A Phase 3 Efficacy and Safety Study of Fosmanogepix for the Treatment of Adult Patients With Invasive Mold Infections.

Официальное название

An Interventional Phase 3, Open-label, Two-cohort Study to Investigate the Efficacy and Safety of Fosmanogepix in Adult Patients With Invasive Mold Infections Caused by Aspergillus Spp., Fusarium Spp., Lomentospora Prolificans, Mucorales Fungi, or Other Multidrug Resistant Molds

Обзор

The purpose of this study is to evaluate the efficacy and safety of fosmanogepix (administered IV or oral) for the treatment of adult patients with invasive mold infections. The study is looking for patients who have been diagnosed with invasive mold infections. The maximum study duration will be approximately 8 months, including a target study treatment duration of 84 days which can be extended up to 180 days and follow-up period. The patient will be assigned to one of two treatment cohorts: Cohort A (primary therapy): Patients will receive either the study drug or institutional standard of care antifungal treatment. Cohort B (salvage treatment; i.e. treatment given after patients did not respond to previous treatments or did not tolerate them): Patients will receive the study drug The primary aim is to compare the all cause mortality with a fixed threshold at Day 42.

Вмешательства

• Препарат Fosmanogepix IV infusion
  Fosmanogepix will be administered IV
• Препарат Standard of care antifungal therapy
  Standard of care antifungal therapy will be administered in accordance with their respective product labels and/or standard practice guidelines
• Препарат Fosmanogepix oral tablet
  Fosmanogepix will be administered orally.

Первичные конечные точки

• Day 42 all-cause mortality rate [Срок оценки: Day 42]

Вторичные конечные точки (11)

• Proportion of patients with overall response of treatment success [Срок оценки: Day 42, Day 84 and up to 180 days]
• Proportion of patients with clinical response of treatment success [Срок оценки: Day 42, Day 84 and up to 180 days]
• Proportion of patients with mycological response of eradication or presumed eradication [Срок оценки: Day 42, Day 84 and up to 180 days]
• Proportion of patients with radiological response of complete response or partial response [Срок оценки: Day 42, Day 84 and up to 180 days]
• All-cause mortality rate at Day 84 [Срок оценки: Day 84]
• Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), treatment-related AEs, adverse events of special interest (AESI), and AEs leading to discontinuation [Срок оценки: Screening up to follow-up 6 weeks after EOST (target duration approximately up to 8 months)]
• Number of patients with clinically significant laboratory abnormalities [Срок оценки: Up to follow-up 6 weeks after EOST (target duration approximately up to 8 months)]
• Number of patients with abnormal neurological examination findings [Срок оценки: Up to follow-up 6 weeks after EOST (target duration approximately up to 8 months)]
• Assessment of 12-lead electrocardiogram corrected QT (Fridericia method) Interval (ECG QTcF Interval) [Срок оценки: Up to follow-up 6 weeks after EOST (target duration approximately up to 8 months)]
• Plasma concentrations versus time of fosmanogepix (prodrug) and manogepix (active moiety) following IV administration [Срок оценки: Pre-dose, 3,6, and 9 hours post-start of the 3-hour IV infusion on Day 3, and at 24 hours (prior to Day 4 dosing)]
• Plasma concentrations versus time of fosmanogepix (prodrug) and manogepix (active moiety) following oral administration [Срок оценки: On days 7, 14, 28, and 42. Post-dose plasma samples will also be collected: 72 hrs and 192 hrs after last dose.]

Критерии участия

Main Inclusion Criteria:

• Diagnosis of proven or probable Invasive mold infection (IMI) defined in accordance with the Revision and Update of the Consensus Definitions of Invasive Fungal Disease from the EORTC/MSGERC as adapted for this study and caused by Aspergillus spp. (in patients with limited treatment options), Fusarium spp., Lomentospora prolificans, Mucorales fungi, or other multi-drug resistant molds.
• Patient's condition allows for appropriate infection source control measures.

Main Exclusion Critera:

• Refractory hematologic malignancy.
• Chronic aspergillosis, aspergilloma, or allergic bronchopulmonary aspergillosis.
• Coronavirus disease 2019 (COVID-19) associated mucormycosis.
• Invasive fungal disease caused by more than one fungal pathogen is not permitted in Cohort A but is permitted in Cohort B.
• Patients with a Karnofsky Performance Status < 20 at Screening.
• Requirement, or anticipated requirement, for hemodialysis, peritoneal dialysis, or hemofiltration.
• Patients with known human immunodeficiency virus infection.
• Ongoing neurological disorders.
• Patients receiving hospice/comfort care only.
• Other medical or psychiatric condition.
• Current use of any prohibited concomitant medication(s).
• Current/ previous administration of an investigational drug within 30 days.
• Prior enrollment in this or any previous study of fosmanogepix.
• Moderate or severe hepatic impairment.
• Patient who is pregnant or lactating.
• Known hypersensitivity to fosmanogepix, manogepix, or any of their excipients.

