AzTrials
AzTrials

Cryptococcal MeningitisPhase 1/2EnACTNCT04031833

Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial (EnACT)

A Phase 1/2 study testing MAT2203 and Amphotericin B in people with Cryptococcal Meningitis, run by Matinas BioPharma Nanotechnologies, Inc. at 1 site in Uganda.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cryptococcal Meningitis
What is being tested?
MAT2203 and Amphotericin B
Could I receive a placebo?
No, everyone receives an active treatment
How many people
178 participants
Where
1 siteUganda
Study dates
24 Oct 2019to 15 Feb 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 15Show fewer
  • 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)

Trial locations and contacts

1 site in 1 country.

Uganda1 site

  • Infectious Disease Institute

    Kampala

Other trials in Uganda

About this study

Official title: Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial

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.

Read the 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.

Being tested
MAT2203, Amphotericin B
Medical subject headings
Meningitis, Cryptococcal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MAT2203Drug

    Also called oral amphotericin B

    Encochleated amphotericin B

  • Amphotericin BDrug

    Intravenous amphotericin B

Study groups in NCT04031833
Study groupRoleWhat they receive
Phase 1a single ascending dose studyExperimentalPhase IA will consist of a single ascending dose study in 9 participants to test three doses to determine the max tolerated dose.
Receives: Drug: MAT2203
Phase 1b multiple day dosingExperimental9 subjects will receive the Phase Ia 100% tolerated MAT2203 dose for 7 days.
Receives: Drug: MAT2203
Phase 2 safety and tolerabilityExperimentalSafety, tolerability, and microbiologic efficacy of MAT2203 among HIV-infected patients with cryptococcal meningitis compared with standard IV AMB.
Receives: Drug: MAT2203; Drug: Amphotericin B

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Highest dose tolerated without inducing vomiting

    Proportion of cAMB daily dose received and tolerated without vomiting within 30 minutes.

    Measured: 7 days

  2. Evidence of fungicidal activity

    CSF early fungicidal activity (EFA) during 2-week induction therapy

    Measured: 2 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jul 2019
  2. Study start24 Oct 2019
  3. Primary completion14 Nov 2022
  4. Study completion15 Feb 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
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)
Enrolment
178 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04031833
Sponsor's protocol ID
MB-70007
Acronym
EnACT
Status last verified
Mar 2023
First submitted
22 Jul 2019
Last updated
31 Mar 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Ahimbisibwe C, Kwizera R, Ndyetukira JF, Namujju OC, Sadiq A, Atukunda M, Skipper CP, Boulware DR, Meya DB. Experience of research nurses with oral encochleated amphotericin B for treatment of cryptococcal meningitis in a resource-limited setting. BMC Infect Dis. 2025 Jul 15;25(1):920. doi: 10.1186/s12879-025-11319-1.

    PubMed 40665233

  • Sadiq A, Kwizera R, Kiiza TK, Ayebare P, Ahimbisibwe C, Ndyetukira JF, Boulware DR, Meya DB. Experiences, challenges, gaps, and strategies for counselling persons presenting with advanced HIV-associated meningitis in Uganda. AIDS Res Ther. 2025 Feb 19;22(1):21. doi: 10.1186/s12981-025-00705-z.

    PubMed 39972326

  • Kimuda S, Kwizera R, Dai B, Kigozi E, Kasozi D, Rutakingirwa MK, Tukundane A, Shifah N, Luggya T, Luswata A, Ndyetukira JF, Yueh SL, Mulwana S, Wele A, Bahr NC, Meya DB, Boulware DR, Skipper CP. Comparison of Early Fungicidal Activity and Mortality Between Daily Liposomal Amphotericin B and Daily Amphotericin B Deoxycholate for Cryptococcal Meningitis. Clin Infect Dis. 2025 Feb 5;80(1):153-159. doi: 10.1093/cid/ciae326.

    PubMed 38943665

  • Boulware DR, Atukunda M, Kagimu E, Musubire AK, Akampurira A, Tugume L, Ssebambulidde K, Kasibante J, Nsangi L, Mugabi T, Gakuru J, Kimuda S, Kasozi D, Namombwe S, Turyasingura I, Rutakingirwa MK, Mpoza E, Kigozi E, Muzoora C, Ellis J, Skipper CP, Matkovits T, Williamson PR, Williams DA, Fieberg A, Hullsiek KH, Abassi M, Dai B, Meya DB. Oral Lipid Nanocrystal Amphotericin B for Cryptococcal Meningitis: A Randomized Clinical Trial. Clin Infect Dis. 2023 Dec 15;77(12):1659-1667. doi: 10.1093/cid/ciad440.

    PubMed 37606364

  • 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.

    PubMed 32747357

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing MAT2203 and Amphotericin B in people with Cryptococcal Meningitis, run by Matinas BioPharma Nanotechnologies, Inc. at 1 site in Uganda.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Highest dose tolerated without inducing vomiting (time frame: 7 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04031833, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in