Rezafungin for Liver Transplant Infection

Overseen By Fernanda Silveira, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Fernanda P Silveira, MD, MS

Disqualifiers: Active candidiasis, Echinocandin allergy, Pregnancy, 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: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, rezafungin, to determine its effectiveness in preventing serious fungal infections in liver transplant recipients. The study compares those receiving rezafungin to past patients who received standard treatments or no treatment, assessing which group experiences fewer infections. Ideal participants are liver transplant recipients with specific risk factors, such as complex surgery or recent fungal infections. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that rezafungin is likely to be safe for humans?

Research has shown that rezafungin, the treatment under study, has been tested in other contexts. In a study involving 207 patients, the treatment was generally well-tolerated over about 14 days. Although the study did not specify side effects, the large number of participants suggests that any serious issues would likely have been detected. Rezafungin belongs to the echinocandin group of medicines, often used to treat fungal infections. This group is known for having fewer side effects compared to some other antifungal treatments. Therefore, rezafungin appears to have a promising safety profile, but participating in a clinical trial will provide more personalized information about its effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Rezafungin is unique because it offers a new approach to preventing fungal infections after liver transplants. Unlike the standard options like fluconazole and voriconazole, rezafungin requires less frequent dosing, with a once-weekly IV administration after the initial dose. This not only improves convenience for patients but also ensures a more consistent therapeutic presence in the body. Researchers are excited about its potential to provide effective protection against infections with a simplified regimen, potentially improving outcomes for transplant patients.

What evidence suggests that rezafungin might be an effective treatment for preventing infections after liver transplant?

Studies have shown that rezafungin effectively prevents serious fungal infections. In this trial, some participants will receive rezafungin, which research indicates can greatly reduce the risk of these infections after a liver transplant. Earlier studies found rezafungin to be as effective as other treatments, such as caspofungin, for treating serious fungal infections. This treatment offers long-lasting protection with fewer hospital visits, making it both convenient and effective. Overall, evidence supports rezafungin as a promising option for managing and preventing fungal infections in liver transplant patients. ^{1 2 3 4 6}

Who Is on the Research Team?

Fernanda Silveira

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for individuals who have recently undergone a liver transplant and are at risk of developing invasive fungal infections. Participants should not have had any prior antifungal prophylaxis that would interfere with the study.

Inclusion Criteria

I have received a liver transplant.

I have risk factors for fungal infections after my transplant.

Exclusion Criteria

Participants perceived not to survive past 7 days after transplant

Participants with a history of allergy to an echinocandin

Pregnant participants

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Rezafungin 400 mg IV once within 24 hours of liver transplant, followed by 200 mg IV once weekly for a total duration of 4 weeks

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Extended Follow-up

Participants are monitored for long-term outcomes such as fungal-free survival, graft rejection, and antifungal resistance

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Rezafungin

Trial Overview The study tests rezafungin, a new medication, against standard antifungal treatments to prevent fungal infections after liver transplantation. Patients will be randomly assigned to receive either rezafungin or the standard care and monitored for infection rates.

How Is the Trial Designed?

Group I: Prospective Intervention Cohort Experimental Treatment 1 Intervention

Rezafungin 400 mg IV once within 24 hours of liver transplant, followed by 200 mg IV once weekly for a total duration of 4 weeks

Group II: Prospective Control Cohort Active Control 1 Intervention

Patients who receive fluconazole/voriconazole or no antifungal prophylaxis as part of UPMC's risk-based antifungal prophylaxis standard of care after liver transplant

Group III: Historical Control Group Active Control 1 Intervention

Patients at risk for IFI who received fluconazole/voriconazole for antifungal prophylaxis after liver transplant in the two years preceding the study

Who Is Running the Clinical Trial?

Fernanda P Silveira, MD, MS

Lead Sponsor

Trials

2

Recruited

400+

Melinta Therapeutics

Industry Sponsor

Trials

1

Recruited

390+

Published Research Related to This Trial

Rezafungin demonstrated strong in vitro activity against both common and rare Candida species, with MIC90 values indicating effectiveness at very low concentrations (0.06-2 mg/L) across various species.

It was particularly effective against azole-resistant strains of Candida, showing similar efficacy to other echinocandins, except for caspofungin, suggesting it could be a valuable treatment option for resistant infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro activity of rezafungin against common and rare Candida species and Saccharomyces cerevisiae. Tóth, Z., Forgács, L., Locke, JB., et al.[2020]

Rezafungin, a new echinocandin drug, shows strong potential as a first-line treatment for invasive fungal infections due to its unique chemical stability and prolonged pharmacokinetics, which allows for easier administration compared to other similar drugs.

In laboratory and animal studies, rezafungin has demonstrated potent activity against a wide range of fungal pathogens, supported by promising results from ongoing clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the Novel Echinocandin Antifungal Rezafungin: Animal Studies and Clinical Data. Zhao, Y., Perlin, DS.[2020]

Rezafungin demonstrated non-inferiority to caspofungin in terms of day 30 all-cause mortality rates in patients with candidaemia and invasive candidiasis, with both treatments showing a mortality rate of 19%.

