Trial Outcomes & Findings for Defining Immune Tolerance in ANCA-associated Vasculitis (AAV) (NCT NCT01934504)
NCT ID: NCT01934504
Last Updated: 2016-05-20
Results Overview
Identification of biomarkers associated with clinical tolerance in patients with ANCA-associated vasculitis by comparative immunophenotyping of individual leukocyte subsets from tolerant and non-tolerant patients with AAV. Due to early study termination, data was not available to evaluate this endpoint.
Recruitment status
TERMINATED
Target enrollment
33 participants
Primary outcome timeframe
Difference from baseline to week 26
Results posted on
2016-05-20
Participant Flow
Participants diagnosed with granulomatosis with polyangiitis (Wegener's, GPA) or microscopic polyangiitis, and a history positive for the presence of MPO-ANCA+ during disease flares were recruited for 3 cohorts; healthy participants were recruited for 1 cohort. Participants were recruited from 3 sites in Great Britain from Dec 2013 to Feb 2015.
Participant milestones
| Measure |
Tolerant AAV
Subjects in the Tolerant ANCA-associated vasculitis (AAV) cohort have been in clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) scores of zero and have been off all immunosuppression medications for at least 2 years prior to screening. Subjects have blood samples and other assessments collected for analysis at Week 0 and Week 26.
|
Non-Tolerant AAV
Subjects in the Non-Tolerant ANCA-associated vasculitis (AAV) cohort have had a disease exacerbation and re-institution of immunosuppressive therapy in the past 5 years. Subjects have also been in clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) scores of zero and on minimal maintenance therapy for at least 3 months prior to screening. Subjects have blood samples and other assessments collected for analysis at Week 0 and Week 26.
|
Healthy Controls
Healthy participants without autoimmune disease. Subjects have blood samples and other assessments collected for analysis at Week 0 and Week 26.
|
AAV Discontinuing Immunosuppression
Subjects in the ANCA-associated vasculitis (AAV) Discontinuing Immunosuppression group have been in clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis BVAS/WG) scores of zero and on minimal maintenance therapy for at least 2 years prior to screening. The subjects' primary physicians have planned to discontinue immunosuppression medication in the next year after screening. Subjects have blood samples and other assessments collected for analysis at Week 0 and at 8 weeks after discontinuation of immunosuppression medication.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
3
|
16
|
8
|
|
Overall Study
COMPLETED
|
5
|
3
|
11
|
1
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
5
|
7
|
Reasons for withdrawal
| Measure |
Tolerant AAV
Subjects in the Tolerant ANCA-associated vasculitis (AAV) cohort have been in clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) scores of zero and have been off all immunosuppression medications for at least 2 years prior to screening. Subjects have blood samples and other assessments collected for analysis at Week 0 and Week 26.
|
Non-Tolerant AAV
Subjects in the Non-Tolerant ANCA-associated vasculitis (AAV) cohort have had a disease exacerbation and re-institution of immunosuppressive therapy in the past 5 years. Subjects have also been in clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) scores of zero and on minimal maintenance therapy for at least 3 months prior to screening. Subjects have blood samples and other assessments collected for analysis at Week 0 and Week 26.
|
Healthy Controls
Healthy participants without autoimmune disease. Subjects have blood samples and other assessments collected for analysis at Week 0 and Week 26.
|
AAV Discontinuing Immunosuppression
Subjects in the ANCA-associated vasculitis (AAV) Discontinuing Immunosuppression group have been in clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis BVAS/WG) scores of zero and on minimal maintenance therapy for at least 2 years prior to screening. The subjects' primary physicians have planned to discontinue immunosuppression medication in the next year after screening. Subjects have blood samples and other assessments collected for analysis at Week 0 and at 8 weeks after discontinuation of immunosuppression medication.
