Fosmanogepix for Candida Blood Infection

Recruiting at 50 trial locations

Overseen By Marc Engelhardt, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Basilea Pharmaceutica

Must not be taking: Systemic antifungals

Disqualifiers: Neurological disorders, HIV, Hepatitis, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Up to 6 weeks

450 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called Fosmanogepix) for the potential treatment of candidemia and/or invasive candidiasis, a life-threatening fungal infection caused by several species of yeast called Candida. The study is seeking patients who have a diagnosis of candidemia and/or invasive candidiasis. Two-thirds of all patients will receive the study medication fosmanogepix Intravenous (IV) infusion followed by optional fosmanogepix tablets. One-third of all patients will receive a standard of care regimen of caspofungin Intravenous (IV) infusion followed by optional fluconazole capsules. Fosmanogepix or caspofungin will first be given as an Intravenous (IV) infusion directly into a vein in the arm each day at the study clinic. Fosmanogepix tablets or fluconazole capsules will be taken orally by mouth daily either at the study clinic, or at home if patients are well enough to be discharged from the hospital. The treatment effect in patients receiving fosmanogepix to those receiving caspofungin/ fluconazole will be compared. The primary aim is to show that fosmanogepix is not inferior (not worse) to caspofungin/ fluconazole with a noninferiority margin of 15%. The duration of study treatment and number of study visits will vary depending on how long the patient will be treated for the infection. Treatment will continue for a maximum of 6 weeks depending on when the infection is cleared and whether other symptoms related to the infection have improved. There will also be a follow-up visit 6 weeks after the study treatment was stopped.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that you cannot use any prohibited medications during the study. It's best to discuss your current medications with the study team to see if they are allowed.

What data supports the effectiveness of the drug Fosmanogepix for treating Candida blood infections?

Research shows that Fosmanogepix is effective in treating Candida blood infections, with a study reporting an 89% success rate in clearing the infection without additional antifungals. It is also well-tolerated and has broad-spectrum activity against various fungi, including those resistant to standard treatments. ^{1 2 3 4 5}

Is Fosmanogepix safe for human use?

Fosmanogepix has been shown to be safe and well-tolerated in clinical trials, with no treatment-related adverse events reported in patients with candidemia (a type of blood infection) caused by Candida auris. It has been tested in both intravenous and oral forms, and participants in these studies did not experience significant safety issues. ^{1 2 3 5 6}

What makes the drug Fosmanogepix unique for treating Candida blood infections?

Fosmanogepix is unique because it has a novel mechanism of action that targets the fungal cell wall, which is different from traditional antifungal drugs like azoles and echinocandins. This makes it potentially effective against Candida strains that have developed resistance to other treatments. ^{7 8 9 10 11}

Research Team

Manuel Häckl, MD

Principal Investigator

Basilea Pharmaceutica International Ltd, Allschwil

Eligibility Criteria

This trial is for adults diagnosed with candidemia or invasive candidiasis who understand the study and agree to participate. They must have had a diagnosis within 4 days before joining the trial and be able to undergo necessary procedures like removing catheters if needed.

Inclusion Criteria

I am over 18, understand the study, and agree to participate.

I have been diagnosed with a Candida infection in my blood or other parts of my body within the last 4 days.

I can undergo procedures to control infection, including removing any catheters if needed.

Exclusion Criteria

I am currently pregnant or breastfeeding.

Prior participation in this or any previous study of fosmanogepix.

I am allergic to fosmanogepix, manogepix, caspofungin, echinocandins, fluconazole, or their ingredients.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either fosmanogepix or caspofungin as an IV infusion, with an option to switch to oral tablets or capsules

Up to 6 weeks

Daily visits for IV infusion, with potential for home administration of oral medication

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

1 follow-up visit

Treatment Details

Interventions

• PF-07842805

Trial Overview The trial tests Fosmanogepix, comparing it against standard treatments Caspofungin/Fluconazole for fungal infections caused by Candida. Patients will receive either IV infusions followed by oral tablets of the study drug or standard care, aiming to prove Fosmanogepix is at least as effective.

Participant Groups

Group I: Fosmanogepix IV/oral Experimental Treatment 2 Interventions

Fosmanogepix will be administered as an Intravenous (IV) infusion given directly into a vein. There is an option to switch from the IV infusion to the oral form of fosmanogepix which is taken by mouth. Matching placebos for caspofungin and fluconazole will also be administered (a placebo does not have any medicine in it but looks just like the caspofungin and fluconazole).

