Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial (EnACT) (EnACT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04031833
Recruitment Status : Recruiting
First Posted : July 24, 2019
Last Update Posted : November 1, 2019
Sponsor:
Collaborator:
University of Minnesota
Information provided by (Responsible Party):
Matinas BioPharma Nanotechnologies, Inc.

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.

Condition or disease Intervention/treatment Phase
Cryptococcal Meningitis Drug: MAT2203 Drug: Amphotericin B Phase 1 Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 176 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Phase I: Persons in Uganda without meningitis or active infections Phase II: HIV-infected persons in Uganda with cryptococcal meningitis
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial
Actual Study Start Date : October 24, 2019
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Meningitis

Arm Intervention/treatment
Experimental: Phase 1a single ascending dose study
Phase IA will consist of a single ascending dose study in 9 participants to test three doses to determine the max tolerated dose.
Drug: MAT2203
Encochleated amphotericin B
Other Name: oral amphotericin B

Experimental: Phase 1b multiple day dosing
9 subjects will receive the Phase Ia 100% tolerated MAT2203 dose for 7 days.
Drug: MAT2203
Encochleated amphotericin B
Other Name: oral amphotericin B

Experimental: Phase 2 safety and tolerability
Safety, tolerability, and microbiologic efficacy of MAT2203 among HIV-infected patients with cryptococcal meningitis compared with standard IV AMB.
Drug: MAT2203
Encochleated amphotericin B
Other Name: oral amphotericin B

Drug: Amphotericin B
Intravenous amphotericin B




Primary Outcome Measures :
  1. Highest dose tolerated without inducing vomiting [ Time Frame: 7 days ]
    Proportion of cAMB daily dose received and tolerated without vomiting within 30 minutes.

  2. Evidence of fungicidal activity [ Time Frame: 2 weeks ]
    CSF early fungicidal activity (EFA) during 2-week induction therapy



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04031833


Contacts
Layout table for location contacts
Contact: Theresa Matkovits, Ph.D 862 812-1436 tmatkovits@matinasbiopharma.com
Contact: David Boulware, MD 612 626-9546 boulw001@umn.edu

Locations
Layout table for location information
Uganda
Infectious Disease Institute Recruiting
Kampala, Uganda
Contact: David Meya, MD       david.meya@gmail.com   
Contact: Abdu Musubire, MD    256 77 266 6139    amusubire@gmail.com   
Sponsors and Collaborators
Matinas BioPharma Nanotechnologies, Inc.
University of Minnesota

Layout table for additonal information
Responsible Party: Matinas BioPharma Nanotechnologies, Inc.
ClinicalTrials.gov Identifier: NCT04031833    
Other Study ID Numbers: MB-70007
First Posted: July 24, 2019    Key Record Dates
Last Update Posted: November 1, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Meningitis, Cryptococcal
Meningitis
Central Nervous System Diseases
Nervous System Diseases
Meningitis, Fungal
Central Nervous System Fungal Infections
Mycoses
Cryptococcosis
Central Nervous System Infections
Amphotericin B
Liposomal amphotericin B
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Anti-Bacterial Agents
Antifungal Agents