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Abatacept in the Treatment and Prevention of Active Systemic Lupus Erythematosus (SLE) Flares in Combination With Prednisone

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ClinicalTrials.gov Identifier: NCT00119678
Recruitment Status : Completed
First Posted : July 14, 2005
Results First Posted : May 9, 2011
Last Update Posted : September 22, 2014
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Condition: Systemic Lupus Erythematosus
Interventions: Drug: Abatacept
Drug: Placebo
Drug: Prednisone

  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
263 participants were enrolled in this study and 80 were excluded from the trial due to screening failure. Of the 183 randomized, 3 were not treated and 5 were treated but excluded due to site closure.

Reporting Groups
  Description
Abatacept Participants were administered intravenous (iv) infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, 29 and every 28 days thereafter up to and including Day 337. All participants received a dose based on screening visit weight. Prednisone or prednisone equivalent was administered at an initial oral dose of 30 mg once daily (OD). A standardized prednisone or prednisone equivalent taper procedure was followed whenever the participant's clinical features qualified for British Isles Lupus Assessment Group (BILAG) "C" or "D" status after Day 29. Participants who completed the double-blind period were eligible for the open-label long-term extension period, where all participants were reallocated to abatacept (regardless of randomized treatment in the double-blind period) according to body weight at study entry. Infusions continued every 28 days until abatacept was marketed for SLE or the drug development program discontinued.
Placebo Participants were administered iv infusions of either dextrose 5% solution or normal saline (NS) at a constant rate over approximately 30 minutes on Days 1, 15, 29 and every 28 days thereafter up to and including Day 337. Prednisone or prednisone equivalent was administered at an initial oral dose of 30 mg OD. A standardized prednisone or prednisone equivalent taper procedure was followed whenever the participant’s clinical features qualified for BILAG “C” or “D” status after Day 29. Participants who completed the double-blind period were eligible for the open-label long-term extension period, where all participants were reallocated to abatacept (regardless of randomized treatment in the double-blind period) according to body weight at study entry. Infusions continued every 28 days until abatacept was marketed for SLE or the drug development program discontinued.

Participant Flow for 2 periods

 Period 1:   Double-blind Treatment Period
    Abatacept   Placebo
STARTED   122   61 
RANDOMIZED AND TREATED   121   59 
RANDOMIZED,TREATED, AND ANALYZED   118   57 
COMPLETED   81   35 
NOT COMPLETED   41   26 
Death                1                0 
Adverse Event                7                1 
Lack of Efficacy                21                12 
Lost to Follow-up                1                2 
Participant withdrew consent                4                4 
Participants not meeting study criteria                0                1 
Poor/Non-compliance                3                0 
Pregnancy                0                2 
Not treated                1                2 
Site closed due to non-compliance                3                2 

Period 2:   Open-label Treatment Period
    Abatacept   Placebo
STARTED   110 [1]   0 
COMPLETED   0   0 
NOT COMPLETED   110   0 
Death                1                0 
Adverse Event                3                0 
Lack of Efficacy                9                0 
Lost to Follow-up                3                0 
Participant withdrew consent                4                0 
Participants not meeting study criteria                2                0 
Pregnancy                1                0 
Administrative reasons by sponsor                87                0 
[1] Number of participants treated



  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.
No text entered.

Reporting Groups
  Description
Abatacept Participants were administered intravenous (iv) infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, 29 and every 28 days thereafter up to and including Day 337. All participants received a dose based on screening visit weight. Prednisone or prednisone equivalent was administered at an initial oral dose of 30 mg once daily (OD). A standardized prednisone or prednisone equivalent taper procedure was followed whenever the participant's clinical features qualified for British Isles Lupus Assessment Group (BILAG) "C" or "D" status after Day 29. Participants who completed the double-blind period were eligible for the open-label long-term extension period, where all participants were reallocated to abatacept (regardless of randomized treatment in the double-blind period) according to body weight at study entry. Infusions continued every 28 days until abatacept was marketed for SLE or the drug development program discontinued.
Placebo Participants were administered iv infusions of either dextrose 5% solution or normal saline (NS) at a constant rate over approximately 30 minutes on Days 1, 15, 29 and every 28 days thereafter up to and including Day 337. Prednisone or prednisone equivalent was administered at an initial oral dose of 30 mg OD. A standardized prednisone or prednisone equivalent taper procedure was followed whenever the participant’s clinical features qualified for BILAG “C” or “D” status after Day 29. Participants who completed the double-blind period were eligible for the open-label long-term extension period, where all participants were reallocated to abatacept (regardless of randomized treatment in the double-blind period) according to body weight at study entry. Infusions continued every 28 days until abatacept was marketed for SLE or the drug development program discontinued.
Total Total of all reporting groups