Group II: Caspofungin IV/ Fluconazole oral Active Control 3 Interventions

Caspofungin will be administered as an intravenous (IV) infusion given directly into a vein. There is an option to switch from the IV infusion to oral fluconazole which is taken by mouth. Matching placebos for fosmanogepix will also be administered (a placebo does not have any medicine in it but looks just like the medicine fosmanogepix being studied).

PF-07842805 is already approved in United States, European Union for the following indications:

Approved in United States as Fosmanogepix for:

• Invasive candidiasis
• Invasive aspergillosis
• Scedosporiosis
• Fusariosis
• Mucormycosis
• Cryptococcosis
• Coccidioidomycosis

Approved in European Union as Fosmanogepix for:

• Orphan designation for invasive candidiasis, invasive aspergillosis, cryptococcosis, coccidioidomycosis, and rare mold infections caused by Scedosporium spp., Fusarium spp., and Mucorales fungi

Who Is Running the Clinical Trial?

Basilea Pharmaceutica

Lead Sponsor

Trials

53

Recruited

9,900+

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Biomedical Advanced Research and Development Authority

Collaborator

Trials

108

Recruited

574,000+

Findings from Research

Fosmanogepix, an antifungal prodrug, was found to be safe and well tolerated in a Phase 1b study involving 21 adult patients with acute myeloid leukemia (AML) and neutropenia, with no serious adverse events leading to discontinuation.

The pharmacokinetics of fosmanogepix were comparable to previous studies in healthy volunteers, indicating consistent absorption and elimination, which supports its potential use in treating invasive fungal diseases during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1b safety and pharmacokinetics of intravenous and oral fosmanogepix in patients with acute myeloid leukaemia and neutropenia. Cornely, OA., Ostermann, H., Koehler, P., et al.[2023]

Fosmanogepix (FMGX) demonstrated a high treatment success rate of 89% in a study of 9 participants with candidemia caused by Candida auris, indicating its efficacy against this resistant fungal infection.

The treatment was well-tolerated with no reported adverse events, suggesting that FMGX is a safe option for patients with limited antifungal treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy and Safety of a Novel Antifungal, Fosmanogepix, in Patients with Candidemia Caused by Candida auris: Results from a Phase 2 Trial. Vazquez, JA., Pappas, PG., Boffard, K., et al.[2023]

Fosmanogepix, currently in Phase 2 trials, is a promising antifungal that effectively targets invasive fungal infections caused by Candida, Aspergillus, and other rare molds, showing significant in vivo efficacy in various animal models.

Its unique mechanism of action allows it to remain effective against resistant strains of fungi, and it has high oral bioavailability (>90%), making it easy to switch between intravenous and oral forms without losing effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fosmanogepix: A Review of the First-in-Class Broad Spectrum Agent for the Treatment of Invasive Fungal Infections. Shaw, KJ., Ibrahim, AS.[2021]

In a Phase 2 trial involving 20 non-neutropenic adults with candidaemia, fosmanogepix demonstrated an 80% treatment success rate, effectively clearing Candida from blood cultures without additional antifungal treatment.

Fosmanogepix was well tolerated, with no serious treatment-related adverse events, and showed strong in vitro activity against Candida species, indicating its potential as a safe and effective antifungal option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical safety and efficacy of novel antifungal, fosmanogepix, for the treatment of candidaemia: results from a Phase 2 trial. Pappas, PG., Vazquez, JA., Oren, I., et al.[2023]

Manogepix is a highly effective antifungal agent, showing significantly lower minimum inhibitory concentrations (MIC) against Candida spp. and C. neoformans compared to traditional antifungals like anidulafungin, micafungin, and fluconazole, making it a promising option for treating resistant fungal infections.

The drug demonstrated potent activity against a wide range of contemporary fungal isolates, including those resistant to other treatments, indicating its potential utility in clinical settings for difficult-to-treat infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antimicrobial activity of manogepix, a first-in-class antifungal, and comparator agents tested against contemporary invasive fungal isolates from an international surveillance programme (2018-2019). Pfaller, MA., Huband, MD., Flamm, RK., et al.[2021]

Manogepix (APX001A) shows broad-spectrum antifungal activity against various yeast species, with low minimum inhibitory concentrations (MICs) for most tested isolates, indicating its potential as an effective treatment option.

However, a correlation was found between increased manogepix MICs and fluconazole resistance in some isolates, suggesting that further research is needed to understand the mechanisms behind this resistance and to optimize dosing strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Manogepix (APX001A) Displays Potent In Vitro Activity against Human Pathogenic Yeast, but with an Unexpected Correlation to Fluconazole MICs. Arendrup, MC., Jørgensen, KM.[2021]

In a study using a clinical blood culture simulation model with 117 organism/antifungal combinations, BacT/Alert FA PLUS and Bactec Plus Aerobic/F bottles effectively allowed for the recovery of Candida species, including C. auris, even in the presence of high antifungal concentrations, indicating their reliability for diagnosing candidemia.

