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

Basilea Pharmaceutica

Status and phase: Enrolling; Phase 3

Conditions: Candidemia; Candidiasis, Invasive

Treatments: Drug: Fluconazole; Drug: Fosmanogepix; Drug: Placebo; Drug: Caspofungin

Study type: Interventional

Funder types: Industry; Other U.S. Federal agency

Identifiers

NCT05421858

2022-500455-23-00 (Other Identifier)

FMGX-CS-301

Details and patient eligibility

About

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.

Enrollment: 450 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients ≥ 18 years (or the minimum country-specific age of consent if > 18) at Screening who have provided signed informed consent indicating that they understand the purpose of, and procedures required for, the study, and are willing to participate in the study.
2. Diagnosis of candidemia and/or invasive candidiasis based on a blood or non-blood specimen obtained within ≤ 96 hours (4 days) before randomization.
3. Patient's condition allows for appropriate infection source control measures, including removal of pre-existing intravascular catheters and devices, if necessary.

Exclusion criteria

1. Existing infection

   1. Infection known to be due to Candida krusei, in blood or any other normally sterile site.
   2. Inappropriate fungal infection source control.
   3. Diagnosis of certain deep-seated Candida infections.

2. Life expectancy of < 72 hours in the opinion of the investigator.

3. Requirement, or expected requirement, for hemodialysis.

4. Ongoing medical history of neurological disorders.

5. Patients with known human immunodeficiency virus infection, who have CD4+ count < 200/mm3 or viral load > 400 copies/mL), or who have had an active opportunistic infection within 6 months prior to Screening.

6. Other medical or psychiatric condition or laboratory abnormality that may increase the risk of study participation or make the patient inappropriate for the study.

7. Current use of any prohibited concomitant medications or those unwilling/unable to use a permitted concomitant medication.

8. Received > 2 days (> 48 hours) equivalent of prior systemic antifungal treatment at approved doses and frequency to treat the current episode of candidemia (e.g., > 2 doses of a once daily antifungal agent or > 4 doses of a twice daily antifungal agent), within the 96 hours prior to randomization (except for non-susceptible Candida spp. and for patients who develop candidemia or invasive candidiasis while on prophylaxis with an azole or amphotericin B).

9. Previous administration with an investigational drug or investigational vaccine within 30 days or 5 half-lives preceding the first dose of study drug used in this study (whichever is longer).

10. Prior participation in this or any previous study of fosmanogepix.

11. Moderate or severe hepatic impairment, active viral hepatitis B or C, ALT or AST ≥ 5 × ULN or total bilirubin > 3 × ULN unless this is due to isolated hyperbilirubinemia or documented Gilbert's syndrome.

12. Female patient is pregnant or lactating.

13. Known hypersensitivity to fosmanogepix, manogepix, caspofungin, any echinocandin, fluconazole or to any of their excipients.

14. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and Sponsor and Sponsor delegate employees directly involved in the conduct of the study and their family members.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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450 participants in 2 patient groups

Fosmanogepix IV/oral

Experimental group

Description:

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).

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Fosmanogepix

Drug: Fosmanogepix

Drug: Placebo

Caspofungin IV/ Fluconazole oral

Active Comparator group

Description:

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).

Treatment:

Drug: Caspofungin

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Fluconazole