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Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial (EnACT)

Sponsor
Matinas BioPharma Nanotechnologies, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04031833
Collaborator
University of Minnesota (Other)
176
Enrollment
1
Location
3
Arms
35.3
Anticipated Duration (Months)
5
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
176 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
Phase I: Persons in Uganda without meningitis or active infections Phase II: HIV-infected persons in Uganda with cryptococcal meningitisPhase I: Persons in Uganda without meningitis or active infections Phase II: HIV-infected persons in Uganda with cryptococcal meningitis
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial
Actual Study Start Date :
Oct 24, 2019
Anticipated Primary Completion Date :
Jun 1, 2022
Anticipated Study Completion Date :
Oct 1, 2022

Arms and Interventions

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

    Outcome Measures

    Primary Outcome Measures

    1. Highest dose tolerated without inducing vomiting [7 days]

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

    2. Evidence of fungicidal activity [2 weeks]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Infectious Disease Institute Kampala Uganda

    Sponsors and Collaborators

    • Matinas BioPharma Nanotechnologies, Inc.
    • University of Minnesota

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Matinas BioPharma Nanotechnologies, Inc.
    ClinicalTrials.gov Identifier:
    NCT04031833
    Other Study ID Numbers:
    • MB-70007
    First Posted:
    Jul 24, 2019
    Last Update Posted:
    Mar 4, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Meningitis, Cryptococcal
    Meningitis
    Amphotericin B
    Liposomal amphotericin B

    Study Results

    No Results Posted as of Mar 4, 2022