Clarification of Abatacept Effects in SLE With Integrated Biologic and Clinical Approaches (ABC)

• ClinicalTrials.gov Identifier: NCT02270957
• Recruitment Status: Completed
• First Posted: October 22, 2014
• Results First Posted: November 25, 2020
• Last Update Posted: January 26, 2022
• Sponsor: Oklahoma Medical Research Foundation
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Oklahoma Medical Research Foundation

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Systemic Lupus Erythematosus
• Interventions: Biological: Abatacept; Other: Placebo
• Enrollment: 66

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Abatacept	Placebo
Arm/Group Description	Patients receive Abatacept 125 mg subcutaneously weekly for six months. An optional continuation up until 12 months is allowed. Background immune suppressants are withdrawn at the beginning of the study and the option of depomedrol up to 320 mg total (in divided doses) is allowed at any time up through the visit 2 months after study medication is started. After this additional rescue is allowed with any standard of care treatment and/or open label abatacept (since patients are blinded) but this additional rescue will define non-response in the primary endpoint at six months. Abatacept	Patients receive Placebo but at the time they meet non-response criteria they may elect open label abatacept or any standard of care to treat their SLE
Period Title: Overall Study
Started	31	35
Completed	27	31
Not Completed	4	4
Reason Not Completed
Lack of Efficacy	2	4
Adverse Event	2	0

Baseline Characteristics

Arm/Group Title		Abatacept	Placebo	Total
Arm/Group Description		Patients receive Abatacept 125 mg subcutaneously weekly for six months. An optional continuation up until 12 months is allowed. Background immune suppressants are withdrawn at the beginning of the study and the option of depomedrol up to 320 mg total (in divided doses) is allowed at any time up through the visit 2 months after study medication is started. After this additional rescue is allowed with any standard of care treatment and/or open label abatacept (since patients are blinded) but this additional rescue will define non-response in the primary endpoint at six months. Abatacept	Patients receive Placebo. At any time that they meet non-response criteria (primary endpoint) they may elect to be treated with any standard of care medication or open label abatacept Placebo	Total of all reporting groups
Overall Number of Baseline Participants		31	35	66
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	31 participants	35 participants	66 participants
		43.8 (10.9)	46.9 (11.9)	45.4 (11.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants	35 participants	66 participants
	Female	29 93.5%	34 97.1%	63 95.5%
	Male	2 6.5%	1 2.9%	3 4.5%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	31 participants	35 participants	66 participants
Caucasian		17 54.8%	26 74.3%	43 65.2%
African		8 25.8%	6 17.1%	14 21.2%
Asian		0 0.0%	0 0.0%	0 0.0%
Native American/Alaskan Native		6 19.4%	3 8.6%	9 13.6%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	31 participants	35 participants	66 participants
		31	35	66
anti-dsDNA positive; Measure Type: Number; Unit of measure: Participants
	Number Analyzed	31 participants	35 participants	66 participants
		5	12	17
low complement; Measure Type: Number; Unit of measure: Participants
	Number Analyzed	31 participants	35 participants	66 participants
		5	9	14
Number with at least one BILAG "B" score [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants	35 participants	66 participants
		31 100.0%	35 100.0%	66 100.0%
		[1] Measure Description: The BILAG stands for British Isles Lupus Assessment Group. The BILAG Index is an outcome measure that uses a glossary and a set of scoring rules based on progress over the prior month, in order to assign disease activity in each of nine organ systems as "A" (severe), "B" (moderate) or "C" (mild activity) vs no active disease in prior month.

Outcome Measures

1. Primary Outcome

Title	British Isles Lupus Assessment Group Index-based Combined Lupus Assessment (BICLA)
Description	The British Isles Lupus Assessment Group Index is a scoring system for progress of disease activity over the prior month with a scoring system that rates each organ system as "A" or severe, "B" or moderate, "C" or mild vs no activity in the past month. To meet the BICLA endpoint requires all baseline severe features (BILAG A) improving to moderate (BILAG B), mild or resolved, and all baseline BILAG B features improving to mild or resolved without increase in any other feature on either the BILAG or a different measure called the SLEDAI (SLE Disease Activity Index). Furthermore there must be no increase in Physician's Global Assessment or any rescue medications after the month 2 visit. Only those meeting all of these criteria meet the primary endpoint.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set: All Randomized Patients

