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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 234
- 试验地点
- 90
- 主要终点
- Day 42 all-cause mortality rate
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- 未提供
研究组 & 干预措施
Cohort A: Comparator Antifungal Treatment
Best available therapy (BAT) administered as IV or orally per standard guidelines.
干预措施: Standard of care antifungal therapy (Drug)
Cohort A: Experimental Treatment
Patients will receive the study drug.
Fosmanogepix will be administered as an Intravenous (IV) infusion or in oral form.
干预措施: Fosmanogepix IV infusion (Drug)
Cohort A: Experimental Treatment
Patients will receive the study drug.
Fosmanogepix will be administered as an Intravenous (IV) infusion or in oral form.
干预措施: Fosmanogepix oral tablet (Drug)
Cohort B
Patients will receive the study drug.
Fosmanogepix will be administered as an Intravenous (IV) infusion or in oral form.
干预措施: Fosmanogepix IV infusion (Drug)
Cohort B
Patients will receive the study drug.
Fosmanogepix will be administered as an Intravenous (IV) infusion or in oral form.
干预措施: Fosmanogepix oral tablet (Drug)
结局指标
主要结局
Day 42 all-cause mortality rate
时间窗: Day 42
次要结局
- Proportion of patients with overall response of treatment success(Day 42, Day 84 and up to 180 days)
- Proportion of patients with clinical response of treatment success(Day 42, Day 84 and up to 180 days)
- Proportion of patients with mycological response of eradication or presumed eradication(Day 42, Day 84 and up to 180 days)
- Proportion of patients with radiological response of complete response or partial response(Day 42, Day 84 and up to 180 days)
- All-cause mortality rate at Day 84(Day 84)
- Number of patients with abnormal neurological examination findings(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)(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(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(On days 7, 14, 28, and 42. Post-dose plasma samples will also be collected: 72 hrs and 192 hrs after last dose.)
- 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(Screening up to follow-up 6 weeks after EOST (target duration approximately up to 8 months))
- Number of patients with clinically significant laboratory abnormalities(Up to follow-up 6 weeks after EOST (target duration approximately up to 8 months))