Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial 3

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

Detailed Description
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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.

Official Title
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Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial 3

Conditions
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Cryptococcal Meningitis

Intervention / Treatment
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* Drug: MAT2203
* Drug: Amphotericin B


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MAT2203 Induction / MAT2203 Consolidation<br>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<br>* oral lipid nanocrystal amphotericin B<br>* Other names: cAMB;|
| Experimental: MAT2203 Induction / SOC Consolidation<br>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<br>* oral lipid nanocrystal amphotericin B<br>* Other names: cAMB;|
| Active Comparator: SOC Induction / SOC Consolidation<br>Standard of care induction therapy (IV AMB + 5FC) followed by 4 weeks of standard of care consolidation therapy (fluconazole) | Drug: Amphotericin B<br>* Intravenous Amphotericin B<br>|

What is the study measuring?
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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 |