Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial (EnACT)

NCT04031833 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: MB-70007
• Study Type: interventional
• Target: 178
• Locations: 1 country
• Sites: 1

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.

Conditions

Cryptococcal Meningitis

Outcome Measures

Primary Outcomes (2)

• Highest dose tolerated without inducing vomiting

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

  7 days

• Evidence of fungicidal activity

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

  2 weeks

Study Arms (3)

Phase 1a single ascending dose study

EXPERIMENTAL

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

Drug: MAT2203

Phase 1b multiple day dosing

EXPERIMENTAL

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

Drug: MAT2203

Phase 2 safety and tolerability

EXPERIMENTAL

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

Drug: MAT2203; Drug: Amphotericin B

Interventions

MAT2203 DRUG

Encochleated amphotericin B

Also known as: oral amphotericin B

Phase 1a single ascending dose study; Phase 1b multiple day dosing; Phase 2 safety and tolerability

Amphotericin B DRUG

Intravenous amphotericin B

Phase 2 safety and tolerability

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Matinas BioPharma Nanotechnologies, Inc.: lead
• University of Minnesota: collaborator

Study Sites (1)

Infectious Disease Institute

Kampala, Uganda

Location

Related Publications (5)

• Ahimbisibwe C, Kwizera R, Ndyetukira JF, Namujju OC, Sadiq A, Atukunda M, Skipper CP, Boulware DR, Meya DB. Experience of research nurses with oral encochleated amphotericin B for treatment of cryptococcal meningitis in a resource-limited setting. BMC Infect Dis. 2025 Jul 15;25(1):920. doi: 10.1186/s12879-025-11319-1.

  PMID: 40665233 DERIVED

• Sadiq A, Kwizera R, Kiiza TK, Ayebare P, Ahimbisibwe C, Ndyetukira JF, Boulware DR, Meya DB. Experiences, challenges, gaps, and strategies for counselling persons presenting with advanced HIV-associated meningitis in Uganda. AIDS Res Ther. 2025 Feb 19;22(1):21. doi: 10.1186/s12981-025-00705-z.

  PMID: 39972326 DERIVED

• Kimuda S, Kwizera R, Dai B, Kigozi E, Kasozi D, Rutakingirwa MK, Tukundane A, Shifah N, Luggya T, Luswata A, Ndyetukira JF, Yueh SL, Mulwana S, Wele A, Bahr NC, Meya DB, Boulware DR, Skipper CP. Comparison of Early Fungicidal Activity and Mortality Between Daily Liposomal Amphotericin B and Daily Amphotericin B Deoxycholate for Cryptococcal Meningitis. Clin Infect Dis. 2025 Feb 5;80(1):153-159. doi: 10.1093/cid/ciae326.

  PMID: 38943665 DERIVED

• Boulware DR, Atukunda M, Kagimu E, Musubire AK, Akampurira A, Tugume L, Ssebambulidde K, Kasibante J, Nsangi L, Mugabi T, Gakuru J, Kimuda S, Kasozi D, Namombwe S, Turyasingura I, Rutakingirwa MK, Mpoza E, Kigozi E, Muzoora C, Ellis J, Skipper CP, Matkovits T, Williamson PR, Williams DA, Fieberg A, Hullsiek KH, Abassi M, Dai B, Meya DB. Oral Lipid Nanocrystal Amphotericin B for Cryptococcal Meningitis: A Randomized Clinical Trial. Clin Infect Dis. 2023 Dec 15;77(12):1659-1667. doi: 10.1093/cid/ciad440.

  PMID: 37606364 DERIVED

• 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. Phase I EnACT Trial of the Safety and Tolerability of a Novel Oral Formulation of Amphotericin B. Antimicrob Agents Chemother. 2020 Sep 21;64(10):e00838-20. doi: 10.1128/AAC.00838-20. Print 2020 Sep 21.

  PMID: 32747357 DERIVED

MeSH Terms

Conditions

Meningitis, Cryptococcal

Interventions

Amphotericin B

Condition Hierarchy (Ancestors)

Meningitis, Fungal; Central Nervous System Fungal Infections; Mycoses; Bacterial Infections and Mycoses; Infections; Cryptococcosis; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases; Meningitis; Neuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: July 22, 2019
• First Posted: July 24, 2019
• Study Start: October 24, 2019
• Primary Completion: November 14, 2022
• Study Completion: February 15, 2023
• Last Updated: March 31, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1)