Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 178
- 试验地点
- 1
- 主要终点
- Evidence of fungicidal activity
研究概览
简要总结
This study is designed as two sequential trials. The first is a phase I open label trial to evaluate the safety and tolerability of MAT2203. The maximal tolerated and non-toxic daily dose,will then be moved forward into a multi-day safety trial. The Phase II trial will investigate toxicity and early fungicidal activity (EFA) of MAT2203 with flucytosine.
详细描述
Cryptococcal meningitis has emerged as one of the most frequent and deadly opportunistic infections in HIV patients. Historically, amphotericin B (AMB) has been considered the "gold standard" in antifungal treatments due to its broad spectrum of activity and lack of emergence of resistance. However, the use of AMB is limited by side effects, including nephrotoxicity, anemia, and infusion-related reactions. MAT2203 or encochleated oral amphotericin B (cAMB) is a lipid nano-crystal formulation designed for targeted oral delivery of the antifungal drug AMB for treatment of fungal and parasitic infections.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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
- •Age >18 years
- •Calculated creatinine clearance >70 mL/min/1.73 m2 (measured within 3 months)
- •Written informed consent
- •Cryptococcal meningitis diagnosed by CSF cryptococcal antigen (CRAG)
- •Ability and willingness to provide informed consent
- •Willing to receive protocol-specified lumbar punctures
排除标准
- •Symptomatic Current illness
- •Known significant, untreated health problem
- •Inability to take enteral medicine
- •Pregnant or breast feeding
- •Receiving amphotericin B therapy in past 90 days
- •Presenting Glasgow Coma Scale (GCS) < 15
- •Received 3 or more doses of IV amphotericin therapy within last 30 days
- •Inability to take enteral (oral or nasogastric) medicine
- •Cannot or unlikely to attend regular clinic visits
- •Pregnancy or breastfeeding
- •Receiving chemotherapy or corticosteroids
- •Suspected Paradoxical immune reconstitution inflammatory syndrome (IRIS)
- •Recent initiation of HIV therapy or ART class switch (within 2 weeks)
研究组 & 干预措施
Phase 2 safety and tolerability
Safety, tolerability, and microbiologic efficacy of MAT2203 among HIV-infected patients with cryptococcal meningitis compared with standard IV AMB.
干预措施: MAT2203 (Drug)
Phase 1a single ascending dose study
Phase IA will consist of a single ascending dose study in 9 participants to test three doses to determine the max tolerated dose.
干预措施: MAT2203 (Drug)
Phase 1b multiple day dosing
9 subjects will receive the Phase Ia 100% tolerated MAT2203 dose for 7 days.
干预措施: MAT2203 (Drug)
Phase 2 safety and tolerability
Safety, tolerability, and microbiologic efficacy of MAT2203 among HIV-infected patients with cryptococcal meningitis compared with standard IV AMB.
干预措施: Amphotericin B (Drug)
结局指标
主要结局
Evidence of fungicidal activity
时间窗: 2 weeks
CSF early fungicidal activity (EFA) during 2-week induction therapy
Highest dose tolerated without inducing vomiting
时间窗: 7 days
Proportion of cAMB daily dose received and tolerated without vomiting within 30 minutes.
次要结局
未报告次要终点