Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial 3

Phase 3

Not yet recruiting

• Conditions: Cryptococcal Meningitis
• Interventions: Drug: MAT2203; Drug: Amphotericin B

• Registration Number: NCT05541107
• Lead Sponsor: Matinas BioPharma Nanotechnologies, Inc.

Brief Summary

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

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 Timeline

• Status Verified: 2022-09
• Study First Submitted: 2022-09-12
• Study First Submitted QC: 2022-09-12
• Last Update Submitted: 2022-09-12
• Study First Posted: 2022-09-15
• Last Update Posted: 2022-09-15
• Study Start: 2023-01
• Primary Completion: 2024-10
• Study Completion: 2025-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 270

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MAT2203 Induction / MAT2203 Consolidation	MAT2203	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
MAT2203 Induction / SOC Consolidation	MAT2203	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
SOC Induction / SOC Consolidation	Amphotericin B	Standard of care induction therapy (IV AMB + 5FC) followed by 4 weeks of standard of care consolidation therapy (fluconazole)

Primary Outcome Measures

Name	Time	Method
Survival	2 weeks	All-cause mortality

Secondary Outcome Measures

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