Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 178
- Locations
- 1
- Primary Endpoint
- Evidence of fungicidal activity
Study Overview
Brief Summary
This study is designed as two sequential trials. The first is a phase I open label trial to evaluate the safety and tolerability of MAT2203. The maximal tolerated and non-toxic daily dose,will then be moved forward into a multi-day safety trial. The Phase II trial will investigate toxicity and early fungicidal activity (EFA) of MAT2203 with flucytosine.
Detailed Description
Cryptococcal meningitis has emerged as one of the most frequent and deadly opportunistic infections in HIV patients. Historically, amphotericin B (AMB) has been considered the "gold standard" in antifungal treatments due to its broad spectrum of activity and lack of emergence of resistance. However, the use of AMB is limited by side effects, including nephrotoxicity, anemia, and infusion-related reactions. MAT2203 or encochleated oral amphotericin B (cAMB) is a lipid nano-crystal formulation designed for targeted oral delivery of the antifungal drug AMB for treatment of fungal and parasitic infections.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age >18 years
- •Calculated creatinine clearance >70 mL/min/1.73 m2 (measured within 3 months)
- •Written informed consent
- •Cryptococcal meningitis diagnosed by CSF cryptococcal antigen (CRAG)
- •Ability and willingness to provide informed consent
- •Willing to receive protocol-specified lumbar punctures
Exclusion Criteria
- •Symptomatic Current illness
- •Known significant, untreated health problem
- •Inability to take enteral medicine
- •Pregnant or breast feeding
- •Receiving amphotericin B therapy in past 90 days
- •Presenting Glasgow Coma Scale (GCS) < 15
- •Received 3 or more doses of IV amphotericin therapy within last 30 days
- •Inability to take enteral (oral or nasogastric) medicine
- •Cannot or unlikely to attend regular clinic visits
- •Pregnancy or breastfeeding
- •Receiving chemotherapy or corticosteroids
- •Suspected Paradoxical immune reconstitution inflammatory syndrome (IRIS)
- •Recent initiation of HIV therapy or ART class switch (within 2 weeks)
Arms & Interventions
Phase 2 safety and tolerability
Safety, tolerability, and microbiologic efficacy of MAT2203 among HIV-infected patients with cryptococcal meningitis compared with standard IV AMB.
Intervention: MAT2203 (Drug)
Phase 1a single ascending dose study
Phase IA will consist of a single ascending dose study in 9 participants to test three doses to determine the max tolerated dose.
Intervention: MAT2203 (Drug)
Phase 1b multiple day dosing
9 subjects will receive the Phase Ia 100% tolerated MAT2203 dose for 7 days.
Intervention: MAT2203 (Drug)
Phase 2 safety and tolerability
Safety, tolerability, and microbiologic efficacy of MAT2203 among HIV-infected patients with cryptococcal meningitis compared with standard IV AMB.
Intervention: Amphotericin B (Drug)
Outcomes
Primary Outcomes
Evidence of fungicidal activity
Time Frame: 2 weeks
CSF early fungicidal activity (EFA) during 2-week induction therapy
Highest dose tolerated without inducing vomiting
Time Frame: 7 days
Proportion of cAMB daily dose received and tolerated without vomiting within 30 minutes.
Secondary Outcomes
No secondary outcomes reported