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

NCT05222178 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: HMI-103-101
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

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.

Conditions

Phenylketonurias; PAH Deficiency; Phenylketonuria

Keywords

PKU; Gene editing; AAVHSC

Outcome Measures

Primary Outcomes (2)

• 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

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

  Baseline to Weeks 24-32

Secondary Outcomes (3)

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

  Baseline to Week 104

• To assess durability of response

  Weeks 48-52

• To assess the changes in dietary protein intake

  Baseline to Week 104

Study Arms (3)

Low Dose Cohort

EXPERIMENTAL

HMI-103 delivered IV one time

Drug: HMI-103

Intermediate Dose Cohort

EXPERIMENTAL

HMI-103 delivered IV one time

Drug: HMI-103

High Dose Cohort

EXPERIMENTAL

HMI-103 delivered IV one time

Drug: HMI-103

Interventions

HMI-103 DRUG

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

High Dose Cohort; Intermediate Dose Cohort; Low Dose Cohort

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Homology Medicines, Inc: lead

Study Sites (2)

The Community Health Clinic

Topeka, Indiana, 46571, United States

Location

Clinic for Special Children

Lancaster, Pennsylvania, 17579, United States

Location

MeSH Terms

Conditions

Phenylketonurias

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose Escalation

Study Record Dates

• First Submitted: December 21, 2021
• First Posted: February 3, 2022
• Study Start: June 3, 2022
• Primary Completion: September 14, 2023
• Study Completion: September 14, 2023
• Last Updated: October 10, 2023

Record last verified: 2023-10

Locations

US (2)