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

Phenylketonuria Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05222178
• Other study ID #: HMI-103-101
• Status: Terminated
• Phase: Phase 1
• Start date: June 3, 2022
• Est. completion date: September 14, 2023

Study information

• Verified date: October 2023
• Source: Homology Medicines, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: September 14, 2023
• Est. primary completion date: September 14, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• PAH Deficiency
• Phenylketonuria
• Phenylketonurias

Intervention

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

Locations

Country	Name	City	State
United States	Clinic for Special Children	Lancaster	Pennsylvania
United States	The Community Health Clinic	Topeka	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Homology Medicines, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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	Baseline to Week 104
Secondary	To assess durability of response	Incidence of plasma Phe = 360 µmol/L during Weeks 48-52 post-administration of HMI-103	Weeks 48-52
Secondary	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	Baseline to Week 104