Trial Outcomes & Findings for Clarification of Abatacept Effects in SLE With Integrated Biologic and Clinical Approaches (NCT NCT02270957)
NCT ID: NCT02270957
Last Updated: 2022-01-26
Results Overview
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.
COMPLETED
PHASE2
66 participants
6 months
2022-01-26
Participant Flow
Participant milestones
| Measure |
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 Background immune suppressants are withdrawn at the beginning of the study and the option of depomedrol up to 320 mg total (in divided doses) is allowed at any time up through the visit 2 months after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.
Abatacept
|
Placebo
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
|
|---|---|---|
|
Overall Study
STARTED
|
31
|
35
|
|
Overall Study
COMPLETED
|
27
|
31
|
|
Overall Study
NOT COMPLETED
|
4
|
4
|
Reasons for withdrawal
| Measure |
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 Background immune suppressants are withdrawn at the beginning of the study and the option of depomedrol up to 320 mg total (in divided doses) is allowed at any time up through the visit 2 months after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.
Abatacept
|
Placebo
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
|
|---|---|---|
|
Overall Study
Lack of Efficacy
|
2
|
4
|
|
Overall Study
Adverse Event
|
2
|
0
|
Baseline Characteristics
Clarification of Abatacept Effects in SLE With Integrated Biologic and Clinical Approaches
Baseline characteristics by cohort
| Measure |
Abatacept
n=31 Participants
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
|
Placebo
n=35 Participants
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
n=66 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
43.8 years
STANDARD_DEVIATION 10.9 • n=5 Participants
|
46.9 years
STANDARD_DEVIATION 11.9 • n=7 Participants
|
45.4 years
STANDARD_DEVIATION 11.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
63 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
17 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native American/Alaskan Native
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
31 participants
n=5 Participants
|
35 participants
n=7 Participants
|
66 participants
n=5 Participants
|
|
anti-dsDNA positive
|
5 participants
n=5 Participants
|
12 participants
n=7 Participants
|
17 participants
n=5 Participants
|
|
low complement
|
5 participants
n=5 Participants
|
9 participants
n=7 Participants
|
14 participants
n=5 Participants
|
|
Number with at least one BILAG "B" score
|
31 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
66 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: Full Analysis Set: All Randomized Patients
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.
Outcome measures
| Measure |
Abatacept
n=31 Participants
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
|
Placebo
n=35 Participants
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
|
|---|---|---|
|
British Isles Lupus Assessment Group Index-based Combined Lupus Assessment (BICLA)
|
8 Participants
|
8 Participants
|
POST_HOC outcome
Timeframe: 6 monthsPopulation: Full Analysis Set
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.
Outcome measures
| Measure |
Abatacept
n=31 Participants
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
|
Placebo
n=35 Participants
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
|
|---|---|---|
|
SLE Responder Index-4 (SRI-4)
|
9 Participants
|
8 Participants
|
POST_HOC outcome
Timeframe: Comparison of Baseline to 6 monthsPopulation: Full Analysis Set of all randomized patients
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
Outcome measures
| Measure |
Abatacept
n=31 Participants
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
|
Placebo
n=35 Participants
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
|
|---|---|---|
|
4 Point Improvement in the SLE Disease Activity Index (SLEDAI)
|
9 Participants
|
8 Participants
|
Adverse Events
Abatacept
Placebo
Serious adverse events
| Measure |
Abatacept
n=31 participants at risk
Patients receive Abatacept 125 mg subcutaneously weekly for six months.
|
Placebo
n=35 participants at risk
Patients receive Placebo subcutaneously weekly for six months.
|
|---|---|---|
|
Gastrointestinal disorders
gastroenteritis
|
3.2%
1/31 • Number of events 1 • 12 months
|
0.00%
0/35 • 12 months
|
|
Infections and infestations
viral syndrome
|
3.2%
1/31 • Number of events 1 • 12 months
|
2.9%
1/35 • Number of events 1 • 12 months
|
|
Blood and lymphatic system disorders
sickle cell crisis
|
3.2%
1/31 • Number of events 1 • 12 months
|
0.00%
0/35 • 12 months
|
|
Musculoskeletal and connective tissue disorders
fracture
|
3.2%
1/31 • Number of events 1 • 12 months
|
0.00%
0/35 • 12 months
|
|
Psychiatric disorders
suicidal ideation
|
3.2%
1/31 • Number of events 1 • 12 months
|
0.00%
0/35 • 12 months
|
|
Gastrointestinal disorders
cholecystitis
|
3.2%
1/31 • Number of events 1 • 12 months
|
0.00%
0/35 • 12 months
|
|
Cardiac disorders
cardiac valve dysfunction
|
0.00%
0/31 • 12 months
|
2.9%
1/35 • Number of events 1 • 12 months
|
|
Social circumstances
opiate overdose
|
0.00%
0/31 • 12 months
|
2.9%
1/35 • Number of events 1 • 12 months
|
|
Respiratory, thoracic and mediastinal disorders
respiratory compromise
|
0.00%
0/31 • 12 months
|
2.9%
1/35 • Number of events 1 • 12 months
|
|
Renal and urinary disorders
Acute renal failure
|
0.00%
0/31 • 12 months
|
2.9%
1/35 • Number of events 1 • 12 months
|
|
Renal and urinary disorders
blocked ureter
|
0.00%
0/31 • 12 months
|
2.9%
1/35 • Number of events 1 • 12 months
|
Other adverse events
| Measure |
Abatacept
n=31 participants at risk
Patients receive Abatacept 125 mg subcutaneously weekly for six months.
|
Placebo
n=35 participants at risk
Patients receive Placebo subcutaneously weekly for six months.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
bronchitis
|
16.1%
5/31 • Number of events 5 • 12 months
|
11.4%
4/35 • Number of events 5 • 12 months
|
|
Gastrointestinal disorders
gastroenteritis
|
54.8%
17/31 • Number of events 18 • 12 months
|
31.4%
11/35 • Number of events 11 • 12 months
|
|
Infections and infestations
oral candida
|
0.00%
0/31 • 12 months
|
22.9%
8/35 • Number of events 8 • 12 months
|
|
Injury, poisoning and procedural complications
injection site reaction
|
12.9%
4/31 • Number of events 4 • 12 months
|
8.6%
3/35 • Number of events 4 • 12 months
|
|
Skin and subcutaneous tissue disorders
rash
|
6.5%
2/31 • Number of events 2 • 12 months
|
11.4%
4/35 • Number of events 6 • 12 months
|
|
Ear and labyrinth disorders
otitis media
|
3.2%
1/31 • Number of events 1 • 12 months
|
11.4%
4/35 • Number of events 5 • 12 months
|
|
Infections and infestations
urinary tract infection
|
16.1%
5/31 • Number of events 7 • 12 months
|
48.6%
17/35 • Number of events 24 • 12 months
|
|
Infections and infestations
upper respiratory infection
|
48.4%
15/31 • Number of events 20 • 12 months
|
45.7%
16/35 • Number of events 27 • 12 months
|
|
Infections and infestations
influenza
|
3.2%
1/31 • Number of events 1 • 12 months
|
8.6%
3/35 • Number of events 4 • 12 months
|
|
Infections and infestations
sinusitis
|
12.9%
4/31 • Number of events 4 • 12 months
|
22.9%
8/35 • Number of events 14 • 12 months
|
|
Infections and infestations
vaginal yeast infestation
|
3.2%
1/31 • Number of events 1 • 12 months
|
14.3%
5/35 • Number of events 7 • 12 months
|
Additional Information
Joan T. Merrill, M.D.
Oklahoma Medical Research Foundation
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place