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

Официальное название

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

Обзор

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.

Вмешательства

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

Первичные конечные точки

• Proportion of patients alive at Day 30 [Срок оценки: Day 30]
• Proportion of patients with an overall response of treatment success at end of study treatment (EOST) [Срок оценки: EOST (up to Day 42)]

Вторичные конечные точки (12)

• Proportion of patients with an overall response of treatment success at Day 7 [Срок оценки: Day 7]
• Proportion of patients with an overall response of treatment success at Day 14 [Срок оценки: Day 14]
• Proportion of patients with an overall response of treatment success at end of IV treatment (EOIV) [Срок оценки: up to Day 42]
• Proportion of patients with an overall response of treatment success (sustained) at follow-up 6 weeks after EOST [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Screening up to follow-up 6-weeks after EOST (approximately up to 12,5 weeks)]
• Number of patients with clinically significant laboratory abnormalities [Срок оценки: Baseline up to follow-up 6-weeks after EOST (approximately up to 12,5 weeks)]
• Number of patients with abnormal neurological examination findings [Срок оценки: Baseline up to follow-up 6-weeks after EOST (approximately up to 12,5 weeks)]
• Assessment of 12-lead electrocardiogram (ECGs) [Срок оценки: 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) [Срок оценки: Day 3: 0, 3, 6, 9 and 24 hours post-dose; Day 7, 14, 21, 28, 35; EOST: 72 and 192 hours post-dose]

Критерии участия

Критерии включения

• 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.
• 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.
• Patient's condition allows for appropriate infection source control measures, including removal of pre-existing intravascular catheters and devices, if necessary.

Критерии исключения

• Existing infection

• Infection known to be due to Candida krusei, in blood or any other normally sterile site.
• Inappropriate fungal infection source control.
• Diagnosis of certain deep-seated Candida infections.
• Life expectancy of < 72 hours in the opinion of the investigator.
• Requirement, or expected requirement, for hemodialysis, peritoneal dialysis, or hemofiltration.
• 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).
• 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.
• Other medical or psychiatric condition or laboratory abnormality that may increase the risk of study participation or make the patient inappropriate for the study.
• Current use of any prohibited concomitant medications or those unwilling/unable to use a permitted concomitant medication.
• 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).
• 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).
• Prior participation in this or any previous study of fosmanogepix.
• 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.
• Female patient is pregnant or lactating.
• Known hypersensitivity to fosmanogepix, manogepix, caspofungin, any echinocandin, fluconazole or to any of their excipients.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 23 центра

• University of Alabama at Birmingham School of Medicine, Department of Medicine — Birmingham
• City of Hope — Duarte
• David Geffen School of Medicine at UCLA — Los Angeles
• UC Davis Medical Center — Sacramento
• Emory University Hospital - Clifton Road — Atlanta
• Augusta University Medical Center — Augusta
• Indiana University Methodist Hospital — Indianapolis
• University of Kentucky College of Medicine — Lexington
• … и ещё 15 центров

Китай · 19 центров

• China-Japan Friendship Hospital — Пекин
• The First Affiliated Hospital of Bengbu Medical College — Bengbu
• West China Hospital, Sichuan University — Чэнду
• Guangzhou First People's Hospital — Гуанчжоу
• The First Affiliated Hospital of Guangzhou Medical University — Гуанчжоу
• Zhejiang Provincal Hospital of Chinese Medicine — Ханчжоу
• Zhejiang Provincial People's Hospital — Ханчжоу
• Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine — Ханчжоу
• … и ещё 11 центров

Италия · 10 центров

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Тайвань · 8 центров

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Бельгия · 7 центров

• General Hospital Saint-Jan — Bruges
• University Hospital Brussels — Brussels
• Saint Luc University Hospital, Department of Internal Medicine — Brussels
• Erasme Hospital, Department of Infectious and Tropical Diseases — Brussels
• Jessa Hospital — Hasselt
• University Hospitals Leuven, Campus Gasthuisberg, Department of Infectious Diseases — Leuven
• UCL Mont-Godinne University Hospitals — Yvoir

Испания · 7 центров

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Аргентина · 6 центров

• Central Hospital de San Isidro Melchor Posse — Buenos Aires
• Buenos Aires Italian Hospital, Department of Infectious Diseases — Buenos Aires
• Cordoba Private University Hospital, Department of Infectious Diseases — Córdoba
• Italian Hospital of La Plata, Department of Infectious Diseases — La Plata
• Central Hospital Mendoza — Mendoza
• British Sanatorium SA — Rosario

Австралия · 6 центров

• Westmead Hospital — Sydney
• Princess Alexandra Hospital — Woolloongabba
• Peter MacCallum Cancer Center, State — Melbourne
• The Alfred Hospital — Melbourne
• Royal Melbourne Hospital — Parkville
• Monash Medical Center Clayton — Clayton

Колумбия · 6 центров

• Cardiomet CEQUIN Foundation, Department of Nephrology — Armenia
• Hospital Alma Mater de Antioquia — Medellín
• Luz Castro de Gutierrez Medellin General Hospital, Research Center — Medellín
• Pablo Tobon Uribe Hospital — Medellín
• High Technology Medical Institute S.A.S, IMAT S.A.S. — Montería
• Somer Clinic — Rionegro

Франция · 6 центров

• Amiens Picardie University Hospital - South, Intensive Care Unit (ICU) — Amiens
• … и ещё 5 центров

Германия · 6 центров

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Греция · 6 центров

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Бразилия · 5 центров

• HC-UFPR — Curitiba
• Hospital Our Lady of Grace — Curitiba
• Porto Alegre Clinical Hospital (HCPA), Infectious Diseases / Internal Medicine — Porto Alegre
• Pontifical University Of Rio Grande Do Sul (PUCRS) - St. Luke Hospital — Porto Alegre
• Santa Marcelina Hospital — São Paulo

Израиль · 5 центров

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ЮАР · 5 центров

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Таиланд · 5 центров

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Австрия · 4 центра

• University Hospital Graz, Department of Internal Medicine — Graz
• Kepler University Hospital GmbH, Department of Pulmonology, Clinical Department of Infecti — Linz
• Medical University Vienna — Vienna
• Hospital Favoriten, Department of Internal Medicine IV - Infectious Diseases and Tropical — Vienna

South Korea · 4 центра

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Болгария · 3 центра

• Eurohospital University Hospital — Plovdiv
• University Medical Center "N. I. Pirogov", Burns and Plastic Surgery Clinic — Sofia
• University Medical Center "N. I. Pirogov", Clinic of Purulent-Septic Surgery — Sofia

Сингапур · 3 центра

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Идентификаторы

NCT: NCT05421858 · FMGX-CS-301 · 2022-500455-23-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