Liposomal Amphotericin B + Flucytosine for Fungal Infection

(LAmB-FAST Trial)

Recruiting at 10 trial locations

Overseen By Thuy Le, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Duke University

Disqualifiers: Severe allergy, Neutropenia, Meningitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 14

428 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that participants should not have received more than 2 doses of conventional amphotericin B, which might imply some restrictions on similar treatments.

What evidence supports the effectiveness of the drug Liposomal Amphotericin B in treating fungal infections?

Liposomal Amphotericin B has been shown to be effective in treating various fungal infections, including those caused by Candida, Aspergillus, and Cryptococcus, with improved safety and tolerability compared to its conventional form. It is also recommended in international guidelines for treating these infections, and studies have reported high rates of fungal eradication in patients. ^{1 2 3 4 5}

Is liposomal Amphotericin B safe for human use?

Liposomal Amphotericin B is generally well tolerated in humans, with fewer and milder side effects compared to conventional Amphotericin B. It has been used safely in patients undergoing high-dose therapy and bone marrow transplantation, with only a few cases of adverse effects. ^{6 7 8 9 10}

How does the drug Liposomal Amphotericin B + Flucytosine differ from other treatments for fungal infections?

This drug combination is unique because Liposomal Amphotericin B is a less toxic form of the traditional antifungal Amphotericin B, reducing kidney-related side effects, while Flucytosine is an oral medication that is particularly effective for certain infections like cryptococcal meningitis. Together, they offer a potentially more tolerable and effective treatment option for fungal infections, especially in patients with compromised immune systems. ^{3 11 12 13 14}

What is the purpose of this trial?

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?

Research Team

Thuy Le, MD, PhD

Principal Investigator

Duke University

Eligibility Criteria

This trial is for individuals with HIV-associated talaromycosis, a fungal infection. Participants must meet certain health criteria to join, but specific inclusion and exclusion details are not provided here.

Inclusion Criteria

I am an adult with HIV, with or without antiretroviral therapy.

My infection has been confirmed by lab tests.

Exclusion Criteria

Known severe allergy to AmB or 5FC

Absolute neutrophil count less than 500 cells

Pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive either a single 10 mg/kg dose of liposomal amphotericin B (LAmB) or 14 days of deoxycholate amphotericin B (DAmB), with or without flucytosine (5FC)

14 days

Daily visits for 14 days

Maintenance Therapy

Participants receive itraconazole maintenance therapy, guided by either HIV viral load or CD4 count

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Treatment Details

Interventions

• Flucytosine
• Liposomal Amphotericin B

Trial Overview The LAmB-FAST trial is testing whether a single dose of Liposomal Amphotericin B (LAmB) is more effective than the standard 14-day treatment with Deoxycholate Amphotericin B (DAmB), and if adding Flucytosine (5FC) improves outcomes. It also examines different strategies for stopping maintenance therapy to prevent relapse.

Participant Groups

Group I: Liposomal Amphotericin B (LAmB) plus Flucytosine (5FC) placebo Experimental Treatment 2 Interventions

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

Group II: Liposomal Amphotericin B (LAmB) plus Flucytosine (5FC) Experimental Treatment 2 Interventions

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

Group III: Deoxycholate Amphotericin B (DAmB) plus Flucytosine (5FC) Experimental Treatment 2 Interventions

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

Group IV: Deoxycholate Amphotericin B (DAmB) plus Flucytosine (5FC) placebo Active Control 2 Interventions

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

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Pham Ngoc Thach University of Medicine

Collaborator

Trials

5

Recruited

2,700+

Maharat Nakhon Ratchasima Hospital

Collaborator

Trials

3

Recruited

3,800+

Chiang Mai University

Collaborator

Trials

136

Recruited

36,800+

Bach Mai Hospital

Collaborator

Trials

10

Recruited

29,300+

Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

Collaborator

Trials

23

Recruited

16,500+

Viatris Inc.

Industry Sponsor

Trials

11

Recruited

5,600+

National Hospital for Tropical Diseases, Hanoi, Vietnam

Collaborator

Trials

12

Recruited

12,500+

Gilead Sciences

Industry Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Collaborator

Trials

3

Recruited

10,500+

Findings from Research

Lipid formulations of amphotericin B, such as liposomal amphotericin B, show reduced renal toxicity compared to traditional amphotericin B deoxycholate, but no formulation has demonstrated superior efficacy in well-designed studies.

A recent study found that while a standard dose of liposomal amphotericin B showed a numerically better response rate for treating invasive fungal infections compared to a higher loading dose, the increased nephrotoxicity in the loading dose group suggests it should not be used in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Lipid formulations of amphotericin B in the management of invasive fungal infections]. Fohrer, C., Nivoix, Y., Moulin, JC., et al.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Review of comparative studies between conventional and liposomal amphotericin B (Ambisome) in neutropenic patients with fever of unknown origin and patients with systemic mycosis. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Treatment of cryptococcosis with liposomal amphotericin B (AmBisome) in 23 patients with AIDS. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Liposomal amphotericin B. Therapeutic use in the management of fungal infections and visceral leishmaniasis. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Liposomal amphotericin B-the past. [2022]

5. China pubmed.ncbi.nlm.nih.gov

[Clinical study of amphotericin B in the treatment of invasive fungal infection in 111 hematological disorder patients with neutrocytopenia]. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Experience with liposomal Amphotericin-B in 60 patients undergoing high-dose therapy and bone marrow or peripheral blood stem cell transplantation. [2019]

7. Italy pubmed.ncbi.nlm.nih.gov

Deoxycholate amphotericin for management of mucormycosis: a retrospective cohort study from South India. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of amphotericin B formulations: a network meta-analysis and a multicriteria decision analysis. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Treatment of systemic fungal infections with liposomal amphotericin B. [2013]

10. England pubmed.ncbi.nlm.nih.gov

Randomized double-blind study of liposomal amphotericin B (Ambisome) prophylaxis of invasive fungal infections in bone marrow transplant recipients. [2013]

11. England pubmed.ncbi.nlm.nih.gov

Antifungal agents. Part I. Amphotericin B preparations and flucytosine. [2013]

12. Austria pubmed.ncbi.nlm.nih.gov

[New aspects in treatment of systemic mycoses]. [2013]

13. United States pubmed.ncbi.nlm.nih.gov

New methods for delivery of antifungal agents. [2019]

14. France pubmed.ncbi.nlm.nih.gov

[Lipid formulations of amphotericin B in the management of invasive fungal infections]. [2019]