Arm/Group Title	Abatacept	Placebo
Arm/Group Description:	Patients receive Abatacept 125 mg subcutaneously weekly for six months. An optional continuation up until 12 months is allowed. Background immune suppressants are withdrawn at the beginning of the study and the option of depomedrol up to 320 mg total (in divided doses) is allowed at any time up through the visit 2 months after study medication is started. After this additional rescue is allowed with any standard of care treatment and/or open label abatacept (since patients are blinded) but this additional rescue will define non-response in the primary endpoint at six months. Abatacept	Patients receive Abatacept 125 mg subcutaneously weekly for six months. An optional continuation up until 12 months is allowed. Background immune suppressants are withdrawn at the beginning of the study and the option of depomedrol up to 320 mg total (in divided doses) is allowed at any time up through the visit 2 months after study medication is started. After this additional rescue is allowed with any standard of care treatment and/or open label abatacept (since patients are blinded) but this additional rescue will define non-response in the primary endpoint at six months. Placebo
Overall Number of Participants Analyzed	31	35
Measure Type: Count of Participants; Unit of Measure: Participants
	8 25.8%	8 22.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abatacept, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	>0.999
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

2. Post-Hoc Outcome

Title	SLE Responder Index-4 (SRI-4)
Description	Comparing the endpoint date at six months to Baseline, there must be a 4 point decreased in SLEDAI score (SLEDAI is defined as the SLE Disease Activity Index). The SLEDAI is a discontinuous scale in which each type of sign or symptom of active SLE is assigned a fixed number of points. Although the scale includes possible signs or symptoms adding up to more than 100 points it is rare for any (even very severe) patient to ever have a total score > 20. To meet the SLE Responder Index endpoint, There must also be no worsening of BILAG (British Isles Lupus Assessment Group Index (described in the primary endpoint section) and no worsening of PGA (a visual analogue scale reflecting physicians global assessment) by more than 10% of the scale. To meet this endpoint there must also be no new or increased medication initiated after Baseline other than the steroid rescues up to Month 2.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Abatacept	Placebo
Arm/Group Description:	Patients receive Abatacept 125 mg subcutaneously weekly for six months. An optional continuation up until 12 months is allowed. Background immune suppressants are withdrawn at the beginning of the study and the option of depomedrol up to 320 mg total (in divided doses) is allowed at any time up through the visit 2 months after study medication is started. After this additional rescue is allowed with any standard of care treatment and/or open label abatacept (since patients are blinded) but this additional rescue will define non-response in the primary endpoint at six months. Abatacept	Patients receive Placebo but if the primary endpoint is met as "non-response" at any time they may elect any standard of care treatment or may initiate abatacept open label. Placebo
Overall Number of Participants Analyzed	31	35
Measure Type: Count of Participants; Unit of Measure: Participants
	9 29.0%	8 22.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abatacept, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.587
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

3. Post-Hoc Outcome

Title	4 Point Improvement in the SLE Disease Activity Index (SLEDAI)
Description	The SLEDAI is a discontinuous scoring system that weights disease activity not by severity of individual symptoms but by the weighting of organs. This makes it less robust for comparing one group of patients to another, but it is quite useful to gave numbers of patients with improvement, since to lower the score a rigorous improvement must be documented
Time Frame	Comparison of Baseline to 6 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set of all randomized patients

Arm/Group Title	Abatacept	Placebo
Arm/Group Description:	Patients receive Abatacept 125 mg subcutaneously weekly for six months. An optional continuation up until 12 months is allowed. Background immune suppressants are withdrawn at the beginning of the study and the option of depomedrol up to 320 mg total (in divided doses) is allowed at any time up through the visit 2 months after study medication is started. After this additional rescue is allowed with any standard of care treatment and/or open label abatacept (since patients are blinded) but this additional rescue will define non-response in the primary endpoint at six months. Abatacept	Patients receive Abatacept 125 mg subcutaneously weekly for six months. An optional continuation up until 12 months is allowed. Background immune suppressants are withdrawn at the beginning of the study and the option of depomedrol up to 320 mg total (in divided doses) is allowed at any time up through the visit 2 months after study medication is started. After this additional rescue is allowed with any standard of care treatment and/or open label abatacept (since patients are blinded) but this additional rescue will define non-response in the primary endpoint at six months. Placebo
Overall Number of Participants Analyzed	31	35
Measure Type: Count of Participants; Unit of Measure: Participants
	9 29.0%	8 22.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abatacept, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.587
	Comments	None of the endpoints were met in any pre-specified unbiased Full Analysis Set analysis
	Method	Chi-squared
	Comments	[Not Specified]

