percent Change From Baseline on Day 85 in Participants Positive for Serum Rheumatoid Factor During Abatacept or Placebo Administration   [ Time Frame: Day 1 to Day 85 (or early termination) ]

10.  Secondary:   Short Term Period: Number of Participants With Laboratory Abnormalities in Hematology at Baseline (Day 1) to End of Period (Day 85)   [ Time Frame: Day 1 to Day 85 (or early termination) ]

11.  Secondary:   Short Term Period: Number of Participants With Laboratory Abnormalities in Serum Chemistry at Baseline and on Treatment up to Day 85   [ Time Frame: Day 1 to Day 85 (or early termination) ]

12.  Secondary:   Short Term Period: Mean Change From Baseline at Day 85 in Blood Pressure After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS   [ Time Frame: Day 1 to Day 85 (or early termination) ]

13.  Secondary:   Short Term Period: Mean Change From Baseline at Day 85 in Pulse Rate After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS   [ Time Frame: Day 1 to Day 85 (or early termination) ]

14.  Secondary:   Short Term Period: Mean Change From Screening to Day 85 in Electrocardiogram (QT, PR Intervals, QRS Width) After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS   [ Time Frame: Screening to Day 85 (or early termination) ]

15.  Secondary:   Short Term Period: Mean Change From Screening at Day 85 in ECG (Heart Rate) After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS   [ Time Frame: Screening to Day 85 (or early termination) ]

16.  Secondary:   Overall Study ST and LTE Periods: Number of Participants With Anti-abatacept Antibodies and/or Anti-cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Antibodies   [ Time Frame: ST: Day 1 to Day 85; LTE: Day 85 to 168 days post last dose ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Error resulted in 4 participants being treated with study drug they were not randomized to receive. ST data were summarized by study drug participants actually received while LT data were summarized by what participants were randomized to receive.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


No publications provided by Bristol-Myers Squibb

Publications automatically indexed to this study:

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00254293     History of Changes
Other Study ID Numbers: IM101-063
Study First Received: November 15, 2005
Results First Received: August 20, 2013
Last Updated: March 3, 2014
Health Authority: United States: Food and Drug Administration