HivPhase 2/3PLATFORM-CMNCT06666322
Platform Trial For Cryptococcal Meningitis (PLATFORM-CM)
A Phase 2/3 study testing Oteseconazole - antifungal therapy 1, Turletricin injection - antifungal therapy 2 and Turletricin Injection - antifungal therapy 3 in people with Hiv and Cryptococcal Meningitis, run by David Boulware at 2 sites in Uganda.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hiv, Cryptococcal Meningitis
- What is being tested?
- Oteseconazole - antifungal therapy 1, Turletricin injection - antifungal therapy 2 and Turletricin Injection - antifungal therapy 3
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,000 participants
- Where
- 2 sitesUganda
- Study dates
- 28 May 2025to 21 Apr 2032
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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
- CSF cryptococcal antigen (CrAg) positive meningitis
- Living with HIV
- 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).
Who cannot join
- Received 3 or more doses of antifungal therapy for meningitis within last 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)
Show all 10Show fewer
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Uganda2 sites, 2 recruiting
- Recruiting
Infectious Diseases Institute
Kampala
David Meya, PhD, david.meya@gmail.com
- Recruiting
Mbarara University of Science and Technology
Mbarara
Conrad Muzoora, MBChB MMed, 256772547175, conradmuzoora@gmail.com
About this study
Official title: Platform Trial For Cryptococcal Meningitis
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.
- Conditions
- Hiv, Cryptococcal Meningitis
- Being tested
- Standard of care, Oteseconazole - antifungal therapy 1, Turletricin injection - antifungal therapy 2, Turletricin Injection - antifungal therapy 3, Oteseconazole with Flucytosine - antifungal therapy 4
- Keywords
- cryptococcus
- Medical subject headings
- Acquired Immunodeficiency Syndrome, Meningitis, Cryptococcal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard of careDrug
2022 WHO First Line Induction Therapy:
- Liposomal Amphotericin B 10mg/kg IV given once
- Flucytosine 100mg/kg/day for 14 days in divided doses
- 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 1Drug
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.
Turletricin injection - antifungal therapy 2Drug
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
Turletricin Injection - antifungal therapy 3Drug
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 with Flucytosine - antifungal therapy 4Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Control group | Active comparator | randomized to standard of care Receives: Drug: Standard of care |
| Experimental group 1 | Experimental | randomized to experimental antifungal therapy #1 Receives: Drug: Oteseconazole - antifungal therapy 1 |
| Experimental group 2 | Experimental | randomized to experimental antifungal therapy #2 Receives: Drug: Turletricin injection - antifungal therapy 2 |
| Experimental group 3 | Experimental | randomized to experimental antifungal therapy #3 Receives: Drug: Turletricin Injection - antifungal therapy 3 |
| Experimental group 4 | Experimental | randomized to experimental antifungal therapy #4 Receives: Drug: Oteseconazole with Flucytosine - antifungal therapy 4 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 weeks
All-cause mortality
measured at 2-weeks
Measured: 2 weeks
Secondary outcomes (9)
Desirability of Outcome Response (DOOR) as ordinal ranked maximum score tested by Win Ratio.
- Death by 18-weeks
- Serious Adverse Event through 18 weeks (e.g. all-cause re- hospitalization, permanent neurologic deficit, etc.), lost to follow up before 10-weeks.
- Grade 4 lab adverse event by 10 weeks, early discontinuation of study drug, or lost to follow up after 10 weeks.
- Grade 3 lab adverse event by 10 weeks OR study drug interruption or dose reduction
- Survival through 18-weeks
Measured: 18 weeks
Survival time through 18 weeks without Cryptococcus culture-positive relapse of meningitis
number of participants
Measured: 18 weeks
CSF culture sterility (cumulative incidence over 18 weeks)
Measured: 18 weeks
18-week survival time
Measured: 18 weeks
Use of rescue/additional IV amphotericin beyond scheduled use
Measured: 18 weeks
Modified Rankin score on functional status at 18 weeks
Measured: 18 weeks
Incidence of laboratory abnormalities by Grade 1-5
Measured: 10 weeks
Incidence of serious adverse events
Measured: 18 weeks
Incidence of study drug discontinuation or interruption >1 day due to toxicity, by adverse event grade.
