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A Study of Abatacept in Patients With Active Crohn's Disease

This study has been terminated.
(Sponsor Decision)
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00406653
First received: December 1, 2006
Last updated: September 10, 2010
Last verified: September 2010
History of Changes
Results First Received: July 30, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Crohn's Disease
Interventions: Drug: abatacept
Drug: placebo

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Abatacept (ABA) 30/~10 mg/kg, Induction Period (IP) During IP, abatacept administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (10 mg/kg group).
ABA ~10 mg/kg, IP During IP, abatacept administered IV on Days IP-1, IP-15, IP-29, and IP-57 at a dose of ~10 mg/kg (weight-tiered).
ABA 3 mg/kg, IP During IP, abatacept administered IV on Days IP-1, IP-15, IP-29, and IP-57 at a dose of 3 mg/kg (fixed dose).
Placebo, IP During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
ABA ~10 mg/kg, Maintenance Period (MP) During MP, abatacept administered IV at a dose of ~10 mg/kg (weight-tiered dosing) every 28 days starting Day MP-1.
Placebo, MP During MP, placebo was administered IV at 28-day intervals starting on Day MP-1.
ABA ~10 mg/kg, Open-Label Period (OL) During OL, abatacept administered IV at a dose of ~10 mg/kg (weight-tiered dosing) every 28 days starting Day OL-1.

Participant Flow for 3 periods

 Period 1:   Induction Period
    Abatacept (ABA) 30/~10 mg/kg, Induction Period (IP)     ABA ~10 mg/kg, IP     ABA 3 mg/kg, IP     Placebo, IP     ABA ~10 mg/kg, Maintenance Period (MP)     Placebo, MP     ABA ~10 mg/kg, Open-Label Period (OL)  
STARTED     65     128     130     128     0     0     0  
COMPLETED     50     94     112     102     0     0     0  
NOT COMPLETED     15     34     18     26     0     0     0  
Adverse Event                 1                 10                 4                 11                 0                 0                 0  
Lack of Efficacy                 11                 14                 8                 10                 0                 0                 0  
Lost to Follow-up                 0                 2                 0                 0                 0                 0                 0  
Withdrawal of Consent                 2                 5                 1                 2                 0                 0                 0  
Subject No Longer Meets Study Criteria                 0                 0                 0                 2                 0                 0                 0  
Pregnancy                 1                 0                 0                 0                 0                 0                 0  
Declined participation but followup done                 0                 2                 1                 1                 0                 0                 0  
Given prohibited drug                 0                 1                 2                 0                 0                 0                 0  
Incarcerated                 0                 0                 1                 0                 0                 0                 0  
Patient relocated                 0                 0                 1                 0                 0                 0                 0  

Period 2:   Maintenance Period
    Abatacept (ABA) 30/~10 mg/kg, Induction Period (IP)     ABA ~10 mg/kg, IP     ABA 3 mg/kg, IP     Placebo, IP     ABA ~10 mg/kg, Maintenance Period (MP)     Placebo, MP     ABA ~10 mg/kg, Open-Label Period (OL)  
STARTED     0     0     0     0     44 [1]   46 [2]   0  
COMPLETED     0     0     0     0     14     10     0  
NOT COMPLETED     0     0     0     0     30     36     0  
Adverse Event                 0                 0                 0                 0                 1                 1                 0  
Lack of Efficacy                 0                 0                 0                 0                 20                 26                 0  
Lost to Follow-up                 0                 0                 0                 0                 2                 1                 0  
Withdrawal of Consent                 0                 0                 0                 0                 2                 0                 0  
Pregnancy                 0                 0                 0                 0                 0                 1                 0  
Administrative Reason By Sponsor                 0                 0                 0                 0                 4                 7                 0  
Error in disease score evaluation                 0                 0                 0                 0                 1                 0                 0  
[1] At end of IP, 44 participants met response criteria and were randomly assigned to abatacept in MP.
[2] At end of IP, 46 participants met response criteria and were randomly assigned to placebo in MP.

Period 3:   Open-Label Period
    Abatacept (ABA) 30/~10 mg/kg, Induction Period (IP)     ABA ~10 mg/kg, IP     ABA 3 mg/kg, IP     Placebo, IP     ABA ~10 mg/kg, Maintenance Period (MP)     Placebo, MP     ABA ~10 mg/kg, Open-Label Period (OL)  
STARTED     0     0     0     0     0     0     324 [1]
COMPLETED     0     0     0     0     0     0     0  
NOT COMPLETED     0     0     0     0     0     0     324  
Death                 0                 0                 0                 0                 0                 0                 1  
Adverse Event                 0                 0                 0                 0                 0                 0                 18  
Lack of Efficacy                 0                 0                 0                 0                 0                 0                 160  
Lost to Follow-up                 0                 0                 0                 0                 0                 0                 6  
Withdrawal of Consent                 0                 0                 0                 0                 0                 0                 11  
Subject No Longer Meets Study Criteria                 0                 0                 0                 0                 0                 0                 1  
Pregnancy                 0                 0                 0                 0                 0                 0                 2  
Administrative Reason By Sponsor                 0                 0                 0                 0                 0                 0                 115  
Declined participation but followup done                 0                 0                 0                 0                 0                 0                 8  
Discontinued by Sponsor                 0                 0                 0                 0                 0                 0                 1  
Refused followup                 0                 0                 0                 0                 0                 0                 1  
[1] All completing IP but failing response criteria and those completing or relapsing on MP entered OL.



  Baseline Characteristics
  Hide Baseline Characteristics

Reporting Groups
  Description
ABA 30/~10 mg/kg, Induction Period (IP) During IP, abatacept administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (10 mg/kg group).
ABA ~10 mg/kg, IP During IP, abatacept administered IV on Days IP-1, IP-15, IP-29, and IP-57 at a dose of ~10 mg/kg (weight-tiered).
ABA 3 mg/kg, IP During IP, abatacept administered IV on Days IP-1, IP-15, IP-29, and IP-57 at a dose of 3 mg/kg (fixed dose).
Placebo, IP During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
Total Total of all reporting groups

Baseline Measures
    ABA 30/~10 mg/kg, Induction Period (IP)     ABA ~10 mg/kg, IP     ABA 3 mg/kg, IP     Placebo, IP     Total  
Number of Participants  
[units: participants]
 		  65     128     130     128     451  
Age  
[units: years]
Mean ± Standard Deviation 		  36.0  ± 11.12     38.6  ± 12.90     36.9  ± 13.35     38.0  ± 12.98     37.6  ± 12.81  
Age, Customized  
[units: Participants]
 		         
<30 years     23     37     51     41     152  
Between 30 and 50 years     35     64     57     64     220  
>50 years     7     27     22     23     79  
Gender  
[units: participants]
 		         
Female     38     78     78     83     277  
Male     27     50     52     45     174  
Region of Enrollment  
[units: participants]
 		         
United States     24     45     46     38     153  
Italy     0     5     5     5     15  
Switzerland     2     4     3     1     10  
India     1     3     2     2     8  
France     6     8     7     7     28  
Czech Republic     1     2     0     2     5  
Mexico     1     4     0     3     8  
Puerto Rico     1     0     0     2     3  
Canada     8     18     22     27     75  
Brazil     3     7     6     6     22  
Belgium     2     7     9     13     31  
Korea, Democratic People's Republic of     1     1     1     1     4  
Denmark     1     4     10     2     17  
Australia     6     10     13     13     42  
South Africa     5     5     1     2     13  
Germany     0     2     2     3     7  
Netherlands     3     3     3     1     10  
Inadequate Response/Intolerance to Prior Anti-Tumor Necrosis Factor (TNF) Agent Therapy [1]
[units: Participants]
 		         
Inadequate Response/Intolerance To Prior Agents     42     86     77     77     282  
No Inadequate Response/Intolerance To Prior Agents     23     42     53     51     169  
Crohn's Disease (CD) Duration [2]
[units: Years]
Mean ± Standard Deviation 		  8.4  ± 7.49     9.9  ± 8.74     9.2  ± 7.98     9.8  ± 8.29     9.5  ± 8.21  
Crohn's Disease Activity Index (CDAI) [3]
[units: points]
Mean ± Standard Deviation 		  320.6  ± 61.59     318.9  ± 65.08     317.9  ± 59.87     320.7  ± 72.09     319.4  ± 65.03  
Inflammatory Bowel Disease Questionnaire (IBDQ) Score [4]
[units: units on a scale]
Mean ± Standard Deviation 		  119.9  ± 26.22     117.3  ± 30.60     121.1  ± 28.0     119.6  ± 31.17     119.5  ± 29.36  
[1] Prior to this study, participants had an inadequate response and/or intolerance to an approved anti-tumor necrosis factor (TNF) agent at an approved labeled dose for at least 8 weeks.
[2] Clinical diagnosis of CD with active disease confirmed by endoscopic, histologic, or radiographic evidence using established diagnostic criteria.
[3] CDAI is a composite index consisting of a weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to ~600 points. Clinical response=CDAI reduction ≥100 points or absolute CDAI <150 points. Clinical remission=CDAI <150 points. Moderate to severe disease=CDAI ≥220 and ≤450 points.
[4] IBDQ was used to measure disease specific quality of life. The IBDQ consists of a self-administered 32-item questionnaire that evaluates quality of life across 4 dimensional scores: Bowel, Systemic, Social and Emotional. The response to each question can range from 1 to 7, with 1 indicating severe problem and 7 indicating normal health. The total IBDQ is computed as the sum of the responses to the individual IBDQ questions. The total score can range between 32 to 224 with higher scores indicating a better quality of life.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Induction Period (IP); Number of Participants With Crohn's Disease Activity Index (CDAI)-Defined Clinical Response at Both Day IP-57 and Day IP-85   [ Time Frame: At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12). ]
  Show Outcome Measure 1

2.  Primary:   Maintenance Period (MP); Number of Participants In CDAI-Defined Clinical Remission (CDAI <150) at Day MP-365 (12 Months)   [ Time Frame: Day MP-365 (12 months) of maintenance therapy ]
  Show Outcome Measure 2

3.  Primary:   Open-Label Extension Period (OL); Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and Discontinuation Due to AEs   [ Time Frame: Between Day OL-1 and Day OL-617 ]
  Show Outcome Measure 3

4.  Primary:   OL; Number of Participants With Adverse Events (AEs) of Special Interest   [ Time Frame: Between Day OL-1 and Day OL-617 ]
  Show Outcome Measure 4

5.  Secondary:   IP; Number of Participants in CDAI-defined Clinical Remission at Both Day IP-57 and Day IP-85 (Key Secondary Outcome)   [ Time Frame: At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12) of induction therapy ]
  Show Outcome Measure 5

6.  Secondary:   IP; Number of Participants With CDAI-Defined Clinical Response at Both Day IP-57 and Day IP-85 Analyzed by Cochran-Armitage Trend Test for Dose-Response Relationship   [ Time Frame: At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12) of induction therapy ]
  Show Outcome Measure 6

7.  Secondary:   IP; Change From Baseline to Day IP-85 In Inflammatory Bowel Disease Questionnaire (IBDQ)   [ Time Frame: Baseline, Day IP-85 ]
  Show Outcome Measure 7

8.  Secondary:   IP; Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and Discontinuation Due to AEs   [ Time Frame: Day IP-1 through Day IP-85 ]
  Show Outcome Measure 8

9.  Secondary:   IP; Number of Participants With Adverse Events (AEs) of Special Interest   [ Time Frame: Day IP-1 through Day IP-85 ]
  Show Outcome Measure 9

10.  Secondary:   IP; Number of Participants With Positive Antibody Response to Abatacept (ABA)   [ Time Frame: For participants treated in MP: Day IP-1 (Baseline) to Day MP-1 (Day IP-85); For participants treated in OL directly after IP: Day IP-1 to Day OL-1; For participants treated only in IP: All measurements after Day IP-1 (including follow-up visits) ]
  Show Outcome Measure 10

11.  Secondary:   IP; Number of Participants With CDAI-Defined Clinical Response at Both Day IP-57 and Day IP-85 Among Participants With Inadequate Response and/or Intolerance to Anti-Tumor Necrosis Factor (TNF)   [ Time Frame: At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12) of induction therapy ]
  Show Outcome Measure 11

12.  Secondary:   IP; Number of Participants in CDAI-Defined Clinical Remission at Both Day IP-57 and Day IP-85 Among Participants With Inadequate Response and/or Intolerance to Anti-TNF   [ Time Frame: At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12) of induction therapy ]
  Show Outcome Measure 12

13.  Secondary:   IP; Number of Participants Who Are Anti-TNF-Inadequate Responders/Anti-TNF Intolerant With CDAI-Defined Clinical Response at Both Day IP-57 and Day IP-85 Analyzed by Cochran-Armitage Trend Test for Dose-Response Relationship   [ Time Frame: At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12) of induction therapy ]
  Show Outcome Measure 13

14.  Secondary:   MP; Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and Discontinuation Due To AEs   [ Time Frame: Between Day IP-85 and Day MP-365 ]
  Show Outcome Measure 14

15.  Secondary:   MP; Number of Participants With Adverse Events (AEs) of Special Interest:   [ Time Frame: Between Day IP-85 and Day MP-365 ]
  Show Outcome Measure 15

16.  Secondary:   MP; Number of Participants With Positive Antibody Response to Abatacept   [ Time Frame: For participants not entering OL: All measurements after Day MP-1 (including follow-up visits); For participants entering OL: From first measurement after Day MP-1 to Day MP-365 (Day OL-1) ]
  Show Outcome Measure 16

17.  Secondary:   MP; Number of Participants With CDAI-defined Clinical Response at Day MP-365.   [ Time Frame: Day MP-365 ]
  Show Outcome Measure 17

