Trial record 1 of 1 for:    ulcerative colitis abatacept
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A Study of Abatacept in Patients With Active Ulcerative Colitis

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00410410
First received: December 11, 2006
Last updated: November 4, 2010
Last verified: November 2010
Results First Received: August 12, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Ulcerative Colitis
Interventions: Drug: abatacept (ABA)
Drug: placebo
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
In this study, a first cohort (Induction Period First Cohort, IP1C) of 490 participants was randomized and used for analysis of the primary endpoint. Following randomization of IP1C, a second cohort (IP2C) of 146 participants was randomized to provide a sufficient number of participants for the Maintenance Period.

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
Induction Period Cohort 1 (IP1C)-Abatacept (ABA) 30/~10 mg/kg During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
IP1C-ABA ~10 mg/kg During IP, abatacept was administered IV on Days IP-1,IP-15, IP-29, and IP-57 at a dose of ~10 mg/kg (weight-tiered).
IP1C-ABA 3 mg/kg During IP, abatacept was administered IV on Days IP-1, IP-15, IP-29, and IP-57 at a dose of 3 mg/kg (fixed dose).
IP1C-Placebo During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
IP Cohort 2 (IP2C)-ABA 30/~10 mg/kg During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
IP2C-ABA ~10 mg/kg During IP, abatacept was administered IV on Days IP-1,IP-15, IP-29, and IP-57 at a dose of ~10 mg/kg (weight-tiered).
ABA ~10 mg/kg, Maintenance Period (MP) During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
Placebo, MP During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
ABA ~10 mg/kg, Open-Label Period (OL) During OL, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day OL-1.

Participant Flow for 3 periods

Period 1:   Induction Period (IP)
    Induction Period Cohort 1 (IP1C)-Abatacept (ABA) 30/~10 mg/kg     IP1C-ABA ~10 mg/kg     IP1C-ABA 3 mg/kg     IP1C-Placebo     IP Cohort 2 (IP2C)-ABA 30/~10 mg/kg     IP2C-ABA ~10 mg/kg     ABA ~10 mg/kg, Maintenance Period (MP)     Placebo, MP     ABA ~10 mg/kg, Open-Label Period (OL)  
STARTED     141     139     70     140     51     50     0     0     0  
COMPLETED     106     104     53     120     19     21     0     0     0  
NOT COMPLETED     35     35     17     20     32     29     0     0     0  
Death                 1                 0                 0                 0                 0                 0                 0                 0                 0  
Adverse Event                 3                 4                 2                 4                 1                 0                 0                 0                 0  
Lack of Efficacy                 26                 24                 8                 8                 7                 7                 0                 0                 0  
Lost to Follow-up                 2                 2                 2                 3                 0                 1                 0                 0                 0  
Withdrawal by Subject                 3                 5                 3                 5                 2                 0                 0                 0                 0  
Subject No Longer Meets Study Criteria                 0                 0                 1                 0                 0                 0                 0                 0                 0  
Poor/Non-compliance                 0                 0                 0                 0                 0                 0                 0                 0                 0  
Pregnancy                 0                 0                 0                 0                 0                 0                 0                 0                 0  
Administrative Reason By Sponsor                 0                 0                 0                 0                 22                 21                 0                 0                 0  
Other                 0                 0                 1                 0                 0                 0                 0                 0                 0  

Period 2:   Maintenance Period (MP)
    Induction Period Cohort 1 (IP1C)-Abatacept (ABA) 30/~10 mg/kg     IP1C-ABA ~10 mg/kg     IP1C-ABA 3 mg/kg     IP1C-Placebo     IP Cohort 2 (IP2C)-ABA 30/~10 mg/kg     IP2C-ABA ~10 mg/kg     ABA ~10 mg/kg, Maintenance Period (MP)     Placebo, MP     ABA ~10 mg/kg, Open-Label Period (OL)  
STARTED     0     0     0     0     0     0     65 [1]   66 [2]   0  
COMPLETED     0     0     0     0     0     0     15     11     0  
NOT COMPLETED     0     0     0     0     0     0     50     55     0  
Death                 0                 0                 0                 0                 0                 0                 1                 0                 0  
Adverse Event                 0                 0                 0                 0                 0                 0                 1                 3                 0  
Lack of Efficacy                 0                 0                 0                 0                 0                 0                 25                 24                 0  
Lost to Follow-up                 0                 0                 0                 0                 0                 0                 1                 2                 0  
Withdrawal by Subject                 0                 0                 0                 0                 0                 0                 1                 1                 0  
Administrative Reason By Sponsor                 0                 0                 0                 0                 0                 0                 21                 25                 0  
[1] At end of IP, 65 participants met response criteria and were randomly assigned to abatacept in MP.
[2] At end of IP, 66 participants met response criteria and were randomly assigned to placebo in MP.