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

Открытое

Основная цель

Лечение

Центры проведения

США · 19 центров

• 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
• Memorial Healthcare System — Hollywood
• Rush University Medical Center, Division of Infectious Diseases — Chicago
• University of Kentucky Medical Center, Division of Infectious Diseases — Lexington
• Johns Hopkins Hospital — Baltimore
• … и ещё 11 центров

Тайвань · 7 центров

• Kaohsiung Medical University Chung-Ho Memorial Hospital — Kaohsiung City
• China Medical University Hospital — Taichung
• Taichung Veterans General Hospital — Taichung
• National Taiwan University Hospital — Taipei
• Taipei Medical University Hospital — Taipei
• Taipei Veterans General Hospital — Taipei
• Linkou Chang Gung Memorial Hospital — Taoyuan

Австралия · 6 центров

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

Италия · 6 центров

• IRCCS Policlinic Hospital San Martino — Genova
• Maggiore Polyclinic Hospital, Foundation IRCCS Ca' Granda — Milan
• University Polyclinic Hospital of Modena — Modena
• Polyclinic San Matteo, IRCCS — Pavia
• University Hospital of Pisa — Pisa
• Giuliano Isontina University Health Authority — Trieste

Испания · 6 центров

• University Hospital Virgen Macarena — Seville
• Hospital del Mar, Department of Infectious Diseases — Barcelona
• Hospital de la Santa Creu i Sant Pau — Barcelona
• University Hospital Cruces — Barakaldo
• Hospital de la Santa Creu i Sant Pau — Barcelona
• University Hospital Ramon y Cajal, Department of Infectious Diseases — Madrid

Бельгия · 4 центра

• Charleroi Grand Hospital (GHDC) - Les Viviers Site — Charleroi
• Jessa Hospital — Hasselt
• University Hospitals Leuven, Campus Gasthuisberg, Department of Hematology — Leuven
• UCL Mont-Godinne University Hospitals — Yvoir

Греция · 4 центра

• "LAIKO" General Hospital — Athens
• General Hospital of Athens "Evangelismos" — Athens
• University General Hospital "Attikon", 2nd Department of Internal Medicine, Propaedeutic, — Athens
• General Hospital of Thessaloniki "Ippokratio" — Thessaloniki

Израиль · 4 центра

• Rambam Health Care Campus, Institute of Infectious Diseases — Haifa
• Chaim Sheba Medical Center, Department of Infectious Diseases — Ramat Gan
• The Tel Aviv Sourasky Medical Center, Infectious Diseases Unit — Tel Aviv
• Shamir Medical Center, Department of Infectious Diseases — Ẕerifin

Таиланд · 4 центра

• Faculty of Medicine, Siriraj Hospital — Bangkok
• Maharaj Nakorn Chiang Mai Hospital — Chiang Mai
• Songklanagarind Hospital — Hat Yai
• Srinagarind Hospital — Khon Kaen

Бразилия · 3 центра

• Porto Alegre Clinical Hospital (HCPA) — Porto Alegre
• Hospital A.C.Camargo ("Antonio Prudente" Foundation) — São Paulo
• "Santa Marcelina" Hospital — São Paulo

Канада · 3 центра

• University of Alberta — Edmonton
• Juravinski Hospital - Hamilton Health Sciences — Hamilton
• Vancouver Coastal Health Research Institute (VCHRI) — Vancouver

Франция · 3 центра

• Nantes University Hospital Center - Hotel Dieu Hospital, Department of Infectious and Trop — Nantes
• Necker Children's Hospital, Department of Infectious and Tropical Diseases — Paris
• Rennes University Hospital Center - Pontchaillou Site — Rennes

Германия · 3 центра

• University Hospital Cologne, Internal Medicine I - Oncology, Hematology, Clinical Infectio — Cologne
• University Medical Center of Johannes Gutenberg University Mainz — Mainz
• Frankfurt University Clinic — Frankfurt

Австрия · 2 центра

• Kepler University Hospital GmbH, Department of Internal Medicine IV - Pulmonology — Linz
• Medical University Vienna, Department of Internal Medicine I, Clinical Department of Infec — Vienna

Нидерланды · 2 центра

• Radboud University Medical Center (Radboudumc), Department of Intensive Care — Nijmegen
• Erasmus Medical Center, Deoartment of Infectious Diseases — Rotterdam

Идентификаторы

NCT: NCT06925321 · FMGX-CS-302 · 2024-516216-16-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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