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Efficacy, Pharmacokinetics, Safety, and Immunogenicity Study of Abatacept Administered Subcutaneously to Treat Rheumatoid Arthritis in Japanese Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01001832
First received: October 26, 2009
Last updated: January 2, 2014
Last verified: January 2014
Results First Received: October 22, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Rheumatoid Arthritis
Interventions: Drug: Intravenous (IV) abatacept
Drug: Subcutaneous (SC) abatacept

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Study started 8 December 2009; short-term period ended 25 February 2011; long-term period ended 26 October 2012.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
171 participants were enrolled, 118 participants were randomized and treated in the short-term period.

Reporting Groups
  Description
Subcutaneous (SC) Abatacept, 125 mg

Short-term period: Participants received SC abatacept, 125 mg, injections weekly, after an intravenous (IV) abatacept loading dose on Day 1, based on body weight. Participants also received SC injections of placebo, with a loading dose of IV abatacept (and not IV placebo) administered on Day 1.

Long-term period: All participants received weekly SC abatacept, 125 mg, for 1 year (52 weeks) without any IV infusions (active or placebo).

Follow-up period was up to 168 days after the last dose of drug.

Intravenous (IV) Abatacept, 125 mg

Short-term period: Participants received IV abatacept, 125 mg, infusions on Days 1, 15, and 29, and every 28 days thereafter until Day 141. Participants also received subcutaneous (SC) injections of placebo.

Long-term period: All participants received weekly SC abatacept, 125 mg, for 1 year (52 weeks) without any IV infusions (active or placebo).

Follow-up period was up to 168 days after the last dose of drug.


Participant Flow for 3 periods

Period 1:   Short-term Period
    Subcutaneous (SC) Abatacept, 125 mg     Intravenous (IV) Abatacept, 125 mg  
STARTED     59     59  
COMPLETED     57     56  
NOT COMPLETED     2     3  
Adverse Event                 2                 3  

Period 2:   Long-term Period
    Subcutaneous (SC) Abatacept, 125 mg     Intravenous (IV) Abatacept, 125 mg  
STARTED     56 [1]   56  
COMPLETED     52     51  
NOT COMPLETED     4     5  
Adverse Event                 2                 1  
Withdrawal by Subject                 1                 0  
Lack of Efficacy                 0                 2  
Not specified                 1                 2  
[1] 1 participant completed the short term period but discontinued before start of the Long-term Period.

Period 3:   Follow-up Period
    Subcutaneous (SC) Abatacept, 125 mg     Intravenous (IV) Abatacept, 125 mg  
STARTED     52     51  
COMPLETED     34     30  
NOT COMPLETED     18     21  
Withdrawal by Subject                 1                 0  
Follow-up no longer required /protocol                 15                 20  
Not specified                 2                 1  



  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
Subcutaneous (SC) Abatacept, 125 mg

Short-term period: Participants received SC abatacept, 125 mg, injections weekly, after an intravenous (IV) abatacept loading dose on Day 1, based on body weight. Participants also received SC injections of placebo, with a loading dose of IV abatacept (and not IV placebo) administered on Day 1.

Long-term period: All participants received weekly SC abatacept, 125 mg, for 1 year (52 weeks) without any IV infusions (active or placebo).

Follow-up period was up to 168 days after the last dose of drug.

Intravenous (IV) Abatacept, 125 mg

Short-term period: Participants received IV abatacept, 125 mg, infusions on Days 1, 15, and 29, and every 28 days thereafter until Day 141. Participants also received subcutaneous (SC) injections of placebo.

Long-term period: All participants received weekly SC abatacept, 125 mg, for 1 year (52 weeks) without any IV infusions (active or placebo).

Follow-up period was up to 168 days after the last dose of drug.

Total Total of all reporting groups

Baseline Measures
    Subcutaneous (SC) Abatacept, 125 mg     Intravenous (IV) Abatacept, 125 mg     Total  
Number of Participants  
[units: participants]
  59     59     118  
Age  
[units: Years]
Mean ± Standard Deviation
  56.1  ± 12.3     55.2  ± 13.6     55.6  ± 12.9  
Gender  
[units: Participants]
     
Female     38     48     86  
Male     21     11     32  
Race/Ethnicity, Customized  
[units: Participants]
     
Japanese     58     59     117  
Asian (not Japanese)     1     0     1  
Duration of Disease  
[units: Years]
Mean ± Standard Deviation
  7.5  ± 9.2     5.3  ± 7.3     6.4  ± 8.3  
Duration of Disease Category  
[units: Participants]
     
