Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial (EnACT)

Matinas BioPharma Nanotechnologies, Inc.178 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

178

Conditions

Cryptococcal Meningitis

Interventions

MAT2203DRUG

Encochleated amphotericin B

Amphotericin BDRUG

Intravenous amphotericin B

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

Locations (1)

Infectious Disease Institute

Kampala, Uganda

Outcomes

Primary Outcomes

Highest dose tolerated without inducing vomiting

Proportion of cAMB daily dose received and tolerated without vomiting within 30 minutes.

Time frame: 7 days

Evidence of fungicidal activity

CSF early fungicidal activity (EFA) during 2-week induction therapy

Time frame: 2 weeks

Data from ClinicalTrials.gov

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