Period 3:   Open-Label Period (OL)
    Induction Period Cohort 1 (IP1C)-Abatacept (ABA) 30/~10 mg/kg     IP1C-ABA ~10 mg/kg     IP1C-ABA 3 mg/kg     IP1C-Placebo     IP Cohort 2 (IP2C)-ABA 30/~10 mg/kg     IP2C-ABA ~10 mg/kg     ABA ~10 mg/kg, Maintenance Period (MP)     Placebo, MP     ABA ~10 mg/kg, Open-Label Period (OL)  
STARTED     0     0     0     0     0     0     0     0     349 [1]
COMPLETED     0     0     0     0     0     0     0     0     0  
NOT COMPLETED     0     0     0     0     0     0     0     0     349  
Death                 0                 0                 0                 0                 0                 0                 0                 0                 1  
Adverse Event                 0                 0                 0                 0                 0                 0                 0                 0                 10  
Lack of Efficacy                 0                 0                 0                 0                 0                 0                 0                 0                 161  
Lost to Follow-up                 0                 0                 0                 0                 0                 0                 0                 0                 4  
Withdrawal by Subject                 0                 0                 0                 0                 0                 0                 0                 0                 20  
Pregnancy                 0                 0                 0                 0                 0                 0                 0                 0                 1  
Administrative Reason By Sponsor                 0                 0                 0                 0                 0                 0                 0                 0                 145  
Other                 0                 0                 0                 0                 0                 0                 0                 0                 7  
[1] 349 entered OL (those who completed IP but failed response criteria, or completed/relapsed on MP).



  Baseline Characteristics
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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.
No text entered.

Reporting Groups
  Description
Induction Period Cohort 1 (IP1C)-ABA 30/~10 mg/kg During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg.
IP1C-ABA ~10 mg/kg During IP, abatacept was administered IV on Days IP-1,IP-15, IP-29,and IP-57 at a dose of ~10 mg/kg (weight-tiered).
IP1C-ABA 3 mg/kg During IP, abatacept was administered IV on Days IP-1, IP-15, IP-29, and IP-57 at a dose of 3 mg/kg (fixed dose).
IP1C-Placebo During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
IP Cohort 2 (IP2C)-ABA 30/~10 mg/kg During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg.
IP2C-ABA ~10 mg/kg During IP, abatacept was administered IV on Days IP-1,IP-15, IP-29,and IP-57 at a dose of ~10 mg/kg (weight-tiered).
Total Total of all reporting groups

Baseline Measures
    Induction Period Cohort 1 (IP1C)-ABA 30/~10 mg/kg     IP1C-ABA ~10 mg/kg     IP1C-ABA 3 mg/kg     IP1C-Placebo     IP Cohort 2 (IP2C)-ABA 30/~10 mg/kg     IP2C-ABA ~10 mg/kg     Total  
Number of Participants  
[units: participants]
  141     139     70     140     51     50     591  
Age, Customized  
[units: participants]
             
<30 years     26     23     18     34     12     4     117  
30-50 years     70     84     35     73     30     32     324  
>50 years     45     32     17     33     9     14     150  
Gender  
[units: participants]
             
Female     57     52     26     66     21     26     248  
Male     84     87     44     74     30     24     343  
Region of Enrollment  
[units: participants]
             