Mycological eradication was achieved more quickly with rezafungin, as 73% of patients showed eradication by day 5 compared to 65% for caspofungin, suggesting a potential early treatment advantage for rezafungin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rezafungin and caspofungin in candidaemia and invasive candidiasis: pooled data from two prospective randomised controlled trials. Thompson, GR., Soriano, A., Honore, PM., et al.[2023]

Rezafungin is a new long-acting echinocandin that shows improved tissue penetration and pharmacokinetics compared to older echinocandins, allowing for potential once-weekly intravenous administration and better flexibility in dosing and storage.

It has a good safety profile with no evidence of toxic effects at higher doses, which may help prevent the development of resistant fungal strains, while maintaining similar efficacy and resistance patterns to existing echinocandins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rezafungin-Mechanisms of Action, Susceptibility and Resistance: Similarities and Differences with the Other Echinocandins. Garcia-Effron, G.[2020]

Rezafungin demonstrated non-inferior efficacy compared to caspofungin in treating candidaemia and invasive candidiasis, with similar rates of global cure at day 14 and 30-day all-cause mortality in a phase 3 trial involving 199 patients.

The safety profile of rezafungin was comparable to caspofungin, with no concerning trends in treatment-emergent or serious adverse events, indicating it is a viable option for patients with invasive fungal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rezafungin versus caspofungin for treatment of candidaemia and invasive candidiasis (ReSTORE): a multicentre, double-blind, double-dummy, randomised phase 3 trial. Thompson, GR., Soriano, A., Cornely, OA., et al.[2023]

Rezafungin acetate is a promising new antifungal treatment that can be administered once a week due to its long half-life, making it convenient for patients.

In studies using neutropenic mouse models, rezafungin showed effective treatment against serious fungal infections, including those caused by azole-resistant Candida albicans and aspergillosis, highlighting its potential for treating invasive fungal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rezafungin treatment in mouse models of invasive candidiasis and aspergillosis: Insights on the PK/PD pharmacometrics of rezafungin efficacy. Miesel, L., Lin, KY., Ong, V.[2023]

Rezafungin, a new echinocandin for treating fungal infections, was found to be safe and well-tolerated in a study of healthy adults, with no serious adverse events reported after a single subcutaneous dose.

The pharmacokinetic profile of rezafungin showed a long half-life of 193 hours and significant exposure, suggesting it could be effective for prolonged treatment, although injection site reactions were a concern that may require formulation adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I randomized, double-blind, single subcutaneous dose escalation study to determine the safety, tolerability, and pharmacokinetics of rezafungin in healthy adult subjects. Gu, K., Ruff, D., Key, C., et al.[2022]

Rezafungin, a long-acting echinocandin, has shown broad-spectrum effectiveness against various Candida and Aspergillus species, including some drug-resistant strains, and is currently in phase III trials.

In a compassionate use case, rezafungin was successfully used for over a year to treat a patient with a multidrug-resistant Candida glabrata infection, indicating its potential safety and efficacy in challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded Access Use of Rezafungin for Salvage Therapy of Invasive Candida glabrata Infection: A Case Report. Adeel, A., Qu, MD., Siddiqui, E., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06774144

NCT06774144 | Rezafungin Prophylaxis in Liver Transplant This is an interventional study to evaluate the efficacy of rezafungin, a new echinocandin, for the prevention of invasive fungal infections (IFIs) after liver ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1600613522256998

Antifungal Prophylaxis in Liver Transplantation Systemic antifungal prophylaxis resulted in a significant reduction in the odds for proven IFI (OR 0.37, 95% CI 0.19–0.72, p = 0.003; Figure 2).

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11784067/

New Perspectives on Antimicrobial Agents: Rezafungin - PMC Rezafungin offers an opportunity to manage extended treatment durations with shorter hospital stays and no extended parenteral access.

4. withpower.com withpower.com/trial/rezafungin-for-liver-transplant-infection-ec445

Rezafungin for Liver Transplant Infection · Info for Participants Rezafungin demonstrated non-inferior efficacy compared to caspofungin in treating candidaemia and invasive candidiasis, with similar rates of global cure at day ...

5. ctv.veeva.com ctv.veeva.com/study/rezafungin-prophylaxis-in-liver-transplant

Rezafungin Prophylaxis in Liver Transplant This is an interventional study to evaluate the efficacy of rezafungin, a new echinocandin, for the prevention of invasive fungal infections ...

6. link.springer.com link.springer.com/article/10.1007/s15010-025-02575-z

Current trends on antifungal prophylaxis in solid organ ... For liver transplant recipients the preferred antifungal for prophylaxis were caspofungin (15/36, 41.7%), fluconazole (14/36, 38.9%), or ...