Safety and Efficacy of HMI-103 in Participants With Classical PKU Due to PAH Deficiency

Phase 1TerminatedNCT05222178

Homology Medicines, Inc3 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Phenylketonurias PAH Deficiency Phenylketonuria

Interventions

HMI-103DRUG

HMI-103 is an AAVHSC15 capsid containing a functional copy of the human PAH gene

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 Years

Medical Language ↔ Plain English

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.

Locations (2)

The Community Health Clinic

Topeka, Indiana, United States

Clinic for Special Children

Lancaster, Pennsylvania, United States

Outcomes

Primary Outcomes

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

Time frame: Baseline to Week 104

To evaluate the efficacy of HMI-103 on reduction of plasma Phe concentration at each dose level

Mean percent change from baseline at Weeks 24-32 in plasma Phe concentration within each dose cohort post-administration of HMI-103

Time frame: Baseline to Weeks 24-32

Secondary Outcomes

To evaluate the effect of HMI-103 on plasma Phe concentration relative to treatment guidelines for PKU

Incidence of plasma Phe of ≤ 360 μmol/L within each dose cohort at each timepoint post-administration of HMI-103

Time frame: Baseline to Week 104

To assess durability of response

Incidence of plasma Phe ≤ 360 μmol/L during Weeks 48-52 post-administration of HMI-103

Time frame: Weeks 48-52

To assess the changes in dietary protein intake

Change from baseline in natural and total protein intake (g/day) at each timepoint post-administration of HMI-103

Time frame: Baseline to Week 104

Data from ClinicalTrials.gov

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