Clinical trial NCT05222178: Safety and Efficacy of HMI-103 in Participants With Classical PKU Due to PAH Deficiency
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Phenylketonurias
PAH Deficiency
Phenylketonuria
Keywords: PKU
Gene editing
AAVHSC
Lead sponsor: Homology Medicines, Inc
Sponsor class: INDUSTRY
First posted: 2022-02-03
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose Escalation
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Baseline to Week 104
measure: To evaluate the efficacy of HMI-103 on reduction of plasma Phe concentration at each dose level
timeFrame: Baseline to Weeks 24-32
Secondary outcomes:
measure: To evaluate the effect of HMI-103 on plasma Phe concentration relative to treatment guidelines for PKU
timeFrame: Baseline to Week 104
measure: To assess durability of response
timeFrame: Weeks 48-52
measure: To assess the changes in dietary protein intake
timeFrame: Baseline to Week 104
Other outcomes:
Locations:
city: Topeka
country: United States
facility: The Community Health Clinic
state: Indiana
city: Lancaster
country: United States
facility: Clinic for Special Children
state: Pennsylvania
Study officials:
References: