Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial (EnACT)

Cryptococcal Meningitis Clinical Trial

— EnACT  

Official title:

Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04031833
• Other study ID #: MB-70007
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 24, 2019
• Est. completion date: February 15, 2023

Study information

• Verified date: March 2023
• Source: Matinas BioPharma Nanotechnologies, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 178
• Est. completion date: February 15, 2023
• Est. primary completion date: November 14, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Cryptococcal Meningitis
• Meningitis
• Meningitis, Cryptococcal

Intervention

Drug:
• MAT2203
Encochleated amphotericin B
• Amphotericin B
Intravenous amphotericin B

Locations

Country	Name	City	State
Uganda	Infectious Disease Institute	Kampala

Sponsors (2)

Lead Sponsor	Collaborator
Matinas BioPharma Nanotechnologies, Inc.	University of Minnesota

Country where clinical trial is conducted

Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Highest dose tolerated without inducing vomiting	Proportion of cAMB daily dose received and tolerated without vomiting within 30 minutes.	7 days
Primary	Evidence of fungicidal activity	CSF early fungicidal activity (EFA) during 2-week induction therapy	2 weeks