Safety and Efficacy of HMI-103 in Participants With Classical PKU Due to PAH Deficiency
- Registration Number
- NCT05222178
- Lead Sponsor
- Homology Medicines, Inc
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 3
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Intermediate Dose Cohort HMI-103 HMI-103 delivered IV one time High Dose Cohort HMI-103 HMI-103 delivered IV one time Low Dose Cohort HMI-103 HMI-103 delivered IV one time
- Primary Outcome Measures
Name Time Method 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 Baseline to Week 104 To evaluate the efficacy of HMI-103 on reduction of plasma Phe concentration at each dose level 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
- Secondary Outcome Measures
Name Time Method To evaluate the effect of HMI-103 on plasma Phe concentration relative to treatment guidelines for PKU Baseline to Week 104 Incidence of plasma Phe of ≤ 360 μmol/L within each dose cohort at each timepoint post-administration of HMI-103
To assess durability of response Weeks 48-52 Incidence of plasma Phe ≤ 360 μmol/L during Weeks 48-52 post-administration of HMI-103
To assess the changes in dietary protein intake Baseline to Week 104 Change from baseline in natural and total protein intake (g/day) at each timepoint post-administration of HMI-103
Trial Locations
- Locations (2)
The Community Health Clinic
🇺🇸Topeka, Indiana, United States
Clinic for Special Children
🇺🇸Lancaster, Pennsylvania, United States