NCT06666322

Platform Trial For Cryptococcal Meningitis

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 2,000 (estimated)
• Sponsor: University of Minnesota · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
DRUG	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
DRUG	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.
DRUG	Sfu-AM2-19 Injection - antifungal therapy 2	SF001 2.0 mg/kg IV administered on day 1, followed by 1.5 mg/kg on day 8 with Fluconazole 1200mg/day and flucytosine 100mg/day in divided doses x 14 days
DRUG	Antifungal therapy 3	To be determined
DRUG	Antifungal therapy 4	To be determined

Timeline

• Start date: 2025-05-28
• Primary completion: 2032-04-21
• Completion: 2032-04-21
• First posted: 2024-10-30
• Last updated: 2026-01-07

Locations

2 sites across 1 country: Uganda

Regulatory

• FDA-regulated drug study