Measured: 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2024
- Study start28 May 2025
- Primary completion21 Apr 2032 (estimated)
- Study completion21 Apr 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HivStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- David Boulware
- Sponsor type
- University, hospital or other
- Collaborators
- Infectious Diseases Institute, Uganda, University of Minnesota
- Responsible party
- Sponsor-investigator, David Boulware, University of Minnesota
- Investigators
- David R Boulware, MD, MPH, Principal investigator, University of MinnesotaDavid B Meya, MBChB, MMed, PhD, Principal investigator, Uganda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06666322
- Sponsor's protocol ID
- IDIM-2024-32879
- Acronym
- PLATFORM-CM
- Status last verified
- Jul 2026
- First submitted
- 29 Oct 2024
- Last updated
- 27 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified dataset will be shared after publication in accordance with ICJME standards.
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Platform Trial For Cryptococcal Meningitis
- ClinicalTrials.gov ID
- NCT06666322
- Acronym / sponsor ID
- PLATFORM-CM / IDIM-2024-32879
- Conditions
- Hiv, Cryptococcal Meningitis
- Keywords
- cryptococcus
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- David BoulwareUniversity, hospital or other
- Collaborators
- Infectious Diseases Institute, Uganda, University of Minnesota
- Study start
- 28 May 2025 (actual)
- Primary completion
- 21 Apr 2032 (estimated)
- Study completion
- 21 Apr 2032 (estimated)
- First posted
- 30 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Control group | Active comparator | Drug: Standard of carerandomized to standard of care |
| Experimental group 1 | Experimental | Drug: Oteseconazole - antifungal therapy 1randomized to experimental antifungal therapy #1 |
| Experimental group 2 | Experimental | Drug: Turletricin injection - antifungal therapy 2randomized to experimental antifungal therapy #2 |
| Experimental group 3 | Experimental | Drug: Turletricin Injection - antifungal therapy 3randomized to experimental antifungal therapy #3 |
| Experimental group 4 | Experimental | Drug: Oteseconazole with Flucytosine - antifungal therapy 4randomized to experimental antifungal therapy #4 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- CSF cryptococcal antigen (CrAg) positive meningitis
- Living with HIV
- Ability and willingness to provide informed consent
- Willing to receive protocol-specified lumbar punctures
- Age >= 18 years
Key exclusion criteria (10 listed)
- Received 3 or more doses of antifungal therapy for meningitis within last 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard of care2022 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 | Control group |
| Oteseconazole - antifungal therapy 1Oteseconazole, 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 | Experimental group 1 |
| Turletricin injection - antifungal therapy 2SF001 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 | Experimental group 2 |
| Turletricin Injection - antifungal therapy 3SF001 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 | Drug | Experimental group 3 |
| Oteseconazole with Flucytosine - antifungal therapy 4Oteseconazole, 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. | Drug | Experimental group 4 |
Primary outcome
Rate of cerebrospinal fluid (CSF) Cryptococcus clearance (Early Fungicidal Activity, or EFA)
Time frame: 2 weeks
quantified by the change of log 10 Cryptococcus CFU/mL CSF/day as measured by serial quantitative CSF fungal cultures over ~2 weeks.
All-cause mortality
Time frame: 2 weeks
measured at 2-weeks
9 secondary outcomes
Desirability of Outcome Response (DOOR) as ordinal ranked maximum score tested by Win Ratio.
Time frame: 18 weeks
Survival time through 18 weeks without Cryptococcus culture-positive relapse of meningitis
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2026.
- Individual participant dataSharing planned: Yes. De-identified dataset will be shared after publication in accordance with ICJME standards.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
David R Boulware, MD, MPH principal investigator
University of Minnesota
David B Meya, MBChB, MMed, PhD principal investigator
Uganda
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Oteseconazole - antifungal therapy 1, Turletricin injection - antifungal therapy 2 and Turletricin Injection - antifungal therapy 3 in people with Hiv and Cryptococcal Meningitis, run by David Boulware at 2 sites 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 6 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 27 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact David Boulware, MD, MPH (612-624-9996, coat.trial@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of cerebrospinal fluid (CSF) Cryptococcus clearance (Early Fungicidal Activity, or EFA) (time frame: 2 weeks). 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?
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 27 Jul 2026.