|
|---|---|---|---|---|
|
Overall Study
Protocol Deviation
|
0
|
0
|
0
|
2
|
|
Overall Study
Study Terminated by Sponsor
|
1
|
0
|
5
|
5
|
Baseline Characteristics
Defining Immune Tolerance in ANCA-associated Vasculitis (AAV)
Baseline characteristics by cohort
| Measure |
Tolerant AAV
n=6 Participants
Subjects in the Tolerant ANCA-associated vasculitis (AAV) cohort have been in clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) scores of zero and have been off all immunosuppression medications for at least 2 years prior to screening. Subjects have blood samples and other assessments collected for analysis at Week 0 and Week 26.
|
Non-Tolerant AAV
n=3 Participants
Subjects in the Non-Tolerant ANCA-associated vasculitis (AAV) cohort have had a disease exacerbation and re-institution of immunosuppressive therapy in the past 5 years. Subjects have also been in clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) scores of zero and on minimal maintenance therapy for at least 3 months prior to screening. Subjects have blood samples and other assessments collected for analysis at Week 0 and Week 26.
|
Healthy Controls
n=16 Participants
Healthy participants without autoimmune disease. Subjects have blood samples and other assessments collected for analysis at Week 0 and Week 26.
|
AAV Discontinuing Immunosuppression
n=8 Participants
Subjects in the ANCA-associated vasculitis (AAV) Discontinuing Immunosuppression group have been in clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis BVAS/WG) scores of zero and on minimal maintenance therapy for at least 2 years prior to screening. The subjects' primary physicians have planned to discontinue immunosuppression medication in the next year after screening. Subjects have blood samples and other assessments collected for analysis at Week 0 and at 8 weeks after discontinuation of immunosuppression medication.
|
Total
n=33 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
10 Participants
n=36 Participants
|
|
Age, Categorical
>=65 years
|
5 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
12 Participants
n=27 Participants
|
5 Participants
n=483 Participants
|
23 Participants
n=36 Participants
|
|
Age, Continuous
|
73.7 years
STANDARD_DEVIATION 13.5 • n=93 Participants
|
58.3 years
STANDARD_DEVIATION 7.6 • n=4 Participants
|
69.4 years
STANDARD_DEVIATION 7.1 • n=27 Participants
|
64.8 years
STANDARD_DEVIATION 7.5 • n=483 Participants
|
68.1 years
STANDARD_DEVIATION 9.3 • n=36 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
5 Participants
n=483 Participants
|
18 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
15 Participants
n=36 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
16 Participants
n=27 Participants
|
8 Participants
n=483 Participants
|
33 Participants
n=36 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
2 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
2 Participants
n=483 Participants
|
2 Participants
n=36 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
15 Participants
n=27 Participants
|
6 Participants
n=483 Participants
|
29 Participants
n=36 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Region of Enrollment
United Kingdom
|
6 participants
n=93 Participants
|
3 participants
n=4 Participants
|
16 participants
n=27 Participants
|
8 participants
n=483 Participants
|
33 participants
n=36 Participants
|
PRIMARY outcome
Timeframe: Difference from baseline to week 26Population: No analyses were performed due to slow enrollment and early study closure.
Identification of biomarkers associated with clinical tolerance in patients with ANCA-associated vasculitis by comparative immunophenotyping of individual leukocyte subsets from tolerant and non-tolerant patients with AAV. Due to early study termination, data was not available to evaluate this endpoint.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to Week 26Population: No analyses were performed due to slow enrollment and early study closure.
Measurement of the stability of a tolerance immune signature in patients with AAV over time. Due to early study termination, data was not available to evaluate this endpoint.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to Week 26Population: No analyses were performed due to slow enrollment and early study closure.
Correlation of possible changes in the tolerance signature with changes in clinical status. Due to early study termination, data was not available to evaluate this endpoint.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to 8 Weeks Post-Immunosuppression WithdrawalPopulation: No analyses were performed due to slow enrollment and early study closure.
Definition of an immune signature associated with maintenance immunosuppression. Due to early study termination, data was not available to evaluate this endpoint.
Outcome measures
Outcome data not reported
Adverse Events
Tolerant AAV
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Non-Tolerant AAV
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Healthy Controls
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
AAV Discontinuing Immunosuppression
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Director, Clinical Research Operations Program
DAIT/NIAID
Phone: 301-594-7669
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place