Clinical trial NCT05421858: A Phase 3 Efficacy and Safety Study of Fosmanogepix for the Treatment of Adult Participants With Candidemia and/or Invasive Candidiasis.
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Candidemia
Candidiasis, Invasive
Keywords: Fungal infection
Candida
Anti-fungal
Yeast
Lead sponsor: Basilea Pharmaceutica
Sponsor class: INDUSTRY
Collaborators: name: Biomedical Advanced Research and Development Authority
First posted: 2022-06-16
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of patients alive at Day 30
timeFrame: Day 30
measure: Proportion of patients with an overall response of treatment success at end of study treatment (EOST)
timeFrame: EOST (up to Day 42)
Secondary outcomes:
measure: Proportion of patients with an overall response of treatment success at Day 7
timeFrame: Day 7
measure: Proportion of patients with an overall response of treatment success at Day 14
timeFrame: Day 14
measure: Proportion of patients with an overall response of treatment success at end of IV treatment (EOIV)
timeFrame: up to Day 42
measure: Proportion of patients with an overall response of treatment success (sustained) at follow-up 6 weeks after EOST
timeFrame: approximately up to 12,5 weeks
measure: Proportion of patients with clinical response of success at Day 7, 14, EOIV, EOST, Follow-up 6- weeks after EOST
timeFrame: Day 14, EOIV (up to Day 42), EOST (up to Day 42), Follow-up 6-weeks after EOST]
measure: Proportion of patients with mycological response of eradication or presumed eradication at Day 7, 14, EOIV, EOST, Follow-up 6-weeks after EOST
timeFrame: Day 14, EOIV (up to Day 42), EOST (up to Day 42), Follow-up 6-weeks after EOST
measure: Time to first negative blood culture in patients on fosmanogepix compared to caspofungin/fluconazole
timeFrame: Baseline up to follow-up 6-weeks after EOST (approximately up to 12,5 weeks)
measure: 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
timeFrame: Screening up to follow-up 6-weeks after EOST (approximately up to 12,5 weeks)
measure: Number of patients with clinically significant laboratory abnormalities
timeFrame: Baseline up to follow-up 6-weeks after EOST (approximately up to 12,5 weeks)
measure: Number of patients with abnormal neurological examination findings
timeFrame: Baseline up to follow-up 6-weeks after EOST (approximately up to 12,5 weeks)
measure: Assessment of 12-lead electrocardiogram (ECGs)
timeFrame: Baseline up to follow-up 6-weeks after EOST (approximately up to 12,5 weeks)
measure: Plasma concentrations versus time of fosmanogepix (prodrug) and manogepix (active moiety)
timeFrame: Day 3: 0, 3, 6, 9 and 24 hours post-dose; Day 7, 14, 21, 28, 35; EOST: 72 and 192 hours post-dose
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Atlanta
country: United States
facility: Emory University Hospital - Clifton Road
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Methodist Hospital
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky College of Medicine
state: Kentucky
city: Detroit
country: United States
facility: Henry Ford Hospital, Department of Medicine, Division of Infectious Diseases
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine, Infectious Diseases Clinical Research Unit
state: Missouri
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Houston
country: United States
facility: Houston Methodist Hospital - Texas Medical Center
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Center, State
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Clayton
country: Australia
facility: Monash Medical Center Clayton
city: Graz
country: Austria
facility: University Hospital Graz, Department of Internal Medicine
city: Linz
country: Austria
facility: Kepler University Hospital GmbH, Department of Pulmonology, Clinical Department of Infectious Diseases
city: Vienna
country: Austria
facility: Medical University Vienna
city: Vienna
country: Austria
facility: Hospital Favoriten, Department of Internal Medicine IV - Infectious Diseases and Tropical Medicine
city: Brugge
country: Belgium
facility: General Hospital Saint-Jan
city: Brussels
country: Belgium
facility: University Hospital Brussels
city: Brussels
country: Belgium
facility: Saint Luc University Hospital, Department of Internal Medicine
city: Brussels
country: Belgium
facility: Erasme Hospital, Department of Infectious and Tropical Diseases
city: Hasselt
country: Belgium
facility: Jessa Hospital
city: Leuven
country: Belgium
