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

Phase 3

Recruiting

• Conditions: Candidemia; Candidiasis, Invasive
• Interventions: Drug: Fosmanogepix; Drug: Caspofungin; Drug: Placebo; Drug: Fluconazole

• Registration Number: NCT05421858
• Lead Sponsor: Basilea Pharmaceutica

Brief 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.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-06-07
• Study First Submitted QC: 2022-06-14
• Study First Posted: 2022-06-16
• Study Start: 2024-12-11
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-13
• Last Update Posted: 2025-05-16
• Primary Completion: 2028-01-30
• Study Completion: 2028-01-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 450

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. If the patient is unable to consent for himself/herself, a legally authorized representative must provide informed consent on his/her behalf.
2. Diagnosis of candidemia and/or invasive candidiasis based on a blood or non-blood specimen obtained within ≤ 96 hours (4 days) before randomization, and on clinical criteria judged attributable to candidemia/invasive candidiasis occurring at any time from ≤ 12 hours prior to the qualifying positive index culture being taken through to 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, peritoneal dialysis, or hemofiltration.

4. Ongoing neurological disorders, including specified conditions presenting with a CTCAE Grade ≥ 2 (neurological symptoms that are considered to be a consequence of the current episode of candidemia / invasive candidiasis are not exclusionary).

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 and/or invasive candidiasis (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, known 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fosmanogepix IV/oral	Placebo	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).
Caspofungin IV/ Fluconazole oral	Placebo	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).
Fosmanogepix IV/oral	Fosmanogepix	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).
Caspofungin IV/ Fluconazole oral	Caspofungin	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).
Caspofungin IV/ Fluconazole oral	Fluconazole	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).

Primary Outcome Measures

Name	Time	Method
Proportion of patients alive at Day 30	Day 30
Proportion of patients with an overall response of treatment success at end of study treatment (EOST)	EOST (up to Day 42)

Secondary Outcome Measures

Name	Time	Method
Proportion of patients with an overall response of treatment success at end of IV treatment (EOIV)	up to Day 42
Proportion of patients with an overall response of treatment success (sustained) at follow-up 6 weeks after EOST	approximately up to 12,5 weeks
Proportion of patients with clinical response of success at Day 7, 14, EOIV, EOST, Follow-up 6- weeks after EOST	Day 14, EOIV (up to Day 42), EOST (up to Day 42), Follow-up 6-weeks after EOST]
Proportion of patients with mycological response of eradication or presumed eradication at Day 7, 14, EOIV, EOST, Follow-up 6-weeks after EOST	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 patients on fosmanogepix compared to caspofungin/fluconazole	Baseline up to follow-up 6-weeks after EOST (approximately up to 12,5 weeks)
Incidence of treatment-emergent adverse event (TEAEs), serious adverse events (SAEs), treatment-related adverse events (AEs), adverse events of special interest (AESI)and AEs leading to discontinuation	Screening up to follow-up 6-weeks after EOST (approximately up to 12,5 weeks)
Number of patients with clinically significant laboratory abnormalities	Baseline up to follow-up 6-weeks after EOST (approximately up to 12,5 weeks)
Number of patients with abnormal neurological examination findings	Baseline up to follow-up 6-weeks after EOST (approximately up to 12,5 weeks)
Assessment of 12-lead electrocardiogram (ECGs)	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
Proportion of patients with an overall response of treatment success at Day 14	Day 14
Proportion of patients with an overall response of treatment success at Day 7	Day 7

Trial Locations

Locations (70)

Hospital San Raffaele, IRCCS; 🇮🇹 Milan, Italy

Polyclinic San Matteo, IRCCS; 🇮🇹 Pavia, Italy

University Hospital of Pisa; 🇮🇹 Pisa, Italy

Emory University Hospital - Clifton Road; 🇺🇸 Atlanta, Georgia, United States

Kepler University Hospital GmbH, Department of Pulmonology, Clinical Department of Infectious Diseases; 🇦🇹 Linz, Austria

Medical University Vienna; 🇦🇹 Vienna, Austria

Hospital Favoriten, Department of Internal Medicine IV - Infectious Diseases and Tropical Medicine; 🇦🇹 Vienna, Austria

University Hospital Ulm, Comprehensive Infectious Diseases Center Ulm (CIDCU); 🇩🇪 Ulm, Baden-Wuerttemberg, Germany

University Hospital Heidelberg, Clinic for Anesthesiology; 🇩🇪 Heidelberg, Germany

"LAIKO" General Hospital; 🇬🇷 Athens, Greece

"Sotiria" Chest Diseases Hospital of Athens; 🇬🇷 Athens, Greece

General Hospital of Thessaloniki "Ippokratio"; 🇬🇷 Thessaloniki, Greece

Ryexo Clinical Research; 🇿🇦 Pretoria, South Africa

Practice of R Moodley and MI Sarvan - Umhlanga; 🇿🇦 Umhlanga, South Africa

University Hospital Virgen Macarena; 🇪🇸 Seville, Andalusia, Spain

University Hospital Nuestra Senora de Valme; 🇪🇸 Seville, Andalusia, Spain

Hospital Clinic of Barcelona, Department of Infectious Diseases; 🇪🇸 Barcelona, Catalonia, Spain

