A Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety and Efficacy of HMI-103 Administered Intravenously in Adult Participants With Classical PKU Due to PAH Deficiency
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- To measure incidence and severity of Treatment Emergent Adverse Events (TEAEs) and adverse events of special interest (AESIs) of a single administration of HMI-103
研究概览
简要总结
This is an open-label, sequential ascending dose-escalation, Phase 1 study to evaluate the safety and efficacy of a single intravenous (I.V.) administration of HMI-103, a gene editing development candidate, in adult participants aged 18 to 55 years, inclusive, with classical PKU due to PAH deficiency who have uncontrolled disease despite Phe restricted dietary management.
详细描述
This is an open-label, sequential ascending dose-escalation, Phase 1 study to evaluate the safety and efficacy of a single intravenous administration of HMI-103, a gene editing development candidate, in adult participants aged 18 to 55 years, inclusive, with classical PKU due to PAH deficiency who have uncontrolled disease despite Phe-restricted dietary management. Up to 3 dose levels of HMI-103 may be investigated. At a given dose level, 3 participants are planned to be enrolled and dosed. Participant dosing will be staggered.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults 18-55 years of age at the time of informed consent
- •Diagnosis of classical phenylketonuria (PKU) due to PAH deficiency
- •Four baseline plasma Phe values with a concentration of ≥ 600 μmol/L and at least one historical value ≥ 600 μmol/L in the preceding 24 months.
- •Participants must have uncontrolled classical PKU disease (despite Phe-restricted dietary management) in the judgment of the investigator and confirmed by the independent DMC at the end of the Screening period.
- •Participant has the ability and willingness to maintain their baseline diet, for the duration of the trial, unless otherwise directed
排除标准
- •Subjects with PKU that is not due to PAH deficiency
- •Presence of anti-AAVHSC15 neutralizing antibodies
- •Participants who are well controlled on a Phe-restricted diet.
- •Hemoglobin A1c >6.5% or fasting glucose >126 mg/dL
- •Liver function tests > ULN
- •International normalized ratio (INR) > 1.2
- •Hematology values outside of the normal range
- •Previously received gene therapy for the treatment of any condition.
研究组 & 干预措施
Low Dose Cohort
HMI-103 delivered IV one time
干预措施: HMI-103 (Drug)
Intermediate Dose Cohort
HMI-103 delivered IV one time
干预措施: HMI-103 (Drug)
High Dose Cohort
HMI-103 delivered IV one time
干预措施: HMI-103 (Drug)
结局指标
主要结局
To measure incidence and severity of Treatment Emergent Adverse Events (TEAEs) and adverse events of special interest (AESIs) of a single administration of HMI-103
时间窗: Baseline to Week 104
To evaluate the efficacy of HMI-103 on reduction of plasma Phe concentration at each dose level
时间窗: Baseline to Weeks 24-32
Mean percent change from baseline at Weeks 24-32 in plasma Phe concentration within each dose cohort post-administration of HMI-103
次要结局
- To evaluate the effect of HMI-103 on plasma Phe concentration relative to treatment guidelines for PKU(Baseline to Week 104)
- To assess durability of response(Weeks 48-52)
- To assess the changes in dietary protein intake(Baseline to Week 104)