Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis - Study Results

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:	Systemic Lupus Erythematosus
Interventions:	Drug: Corticosteroids (prednisone or prednisolone) Drug: Abatacept Drug: Mycophenolate mofetil (MMF)

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
423 participants were enrolled and screened; 300 were randomized. Of the 123 participants who were not randomized, 114 participants did not meet the study criteria; 5 participants withdrew Consent; 1 pregnancy; 1 death; 1 administrative reason by sponsor; 1 other reason.

Reporting Groups

	Description
Abatacept 30/10 mg/kg	Abatacept 30/10 mg/kg regimen by IV infusion: abatacept 30 mg/kg (by weight) on Days 1, 15, 29, and 57, followed by abatacept approximating 10 mg/kg on Days 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337 in addition to oral MMF and oral prednisone or prednisone-equivalent
Abatacept 10/10 mg/kg	Abatacept 10/10 mg/kg regimen by IV infusion: abatacept approximating 10 mg/kg on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337 in addition to oral MMF and oral prednisone or prednisone-equivalent
Placebo	Placebo (Dextrose 5% in water [D5W]) or Normal Saline (NS) by IV infusion on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337 in addition to oral MMF and oral prednisone or prednisone-equivalent

Participant Flow: Overall Study

	Abatacept 30/10 mg/kg	Abatacept 10/10 mg/kg	Placebo
STARTED	99 ^[1]	99 ^[2]	100
COMPLETED	76 ^[3]	74 ^[3]	78 ^[3]
NOT COMPLETED	23	25	22
Death	1	1	5
Adverse Event	15	13	9
Lack of Efficacy	5	6	4
Withdrawal by Subject	1	1	2
Participant no longer met study criteria	1	1	2
Poor / Non-compliance	0	1	0
Pregnancy	0	2	0

[1]	1 participant died before receiving the first dose of study medication
[2]	1 participant took infliximab on day 1 and was discontinued before receiving study medication.
[3]	Completed the double blind period

Baseline Characteristics

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Reporting Groups

	Description
Abatacept 30/10 mg/kg	Abatacept 30/10 mg/kg regimen by IV infusion: abatacept 30 mg/kg (by weight) on Days 1, 15, 29, and 57, followed by abatacept approximating 10 mg/kg on Days 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337 in addition to oral MMF and oral prednisone or prednisone-equivalent
Abatacept 10/10 mg/kg	Abatacept 10/10 mg/kg regimen by IV infusion: abatacept approximating 10 mg/kg on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337 in addition to oral MMF and oral prednisone or prednisone-equivalent
Placebo	Placebo (Dextrose 5% in water [D5W]) or Normal Saline (NS) by IV infusion on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337 in addition to oral MMF and oral prednisone or prednisone-equivalent

Baseline Measures

	Abatacept 30/10 mg/kg	Abatacept 10/10 mg/kg	Placebo	Total
Number of Participants [units: participants]	99	99	100	298
Age, Customized [units: Participants]
16 - 29 years	55	52	46	153
30 - 39 years	28	30	33	91
40 - 49 years	10	10	18	38
50 - 59 years	5	6	2	13
>= 60 years	1	1	1	3
Gender [units: participants]
Female	84	86	81	251
Male	15	13	19	47
Race [units: Participants]
White	28	45	38	111
Black/African American	6	3	5	14
American Indian/Alaska Native	0	1	0	1
Native Hawaiian/Other Pacific Islander	1	0	0	1
Other Asian	60	49	55	164
Other	4	1	2	7
Weight, Group [units: participants]
<60 kg	54	55	45	154
60 - 100 kg	42	43	51	136
>100 kg	3	1	4	8

Outcome Measures

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1. Primary:

Kaplan-Meier Estimates for Median Time to First Confirmed Complete Renal Response ([CRR] Confirmed at Two Consecutive Visits) During Double Blind Period [ Time Frame: Day 1 (randomization) to 12 months. ]

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2. Primary:

Number of Participants With Confirmed CRR (Confirmed at Two Consecutive Visits) During Double Blind Period [ Time Frame: Within 12 months ]

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3. Secondary:

Participants Achieving a Confirmed CRR (Confirmed at Two Consecutive Visits) at Month 12 During Double Blind Period [ Time Frame: at Month 12 ]

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4. Secondary:

Time to Achieve First Confirmed Renal Improvement (RI) During Double Blind Period (as Determined by Kaplan-Meier Methodology) [ Time Frame: Day 1 (randomization) to 12 months. ]

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5. Secondary:

Participants Achieving Renal Improvement (RI) or CRR at Month 12 During Double Blind Period [ Time Frame: at Month 12 ]

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6. Secondary:

Number of Months CRR Was Maintained During Double Blind Period [ Time Frame: Day 1 (randomization) to 12 Months ]

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7. Secondary:

