A Phase 1/2 Open-Label, Randomized, Concurrently-Controlled, Dose Escalation Study to Evaluate the Safety and Efficacy of HMI-102 in Adult PKU Subjects With PAH Deficiency
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 25
- 主要终点
- Change from baseline in 12-lead electrocardiograms (ECGs), vital signs, physical examinations (Dose Escalation Phase)
研究概览
简要总结
This is a Phase 1/2, open-label, randomized, concurrently-controlled, dose escalation study to evaluate the safety and efficacy of HMI-102 in adult PKU subjects with PAH deficiency. Participants will receive a single administration of HMI-102 and will be followed for safety and efficacy for 1 year.
详细描述
Part 1 of this study will evaluate the safety and efficacy of HMI-102 gene therapy in adult subjects with PKU due to PAH deficiency. Subjects will receive a single dose of HMI-102 administered intravenously. Up to 3 dose levels of HMI-102 may be investigated in this study. At a given dose level, a minimum of 2 subjects will be enrolled and dosed. Dosing of the first two subjects will be staggered. Following evaluation of data from the first 2 subjects in a cohort, a decision can be made to either escalate to the next dose level or expand the cohort at the selected dose level. Additional doses may be added by HMI to investigate intermediate or higher doses.
In Part 2 dose expansion, evaluation of up to 2 dose levels is planned. Subjects will be randomized to receive HMI-102 or a concurrent delayed treatment control arm. Subjects in the delayed treatment control will be eligible to receive HMI-102 after 28 weeks.
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 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 phenylketonuria (PKU) due to PAH deficiency
- •Two plasma Phe values with a concentration of ≥ 600 μmol/L drawn at least 72 hours apart during the screening period and at least one historical value ≥ 600 μmol/L in the preceding 24 months.
- •Subject has the ability and willingness to maintain their baseline diet, whether Phe-restricted or unrestricted 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
- •ALT > ULN and AST > ULN
- •Alkaline phosphatase > ULN.
- •Total bilirubin > ULN, direct bilirubin > ULN
- •Serum creatinine >1.5x ULN
- •International normalized ratio (INR) > 1.2
- •Hematology values outside of the normal range (hemoglobin <11.0 g/dL for males or <10.0 g/dL for females; white blood cells (WBC) <3,000/μL; absolute neutrophils <1500/μL; platelets <100,000/μL)
- •Hemoglobin A1c >6.5% or fasting glucose >126 mg/dL
- •Any clinically significant abnormal laboratory result at screening, in the opinion of the Investigator
- •Contraindication to corticosteroid use or conditions that could worsen in the presence of corticosteroids, as assessed and determined by the investigator
- •Previously received gene therapy for the treatment of any condition.
结局指标
主要结局
Change from baseline in 12-lead electrocardiograms (ECGs), vital signs, physical examinations (Dose Escalation Phase)
时间窗: Baseline to Week 52
Subjects change from baseline in 12-lead electrocardiograms (ECGs), vital signs, physical examinations
Change from baseline in Plasma Phe Concentration (Dose Escalation Phase)
时间窗: Weeks 24-28
Change from baseline in plasma Phe concentration during Weeks 24-28
Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Escalation Phase)
时间窗: Baseline to Week 52
Subjects with at least one TEAE or serious TEAE
Change from baseline in mean Plasma Phe Concentration (Dose Expansion Phase)
时间窗: Weeks 24-28
Change from baseline in mean plasma Phe concentration during Weeks 24-28
Change from baseline in clinical laboratory values (Dose Escalation Phase)
时间窗: Baseline to Week 52
Change in serum chemistry values including liver function tests, hematology, and urinalysis
Incidence of sustained plasma Phe concentration of ≤360 μmol/L at 28 weeks post dose (Dose Escalation Phase)
时间窗: Week 28
Subjects achieving a sustained plasma Phe concentration ≤360 μmol/L at 28 weeks post dose
次要结局
- Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Expansion Phase)(Baseline to Week 52)
- Incidence of plasma Phe concentration thresholds up to Week 52 post administration of HMI-102 (Dose Expansion Phase)(Baseline to Week 52)
- Change from baseline in total protein intake at Week 52 post-administration of HMI-102 (Dose Expansion Phase)(Week 52)
- Incidence of plasma Phe concentration thresholds up to Week 28 post administration of HMI-102 (Dose Expansion Phase)(Baseline to Week 28)