Echinocandins, while commonly used for treating candidemia, may not be effective against certain Candida species due to their potential for developing resistance, suggesting that alternative antifungal agents like azoles and amphotericin B should be considered for better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficient Recovery of Candida auris and Five Other Medically Important Candida Species from Blood Cultures Containing Clinically Relevant Concentrations of Antifungal Agents. Posteraro, B., Menchinelli, G., Ivagnes, V., et al.[2023]

A two-month-old infant developed hematogenous Candida osteomyelitis as a complication of Candida septicemia during parenteral hyperalimentation, highlighting the need for increased awareness of this rare condition in infants.

Treatment with flucytosine was highly effective, leading to full recovery, and the drug is noted for its low toxicity and oral administration option, making it a suitable choice for treating this infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Candida osteomyelitis as a complication of parenteral nutrition in an infant. Successful treatment with flucytosine. Berant, M., Kristal, C., Wagner, Y.[2013]

In a study of 29 cases of candidaemia, antifungal therapy was found to be compliant with treatment guidelines in 74% to 89% of cases, indicating a generally adequate use of antifungal drugs.

However, only 37% of treatments complied with guidelines before identifying the Candida species, and this dropped to 26% after identification, with many cases attributed to lower dosages of fluconazole.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Restropective investigation about the treatment of candidaemia in a French university hospital in 2004]. Herbin, G., Goubin, P., Duhamel, C., et al.[2020]

In a study of 68 patients with bloodstream infections, Candida albicans was the most common species identified, accounting for 73.5% of cases, indicating its continued dominance in fungaemia across various clinical wards.

All Candida isolates were found to be susceptible to amphotericin B, while 15.7% showed decreased susceptibility to fluconazole and 24% to itraconazole, highlighting the importance of monitoring antifungal resistance in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aetiology and antifungal susceptibility of yeast bloodstream infections in a Hungarian university hospital between 1996 and 2000. Dóczi, I., Dósa, E., Hajdú, E., et al.[2020]

Meyerozyma (Pichia) guilliermondii is a significant opportunistic pathogen, being the third most commonly isolated yeast from blood cultures in a Turkish hospital, accounting for 20.6% of cases, particularly affecting patients in pediatric and intensive care units.

Molecular identification methods showed a high consistency (99.3%) with biochemical methods for identifying M. guilliermondii, and some strains exhibited resistance to common antifungal medications like fluconazole, indicating the need for careful monitoring and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The identification of Meyerozyma guilliermondii from blood cultures and surveillance samples in a university hospital in Northeast Turkey: A ten-year survey. Cebeci Güler, N., Tosun, I., Aydin, F.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase 1b safety and pharmacokinetics of intravenous and oral fosmanogepix in patients with acute myeloid leukaemia and neutropenia. [2023]

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

Clinical Efficacy and Safety of a Novel Antifungal, Fosmanogepix, in Patients with Candidemia Caused by Candida auris: Results from a Phase 2 Trial. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Fosmanogepix: A Review of the First-in-Class Broad Spectrum Agent for the Treatment of Invasive Fungal Infections. [2021]

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

Clinical safety and efficacy of novel antifungal, fosmanogepix, for the treatment of candidaemia: results from a Phase 2 trial. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Antimicrobial activity of manogepix, a first-in-class antifungal, and comparator agents tested against contemporary invasive fungal isolates from an international surveillance programme (2018-2019). [2021]

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

Manogepix (APX001A) Displays Potent In Vitro Activity against Human Pathogenic Yeast, but with an Unexpected Correlation to Fluconazole MICs. [2021]

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

Efficient Recovery of Candida auris and Five Other Medically Important Candida Species from Blood Cultures Containing Clinically Relevant Concentrations of Antifungal Agents. [2023]

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

Candida osteomyelitis as a complication of parenteral nutrition in an infant. Successful treatment with flucytosine. [2013]

9. France pubmed.ncbi.nlm.nih.gov

[Restropective investigation about the treatment of candidaemia in a French university hospital in 2004]. [2020]

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

Aetiology and antifungal susceptibility of yeast bloodstream infections in a Hungarian university hospital between 1996 and 2000. [2020]

11. France pubmed.ncbi.nlm.nih.gov

The identification of Meyerozyma guilliermondii from blood cultures and surveillance samples in a university hospital in Northeast Turkey: A ten-year survey. [2022]