Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial (EnACT)

Matinas BioPharma

Status and phase: Completed; Phase 2; Phase 1

Conditions: Cryptococcal Meningitis

Treatments: Drug: Amphotericin B; Drug: MAT2203

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04031833

MB-70007

Details and patient eligibility

About

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.

Full 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.

Enrollment: 178 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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178 participants in 3 patient groups

Phase 1a single ascending dose study

Experimental group

Description:

Phase IA will consist of a single ascending dose study in 9 participants to test three doses to determine the max tolerated dose.

Treatment:

Drug: MAT2203

Phase 1b multiple day dosing

Experimental group

Description:

9 subjects will receive the Phase Ia 100% tolerated MAT2203 dose for 7 days.

Treatment:

Drug: MAT2203

Phase 2 safety and tolerability

Experimental group

Description:

Safety, tolerability, and microbiologic efficacy of MAT2203 among HIV-infected patients with cryptococcal meningitis compared with standard IV AMB.

Treatment:

Drug: MAT2203

Drug: Amphotericin B