Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial (EnACT)

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.

Inclusion criteria

• Phase 1:

• Age >18 years
• Calculated creatinine clearance >70 mL/min/1.73 m2 (measured within 3 months)
• Written informed consent

Phase 2:

• Cryptococcal meningitis diagnosed by CSF cryptococcal antigen (CRAG)
• Ability and willingness to provide informed consent
• Willing to receive protocol-specified lumbar punctures

Exclusion criteria

• Phase 1:

• 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
• Phase 2:

• 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)