<= 2 years     25     30     55  
>2 to <= 5 years     7     11     18  
>5 to <= 10 years     10     6     16  
>10 years     17     12     29  
Tender Joint Count [1]
[units: Number of joints]
Mean ± Standard Deviation
  20.9  ± 9.3     22.3  ± 9.9     21.6  ± 9.6  
Swollen Joint Count [2]
[units: Number of joints]
Mean ± Standard Deviation
  16.4  ± 7.0     17.6  ± 7.2     17.0  ± 7.1  
DAS28-CRP [3]
[units: Units on a scale]
Mean ± Standard Deviation
  5.62  ± 0.84     5.95  ± 0.91     5.79  ± 0.89  
HAQ Score [4]
[units: Units on a scale]
Mean ± Standard Deviation
  1.28  ± 0.690     1.32  ± 0.64     1.30  ± 0.66  
Methotrexate dose [5]
[units: mg/week]
Mean ± Standard Deviation
  7.3  ± 1.0     7.3  ± 1.0     7.3  ± 0.9  
[1] The number of joints the participant finds painful (tender) is counted by the investigator.
[2] the number of the participants' joints that the investigator observes is swollen.
[3] The Disease Activity Score 28 using C-Reactive Protein (DAS28-CRP) is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient’s global assessment of health (ranging from very good to very bad). These measures are then fed into a complex mathematical formula to produce the overall DAS (greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)
[4] The Health Assessment Questionnaire(HAQ) Disability Index (DI) assesses patients' functional ability by rating their abilities over the previous week. At least 2 questions are asked from each of 8 categories: dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities. Patients rate difficulty performing specific tasks: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The sum of the categories score (the highest scored item in the category) is divided by the number of categories answered, yielding a score from 0-3.
[5] The methotrexate dose is the calculated weekly total dose in the week ending at the first dose date of the Short-term Period.



  Outcome Measures
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1.  Primary:   Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Day 169 in Short Term Period   [ Time Frame: Day 169 ]

2.  Primary:   Percentage of Participants With Sustained American College of Rheumatology (ACR) Response at Day 533 in Long Term Period - All Randomized and Treated Participants During the Long Term Period   [ Time Frame: Day 533 ]

3.  Primary:   Mean Change From Baseline in HAQ-DI Score at Day 533 in Long Term Period   [ Time Frame: Baseline to Day 533 ]

4.  Primary:   Percentage of Participants With Health Assessment Questionnaire (HAQ) Response at Day 533 in Long Term Period   [ Time Frame: Day 533 ]

5.  Primary:   Mean Change in DAS28-CRP From Baseline at Day 533 in Long Term Period   [ Time Frame: Baseline to Day 533 ]

6.  Secondary:   Percentage of Participants With American College of Rheumatology 50 (ACR50) and American College of Rheumatology 70 (ACR70) Responses at Day 169 in Short Term Period   [ Time Frame: Day 169 ]

7.  Secondary:   Mean Change From Baseline in HAQ-DI Score at Day 169 in Short Term Period   [ Time Frame: Baseline to Day 169 ]

8.  Secondary:   Percentage of Participants With HAQ Response at Day 169 in the Short Term Period   [ Time Frame: Day 169 ]

9.  Secondary:   Mean Change From Baseline at Six Months in DAS28-CRP - All Treated Participants   [ Time Frame: Baseline to 6 Months ]

10.  Secondary:   Percentage of Participants With European League Against Rheumatism (EULAR)-Defined Low Disease Activity Score (LDAS) and EULAR-defined Remission (REM) at Day 169 in Short Term Period   [ Time Frame: Day 169 ]

11.  Secondary:   Percentage of Participants With European League Against Rheumatism (EULAR)-Defined Low Disease Activity Score (LDAS) and EULAR-defined Remission (REM) at Day 533 in Long Term Period   [ Time Frame: Day 533 ]

12.  Secondary:   Short-term Period: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, and Discontinuations Due to AEs   [ Time Frame: Baseline to Day 169 ]

13.  Secondary:   Long-term Period: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, and Discontinuations Due to AEs   [ Time Frame: Baseline to Day 533 and up to 56 days following last dose in Long-Term period ]

14.  Secondary:   Short-term Period: Number of Participants With Hematology Laboratory Values Meeting the Criteria for Marked Abnormality   [ Time Frame: Baseline to Day 169 ]

15.  Secondary:   Long-term Period: Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria   [ Time Frame: Baseline to Day 533 ]

16.  Secondary:   Short-term Period: Number of Participants With Liver and Kidney Function Laboratory Values Meeting the Criteria for Marked Abnormality   [ Time Frame: Baseline to Day 169 ]

17.  Secondary:   Short-term Period: Number of Participants With Electrolyte Laboratory Values Meeting the Criteria for Marked Abnormality   [ Time Frame: Baseline to Day 169 ]

18.  Secondary:   Long-term Period: Number of Participants With Liver and Kidney Function Laboratory Values Meeting the Criteria for Marked Abnormality   [ Time Frame: Baseline to Day 533 ]

19.  Secondary:   Long-term Period: Number of Participants With Electrolyte Laboratory Values Meeting the Criteria for Marked Abnormality   [ Time Frame: Baseline to Day 533 ]


  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
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  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


Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01001832     History of Changes
Other Study ID Numbers: IM101-250
Study First Received: October 26, 2009
Results First Received: October 22, 2012
Last Updated: January 2, 2014
Health Authority: Japan: Institutional Review Board
Japan: Pharmaceuticals and Medical Devices Agency