Baseline Renal Function Over Time During Double Blind Period [ Time Frame: Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365 ]

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8. Secondary:

Change in Renal Function From Baseline Over Time During Double Blind Period [ Time Frame: Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365 ]

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9. Secondary:

Baseline and Post Baseline Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index During Double Blind Period [ Time Frame: Baseline (Day 1), Post baseline (Month 12 or 28 days after last dose) ]

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10. Secondary:

Change in SLICC / ACR Damage Index From Baseline During Double Blind Period [ Time Frame: Baseline (Day 1), Post-baseline (Month 12 or 28 days after last dose) ]

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11. Secondary:

Baseline Physical Component Summary of the Short Form (SF)-36 During Double Blind Period [ Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365 ]

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12. Secondary:

Change From Baseline in Physical Component Summary of the SF-36 During Double Blind Period [ Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365 ]

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13. Secondary:

Baseline Mental Component Summary of the Short SF-36 During Double Blind Period [ Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365 ]

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14. Secondary:

Change From Baseline in Mental Component Summary of the SF-36 During Double Blind Period [ Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365 ]

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15. Secondary:

Baseline Fatigue as Measured by the Fatigue Visual Analog Scale During Double Blind Period [ Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365 ]

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16. Secondary:

Change in Fatigue From Baseline as Measured by the Fatigue Visual Analog Scale During Double Blind Period [ Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365 ]

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17. Secondary:

Baseline Fatigue as Measured by Fatigue Severity Scale-Krupp During Double Blind Period [ Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365 ]

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18. Secondary:

Change in Fatigue From Baseline as Measured by Fatigue Severity Scale-Krupp During Double Blind Period [ Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365 ]

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19. Secondary:

Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs Reported During the Double-blind Period [ Time Frame: From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first. ]

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20. Secondary:

Participants With AEs of Special Interest During Double-blind Period [ Time Frame: From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first. ]

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21. Secondary:

Participants With Marked Hematology Abnormalities During Double-Blind Period [ Time Frame: From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first. ]

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22. Secondary:

Participants With Marked Laboratory Abnormalities During Double-Blind Period [ Time Frame: From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first. ]

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23. Secondary:

Participants With Marked Liver and Kidney Function Abnormalities During Double-Blind Period [ Time Frame: From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first. ]

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24. Secondary:

Participants With Marked Abnormalities Urinalysis During Double-Blind Period [ Time Frame: From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first. ]

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25. Secondary:

Vital Signs Summary During the Double-blind Period: Systolic Blood Pressure (SBP) [ Time Frame: 0 - 12 Months ]

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26. Secondary:

Vital Signs Summary During the Double Blind Period: Diastolic Blood Pressure (DBP) [ Time Frame: 0 - 12 Months ]

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27. Secondary:

Vital Signs Summary During the Double Blind Period: Heart Rate [ Time Frame: 0 - 12 Months ]

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28. Secondary:

Vital Signs Summary During the Double Blind Period: Temperature [ Time Frame: 0 - 12 Months ]

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29. Secondary:

Number of Participants With Positive Abatacept-induced Responses (ECL Method) Over Time During Double Blind Period [ Time Frame: Day 169, Day 365 ]

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30. Secondary:

Baseline Quantitative Immunoglobulins During Double Blind Period [ Time Frame: Baseline (Day 1) ]

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31. Secondary:

Change in Quantitative Immunoglobulins From Baseline During Double Blind Period [ Time Frame: Day 365 ]

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32. Other Pre-specified:

Number of Participants Achieving Patient Response (PR) at Month 12 During Double Blind Period [ Time Frame: Month 12 ]

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33. Other Pre-specified:

Number of Participants Achieving Renal Response (RR) at Month 12 During Double Blind Period [ Time Frame: Month 12 ]

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34. Primary:

Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) During Open Label Period [ 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 ]

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: Yes

35. Primary:

Number of Participants With Marked Laboratory Abnormalities During Open Label Period [ 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 ]

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: Yes

36. Secondary:

Number of Months Complete Renal Response Was Maintained During Open Label Period [ Time Frame: 12 Months to termination of the open label phase ]

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

37. Secondary:

Durability of Efficacy: Renal Improvement During Open Label Period [ Time Frame: 12 Months to termination of the open label phase ]

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

38. Secondary:

Durability of Efficacy - SLICC/ACR Damage Index During Open Label Period [ Time Frame: 12 Months to termination of the open label phase ]

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

39. Secondary:

Immunogenicity and Corticosteroid Use During Open Label Period [ Time Frame: 12 Months to termination of the open label phase ]

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

Serious Adverse Events

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Other Adverse Events

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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

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
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Results Point of Contact:

Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com

No publications provided

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00430677 History of Changes
Other Study ID Numbers:	IM101-075
Study First Received:	February 1, 2007
Results First Received:	February 13, 2012
Last Updated:	April 13, 2012
Health Authority:	United States: Food and Drug Administration