Diffuse Alveolar Hemorrhage, Antineutrophil Cytoplasmic Antibody Positive Vasculitis
Conditions
Brief summary
The purpose of this study is to determine the 72-hour pharmacokinetics of emulsified avacopan at a dose of 30 mg twice daily given to up to 6 patients with active severe GPA or MPA with diffuse alveolar hemorrhage (DAH) requiring mechanical ventilation for respiratory support.
Interventions
DRUGAvacopan
Avacopan capsules will be solubilized in heated water and administered to patients with Diffuse Alveolar Hemorrhage (DAH) due to GPA or MPA via nasogatric tube.
Sponsors
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Fulfillment of the definitions of the Second Chapel Hill Consensus Conference for ANCA-associated vasculitis (either granulomatosis with polyangiitis (GPA) or microscopic polyangiitis MPA). * Positivity for ANCA, directed against PR3 or MPO. * Diffuse alveolar hemorrhage. * Respiratory failure requiring mechanical ventilation. * Severe newly diagnosed disease or severe relapsing disease. Severe new or relapsing disease is defined as at least one major BVAS/WG item or a score ≥ 3 and the investigator deems standard treatment for severe disease is necessary. * Minimum BVAS-WG of 3. * Requirement of standard-of-care remission induction therapy for active severe ANCA-associated vasculitis (GPA or MPA).
Exclusion criteria
* Diagnosis with eosinophilic granulomatosis with polyangiitis (EGPA, formally Churg-Strauss syndrome) as defined by the Chapel Hill consensus conference. * Allergies: History of severe allergic reaction to avacopan * History of documented anti-glomerular basement membrane disease (anti-GBM disease) * Previous administration of avacopan within the last 5 days. * Concomitant use of a strong CYP3A4 inhibitor. * Aspartate aminotransferase \[AST\], alanine amino transferase \[ALT\], alkaline phosphatase, or total bilirubin elevation \>2.5 times the upper limit of normal (unless attributed to vasculitis) on routine liver function testing obtained within 3 days prior to anticipated treatment with avacopan. * Evidence of prior active or current Hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency (HIV) infection. * Active serious infection, including localized infection. * Pregnancy and breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Avacopan blood level over time | 72 hours | The primary objective of this study is to determine the blood (serum) level changes of Avacopan over time (pharmacokinetics) when Avacopan capsules are solubilized in heated water and administered to patients with Diffuse Alveolar Hemorrhage (DAH) due to GPA or MPA via nasogastric tube. Blood will be drawn pre-dose, post-dose 30 minutes, 1-hour, 2-hour, 4-hour, and 6-hour for the first dose and pre-dose for the remaining 72 hours and stored for analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measure in Markers of Neutrophil Activation on Serum Samples | 72 hours | The exploratory objective is to measure changes in markers of neutrophil activation on serum samples (such as neutrophil elastase and/or neutrophil gelatinase-associated lipocalin (NGAL)) collected during the conduct of this study. This will not cause any additional burden to the subject. Samples will be collected from the one research blood draw already being performed per visit. |
Countries
United States
Contacts
CONTACTJosie Baum
CONTACTMichael Stachowitz
PRINCIPAL_INVESTIGATORUlrich Specks, MD
Mayo Clinic
Outcome results
None listed