Recruiting
Phase 2
Phase 3

Cryptococcal Meningitis

Sponsor:

University of Minnesota

Code:

NCT06666322

Conditions

Hiv

Cryptococcal Meningitis

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Standard of care

Oteseconazole - antifungal therapy 1

Sfu-AM2-19 Injection - antifungal therapy 2

Antifungal therapy 3

Antifungal therapy 4

Study Details

Brief summary:

Cryptococcal meningitis is a fungal infection that causes a severe syndrome of meningitis that is 100% fatal without antifungal therapy. Even with antifungal therapy, mortality rates remain high, especially in low and middle income countries where the ongoing HIV/AIDS pandemic increases the risk of cryptococcosis among persons living with HIV infection. The combination of amphotericin and flucytosine (5-FC) has been the mainstay of therapy for the initial management of cryptococcal meningitis for 4 decades. Indeed, the effective delivery of these first line therapy in Africa can lower mortality to 25%. However, several challenges exist. First, even while 5-FC is included on the WHO list of essential medicines, the availability of 5-FC worldwide is limited. Second, liposomal amphotericin (Ambisome ®) is currently available from a single source supplier, creating risk. Third, current therapies have substantial toxicity. Lastly, with widespread agricultural fungicide use of azoles, the median fluconazole minimum inhibitory concentration (MIC50 ) for Cryptococcus has doubled since 2013. Globally, new or improved antifungals are needed for cryptococcal meningitis, particularly those which have less toxicity, greater efficacy, a prolonged half-life, and minimal drug-drug interactions. As multiple new antifungal medicines are on the horizon, this platform trial utilizes a master protocol to investigate, multiple regimens using standardized eligibility criteria, standardized study schedule of events, and standardized contemporary endpoints.

Conditions

Hiv

Cryptococcal Meningitis

Study ID

NCT06666322

Start date

May 28, 2025

Status verified date

May, 2025

Completion date

Apr 21, 2032

Anticipated

Primary completion date

Apr 21, 2032

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • CSF cryptococcal antigen (CrAg) positive meningitis
  • HIV positive
  • Ability and willingness to provide informed consent
  • Willing to receive protocol-specified lumbar punctures
  • Age >= 18 years
  • Female participants of childbearing potential who are participating in sexual activity that could lead to pregnancy must agree to use reliable forms of contraception (duration will be indicated in each Trial Appendix).

Exclusion Criteria:

  • Received >= 3 doses of antifungal therapy for meningitis treatment or > 6mg/kg of liposomal amphotericin B cumulatively within prior 30 days
  • Inability to take enteral (oral or nasogastric) medicine
  • Cannot or unlikely to attend regular clinic visits
  • Receiving chemotherapy or corticosteroids
  • Receiving hemodialysis or known liver cirrhosis
  • Suspected Paradoxical immune reconstitution inflammatory syndrome (IRIS)
  • Pregnancy or breastfeeding
  • Previous administration of investigational study drug
  • Any condition for which participation would not be in the best interest of the participant or that could limit protocol specified assessments
  • Trial Appendix study-drug specific eligibility criteria

Study Design

Enrollment

2000 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Control group

randomized to standard of care

experimental: Experimental group 1

randomized to experimental antifungal therapy #1

experimental: Experimental group 2

randomized to experimental antifungal therapy #2

experimental: Experimental group 3

randomized to experimental antifungal therapy #3

experimental: Experimental group 4

randomized to experimental antifungal therapy #4

Interventions

Standard of care

2022 WHO First Line Induction Therapy:

1. Liposomal Amphotericin B 10mg/kg IV given once
2. Flucytosine 100mg/kg/day for 14 days in divided doses
3. Fluconazole 1200mg/day for 14 days Consolidation Therapy: Fluconazole 800mg/day from 2 to 10 weeks Secondary Prophylaxis: Fluconazole 200mg/day through 1 year minimum

Oteseconazole - antifungal therapy 1

Oteseconazole, is an azole metalloenzyme inhibitor targeting the fungal sterol, 14α demethylase (CYP51)

  • Loading doses of oral Oteseconazole 600 mg twice daily for 10 days, then 600 mg oteseconazole weekly on weeks 3, 4, 5, and 6.
  • Liposomal Amphotericin B 10 mg/kg IV once.
  • No fluconazole or 5FC to be given.

Sfu-AM2-19 Injection - antifungal therapy 2

Ambisome 10 mg/kg IV administered once Fluconazole 1200mg/day and flucytosine 100mg/day in divided doses x 14 days OR SF001 1.5 mg/kg IV administered on day 1, followed by 1.5 mg/kg on day 8 Fluconazole 1200mg/day and flucytosine 100mg/day in divided doses x 14 days OR SF001 2.0 mg/kg IV administered on day 1, followed by 1.5 mg/kg on day 8 Fluconazole 1200mg/day and flucytosine 100mg/day in divided doses x 14 days

Antifungal therapy 3

To be determined

Antifungal therapy 4

To be determined

Primary outcome measure

  • Rate of cerebrospinal fluid (CSF) Cryptococcus clearance (Early Fungicidal Activity, or EFA) [ Time Frame: 2 weeks ]
  • All-cause mortality [ Time Frame: 2 weeks ]

Central Contacts and Locations

Central contacts

David Boulware, MD, MPH

boulw001@umn.edu

Locations

University of Minnesota

Recruiting

Minneapolis, Minnesota, United States, 55455

Contacts

David Boulware, MD

612-624-9996boulw001@umn.edu

More Information

Sponsor

University of Minnesota

Last update posted

May 31, 2025

Last verified

May, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Minnesota on 2025-05-31.