Safety and Efficacy of HMI-103, a Gene Editing Development Candidate in Adults with Classical PKU due to PAH Deficiency

Clinicaltrials.gov ID# NCT05222178

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.

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.

Recruitment Status: 

Not yet recruiting, anticipated start in March 2022

Primary Investigator:

Michele Spencer-Manzon, MD

Contact Information:

PI: michele.spencer-manzon@yale.edu

Coordinator: michele.jasne@yale.edu

(203) 785-6351 (voicemail)