A Phase 2/3 interventional study of Standard of care and Oteseconazole - antifungal therapy 1 in Hiv and Cryptococcal Meningitis, sponsored by David Boulware. Recruiting at 2 sites in Uganda. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-27.
Sponsored by David Boulware · Phase 2/3, Interventional, and Treatment
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 antifungal regimens using standardized eligibility criteria, standardized study schedule of events, and standardized contemporary endpoints.
54 studies on the registry are indexed under Meningitis, Cryptococcal; 6 are open to participants now.
This study's planned enrollment of 2,000 is above the median of 143 across 35 interventional studies indexed under Meningitis, Cryptococcal.
Browse Meningitis, Cryptococcal studies →David Boulware is the lead sponsor of 2 studies on the registry; 2 are open to participants now.
Compared within Meningitis, Cryptococcal, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Acquired Immunodeficiency Syndrome. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
randomized to standard of care
Drug: Standard of care
randomized to experimental antifungal therapy #1
Drug: Oteseconazole - antifungal therapy 1
randomized to experimental antifungal therapy #2
Drug: Turletricin injection - antifungal therapy 2
randomized to experimental antifungal therapy #3
Drug: Turletricin Injection - antifungal therapy 3
randomized to experimental antifungal therapy #4
Drug: Oteseconazole with Flucytosine - antifungal therapy 4
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, 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.
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
SF001 3.0 mg/kg IV administered on day 1, 8, and 15 with fluconazole 1200mg/day and flucytosine 100mg/day in divided doses x 14 days
Oteseconazole, is an azole metalloenzyme inhibitor targeting the fungal sterol, 14α demethylase (CYP51) ● Loading doses of oral Oteseconazole 600 mg twice daily for 12 days, then 600 mg oteseconazole weekly on weeks 3 to 12. ● Liposomal Amphotericin B 10 mg/kg IV once. ● Flucytosine 100mg/kg given for 7 days.
Rate of cerebrospinal fluid (CSF) Cryptococcus clearance (Early Fungicidal Activity, or EFA)
quantified by the change of log 10 Cryptococcus CFU/mL CSF/day as measured by serial quantitative CSF fungal cultures over \~2 weeks.
Time frame: 2 weeks
All-cause mortality
measured at 2-weeks
Time frame: 2 weeks
Desirability of Outcome Response (DOOR) as ordinal ranked maximum score tested by Win Ratio.
1. Death by 18-weeks 2. Serious Adverse Event through 18 weeks (e.g. all-cause re- hospitalization, permanent neurologic deficit, etc.), lost to follow up before 10-weeks. 3. Grade 4 lab adverse event by 10 weeks, early discontinuation of study drug, or lost to follow up after 10 weeks. 4. Grade 3 lab adverse event by 10 weeks OR study drug interruption or dose reduction 5. Survival through 18-weeks
Time frame: 18 weeks
Survival time through 18 weeks without Cryptococcus culture-positive relapse of meningitis
number of participants
Time frame: 18 weeks
CSF culture sterility (cumulative incidence over 18 weeks)
Time frame: 18 weeks
18-week survival time
Time frame: 18 weeks
Use of rescue/additional IV amphotericin beyond scheduled use
Time frame: 18 weeks
Modified Rankin score on functional status at 18 weeks
Time frame: 18 weeks
Incidence of laboratory abnormalities by Grade 1-5
Time frame: 10 weeks
Incidence of serious adverse events
Time frame: 18 weeks
Incidence of study drug discontinuation or interruption >1 day due to toxicity, by adverse event grade.
Time frame: 10 weeks
Plan to share: Yes — De-identified dataset will be shared after publication in accordance with ICJME standards.
Supporting information: Study protocol, Statistical analysis plan
Data sharing details ↗ · dataverse.harvard.edu
No publications or documents are linked to this record.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.