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

Candidemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05421858
• Other study ID #: FMGX-CS-301
• Secondary ID: 2022-500455-23-0
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: July 15, 2024
• Est. completion date: July 15, 2027

Study information

• Verified date: April 2024
• Source: Basilea Pharmaceutica
• Contact: Manuel Häckl, MD
• Phone: +41 76 302 53 10
• Email: manuel.haeckl[@]basilea.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 450
• Est. completion date: July 15, 2027
• Est. primary completion date: July 15, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Candidemia
• Candidiasis
• Candidiasis, Invasive

Intervention

Drug:
• Fosmanogepix
IV infusion
• Fosmanogepix
Oral tablet
• Caspofungin
IV infusion
• Fluconazole
Fluconazole oral capsule
• Placebo
Matching placebo for caspofungin (IV infusion)
• Placebo
Matching placebo for fluconazole (oral capsule)
• Placebo
Matching placebo for fosmanogepix (IV infusion)
• Placebo
Matching placebo for fosmanogepix (oral tablet)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Basilea Pharmaceutica

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants alive- United States Food and Drug Administration (US FDA)		Day 30
Primary	Proportion of participants with an overall response of Treatment Success- European Medicines Agency (EMA)		End of study treatment (EOST) (up to Day 42)
Secondary	Proportion of participants alive (EMA)		Day 30
Secondary	Proportion of participants with an overall response of Treatment Success (US FDA)		EOST (up to Day 42)
Secondary	Proportion of participants with an overall response of Treatment Success		Day 14
Secondary	Proportion of participants with an overall response of Treatment Success		End of IV treatment (EOIV) (up to Day 42)
Secondary	Proportion of participants with an overall response of Treatment Success (sustained) at follow up visit		6 weeks after EOST (up to 12 weeks)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	Number of Participants With Laboratory Abnormalities		Baseline up to follow-up 6-weeks after EOST (approximately up to 12 weeks)
Secondary	Assessment of 12-lead electrocardiogram (ECGs)		Baseline up to follow-up 6-weeks after EOST (approximately up to 12 weeks)
Secondary	Number of Participants With Abnormal Neurological Examination Findings		Baseline up to follow-up 6-weeks after EOST (approximately up to 12 weeks)
Secondary	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