United States     43     42     22     55     20     13     195  
Ireland     1     0     0     1     0     1     3  
Italy     7     6     2     3     2     1     21  
Switzerland     1     1     1     2     1     0     6  
United Kingdom     0     0     0     3     2     4     9  
India     12     12     10     10     5     2     51  
France     7     12     6     6     1     5     37  
Czech Republic     0     1     0     0     0     0     1  
Mexico     20     14     10     8     7     9     68  
Puerto Rico     0     1     0     1     0     0     2  
Canada     9     12     2     13     1     3     40  
Brazil     10     5     5     11     4     6     41  
Poland     2     2     0     1     1     0     6  
Belgium     4     6     1     5     0     1     17  
Australia     8     7     4     13     1     1     34  
South Africa     9     8     5     3     2     0     27  
Germany     2     2     0     1     2     2     9  
Netherlands     2     5     1     2     2     1     13  
Korea, Republic of     4     3     1     2     0     1     11  
Participants with Inadequate Response/Intolerance to Prior Anti-Tumor (TNF) Therapy (Infliximab) [1]
[units: participants]
             
Inadequate Response/Intolerant to prior Infliximab     45     46     24     45     21     21     202  
No Inadequate Response/Intolerance to Infliximab     96     93     46     95     30     29     389  
[1] Prior to this study, participants had an inadequate response and/or intolerance to an approved anti-TNF agent at an approved labeled dose for at least 8 weeks. Inadequate response was assessed by the treating physician and was primarily due to lack of efficacy. Because the treating physician determined prior inadequate response, there was no standard definition for this and criteria for determination may have varied between institutions. Intolerance was defined a an inability to achieve doses or treatment durations because of dose limiting side effects.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Induction Period (IP); Number of Participants With Clinical Response (Per Mayo Score) at Week 12: IP Cohort 1 (IP1C)   [ Time Frame: Week 12 (Day IP-85) ]

2.  Primary:   Maintenance Period (MP); Number of Participants With Clinical Response (Per Mayo Score) at Month 12   [ Time Frame: Month 12 (Day MP-365) ]

3.  Primary:   Open-Label Extension Period (OL); Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and AEs Leading to Discontinuation   [ Time Frame: Day OL-1 through the end of the OL ]

4.  Primary:   OL; Number of Participants With AEs of Special Interest   [ Time Frame: Day OL-1 through Day OL-729 ]

5.  Primary:   OL; Number of Participants With Physical Examination Findings   [ Time Frame: Day OL-1 through Day OL-729 ]

6.  Primary:   OL; Number of Participants With Marked Hematology Laboratory Abnormalities   [ Time Frame: Day OL-1 through Day OL-729 ]

7.  Primary:   OL; Number of Participants With Liver and Kidney Function and Electrolyte Laboratory Abnormalities   [ Time Frame: Day OL-1 through Day OL-729 ]

8.  Primary:   OL; Number of Participants With Chemistry and Urinalysis Laboratory Abnormalities   [ Time Frame: Day OL-1 through Day OL-729 ]

9.  Secondary:   IP; Baseline Mayo Score: IP1C   [ Time Frame: Baseline ]

10.  Secondary:   IP; Number of Participants in Clinical Remission (Per Mayo Score) at Week 12: IP1C   [ Time Frame: Week 12 (Day IP-85) ]

11.  Secondary:   IP; Number of Participants in Mucosal Healing (Per Mayo Score) at Week 12: IP1C   [ Time Frame: Week 12 (Day IP-85) ]

12.  Secondary:   IP; Number of Participants With Clinical Response (Per Mayo Score) at Week 12 Analyzed by Cochran-Armitage Trend Test for Dose-Response Relationship: IP1C   [ Time Frame: Week 12 (Day IP-85) ]

13.  Secondary:   IP; Baseline Inflammatory Bowel Disease Questionnaire (IBDQ) Score: IP1C   [ Time Frame: Baseline ]

14.  Secondary:   IP; Mean Change From Baseline To Week 12 in Inflammatory Bowel Disease Questionnaire (IBDQ): IP1C   [ Time Frame: Baseline (Day IP-1), Day IP-85 (Week 12) ]

