Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial (EnACT)

Conditions

Cryptococcal Meningitis

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.

Ahimbisibwe C, Kwizera R, Ndyetukira JF, Namujju OC, Sadiq A, Atukunda M, Skipper CP, Boulware DR, Meya DB.

2025-07-151 citations

10.1186/s12879-025-11319-1

Experiences, challenges, gaps, and strategies for counselling persons presenting with advanced HIV-associated meningitis in Uganda.

Sadiq A, Kwizera R, Kiiza TK, Ayebare P, Ahimbisibwe C, Ndyetukira JF, Boulware DR, Meya DB.

2025-02-191 citations

10.1186/s12981-025-00705-z

Oral Lipid Nanocrystal Amphotericin B for Cryptococcal Meningitis: A Randomized Clinical Trial

David R. Boulware, Mucunguzi Atukunda, Enock Kagimu, Abdu K Musubire, Andrew Akampurira et al. (29 authors)

Clinical Infectious Diseases2023-08-2253 citations

10.1093/cid/ciad440

Phase I EnACT Trial of the Safety and Tolerability of a Novel Oral Formulation of Amphotericin B.

Skipper CP, Atukunda M, Stadelman A, Engen NW, Bangdiwala AS, Hullsiek KH, Abassi M, Rhein J, Nicol MR, Laker E, Williams DA, Mannino R, Matkovits T, Meya DB, Boulware DR.

2020-09-2140 citations

10.1128/aac.00838-20

Interventions

DRUGMAT2203

Encochleated amphotericin B

DRUGAmphotericin B

Intravenous amphotericin B

Study design

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Phase I: Persons in Uganda without meningitis or active infections Phase II: HIV-infected persons in Uganda with cryptococcal meningitis

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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)

Design outcomes

Primary

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

Countries

Uganda

Outcome results

None listed