A Study to Learn About the Study Medicine (Called Fosmanogepix/ PF-07842805) in People With Candidemia and/or Invasive Candidiasis.

Study Overview
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Brief Summary
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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 participants who have a diagnosis of candidemia or invasive candidiasis. Two-thirds of all participants will receive the study medication fosmanogepix Intravenous (IV) infusion followed by optional fosmanogepix tablets. One-third of all participants will receive a standard of care regimen of caspofungin Intravenous (IV) infusion followed by optional fluconazole capsules. Fosmaogepix or caspofungin will first be given as an Intravenous (IV) infusion directly into a vein in the arm each day at the study clinic. Fosmaogepix tablets or fluconazole capsules will be taken orally by mouth daily either at the study clinic, or at home if participants are well enough to be discharged from the hospital. We will compare the experience of people receiving fosmanogepix to those receiving caspofungin/ fluconazole. This will help us determine if fosmanogepix is safe and effective. Participants will continue treatment for a maximum of 6 weeks depending on whether the infection has cleared and whether the symptoms related to the infection has improved. During this time, they will have study visits for up to 10 times. There will also be a follow-up visit 6 weeks after the study treatment was stopped.

Official Title
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AN INTERVENTIONAL EFFICACY AND SAFETY PHASE 3 DOUBLE-BLIND, 2-ARM STUDY TO INVESTIGATE IV FOLLOWED BY ORAL FOSMANOGEPIX (PF-07842805) COMPARED WITH IV CASPOFUNGIN FOLLOWED BY ORAL FLUCONAZOLE IN ADULT PARTICIPANTS WITH CANDIDEMIA AND/OR INVASIVE CANDIDIASIS.

Conditions
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Candidemia, Candidiasis, Invasive

Intervention / Treatment
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* Drug: PF-07842805
* Drug: Caspofungin
* Drug: PF-07842805
* Drug: Fluconazole
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of candidemia and/or invasive candidiasis defined by: A culture positive for yeast or Candida species, a positive Gram stain (or other method of direct microscopy) for yeast from blood or specimen from a normally sterile site, or a positive result for Candida using a Sponsor-approved rapid diagnostic test from a blood sample. Presence of one or more clinical criteria attributable to candidemia/invasive candidiasis: fever, hypothermia, hypotension, tachypnea ,tachycardia, and local signs associated with organ/site infected with Candida, and/or radiologic findings suggesting invasive candidiasis. Exclusion Criteria: Existing infections including: infections due to Candida krusei (in blood or any other normally sterile site), inappropriate fungal infection source control, diagnosis of certain deep-seated Candida infections, or temporally related proven bacterial infection at the same or contiguous infection site. Requirement, or expected requirement, for hemodialysis Received greater than 2 days equivalent of prior systemic antifungal treatment to treat the current episode of candidemia, within the 96 hours before to study enrolment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fosmanogepix (PF-07842805) IV/oral<br>Fosmanogepix will be administered as an Intravenous (IV) infusion given directly into a vein in the arm. 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). | Drug: PF-07842805<br>* PF-07842805 (IV infusion)<br>Drug: PF-07842805<br>* PF-07842805 oral tablet<br>Drug: Placebo<br>* Matching placebo (IV infusion)<br>Drug: Placebo<br>* Matching placebo (tablet or capsule)<br>|
| Active Comparator: Caspofungin IV/ Fluconazole oral<br>Caspofungin will be administered as an intravenous (IV) infusion given directly into a vein in the arm. 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). | Drug: Caspofungin<br>* Caspofungin (IV infusion)<br>Drug: Fluconazole<br>* Fluconazole oral capsule<br>Drug: Placebo<br>* Matching placebo (IV infusion)<br>Drug: Placebo<br>* Matching placebo (tablet or capsule)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants alive- United States Food and Drug Administration (US FDA) |  | Day 30 | 
| Proportion of participants with an overall response of Treatment Success- European Medicines Agency (EMA)/Japan |  | End of study treatment (EOST) (up to Day 42) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants alive (EMA/Japan) |  | Day 30 | 
| Proportion of participants with an overall response of Treatment Success (US FDA) |  | EOST (up to Day 42) | 
| Proportion of participants with an overall response of Treatment Success |  | Day 14 | 
| Proportion of participants with an overall response of Treatment Success |  | End of IV treatment (EOIV) (up to Day 42) | 
| Proportion of participants with an overall response of Treatment Success (sustained) at follow up visit |  | 6 weeks after EOST (up to 12 weeks) | 
| Proportion of participants with Clinical response of Success |  | Day 14, EOIV (up to Day 42), EOST (up to Day 42), Follow-up 6-weeks after EOST | 
| Proportion of participants with Mycological response of Eradication or Presumed Eradication |  | Day 14, EOIV (up to Day 42), EOST (up to Day 42), Follow-up 6-weeks after EOST | 
| Time to first negative blood culture in participants on fosmanogepix compared to caspofungin/fluconazole |  | Baseline up to follow-up 6-weeks after EOST (approximately up to 12 weeks) | 
| Incidence of treatment-emergent adverse event (TEAEs), serious adverse events (SAEs), and treatment-related adverse events (AEs) and AEs leading to discontinuation |  | Screening up to 28 days after the last dose of study drug (approximately up to 14 Weeks) | 
| Number of Participants With Laboratory Abnormalities |  | Baseline up to follow-up 6-weeks after EOST (approximately up to 12 weeks) | 
| Assessment of 12-lead electrocardiogram (ECGs) |  | Baseline up to follow-up 6-weeks after EOST (approximately up to 12 weeks) | 
| Number of Participants With Abnormal Neurological Examination Findings |  | Baseline up to follow-up 6-weeks after EOST (approximately up to 12 weeks) | 
| Plasma concentrations versus time of fosmanogepix (prodrug) and manogepix (active moiety) |  | Day 3: 0, 3, 6, 9 and 24 hours post-dose; Day 7, 14, 21, 28, 35 post-dose; EOST: 72 and 192 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fungal infection, Candida, Anti-fungal, Yeast