15.  Secondary:   IP; Number of Participants With Mayo Rectal Bleeding Subscores Indicating Mild Disease (≤1 Point) at Week 12: IP1C   [ Time Frame: Day IP-85 (Week 12) ]

16.  Secondary:   IP; Number of Participants With Mayo Stool Frequency Subscores Indicating Mild Disease (≤1 Point) at Week 12: IP1C   [ Time Frame: Day IP-85 (Week 12) ]

17.  Secondary:   IP; Number of Participants With Mayo Physician Global Assessment (PGA) Subscores Indicating Mild Disease (≤1 Point) at Week 12: IP1C   [ Time Frame: Day IP-85 (Week 12) ]

18.  Secondary:   IP; Number of Participants Who Are Anti-TNF-Inadequate Responders/Anti-TNF Intolerant With Clinical Response At Week 12 Analyzed by Cochran-Armitage Trend Test for Dose-Response Relationship: IP1C   [ Time Frame: Week 12 (Day IP-85) ]

19.  Secondary:   IP; Number of Participants With Clinical Response At Week 12 Among Participants With Anti-TNF (Infliximab) Failure/Intolerance: IP1C   [ Time Frame: Week 12 (Day IP-85) ]

20.  Secondary:   IP; Number of Participants in Clinical Remission at Week 12 Among Participants With Anti-TNF (Infliximab) Failure/Intolerance: IP1C   [ Time Frame: Week 12 (Day IP-85) ]

21.  Secondary:   IP; Number of Participants in Mucosal Healing at Week 12 Among Participants With Anti-TNF (Infliximab) Failure/Intolerance: IP1C   [ Time Frame: Week 12 (Day IP-85) ]

22.  Secondary:   IP; Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and AEs Leading to Discontinuation: IP1C + IP2C   [ Time Frame: Day IP-1 through Day IP-85 ]

23.  Secondary:   IP; Number of Participants With AEs Of Special Interest: IP1C + IP2C   [ Time Frame: Day IP-1 through Day IP-85 ]

24.  Secondary:   IP; Number of Participants With Physical Examination Findings: IP1C + IP2C   [ Time Frame: Day IP-1 through Day IP-85 ]

25.  Secondary:   IP; Number of Participants With Marked Hematology Laboratory Abnormalities: IP1C   [ Time Frame: Day IP-1 through Day IP-85 ]

26.  Secondary:   IP; Number of Participants With Marked Liver and Kidney Function and Electrolyte Laboratory Abnormalities: IP1C   [ Time Frame: Day IP-1 through Day IP-85 ]

27.  Secondary:   IP; Number of Participants With Marked Chemistry and Urinalysis Laboratory Abnormalities: IP1C   [ Time Frame: Day IP-1 through Day IP-85 ]

28.  Secondary:   IP; Number of Participants With Marked Hematology, Liver and Kidney Function, and Electrolyte Laboratory Abnormalities: IP2C   [ Time Frame: Day IP-1 through Day IP-85 ]

29.  Secondary:   IP; Number of Participants With Marked Chemistry and Urinalysis Laboratory Abnormalities: IP2C   [ Time Frame: Day IP-1 through Day IP-85 ]

30.  Secondary:   IP; Number of Participants With Abatacept-Induced Antibodies: IP1C + IP2C   [ 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) ]

31.  Secondary:   MP; Number of Participants in Clinical Remission at Month 12   [ Time Frame: Month 12 (Day MP-365) ]

32.  Secondary:   MP; Number of Participants With Mayo Endoscopic Subscores Indicating Mucosal Healing (≤1 Point) at Month 12   [ Time Frame: Month 12 (Day MP-365) ]

33.  Secondary:   MP; Number of Participants in Clinical Remission at Both Month 6 and Month 12   [ Time Frame: Month 6 (Day MP-169), Month 12 (Day MP-365) ]

34.  Secondary:   MP; Number of Participants With Baseline Oral Corticosteroid Use Who Have Discontinued Corticosteroids and Achieved Clinical Remission by Month 12   [ Time Frame: Day MP-365 (Month 12) ]

