Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial 3 (EnACT3)
Primary Purpose
Cryptococcal Meningitis
Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
MAT2203
Amphotericin B
Sponsored by
About this trial
This is an interventional treatment trial for Cryptococcal Meningitis
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
MAT2203 Induction / MAT2203 Consolidation
MAT2203 Induction / SOC Consolidation
SOC Induction / SOC Consolidation
Arm Description
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
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
Standard of care induction therapy (IV AMB + 5FC) followed by 4 weeks of standard of care consolidation therapy (fluconazole)
Outcomes
Primary Outcome Measures
Survival
All-cause mortality
Secondary Outcome Measures
Meningitis-free survival
Survival time without Cryptococcus culture-positive relapse of meningitis
Evidence of fungicidal activity
Rate of CSF Cryptococcus clearance (early fungicidal activity [EFA])
CSF culture sterility
cumulative incidence of CSF culture sterilization
Full Information
NCT ID
NCT05541107
First Posted
September 12, 2022
Last Updated
September 12, 2022
Sponsor
Matinas BioPharma Nanotechnologies, Inc.
Collaborators
University of Minnesota
1. Study Identification
Unique Protocol Identification Number
NCT05541107
Brief Title
Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial 3
Acronym
EnACT3
Official Title
Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial 3
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 2023 (Anticipated)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
January 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Matinas BioPharma Nanotechnologies, Inc.
Collaborators
University of Minnesota
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cryptococcal Meningitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
270 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
MAT2203 Induction / MAT2203 Consolidation
Arm Type
Experimental
Arm Description
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
Arm Title
MAT2203 Induction / SOC Consolidation
Arm Type
Experimental
Arm Description
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
Arm Title
SOC Induction / SOC Consolidation
Arm Type
Active Comparator
Arm Description
Standard of care induction therapy (IV AMB + 5FC) followed by 4 weeks of standard of care consolidation therapy (fluconazole)
Intervention Type
Drug
Intervention Name(s)
MAT2203
Other Intervention Name(s)
cAMB
Intervention Description
oral lipid nanocrystal amphotericin B
Intervention Type
Drug
Intervention Name(s)
Amphotericin B
Intervention Description
Intravenous Amphotericin B
Primary Outcome Measure Information:
Title
Survival
Description
All-cause mortality
Time Frame
2 weeks
Secondary Outcome Measure Information:
Title
Meningitis-free survival
Description
Survival time without Cryptococcus culture-positive relapse of meningitis
Time Frame
10 weeks
Title
Evidence of fungicidal activity
Description
Rate of CSF Cryptococcus clearance (early fungicidal activity [EFA])
Time Frame
2 weeks
Title
CSF culture sterility
Description
cumulative incidence of CSF culture sterilization
Time Frame
10 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Theresa Matkovits, PhD
Phone
908-505-0975
Email
tmatkovits@matinasbiopharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David R Boulware, MD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David B Meya, MBChB
Organizational Affiliation
Infectious Diseases Institute
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial 3
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