Phase III, Adjudicator-blinded, Randomised Study to Evaluate Efficacy and Safety of Treatment With Olorofim Versus Treatment With AmBisome® Followed by Standard of Care in Patients With Invasive Fungal Disease Caused by Aspergillus Species
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 225
- 试验地点
- 259
- 主要终点
- All-cause mortality
研究概览
简要总结
The purpose of this study is to compare treatment with olorofim versus treatment with AmBisome® followed by standard of care (SOC) in patients with IFD caused by proven IA or probable lower respiratory tract disease Aspergillus species (invasive aspergillosis, IA).
详细描述
The mortality rate in immunosuppressed patients with IA is high even with effective modern antifungal drug treatment. Intrinsic and acquired resistance to azoles and amphotericin B, the two most effective classes of treatment, have been identified in Aspergillus species and are linked to this increased mortality.
Currently marketed antifungal drugs have limitations including limited dosage forms, DDIs, and significant adverse reactions.
For patients with IA who do not respond to or cannot tolerate a triazole therapy, treatment options are even more limited.
Olorofim is an antifungal candidate with a novel mechanism of action offering activity against resistant organisms, differences in safety profile, along with oral dosing, predictable and reliable pharmacokinetic (PK) profile and limited potential for DDIs.
The present study is designed to compare the efficacy, safety, and tolerability of olorofim with that of AmBisome® followed by guideline-based hierarchy standard of care (SOC) in patients with IA whose infection is either refractory to or unsuitable for azole therapy.
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
- Single (Investigator)
盲法说明
Adjudicator and sponsor-blinded.
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
- •Male and female patients ages over 18 years and weighing more than 30 kg
- •Patients with proven IA at any site or probable LRTD IA per EORTC/MSG 2019 criteria as adapted for this study and where the duration of specific therapy for this episode of IA has been ≤ 28 days. For purposes of this inclusion, the duration of specific therapy includes any mould-active therapy given for this episode of IA whether subsequently judged potentially effective or not.
- •Patients requiring therapy with an antifungal agent other than a mould-active azole, and who have had ≤ 96 hours of potentially effective prior therapy. Potentially effective prior therapy includes any agent to which the infecting strain of Aspergillus is likely to be susceptible. There are no exclusions or limitations on such agents (eg, AmBisome® is permitted) other than their duration.
- •AmBisome® is an appropriate therapy for the patient.
排除标准
- •Women who are pregnant or breastfeeding.
- •Known history of allergy, hypersensitivity, or any serious reaction to any component of the study drug
- •Patients with only chronic aspergillosis, aspergilloma, or allergic bronchopulmonary aspergillosis.
- •Suspected mucormycosis (zygomycosis).
- •Patients with a known active second fungal infection of any type, other than candidiasis that can be treated with fluconazole.
- •The requirement for ongoing use of echinocandin as Candida prophylaxis.
- •Microbiological findings (eg, bacteriological, virological) or other potential conditions that are temporally related and suggest a different aetiology for the clinical features.
- •Human immunodeficiency virus (HIV) infection but not currently receiving antiretroviral therapy.
- •Patients with a baseline prolongation of QT using Fridericia's Correction Formula (QTcF) ≥ 500 msec, or at high risk for QT/QTc prolongation.
- •Evidence of hepatic dysfunction.
研究组 & 干预措施
Olorofim
Olorofim versus AmBisome followed by Standard of Care (SOC)
干预措施: Olorofim (Drug)
AmBisome
Olorofim versus AmBisome followed by Standard of Care (SOC)
干预措施: AmBisome® (Drug)
结局指标
主要结局
All-cause mortality
时间窗: Treatment Day 42
To compare all-cause mortality (ACM) at Day 42 following treatment with olorofim versus treatment with AmBisome® followed by standard of care (SOC) in the intent-to-treat (ITT) population of patients with Invasive Fungal Disease (IFD) caused by proven Invasive Aspergillosis (IA) at any site or probable lower respiratory tract disease (LRTD) Aspergillus species (invasive aspergillosis, IA).
次要结局
- Data Review Committee's Assessment of Patient Mortality(Day 42 and 84 and EOT (End of Treatment - Maximum Treatment 84 days [± 7 Days]))
- Quality of life as measured by the 5 Level 5 Dimension (EQ-5D-5L) at Baseline(Days 14 and EOT (End of Treatment - Maximum Treatment 84 days [± 7 Days]))
- Investigator-assessed overall response(Day 14, Day 28, Day 42, Day 84, EOT (End of Treatment - Maximum Treatment 84 days [± 7 Days]), and 4-week Follow-up (FU).)
- Survival status(Day 42, Day 84, and End Of Treatment and at the 4 weeks ± 7 days FU)
- Adjudicated Assessment of Overall outcome(Day 42, Day 84, and End of Treatment (anytime during the study between first administration and Day 84))
- To compare the effects of treatment with olorofim versus treatment with AmBisome® followed by SOC on Galactomannan index.(Day 14, Day 28, Day 42, Day 84, EOT (End of Treatment - Maximum Treatment 84 days [± 7 Days]) and 4-week Follow-up (FU))
- To collect additional olorofim and the disproportionate metabolite H26C pharmacokinetic (PK) data for inclusion in a Population PK model(Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 70, Day 84, and at EOT (End of Treatment - Maximum Treatment 84 days [± 7 Days]))
- Diagnosis of a secondary fungal infection(at any time through End Of Treatment)
- Safety Assessment(up to the Day 84 and 4-week Follow-up (FU))