Phase IIb Study of F901318 as Treatment of Invasive Fungal Infections Due to Lomentospora Prolificans, Scedosporium Spp., Aspergillus Spp., and Other Resistant Fungi in Patients Lacking Suitable Alternative Treatment Options
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 203
- 试验地点
- 82
- 主要终点
- Data Review Committee (DRC) Adjudicated Overall Response at Day 42
研究概览
简要总结
A study to evaluate olorofim (F901318) for the treatment of invasive fungal infections in participants lacking suitable alternative treatment options.
详细描述
An open label, single arm Phase IIb study of olorofim (F901318) in participants with invasive fungal infections with limited treatment options. Participants received study treatment for up to 12 weeks in the main phase of the study. At the Investigator's request and after discussion with the medical monitor, open-label treatment with F901318 could be continued in patients judged by the Investigator to need therapy beyond 84 days and considered likely to continue to benefit from extended treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female aged at least 18 years, or male and female aged 16 years or 17 years and who weigh at least 40 kg whom have given informed consent
- •Ability and willingness to comply with the protocol.
- •Able to take oral medication
- •Females must be non-lactating and at no risk of pregnancy
- •Male with female partners of childbearing potential must either abstain from sexual intercourse or use a highly effective means of contraception
- •Participants with invasive fungal disease
- •Participants who have limited alternative treatment options
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.
- •Participants with chronic aspergillosis, aspergilloma or allergic bronchopulmonary aspergillosis.
- •Human Immunodeficiency Virus (HIV) infection but not currently receiving antiretroviral therapy.
- •Participants with a medical condition that may jeopardize adherence to the protocol or may cause unacceptable additional risk to the participant
- •Previously enrolled participants or participants enrolled in any clinical trial within the last 30 days
- •Participants receiving treatment limited to supportive care due to predicted short survival time.
- •Prohibited concomitant medications.
- •Any exclusion criteria required by local regulatory authorities.
研究组 & 干预措施
Olorofim (F901318)
Olorofim (F901318) was given orally for up to 90 days in the Main Study Phase and could be continued for those participants entering the Extended Treatment Phase.
Patients received fixed doses comprising of a 1-day loading dose of 150 mg of olorofim twice a day followed by a maintenance dose of 90 mg of olorofim twice a day.
Up until Protocol Amendment 06, 58 patients received a weight-based olorofim dosing consisting of a 1-day loading dose of 4 mg/kg/day on Day 1, then a maintenance dose of 2.5 mg/kg/day (divided into 2 or 3 doses). The dose was then adjusted based on plasma levels of olorofim with the maximum total daily dose of 300 mg.
干预措施: Olorofim (Drug)
结局指标
主要结局
Data Review Committee (DRC) Adjudicated Overall Response at Day 42
时间窗: Day 42 in the Main Phase of study treatment
The primary efficacy variable was the DRC-adjudicated overall response at the Day 42 Study Visit, as determined by an independent DRC using a combination of clinical, mycological, and radiological results based on European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. For the primary statistical analysis of overall response rate, values were assigned to the DRC adjudicated overall response as follows: Success (Success-Complete, Success-Partial); Failure (Failure-Stable, Failure-Progression, Death, and participants for whom data at the Day 42 Study Visit could not be collected or participants who were considered not evaluable at the Day 42 Study Visit).
次要结局
- DRC Adjudicated Overall Response at Day 42 for for Scedosporium Species(Day 42 in the Main Phase of study treatment)
- Investigator Assessed Overall Response at Day 84(Day 84 in the Main Phase of study treatment)
- DRC Adjudicated Overall Response at Day 42 for All Aspergillus(Day 42 in the Main Phase of study treatment)
- Investigator Assessed Overall Response at Day 42(Day 42 in the Main Phase of study treatment)
- Investigator Assessed Clinical Response at Day 84(Day 84 in the Main Phase of study treatment)
- All Cause Mortality Rate at Day 42(Day 42 in the Main Phase of study treatment)
- DRC Adjudicated Overall Response at Day 42 for Other Olorofim Susceptible Fungi(Day 42 in the Main Phase of study treatment)
- DRC Adjudicated Overall Response at Day 84(Day 84 in the Main Phase of study treatment)
- DRC Adjudicated Mycological Response at Day 42(Day 42 in the Main Phase of study treatment)
- DRC Adjudicated Mycological Response at Day 84(Day 84 in the Main phase of study treatment)
- DRC Adjudicated Radiological Response at Day 84(Day 84 in the Main Phase of study treatment)
- Investigator Assessed Radiological Response at Day 42(Day 42 in the Main Phase of study treatment)
- DRC Adjudicated Overall Response at Day 42 for Lomentospora Prolificans(Day 42 in the Main Phase of study treatment Day 42 in the Main Phase of study treatment Day 42 in the Main Phase of study treatment Day 42 in the Main Phase of study treatment Day 42 in the Main Phase of study treatment)
- DRC Adjudicated Overall Response at Day 42 for Coccidioides Species(Day 42 in the Main Phase of study treatment)
- Investigator Assessed Mycological Response at Day 42(Day 42 in the Main Phase of study treatment)
- Investigator Assessed Mycological Response at Day 84(Day 84 in the Main Phase of study treatment)
- DRC Adjudicated Radiological Response at Day 42(Day 42 in the Main phase of study treatment)
- DRC Adjudicated Clinical Response at Day 42(Day 42 in the Main phase of study treatment)
- DRC Adjudicated Clinical Response at Day 84(Day 84 in the Main phase of study treatment)
- Investigator Assessed Clinical Response at Day 42(Day 42 in the Main phase of study treatment)
- All Cause Mortality Rate at Day 84(Day 84 in the Main Phase of study treatment)
- Investigator Assessed Radiological Response at Day 84(Day 84 in the Main Phase of study treatment)