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

Primary Purpose

Cryptococcal Meningitis

Status
Completed
Phase
Phase 1
Locations
Uganda
Study Type
Interventional
Intervention
MAT2203
Amphotericin B
Sponsored by
Matinas BioPharma Nanotechnologies, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cryptococcal Meningitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Infectious Disease Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Phase 1a single ascending dose study

Phase 1b multiple day dosing

Phase 2 safety and tolerability

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
July 22, 2019
Last Updated
March 29, 2023
Sponsor
Matinas BioPharma Nanotechnologies, Inc.
Collaborators
University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT04031833
Brief Title
Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial (EnACT)
Acronym
EnACT
Official Title
Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
October 24, 2019 (Actual)
Primary Completion Date
November 14, 2022 (Actual)
Study Completion Date
February 15, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Matinas BioPharma Nanotechnologies, Inc.
Collaborators
University of Minnesota

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cryptococcal Meningitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Phase I: Persons in Uganda without meningitis or active infections Phase II: HIV-infected persons in Uganda with cryptococcal meningitis
Masking
None (Open Label)
Allocation
Randomized
Enrollment
178 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1a single ascending dose study
Arm Type
Experimental
Arm Description
Phase IA will consist of a single ascending dose study in 9 participants to test three doses to determine the max tolerated dose.
Arm Title
Phase 1b multiple day dosing
Arm Type
Experimental
Arm Description
9 subjects will receive the Phase Ia 100% tolerated MAT2203 dose for 7 days.
Arm Title
Phase 2 safety and tolerability
Arm Type
Experimental
Arm Description
Safety, tolerability, and microbiologic efficacy of MAT2203 among HIV-infected patients with cryptococcal meningitis compared with standard IV AMB.
Intervention Type
Drug
Intervention Name(s)
MAT2203
Other Intervention Name(s)
oral amphotericin B
Intervention Description
Encochleated amphotericin B
Intervention Type
Drug
Intervention Name(s)
Amphotericin B
Intervention Description
Intravenous amphotericin B
Primary Outcome Measure Information:
Title
Highest dose tolerated without inducing vomiting
Description
Proportion of cAMB daily dose received and tolerated without vomiting within 30 minutes.
Time Frame
7 days
Title
Evidence of fungicidal activity
Description
CSF early fungicidal activity (EFA) during 2-week induction therapy
Time Frame
2 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Facility Information:
Facility Name
Infectious Disease Institute
City
Kampala
Country
Uganda

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32747357
Citation
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.
Results Reference
derived

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Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial (EnACT)

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