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

• ClinicalTrials.gov Identifier: NCT04031833
• Recruitment Status: Completed
• First Posted: July 24, 2019
• Last Update Posted: March 31, 2023
• Sponsor: Matinas BioPharma Nanotechnologies, Inc.
• Collaborator: University of Minnesota
• Information provided by (Responsible Party): Matinas BioPharma Nanotechnologies, Inc.

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
Cryptococcal Meningitis	Drug: MAT2203; Drug: Amphotericin B	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 (Clinical Trial)
• Actual Enrollment: 178 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 meningitis
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial
• Actual Study Start Date: October 24, 2019
• Actual Primary Completion Date: November 14, 2022
• Actual Study Completion Date: February 15, 2023

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 Name: 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 Name: 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 Name: oral amphotericin B; Drug: Amphotericin B; Intravenous amphotericin B

Outcome Measures

Primary Outcome Measures :

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

Eligibility Criteria

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

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)

Contacts and Locations

Locations

Uganda

Infectious Disease Institute

Kampala, Uganda

Sponsors and Collaborators

Matinas BioPharma Nanotechnologies, Inc.

University of Minnesota

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Matinas BioPharma Nanotechnologies, Inc.
• ClinicalTrials.gov Identifier: NCT04031833
• Other Study ID Numbers: MB-70007
• First Posted: July 24, 2019
• Last Update Posted: March 31, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• 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; Neuroinflammatory Diseases; Nervous System Diseases; Meningitis, Fungal; Central Nervous System Fungal Infections; Mycoses; Bacterial Infections and Mycoses; Infections; Cryptococcosis; Central Nervous System Infections; Central Nervous System Diseases; Amphotericin B; Liposomal amphotericin B; Amebicides; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents; Anti-Bacterial Agents; Antifungal Agents