Liposomal Amphotericin B and Flucytosine Antifungal Strategy for Talaromycosis (LAmB-FAST)

NCT ID: NCT06525389

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

428 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-04-01

Study Completion Date

2031-11-01

Brief Summary

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LAmB-FAST is a factorial randomized controlled trial simultaneously testing two interventions in one trial. LAmB-FAST seeks to inform treatment guidelines on the induction and maintenance therapy of HIV-associated talaromycosis (formerly called penicilliosis) and will answer the following three questions:

1. Is induction therapy using a single 10 mg\\/kg dose of liposomal amphotericin B (LAmB) is more effective than 14 days of the conventional deoxycholate amphotericin B (DAmB)?
2. Is adding flucytosine (5FC) to amphotericin B more effective than amphotericin B alone?
3. Is HIV viral load guided stopping of itraconazole maintenance therapy as effective as the current CD4 guided strategy in the prevention of talaromycosis relapse?

Detailed Description

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Talaromycosis (formerly known as penicilliosis) is caused by the dimorphic fungus Talaromyces marneffei (Tm) endemic in Southeast Asia where it is a leading the cause of death among people with advanced HIV disease (AHD, CD4 count \<200 cells/mm3 and/or WHO disease stage III or IV). Despite the mortality on treatment as high as 30%, current treatment options are limited to just two drugs: amphotericin B deoxycholate (DAmB) - which has substantial toxicity, and itraconazole - which has poor bioavailability.

As a roadmap to identify safer and more effective antifungal strategies, LAmB-FAST applies major advances made in HIV-associated mycoses to accelerate treatment for HIV-associated talaromycosis. First, clinical trials in cryptococcosis showed that shorter courses (5 to 7 days) of DAmB was as effective and less toxic than the standard 14-day course of DAmB. The recent AMBITION cryptococcal meningitis showed that a single 10 mg/kg dose of liposomal amphotericin B (LAmB) was as effective as 7 to 14 days of DAmB but had 30% less toxicity, leading to rapid endorsement by the WHO as the first-line therapy for cryptococcal meningitis in 2022. A single LAmB induction therapy strategy has also been demonstrated in a phase II HIV-associated histoplasmosis trial which showed that a single 10 mg/kg dose of LAmB had similar mortality compared to 2 doses or 14 daily doses of LAmB. Second, the addition of flucytosine (5FC) to DAmB has been shown to improves fungal clearance in the cerebrospinnal fluid and survival of patients with cryptococcal meningitis. These advances in other HIV-associated mycoses lead us to hypothesize that 1) a single 10mg/kg dose of LAmB will be superior to 14 days of DAmB and 2) the addition of 5FC will be superior to DAmB or LAmB alone in the induction therapy of talaromyosis.

LAmB-FAST will test three related but independent specific aims: AIM 1: To determine if a single 10mg/kg dose of LAmB is superior to 14 days of DAmB in Tm complication-free survival. AIM 2:

To determine if combination therapy with 5FC is superior to DAmB or LAmB alone in Tm complication-free survival.

The primary outcome (for both AIM 1 and AIM 2) is hazard of a composite of death, Tm complications, and adverse events (AEs) grade 3 or higher.

The secondary outcomes include:

1. All-cause mortality;
2. Fungal clearance rate over first 14 days;
3. A novel 4-scale hierarchical outcome of i. Mortality, ii. Tm complications, iii. AEs grade 3, iv. Quality of life scores;
4. Rates of Tm DNA and Tm antigen decline over first 12 weeks.

AIM 3 will leverage access to a well-characterized and treated talaromycosis cohort in AIM 1 and AIM 2 to conduct a follow-on nested randomized controlled sub-study testing whether a HIV viral load guided strategy of stopping itraconazole chemoprophylaxis (STOP SHORT) is non-inferior to the current CD4 guided strategy in the prevention of talaromycosis relapse and death.

Conditions

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Talaromycosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Liposomal amphotericin B vs deoxycholate amphotericin B arm is an open label comparison

Flucytosine vs no flucytosine is a placebo controlled comparison

Study Groups

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Deoxycholate Amphotericin B (DAmB) plus Flucytosine (5FC) placebo

DAmB (0.7mg/kg/d IV x 14 days) + 5FC placebo (25 mg/kg oral 3x daily x 14 days)

Group Type ACTIVE_COMPARATOR

Flucytosine (5FC) placebo pill

Intervention Type DRUG

Similar in appearance to flucytosine. Also dosed at 25mg/kg oral 3x daily.

