PAH Deficiency, Phenylketonuria, Phenylketonurias
Conditions
Keywords
PKU, Gene editing, AAVHSC
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.
Interventions
DRUGHMI-103
HMI-103 is an AAVHSC15 capsid containing a functional copy of the human PAH gene
Sponsors
Homology Medicines, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose Escalation
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Outcome results
None listed