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

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ClinicalTrials.gov Identifier: NCT02270957
Recruitment Status : Active, not recruiting
First Posted : October 22, 2014
Results First Posted : November 25, 2020
Last Update Posted : November 17, 2021
Sponsor:
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
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Abatacept Placebo
Hide 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 Background immune suppressants are withdrawn at the beginning of the study and the option of depomedrol up to 320 mg total (in divided doses) is allowed at any time up through the visit 2 months after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
Arm/Group Title Abatacept Placebo Total
Hide 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 Background immune suppressants are withdrawn at the beginning of the study and the option of depomedrol up to 320 mg total (in divided doses) is allowed at any time up through the visit 2 months after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
Hide 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.
1.Primary Outcome
Title British Isles Lupus Assessment Group Index-based Combined Lupus Assessment (BICLA)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: All Randomized Patients
Arm/Group Title Abatacept Placebo
Hide 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%
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Abatacept Placebo
Hide 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%
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set of all randomized patients
Arm/Group Title Abatacept Placebo
Hide 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%
Hide 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]
Time Frame 12 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Abatacept Placebo
Hide 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%)    
Hide 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
Hide 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
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
Layout table for Results Point of Contact information
Name/Title: Joan T. Merrill, M.D.
Organization: Oklahoma Medical Research Foundation
Phone: 405 822 2336
EMail: joan-merrill@omrf.org
Layout table for additonal information
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: November 17, 2021