Deoxycholate Amphotericin B (DAmB)

Intervention Type DRUG

Antifungal dosed at 0.7 mg/kg/day IV x 2 weeks.

Deoxycholate Amphotericin B (DAmB) plus Flucytosine (5FC)

DAmB (0.7 mg/kg/d IV x 14 days) + 5FC (25 mg/kg oral 3x daily x 14 days)

Group Type EXPERIMENTAL

Flucytosine (5FC)

Intervention Type DRUG

Antifungal dosed at 25mg/kg oral 3x daily.

Deoxycholate Amphotericin B (DAmB)

Intervention Type DRUG

Antifungal dosed at 0.7 mg/kg/day IV x 2 weeks.

Liposomal Amphotericin B (LAmB) plus Flucytosine (5FC) placebo

LAmB (10 mg/kg IV x 1 dose) + 5FC placebo (25 mg/kg oral 3x daily x 14 days)

Group Type EXPERIMENTAL

Flucytosine (5FC) placebo pill

Intervention Type DRUG

Similar in appearance to flucytosine. Also dosed at 25mg/kg oral 3x daily.

Liposomal Amphotericin B (LAmB)

Intervention Type DRUG

Antifungal dosed at 10 mg/kg/day IV x one single dose.

Liposomal Amphotericin B (LAmB) plus Flucytosine (5FC)

LAmB (10 mg/kg IV x 1 dose) + 5FC (25 mg/kg oral 3x daily x 14 days)

Group Type EXPERIMENTAL

Flucytosine (5FC)

Intervention Type DRUG

Antifungal dosed at 25mg/kg oral 3x daily.

Liposomal Amphotericin B (LAmB)

Intervention Type DRUG

Antifungal dosed at 10 mg/kg/day IV x one single dose.

Interventions

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Flucytosine (5FC)

Antifungal dosed at 25mg/kg oral 3x daily.

Intervention Type DRUG

Flucytosine (5FC) placebo pill

Similar in appearance to flucytosine. Also dosed at 25mg/kg oral 3x daily.

Intervention Type DRUG

Deoxycholate Amphotericin B (DAmB)

Antifungal dosed at 0.7 mg/kg/day IV x 2 weeks.

Intervention Type DRUG

Liposomal Amphotericin B (LAmB)

Antifungal dosed at 10 mg/kg/day IV x one single dose.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* HIV infected adults (age greater or equal to 18), on ART or no ART
* Definitive talaromycosis confirmed by microscopy, histology, or culture

Exclusion Criteria

* Known severe allergy to AmB or 5FC
* Absolute neutrophil count \<500 cells
* Concurrent cryptococcal or TB meningitis
* Received \> 2 doses of DAmB
* Pregnancy
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

Pham Ngoc Thach University of Medicine

OTHER

Sponsor Role collaborator

Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

OTHER

Sponsor Role collaborator

National Hospital for Tropical Diseases, Hanoi, Vietnam

OTHER_GOV

Sponsor Role collaborator

Bach Mai Hospital

OTHER

Sponsor Role collaborator

Gilead Sciences

INDUSTRY

Sponsor Role collaborator

Viatris Inc.

INDUSTRY

Sponsor Role collaborator

Duke University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Thuy Le, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

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Duke University Medical Center

Durham, North Carolina, United States

Site Status

Bach Mai Hospital

Hanoi, , Vietnam

Site Status

National Hospital for Tropical Diseases

Hanoi, , Vietnam

Site Status

Hospital for Tropical Diseases

Ho Chi Minh City, , Vietnam

Site Status

Pham Ngoc Thach University of Medicine

Ho Chi Minh City, , Vietnam

Site Status

Countries

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United States Vietnam

Central Contacts

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Thuy Le, MD, PhD

Role: CONTACT

919-668-5053

Facility Contacts

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Thuy Le, MD, PhD

Role: primary

919-668-5053

Cuong D Do, MD, PhD

Role: primary

Thach N Pham, MD

Role: primary

Dung T Nguyen, MD

Role: primary

Ly T Vo, MD, PhD

Role: primary

Other Identifiers

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Pro00113856

Identifier Type: -

Identifier Source: org_study_id