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

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Single Group Assignment; Masking: Double Blind (Subject, 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
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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

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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.
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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
Number of Participants [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)
Gender ^[1] [units: participants]
Female	104	55	159
Male	14	2	16
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
Weight ^[1] [units: kilograms] Mean (Standard Deviation)	68.630 (18.717)	69.000 (14.790)	68.750 (17.493)
Systemic Lupus International Collaborative Clinics/American College of Rheumatology(SLICC/ACC) score ^[2] [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]	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.
[2]	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.

[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.

[2]

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

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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 ]

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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 ]

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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. ]

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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

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Other Adverse Events

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

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):

Merrill JT, Burgos-Vargas R, Westhovens R, Chalmers A, D'Cruz D, Wallace DJ, Bae SC, Sigal L, Becker JC, Kelly S, Raghupathi K, Li T, Peng Y, Kinaszczuk M, Nash P. The efficacy and safety of abatacept in patients with non-life-threatening manifestations of systemic lupus erythematosus: results of a twelve-month, multicenter, exploratory, phase IIb, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2010 Oct;62(10):3077-87. doi: 10.1002/art.27601.

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00119678 History of Changes
Other Study ID Numbers:	IM101-042
Study First Received:	June 30, 2005
Results First Received:	January 10, 2011
Last Updated:	September 11, 2014
Health Authority:	United States: Food and Drug Administration