A Phase 3 Efficacy and Safety Study of Fosmanogepix for the Treatment of Adult Participants With Candidemia and/or Invasive Candidiasis

An Interventional Efficacy and Safety Phase 3 Double-blind 2-arm Study to Investigate IV Followed by Oral Fosmanogepix Compared With IV Caspofungin Followed by Oral Fluconazole in Adult Participants With Candidemia and/or Invasive Candidiasis

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.

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 patients are well enough to be discharged from the hospital.

We will compare the experience of patients receiving fosmanogepix to those receiving caspofungin/ fluconazole. This will help us determine if fosmanogepix is safe and effective.

Patients 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.

Study Overview

• Status: Not yet recruiting
• Conditions: Candidemia; Candidiasis, Invasive
• Intervention / Treatment: Drug: Fluconazole; Drug: Fosmanogepix; Drug: Fosmanogepix; Drug: Placebo; Drug: Placebo; Drug: Placebo; Drug: Placebo; Drug: Caspofungin

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Manuel Häckl, MD; Phone Number: +41 76 302 53 10; Email: manuel.haeckl@basilea.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Caspofungin IV/ Fluconazole oral; 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: Fluconazole; Fluconazole oral capsule; Drug: Placebo; Matching placebo for caspofungin (IV infusion); Drug: Placebo; Matching placebo for fluconazole (oral capsule); Drug: Placebo; Matching placebo for fosmanogepix (IV infusion); Drug: Placebo; Matching placebo for fosmanogepix (oral tablet); Drug: Caspofungin; IV infusion
Experimental: Fosmanogepix IV/oral; 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: Fosmanogepix; IV infusion; Drug: Fosmanogepix; Oral tablet; Drug: Placebo; Matching placebo for caspofungin (IV infusion); Drug: Placebo; Matching placebo for fluconazole (oral capsule); Drug: Placebo; Matching placebo for fosmanogepix (IV infusion); Drug: Placebo; Matching placebo for fosmanogepix (oral tablet)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)	End of study treatment (EOST) (up to Day 42)

Secondary Outcome Measures

Outcome Measure	Time Frame
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
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)
Proportion of participants alive (EMA)	Day 30
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 12,5 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; EOST: 72 and 192 hours post-dose

Collaborators and Investigators

• Sponsor: Basilea Pharmaceutica
• Investigators: Study Director: Manuel Häckl, MD, Basilea Pharmaceutica International Ltd, Allschwil

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2024
• Primary Completion (Estimated): July 15, 2027
• Study Completion (Estimated): July 15, 2027

Study Registration Dates

• First Submitted: June 7, 2022
• First Submitted That Met QC Criteria: June 14, 2022
• First Posted (Actual): June 16, 2022

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Candida; Fungal infection; Anti-fungal; Yeast
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections and Mycoses; Sepsis; Mycoses; Invasive Fungal Infections; Fungemia; Candidiasis; Candidemia; Candidiasis, Invasive; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Caspofungin; Fluconazole
• Other Study ID Numbers: FMGX-CS-301; 2022-500455-23-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No