facility: University Hospitals Leuven, Campus Gasthuisberg, Department of Infectious Diseases
city: Yvoir
country: Belgium
facility: UCL Mont-Godinne University Hospitals
city: Plovdiv
country: Bulgaria
facility: Eurohospital University Hospital
city: Sofia
country: Bulgaria
facility: University Medical Center "N. I. Pirogov", Burns and Plastic Surgery Clinic
city: Sofia
country: Bulgaria
facility: University Medical Center "N. I. Pirogov", Clinic of Purulent-Septic Surgery
city: Amiens
country: France
facility: Amiens Picardie University Hospital - South, Intensive Care Unit (ICU)
city: Argenteuil
country: France
facility: Victor Dupouy Hospital Center Argenteuil, Intensive Care Unit
city: Marseille
country: France
facility: Marseille Nord University Hospitals - AP-HM, Medical Intensive Care Unit, Acute Respiratory Distress and Severe Infections
city: Nantes
country: France
facility: Nantes University Hospital Center - Hotel Dieu Hospital, Department of Infectious and Tropical Diseases
city: Tours
country: France
facility: Tours Regional University Hospital Center
city: Ulm
country: Germany
facility: University Hospital Ulm, Comprehensive Infectious Diseases Center Ulm (CIDCU)
state: Baden-Wuerttemberg
city: Gießen
country: Germany
facility: University Hospital Giessen and Marburg GmbH
state: Hessen
city: Cologne
country: Germany
facility: University Hospital Cologne, Department of Internal Medicine I, Clinical Study Centre II for Infectious Diseases
state: North Rhine-Westphalia
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg, Clinic for Anesthesiology
city: Athens
country: Greece
facility: "LAIKO" General Hospital
city: Athens
country: Greece
facility: "Sotiria" Chest Diseases Hospital of Athens
city: Athens
country: Greece
facility: General Hospital of Athens "Evangelismos", 5th Department of Internal Medicine and Infectious Diseases Unit
city: Piraeus
country: Greece
facility: Tzaneio General Hospital
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki "Ippokratio"
city: Haifa
country: Israel
facility: Rambam Health Care Campus, Institute of Infectious Diseases
city: Holon
country: Israel
facility: Edith Wolfson Medical Center, Department of Infectious Diseases
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center, Department of Infectious Diseases
city: Tel Aviv
country: Israel
facility: The Tel Aviv Sourasky Medical Center, Infectious Diseases Unit
city: Zerifin
country: Israel
facility: Shamir Medical Center, Department of Infectious Diseases
city: Cuneo
country: Italy
facility: Hospital "S. Croce e Carle"
city: Genoa
country: Italy
facility: IRCCS Policlinic Hospital San Martino
city: Milan
country: Italy
facility: Maggiore Polyclinic Hospital, Foundation IRCCS Ca' Granda
city: Milan
country: Italy
facility: Hospital San Raffaele, IRCCS
city: Milan
country: Italy
facility: Big Metropolitan Hospital Niguarda Regional Health Authority
city: Pavia
country: Italy
facility: Polyclinic San Matteo, IRCCS
city: Pisa
country: Italy
facility: University Hospital of Pisa
city: Trieste
country: Italy
facility: Giuliano Isontina University Health Authority
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Johannesburg
country: South Africa
facility: Milpark Hospital
city: Pretoria
country: South Africa
facility: Ryexo Clinical Research
city: Pretoria
country: South Africa
facility: University of Pretoria / Steve Biko Academic Hospital
city: Umhlanga
country: South Africa
facility: Practice of R Moodley and MI Sarvan - Umhlanga
city: Seville
country: Spain
facility: University Hospital Virgen Macarena
state: Andalusia
city: Seville
country: Spain
facility: University Hospital Nuestra Senora de Valme
state: Andalusia
city: Barcelona
country: Spain
facility: Hospital del Mar, Department of Infectious Diseases
state: Catalonia
city: Barcelona
country: Spain
facility: Hospital Clinic of Barcelona, Department of Infectious Diseases
state: Catalonia
city: Madrid
country: Spain
facility: University Hospital Ramon y Cajal, Department of Infectious Diseases
state: Community Of Madrid
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: New Taipei City
country: Taiwan
facility: Far Eastern Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
city: Bangkok
country: Thailand
facility: Vajira Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital
city: Hat Yai
country: Thailand
facility: Songklanagarind Hospital
Study officials:
affiliation: Basilea Pharmaceutica International Ltd, Allschwil
name: Manuel Häckl, MD
role: STUDY_DIRECTOR
References: