Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial (EnACT) (EnACT)

Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial

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.

Study Overview

• Status: Completed
• Conditions: Cryptococcal Meningitis
• Intervention / Treatment: Drug: MAT2203; Drug: Amphotericin B

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 Type: Interventional
• Enrollment (Actual): 178
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Uganda
  • Kampala, Uganda
    • Infectious Disease Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1a single ascending dose study; 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; Encochleated amphotericin B; Other Names: oral amphotericin B
Experimental: Phase 1b multiple day dosing; 9 subjects will receive the Phase Ia 100% tolerated MAT2203 dose for 7 days.	Drug: MAT2203; Encochleated amphotericin B; Other Names: oral amphotericin B
Experimental: Phase 2 safety and tolerability; Safety, tolerability, and microbiologic efficacy of MAT2203 among HIV-infected patients with cryptococcal meningitis compared with standard IV AMB.	Drug: MAT2203; Encochleated amphotericin B; Other Names: oral amphotericin B; Drug: Amphotericin B; Intravenous amphotericin B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Matinas BioPharma Nanotechnologies, Inc.
• Collaborators: University of Minnesota

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2019
• Primary Completion (Actual): November 14, 2022
• Study Completion (Actual): February 15, 2023

Study Registration Dates

• First Submitted: July 22, 2019
• First Submitted That Met QC Criteria: July 22, 2019
• First Posted (Actual): July 24, 2019

Study Record Updates

• Last Update Posted (Actual): March 31, 2023
• Last Update Submitted That Met QC Criteria: March 29, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Central Nervous System Infections; Bacterial Infections and Mycoses; Mycoses; Meningitis, Fungal; Central Nervous System Fungal Infections; Cryptococcosis; Meningitis; Meningitis, Cryptococcal; Anti-Infective Agents; Anti-Bacterial Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Amebicides; Amphotericin B; Liposomal amphotericin B
• Other Study ID Numbers: MB-70007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No