Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial (EnACT)

Phase 1

Completed

• Conditions: Cryptococcal Meningitis
• Interventions: Drug: MAT2203; Drug: Amphotericin B

• Registration Number: NCT04031833
• Lead Sponsor: Matinas BioPharma Nanotechnologies, Inc.

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 Timeline

• Study First Submitted: 2019-07-22
• Study First Submitted QC: 2019-07-22
• Study First Posted: 2019-07-24
• Study Start: 2019-10-24
• Primary Completion: 2022-11-14
• Study Completion: 2023-02-15
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-29
• Last Update Posted: 2023-03-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 178

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1a single ascending dose study	MAT2203	Phase IA will consist of a single ascending dose study in 9 participants to test three doses to determine the max tolerated dose.
Phase 1b multiple day dosing	MAT2203	9 subjects will receive the Phase Ia 100% tolerated MAT2203 dose for 7 days.
Phase 2 safety and tolerability	MAT2203	Safety, tolerability, and microbiologic efficacy of MAT2203 among HIV-infected patients with cryptococcal meningitis compared with standard IV AMB.
Phase 2 safety and tolerability	Amphotericin B	Safety, tolerability, and microbiologic efficacy of MAT2203 among HIV-infected patients with cryptococcal meningitis compared with standard IV AMB.

Primary Outcome Measures

Name	Time	Method
Evidence of fungicidal activity	2 weeks	CSF early fungicidal activity (EFA) during 2-week induction therapy
Highest dose tolerated without inducing vomiting	7 days	Proportion of cAMB daily dose received and tolerated without vomiting within 30 minutes.

Trial Locations

Locations (1)

Infectious Disease Institute; 🇺🇬 Kampala, Uganda