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

385 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Rezafungin for liver transplant infection?

Rezafungin has shown strong effectiveness against various Candida species, which are common causes of fungal infections, in multiple studies. It has been effective in treating invasive fungal infections in both human trials and animal models, suggesting it could be beneficial for preventing infections in liver transplant patients. ^{1 2 3 4 5}

Is rezafungin generally safe for humans?

Rezafungin has been tested in clinical trials and found to have a good safety profile, similar to other drugs in its class. In studies, it did not cause serious side effects, though some mild to moderate reactions like injection site redness were noted. ^{3 6 7 8 9}

What makes the drug Rezafungin unique for treating liver transplant infections?

Rezafungin is unique because it is a next-generation echinocandin that can be administered once a week due to its long half-life, offering convenience and potentially better adherence compared to other treatments that require more frequent dosing. It also has a broad spectrum of activity against various fungal pathogens, making it a promising option for preventing and treating invasive fungal infections. ^{1 2 3 5 9}

What is the purpose of this trial?

This is an interventional study to evaluate the efficacy of rezafungin, a new echinocandin, for the prevention of invasive fungal infections (IFIs) after liver transplantation. Patients who receive rezafungin will be compared to a similar group of patients who underwent liver transplantation in the preceding two years for the incidence of IFIs.

Research Team

Fernanda Silveira

Principal Investigator

University of Pittsburgh

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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, 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]

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 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, 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]

References

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

Evaluation of Rezafungin Provisional CLSI Clinical Breakpoints and Epidemiological Cutoff Values Tested against a Worldwide Collection of Contemporaneous Invasive Fungal Isolates (2019 to 2020). [2022]

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

In vitro activity of rezafungin against common and rare Candida species and Saccharomyces cerevisiae. [2020]

3. England 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. [2023]

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

Expanded Access Use of Rezafungin for Salvage Therapy of Invasive Candida glabrata Infection: A Case Report. [2023]

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

Rezafungin treatment in mouse models of invasive candidiasis and aspergillosis: Insights on the PK/PD pharmacometrics of rezafungin efficacy. [2023]

6. United States 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. [2022]

7. United States 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. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

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

9. Switzerland pubmed.ncbi.nlm.nih.gov

Review of the Novel Echinocandin Antifungal Rezafungin: Animal Studies and Clinical Data. [2020]