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

NCT ID: NCT05222178

Last Updated: 2023-10-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-03
• Study Completion Date: 2023-09-14

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.

Conditions

Phenylketonurias; PAH Deficiency; Phenylketonuria

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Low Dose Cohort

HMI-103 delivered IV one time

Group Type: EXPERIMENTAL

HMI-103

Intervention Type: DRUG

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

Intermediate Dose Cohort

HMI-103 delivered IV one time

Group Type: EXPERIMENTAL

HMI-103

Intervention Type: DRUG

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

High Dose Cohort

HMI-103 delivered IV one time

Group Type: EXPERIMENTAL

HMI-103

Intervention Type: DRUG

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

Interventions

HMI-103

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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Homology Medicines, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The Community Health Clinic

Topeka, Indiana, United States

Clinic for Special Children

Lancaster, Pennsylvania, United States

Countries

United States

Other Identifiers

HMI-103-101

Identifier Type: -

Identifier Source: org_study_id