University Hospital Ramon y Cajal, Department of Infectious Diseases; 🇪🇸 Madrid, Community Of Madrid, Spain

China Medical University Hospital; 🇨🇳 Taichung, Taiwan

Taichung Veterans General Hospital; 🇨🇳 Taichung, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan

Siriraj Hospital; 🇹🇭 Bangkok, Thailand

Maharaj Nakorn Chiang Mai Hospital; 🇹🇭 Chiang Mai, Thailand

UC Davis Medical Center; 🇺🇸 Sacramento, California, United States

Indiana University Methodist Hospital; 🇺🇸 Indianapolis, Indiana, United States

University of Kentucky College of Medicine; 🇺🇸 Lexington, Kentucky, United States

Henry Ford Hospital, Department of Medicine, Division of Infectious Diseases; 🇺🇸 Detroit, Michigan, United States

Washington University School of Medicine, Infectious Diseases Clinical Research Unit; 🇺🇸 Saint Louis, Missouri, United States

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

Houston Methodist Hospital - Texas Medical Center; 🇺🇸 Houston, Texas, United States

The University of Texas Health Science Center at Houston; 🇺🇸 Houston, Texas, United States

The Alfred Hospital; 🇦🇺 Melbourne, Victoria, Australia

Monash Medical Center Clayton; 🇦🇺 Clayton, Australia

General Hospital Saint-Jan; 🇧🇪 Brugge, Belgium

University Hospital Brussels; 🇧🇪 Brussels, Belgium

Saint Luc University Hospital, Department of Internal Medicine; 🇧🇪 Brussels, Belgium

Erasme Hospital, Department of Infectious and Tropical Diseases; 🇧🇪 Brussels, Belgium

Jessa Hospital; 🇧🇪 Hasselt, Belgium

University Hospitals Leuven, Campus Gasthuisberg, Department of Infectious Diseases; 🇧🇪 Leuven, Belgium

UCL Mont-Godinne University Hospitals; 🇧🇪 Yvoir, Belgium

Eurohospital University Hospital; 🇧🇬 Plovdiv, Bulgaria

University Medical Center "N. I. Pirogov", Burns and Plastic Surgery Clinic; 🇧🇬 Sofia, Bulgaria

University Medical Center "N. I. Pirogov", Clinic of Purulent-Septic Surgery; 🇧🇬 Sofia, Bulgaria

Amiens Picardie University Hospital - South, Intensive Care Unit (ICU); 🇫🇷 Amiens, France

Victor Dupouy Hospital Center Argenteuil, Intensive Care Unit; 🇫🇷 Argenteuil, France

Nantes University Hospital Center - Hotel Dieu Hospital, Department of Infectious and Tropical Diseases; 🇫🇷 Nantes, France

Tours Regional University Hospital Center; 🇫🇷 Tours, France

University Hospital Cologne, Department of Internal Medicine I, Clinical Study Centre II for Infectious Diseases; 🇩🇪 Cologne, North Rhine-Westphalia, Germany

General Hospital of Athens "Evangelismos", 5th Department of Internal Medicine and Infectious Diseases Unit; 🇬🇷 Athens, Greece

Tzaneio General Hospital; 🇬🇷 Piraeus, Greece

Rambam Health Care Campus, Institute of Infectious Diseases; 🇮🇱 Haifa, Israel

Edith Wolfson Medical Center, Department of Infectious Diseases; 🇮🇱 Holon, Israel

Chaim Sheba Medical Center, Department of Infectious Diseases; 🇮🇱 Ramat Gan, Israel

The Tel Aviv Sourasky Medical Center, Infectious Diseases Unit; 🇮🇱 Tel Aviv, Israel

Shamir Medical Center, Department of Infectious Diseases; 🇮🇱 Zerifin, Israel

Hospital "S. Croce e Carle"; 🇮🇹 Cuneo, Italy

IRCCS Policlinic Hospital San Martino; 🇮🇹 Genoa, Italy

Maggiore Polyclinic Hospital, Foundation IRCCS Ca' Granda; 🇮🇹 Milan, Italy

Giuliano Isontina University Health Authority; 🇮🇹 Trieste, Italy

Kyungpook National University Hospital; 🇰🇷 Daegu, Korea, Republic of

Severance Hospital, Yonsei University Health System; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Ajou University Hospital; 🇰🇷 Suwon, Korea, Republic of

University of Pretoria / Steve Biko Academic Hospital; 🇿🇦 Pretoria, South Africa

Hospital del Mar, Department of Infectious Diseases; 🇪🇸 Barcelona, Catalonia, Spain

Kaohsiung Medical University Chung-Ho Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan

Far Eastern Memorial Hospital; 🇨🇳 New Taipei City, Taiwan

Taipei Medical University Hospital; 🇨🇳 Taipei, Taiwan

Linkou Chang Gung Memorial Hospital; 🇨🇳 Taoyuan City, Taiwan

Songklanagarind Hospital; 🇹🇭 Hat Yai, Thailand