Emulsified avacopan given through a nasogastric tube for patients with ANCA-associated vasculitis and diffuse alveolar hemorrhage

Pharmacokinetics Of Emulsified Avacopan In ANCA-associated Vasculitis With Severe Diffuse Alveolar Hemorrhage

This trial will try giving emulsified avacopan (30 mg twice daily) through a nasogastric tube to up to six ventilated patients with active severe GPA or MPA and diffuse alveolar hemorrhage to see how the drug is absorbed over 72 hours.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Mayo Clinic (Academic / other)
• Locations: 1 site (Rochester, Minnesota)
• Trial ID: NCT07556484 on ClinicalTrials.gov

What this trial studies

This is a Phase 1 pharmacokinetic study enrolling up to six patients with active severe ANCA-associated vasculitis (GPA or MPA) complicated by diffuse alveolar hemorrhage who require mechanical ventilation. Participants will receive emulsified avacopan 30 mg twice daily administered via a nasogastric tube. Blood samples will be collected over a 72-hour period to characterize absorption and systemic exposure. The goal is to define pharmacokinetic behavior of NG-tube–administered avacopan to inform dosing and safety in critically ill, intubated patients.

Who should consider this trial

Good fit: Ideal candidates are ANCA-positive patients with granulomatosis with polyangiitis or microscopic polyangiitis who have diffuse alveolar hemorrhage, require mechanical ventilation, have a BVAS-WG ≥ 3, and need standard-of-care remission induction therapy.

Not a fit: Patients with eosinophilic granulomatosis with polyangiitis (EGPA), known severe allergic reaction to avacopan, or who do not require mechanical ventilation or do not meet inclusion criteria are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, this could enable reliable enteral dosing of avacopan for ventilated patients who cannot swallow pills and guide safe dosing in that setting.

How similar studies have performed: Oral avacopan has shown benefit in prior clinical trials for ANCA-associated vasculitis, but pharmacokinetic data for emulsified avacopan given via nasogastric tube in ventilated patients are limited and this application is novel.

Eligibility criteria

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

Where this trial is running

Rochester, Minnesota

• Mayo Clinic in Rochester — Rochester, Minnesota, United States (Recruiting)

Study contacts

• Principal investigator: Ulrich Specks, MD — Mayo Clinic
• Study coordinator: Josie Baum

Conditions Diffuse Alveolar Hemorrhage; Antineutrophil Cytoplasmic Antibody Positive Vasculitis