Adverse Events

Time Frame	12 months
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Abatacept		Placebo
Arm/Group Description	Patients receive Abatacept 125 mg subcutaneously weekly for six months.		Patients receive Placebo subcutaneously weekly for six months.
All-Cause Mortality
	Abatacept		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/31 (0.00%)		0/35 (0.00%)
Serious Adverse Events
	Abatacept		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/31 (19.35%)		4/35 (11.43%)
Blood and lymphatic system disorders
sickle cell crisis * 1	1/31 (3.23%)	1	0/35 (0.00%)	0
Cardiac disorders
cardiac valve dysfunction * 1 [1]	0/31 (0.00%)	0	1/35 (2.86%)	1
Gastrointestinal disorders
gastroenteritis * 1 [2]	1/31 (3.23%)	1	0/35 (0.00%)	0
cholecystitis * 1	1/31 (3.23%)	1	0/35 (0.00%)	0
Infections and infestations
viral syndrome * 1 [3]	1/31 (3.23%)	1	1/35 (2.86%)	1
Musculoskeletal and connective tissue disorders
fracture * 1 [4]	1/31 (3.23%)	1	0/35 (0.00%)	0
Psychiatric disorders
suicidal ideation * 1	1/31 (3.23%)	1	0/35 (0.00%)	0
Renal and urinary disorders
Acute renal failure * 1 [5]	0/31 (0.00%)	0	1/35 (2.86%)	1
blocked ureter * 1 [6]	0/31 (0.00%)	0	1/35 (2.86%)	1
Respiratory, thoracic and mediastinal disorders
respiratory compromise * 1 [7]	0/31 (0.00%)	0	1/35 (2.86%)	1
Social circumstances
opiate overdose * 1	0/31 (0.00%)	0	1/35 (2.86%)	1
1 Term from vocabulary, MedDRA (10.0); * Indicates events were collected by non-systematic assessment; [1] aortic and mitral valve dysfunction and replacement; [2] Severe gastroenteritis leading to hospitalization; [3] viral sepsis; [4] R tib/fib fracture; [5] prolonged hospitalization after opiate overdose; [6] stent placement; [7] prolonged hospitalization from opiate overdose
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Abatacept		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/31 (93.55%)		35/35 (100.00%)
Ear and labyrinth disorders
otitis media * 1	1/31 (3.23%)	1	4/35 (11.43%)	5
Gastrointestinal disorders
gastroenteritis * 1	17/31 (54.84%)	18	11/35 (31.43%)	11
Infections and infestations
oral candida * 1	0/31 (0.00%)	0	8/35 (22.86%)	8
urinary tract infection * 1	5/31 (16.13%)	7	17/35 (48.57%)	24
upper respiratory infection * 1	15/31 (48.39%)	20	16/35 (45.71%)	27
influenza * 1	1/31 (3.23%)	1	3/35 (8.57%)	4
sinusitis * 1	4/31 (12.90%)	4	8/35 (22.86%)	14
vaginal yeast infestation * 1	1/31 (3.23%)	1	5/35 (14.29%)	7
Injury, poisoning and procedural complications
injection site reaction * 1 [1]	4/31 (12.90%)	4	3/35 (8.57%)	4
Respiratory, thoracic and mediastinal disorders
bronchitis * 1	5/31 (16.13%)	5	4/35 (11.43%)	5
Skin and subcutaneous tissue disorders
rash * 1 [2]	2/31 (6.45%)	2	4/35 (11.43%)	6
1 Term from vocabulary, MedDRA (10.0); * Indicates events were collected by non-systematic assessment; [1] all mild or moderate and none led to discontinuation; [2] these were not expected rashes due to SLE all were suspected drug reactions but all self limited and not leading to discontinuation

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT 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.

Results Point of Contact

• Name/Title: Joan T. Merrill, M.D.
• Organization: Oklahoma Medical Research Foundation
• Phone: 405 822 2336
• EMail: joan-merrill@omrf.org

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

Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3:CD007478. doi: 10.1002/14651858.CD007478.pub2.

Thanou A, James JA, Arriens C, Aberle T, Chakravarty E, Rawdon J, Stavrakis S, Merrill JT, Askanase A. Scoring systemic lupus erythematosus (SLE) disease activity with simple, rapid outcome measures. Lupus Sci Med. 2019 Dec 30;6(1):e000365. doi: 10.1136/lupus-2019-000365. eCollection 2019.

• Responsible Party: Oklahoma Medical Research Foundation
• ClinicalTrials.gov Identifier: NCT02270957
• Other Study ID Numbers: OMRF 13-38
• First Submitted: October 13, 2014
• First Posted: October 22, 2014
• Results First Submitted: October 6, 2020
• Results First Posted: November 25, 2020
• Last Update Posted: January 26, 2022