Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial 3 (EnACT3)

This pivotal, confirmatory trial seeks to independently verify the results observed in the EnACT Phase II Stage 2 trial (MB-70007).

Study Overview

• Status: Not yet recruiting
• Conditions: Cryptococcal Meningitis
• Intervention / Treatment: Drug: MAT2203; Drug: Amphotericin B

Detailed Description

Pivotal, prospective, randomized, open-label, non-inferiority trial to compare the efficacy and safety of step-down induction and consolidation therapy for the treatment of cryptococcal meningitis with oral MAT2203 plus flucytosine to standard of care therapy. Randomization will by 1:1:1 to one of two experimental arms or standard of care.

• Study Type: Interventional
• Enrollment (Anticipated): 270
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Theresa Matkovits, PhD; Phone Number: 908-505-0975; Email: tmatkovits@matinasbiopharma.com

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:

• CSF cryptococcal antigen (CrAg) positive meningitis
• Ability and willingness to provide informed consent
• Willing to receive protocol-specified lumbar punctures

Exclusion Criteria:

• Glasgow Coma Scale < 15 at time of consent
• Received >= 3 doses of amphotericin B within prior 30 days
• Inability to take enteral (oral or nasogastric) medicine
• Cannot or unlikely to attend regular clinic visits
• Receiving chemotherapy or corticosteroids
• Suspected paradoxical immune reconstitution inflammatory syndrome (IRIS)
• Pregnancy or breastfeeding
• Previous administration of MAT2203
• Any condition for which participation would not be in the best interest of the participant or that could limit protocol specified assessments

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MAT2203 Induction / MAT2203 Consolidation; 2 days IV Amphotericin B (AMB) + flucytosine (5FC) followed by oral MAT2203 + 5FC for 12 days of induction therapy followed by MAT2203 +fluconazole for 4 weeks of consolidation therapy	Drug: MAT2203; oral lipid nanocrystal amphotericin B; Other Names: cAMB
Experimental: MAT2203 Induction / SOC Consolidation; 2 days IV AMB + 5FC followed by oral MAT2203 + 5FC for 12 days of induction therapy followed by 4 weeks of standard of care consolidation therapy	Drug: MAT2203; oral lipid nanocrystal amphotericin B; Other Names: cAMB
Active Comparator: SOC Induction / SOC Consolidation; Standard of care induction therapy (IV AMB + 5FC) followed by 4 weeks of standard of care consolidation therapy (fluconazole)	Drug: Amphotericin B; Intravenous Amphotericin B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	All-cause mortality	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Meningitis-free survival	Survival time without Cryptococcus culture-positive relapse of meningitis	10 weeks
Evidence of fungicidal activity	Rate of CSF Cryptococcus clearance (early fungicidal activity [EFA])	2 weeks
CSF culture sterility	cumulative incidence of CSF culture sterilization	10 weeks

Collaborators and Investigators

• Sponsor: Matinas BioPharma Nanotechnologies, Inc.
• Collaborators: University of Minnesota
• Investigators: Principal Investigator: David R Boulware, MD, University of Minnesota; Principal Investigator: David B Meya, MBChB, Infectious Diseases Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2023
• Primary Completion (Anticipated): October 1, 2024
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: September 12, 2022
• First Submitted That Met QC Criteria: September 12, 2022
• First Posted (Actual): September 15, 2022

Study Record Updates

• Last Update Posted (Actual): September 15, 2022
• Last Update Submitted That Met QC Criteria: September 12, 2022
• Last Verified: September 1, 2022

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-70018; CTA 0217 (Other Identifier: Uganda National Drug Authority (NDA))

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