Clinical trial NCT04031833: Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial (EnACT)
Official title: Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cryptococcal Meningitis
Lead sponsor: Matinas BioPharma Nanotechnologies, Inc.
Sponsor class: INDUSTRY
Collaborators: name: University of Minnesota
First posted: 2019-07-24
Enrollment: 178
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase I: Persons in Uganda without meningitis or active infections Phase II: HIV-infected persons in Uganda with cryptococcal meningitis
Primary purpose: TREATMENT

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.

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.

Eligibility 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)

Primary outcomes:
measure: Highest dose tolerated without inducing vomiting
timeFrame: 7 days
measure: Evidence of fungicidal activity
timeFrame: 2 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Kampala
country: Uganda
facility: Infectious Disease Institute
Study officials:
References:
citation: 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.