35.  Secondary:   MP; Mean Change From Baseline to Month 12 in IBDQ   [ Time Frame: Day MP-365 ]

36.  Secondary:   MP; Mean Change From Baseline to Month 12 in Short Form-36 (SF-36)   [ Time Frame: Day MP-365 ]

37.  Secondary:   MP; Number of Participants With Baseline Oral Corticosteroid Use Who Have Discontinued Corticosteroids for 90 Consecutive Days and Achieved Clinical Remission by Month 12   [ Time Frame: Day MP-365 (Month 12) ]

38.  Secondary:   MP; Number of Participants With Mayo Rectal Bleeding Subscores Indicating Mild Disease (≤1 Point) at Month 12   [ Time Frame: Day MP-365 (Month 12) ]

39.  Secondary:   MP; Number of Participants With Mayo Stool Frequency Subscores Indicating Mild Disease (≤1 Point) at Month 12   [ Time Frame: Day MP-365 (Month 12) ]

40.  Secondary:   MP; Number of Participants With Mayo PGA Subscores Indicating Mild Disease (≤1 Point) at Month 12   [ Time Frame: Day MP-365 (Month 12) ]

41.  Secondary:   MP; Number of Participants With Clinical Response at Month 12 Among Participants With Inadequate Response/Intolerance to Prior Anti-TNF Therapy (Infliximab)   [ Time Frame: Month 12 (Day MP-365) ]

42.  Secondary:   MP; Number of Participants With Clinical Remission at Month 12 Among Participants With Inadequate Response/Intolerance to Prior Anti-TNF Therapy (Infliximab)   [ Time Frame: Month 12 (Day MP-365) ]

43.  Secondary:   MP; Number of Participants With Clinical Mucosal Healing at Month 12 Among Participants With Inadequate Response/Intolerance to Prior Anti-TNF Therapy (Infliximab)   [ Time Frame: Month 12 (Day MP-365) ]

44.  Secondary:   MP; Number of Participants With Abatacept-Induced Antibodies   [ Time Frame: For participants not entering OL: All measurements starting 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). ]

45.  Secondary:   MP; Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and AEs Leading to Discontinuation   [ Time Frame: Day MP-1 through Day MP-365 ]

46.  Secondary:   MP; Number of Participants With AEs of Special Interest   [ Time Frame: Day MP-1 through Day MP-365 ]

47.  Secondary:   MP; Number of Participants With Physical Examination Findings   [ Time Frame: Day IP-85 through Day MP-365 ]

48.  Secondary:   MP; Number of Participants With Marked Hematology Laboratory Abnormalities   [ Time Frame: Day IP-85 through Day MP-365 ]

49.  Secondary:   MP; Number of Participants With Marked Chemistry and Urinalysis Laboratory Abnormalities   [ Time Frame: Day IP-85 through Day MP-365 ]

50.  Secondary:   OL; Number of Participants With Clinical Response Over Time   [ Time Frame: Day OL-1 through Day OL-729 ]

51.  Secondary:   OL; Number of Participants With Clinical Remission Over Time   [ Time Frame: Day OL-1 through Day OL-729 ]

52.  Secondary:   OL; Number of Participants With Mayo Endoscopic Subscores Indicating Mucosal Healing (≤1 Point) During OL   [ Time Frame: Open-Label Period (Day OL-1 through Day OL-729) ]

53.  Secondary:   OL; Number of Participants With Clinical Response or Clinical Remission Upon Retreatment With Abatacept Among Those Who Received Abatacept in the IP or MP Period   [ Time Frame: Last Study Visit (Day OL-729) ]

54.  Secondary:   OL; Number of Participants With Abatacept-Induced Antibodies   [ 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) ]

55.  Secondary:   OL; Number of Participants Using Corticosteroids During OL   [ Time Frame: Day OL-1 through Day OL-729 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
This study was terminated after review of the IP1C results due to lack of efficacy. Enrollment for the MP and for IP2C was not completed. Participants in MP, IP2C, and OL were early terminated at the time of study termination.


  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: 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: NCT00410410     History of Changes
Other Study ID Numbers: IM101-108
Study First Received: December 11, 2006
Results First Received: August 12, 2010
Last Updated: November 4, 2010
Health Authority: United States: Food and Drug Administration