Baseline Measures
   Abatacept   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 		 118   57   175 
Age [1] 
[Units: Years]
Median (Full Range) 		 38.0 
 (18.0 to 71.0)  		 36.0 
 (19.0 to 65.0)  		 38.0 
 (18.0 to 71.0) 
[1] 183 participants were randomized, 3 were not treated and 5 were treated but excluded due to site closure. Thus, Abatacept group n=118 and Placebo group n=57.
Gender [1] 
[Units: Participants]
 		     
Female   104   55   159 
Male   14   2   16 
[1] 183 participants were randomized, 3 were not treated and 5 were treated but excluded due to site closure. Thus, Abatacept group n=118 and Placebo group n=57.
Race/Ethnicity, Customized [1] 
[Units: Participants]
 		     
White   74   39   113 
Black/African American   12   4   16 
American Indian/Alaska Native   1   0   1 
Asian   28   13   41 
Other races   3   1   4 
[1] 183 participants were randomized, 3 were not treated and 5 were treated but excluded due to site closure. Thus, Abatacept group n=118 and Placebo group n=57.
Weight [1] 
[Units: Kilograms]
Mean (Standard Deviation) 		 68.630  (18.717)   69.000  (14.790)   68.750  (17.493) 
[1] 183 participants were randomized, 3 were not treated and 5 were treated but excluded due to site closure. Thus, Abatacept group n=118 and Placebo group n=57.
Systemic Lupus International Collaborative Clinics/American College of Rheumatology(SLICC/ACC) score [1] 
[Units: Participants]
 		     
Overall SLICC/ACR score 0   82   38   120 
Overall SLICC/ACR score 1   12   11   23 
Overall SLICC/ACR score 2   15   5   20 
Overall SLICC/ACR score >2   6   1   7 
Overall SLICC/ACR score unavailable   3   2   5 
[1] SLICC/ACR score or damage index is a measure of cumulative damage due to Systemic Lupus Erythematosus (SLE). Damage is defined as non-reversible change (not related to active inflammation) occurring since onset of lupus, ascertained by clinical assessment and present for at least 6 months. A score of 0=no damage, early damage is defined as ≥1. The total maximum score is 48, and increasing score indicates increasing disease severity. 183 participants were randomized, 3 were not treated and 5 were treated but excluded due to site closure. Thus, Abatacept group n=118 and Placebo group n=57.


  Outcome Measures

1.  Primary:   Double Blind Period (DB); Number of Participants Experiencing a New SLE Flare   [ Time Frame: From start of corticosteroid taper to Day 365 ]
  Show Outcome Measure 1

2.  Primary:   Open Label Period (OL); Number of Participants Who Died, Experienced Adverse Events (AEs), Serious AEs, Drug Related AEs or SAEs and Discontinued Due to AEs   [ Time Frame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period ]
  Show Outcome Measure 2

3.  Primary:   OL; Number of Participants With Significant AEs of Special Interest   [ Time Frame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period ]
  Show Outcome Measure 3

4.  Primary:   OL; Number of Participants With Marked Abnormalities (MAs) in Hematology: Hemoglobin, Hematocrit, Erythrocytes and Platelet Count   [ Time Frame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period ]
  Show Outcome Measure 4

5.  Primary:   OL; Number of Participants With MAs in Hematology: Leukocytes, Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)   [ Time Frame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period ]
  Show Outcome Measure 5

6.  Primary:   OL; Number of Participants With MAs in Serum Chemistry: Alkaline Phosphatase (ALP), Aspartate-aminotransferase (AST), Alanine-aminotransferase (ALT), Gamma-glutamyl Transferase (GGT), Bilirubin(Total), Blood Urea Nitrogen (BUN), Creatinine   [ Time Frame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period ]
  Show Outcome Measure 6

7.  Primary:   OL; Number of Participants With MAs in Serum Chemistry: Sodium (Serum), Potassium (Serum), Chloride (Serum), Calcium (Total), Protein (Total)   [ Time Frame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period ]
  Show Outcome Measure 7

8.  Primary:   OL; Number of Participants With MAs in Serum Chemistry: Glucose (Serum), Glucose (Fasting Serum), Albumin, Cholesterol (Total), Triglycerides, Fasting Triglycerides   [ Time Frame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period ]
  Show Outcome Measure 8

9.  Primary:   OL; Number of Participants With MAs in Urinalysis   [ Time Frame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period ]
  Show Outcome Measure 9