18.  Secondary:   MP; Number of Participants in CDAI-defined Clinical Remission at Both Day MP-169 and Day MP-365   [ Time Frame: Day MP-169 ]
  Hide Outcome Measure 18

Measure Type Secondary
Measure Title MP; Number of Participants in CDAI-defined Clinical Remission at Both Day MP-169 and Day MP-365
Measure Description CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant’s Diary kept while on study. CDAI scores range from 0 to ~600 points. Clinical response=CDAI reduction ≥100 points or absolute CDAI <150 points. Clinical remission=CDAI <150 points. Moderate to severe disease=CDAI ≥220 and ≤450 points.
Time Frame Day MP-169  
Safety Issue No  

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.
Due to the early termination of the study after the IP results were reviewed and the primary efficacy endpoint was not achieved, the secondary endpoint analysis for the cohort of participants with clinical remission at both Day MP-169 and Day MP-365 was not conducted for the MP as planned.

Reporting Groups
  Description
ABA ~10 mg/kg, MP During MP, abatacept administered IV at a dose of ~10 mg/kg (weight-tiered dosing) every 28 days starting Day MP-1.
Placebo, MP During MP, placebo was administered IV at 28-day intervals starting on Day MP-1.

Measured Values
    ABA ~10 mg/kg, MP     Placebo, MP  
Number of Participants Analyzed  
[units: participants]
 		  0     0  
MP; Number of Participants in CDAI-defined Clinical Remission at Both Day MP-169 and Day MP-365  
[units: participants]
 		       

No statistical analysis provided for MP; Number of Participants in CDAI-defined Clinical Remission at Both Day MP-169 and Day MP-365



19.  Secondary:   MP; Change From Baseline to Day MP-365 in Short Form-36 (SF-36)   [ Time Frame: Baseline, Day MP-365 ]
  Show Outcome Measure 19

20.  Secondary:   MP; Change From Baseline to Day MP-365 in Inflammatory Bowel Disease Questionnaire (IBDQ)   [ Time Frame: Baseline, Day MP-365 ]
  Show Outcome Measure 20

21.  Secondary:   MP; Number of Participants Who Were Not On Background Corticosteroid Therapy at Day MP-365 Among All Participants Who Received Baseline Corticosteroid Therapy   [ Time Frame: Day MP-365 ]
  Show Outcome Measure 21

22.  Secondary:   MP; Number of Participants Who Were Not On Background Corticosteroid Therapy at Day MP-365 Among Participants Who Received Baseline Corticosteroid Therapy and Who Achieved CDAI-Defined Clinical Remission   [ Time Frame: Day MP-365 ]
  Show Outcome Measure 22

23.  Secondary:   MP; Number of Participants With CDAI-Defined Clinical Response Among Participants With Inadequate Response and/or Intolerance to Anti-Tumor Necrosis Factor (TNF)   [ Time Frame: Day MP-365 ]
  Show Outcome Measure 23

24.  Secondary:   MP; Number of Participants in CDAI-Defined Clinical Remission Among Participants With Inadequate Response and/or Intolerance to Anti-TNF   [ Time Frame: Day MP-365 ]
  Show Outcome Measure 24

25.  Secondary:   OL; Number of Participants Who Were Not On Background Corticosteroid Therapy Among All Participants Who Received Baseline Corticosteroid Therapy   [ Time Frame: Between Day OL-1 and Day OL-617 ]
  Show Outcome Measure 25

26.  Secondary:   OL; Number of Participants With CDAI-defined Clinical Response or Clinical Remission at Day OL-169   [ Time Frame: Day OL-169 ]
  Show Outcome Measure 26

27.  Secondary:   OL; Number of Participants With CDAI-defined Clinical Response or Clinical Remission at Day OL-365   [ Time Frame: Day OL-365 ]
  Show Outcome Measure 27

28.  Secondary:   OL; Number of Participants With Positive Antibody Response to Abatacept   [ Time Frame: For participants receiving OL medication, all measurements starting after Day OL-1 (including follow-up visits and at 56 and 85 days after last dose) ]
  Show Outcome Measure 28

29.  Secondary:   OL; Number of Participants With Pharmacogenomic Marker Activity   [ Time Frame: Between Day OL-1 and Day OL-617 ]
  Show Outcome Measure 29


  Serious Adverse Events
  Show Serious Adverse Events


  Other Adverse Events
  Show Other Adverse Events


  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.


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
No text entered.  


Results Point of Contact:  
Name/Title: BMS 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: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00406653     History of Changes
Other Study ID Numbers: IM101-084
Study First Received: December 1, 2006
Results First Received: July 30, 2010
Last Updated: September 10, 2010
Health Authority: United States: Food and Drug Administration