10.  Secondary:   DB; Number of Participants With a New SLE Flare During the Initial 6 Months   [ Time Frame: From start of corticosteroid taper to 6 months. ]
  Show Outcome Measure 10

11.  Secondary:   DB; Total Number of New SLE Flares Each Participant Experienced   [ Time Frame: From start of corticosteroid taper to Day 365 ]
  Show Outcome Measure 11

12.  Secondary:   DB; Median Number of Days to the First Occurrence of a New SLE Flare   [ Time Frame: From start of corticosteroid taper to confirmation of disease flare or the end of double-blind period ]
  Show Outcome Measure 12

13.  Secondary:   DB; Number of Participants With a Change in the SLICC/ACR Damage Index at 1 Year Compared to Baseline   [ Time Frame: From start of study drug treatment to Day 365 ]
  Show Outcome Measure 13

14.  Secondary:   DB; Number of Participants Who Died, Experienced AEs, Other SAEs or Discontinuations Due to AEs, Drug Related AEs   [ Time Frame: Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier ]
  Show Outcome Measure 14

15.  Secondary:   DB; Number of Participants With Significant AEs of Special Interest   [ Time Frame: Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier ]
  Show Outcome Measure 15

16.  Secondary:   DB; Number of Participants With MAs in Hematology: Hemoglobin, Hematocrit, Erythrocytes and Platelet Count   [ Time Frame: Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier ]
  Show Outcome Measure 16

17.  Secondary:   DB; Number of Participants With MAs in Hematology: Leukocytes, Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)   [ Time Frame: Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier ]
  Show Outcome Measure 17

18.  Secondary:   DB: Number of Participants With MAs in Serum Chemistry: ALP, AST, ALT, GGT, Bilirubin (Total), BUN and Creatinine   [ Time Frame: Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier ]
  Show Outcome Measure 18

19.  Secondary:   DB; Number of Participants With MAs in Serum Chemistry: Sodium (Serum), Potassium (Serum), Chloride (Serum), Calcium (Total),Protein (Total)   [ Time Frame: Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier ]
  Show Outcome Measure 19

20.  Secondary:   DB; Number of Participants With MAs in Serum Chemistry: Glucose (Serum), Glucose (Fasting Serum), Albumin, Cholesterol (Total), Triglycerides, Fasting Triglycerides   [ Time Frame: Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier ]
  Show Outcome Measure 20

21.  Secondary:   DB; Number of Participants With MAs in Urinalysis   [ Time Frame: Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier ]
  Show Outcome Measure 21

22.  Secondary:   DB; Number of Participants With Clinically Significant Abnormal Vital Signs and/or Physical Examination Findings   [ Time Frame: Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier ]
  Show Outcome Measure 22

23.  Secondary:   DB; Number of Participants With Antibodies Specific for CTLA4-T and Abatacept, Following Abatacept Treatment   [ Time Frame: From Day 1 to Day 365 ]
  Show Outcome Measure 23

24.  Secondary:   OL; Number of Participants With a New SLE Flare   [ Time Frame: From start of study drug therapy in open-label period (Day 365), Day 393, 421, 449 and every 28 days thereafter till Day 729. ]
  Show Outcome Measure 24

25.  Secondary:   OL; Number of Participants With a Change in the SLICC/ACR Damage Index at Year 2 Compared to Baseline   [ Time Frame: From start of study drug therapy in open-label period (Day 365) and on Day 729. ]
  Show Outcome Measure 25

26.  Secondary:   OL; Total Number of BILAG A Flares Each Participant Experienced   [ Time Frame: From start of study drug therapy in open-label period (Day 365), Day 393, 421, 449 and every 28 days thereafter till Day 729. ]
  Show Outcome Measure 26

27.  Secondary:   OL; Area Under the Curve (AUC) for Prednisone or Prednisone Equivalent   [ Time Frame: From start of study drug therapy in open-label period (Day 365), Day 393, 421, 449 and every 28 days thereafter till Day 729. ]
  Show Outcome Measure 27

28.  Secondary:   OL; Number of Participants With Antibodies Specific for CTLA4-T and Abatacept, Following Abatacept Treatment   [ Time Frame: After the first dose of open-label period ]
  Show Outcome Measure 28


  Serious Adverse Events


  Other Adverse Events


  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.


  More Information

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


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):


Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00119678     History of Changes
Other Study ID Numbers: IM101-042
First Submitted: June 30, 2005
First Posted: July 14, 2005
Results First Submitted: January 10, 2011
Results First Posted: May 9, 2011
Last Update Posted: September 22, 2014