Clinical Trial

Disease: Phenylketonuria, PKU, (NCT05222178)

Disease info:

Phenylketonuria (PKU) is an inherited metabolic disorder caused by an absence or deficiency of the enzyme phenylalanine hydroxylase (PAH). The disorder is easily detectable via routine newborn screening and treatment usually begins immediately.

PAH is responsible for processing the enzyme phenylalanine, one of the amino acids vital for normal growth and development. In individuals with PKU, PAH fails to convert phenylalanine into tyrosine leading to an accumulation of toxic phenylalanine in the blood and brain. The direct toxic effect of phenylalanine can lead to severe intellectual disability and other symptoms.

The exact disease frequency is unknown but is estimated to be about 1 in every 15,000 births.
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

Name: Julie Jordan, M.D.

Phone: 781-819-0967



California, United States

Children's Health of Orange County (CHOC), Orange, California, United States, 92868


Colorado, United States,

Children's Hospital Coloorado - Anschutz Medical Campus, Aurora, Colorado, United States, 80045


Connecticut, Unites States

Yale University School of Medicine - Yale Genetics, New Haven, Connecticut, United States, 06511


Indiana, United States,

Indiana University School of Medicine University Hospital, Indianapolis, Indiana, United States, 46202


Michigan, United States

Spectrum Health Butterworth Hospital, Gran Rapids, Michigan, United States, 49503


New Jersey,

Atlantic Health - Morristown Medical Center, Morristown, New Jersey, United States, 07960.


New York, United States

John R. Oishei Children's Hospital, Buffalo, New York, United States, 14203


Pennsylvania, United States

Clinic for Special Children, Lancaster, Pennsylvania, United States, 17579


Pittsburgh, United States

UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States, 15224


Tennessee, United States,

Vanderbilt University Medical Center, Nashville, Tennessee, United States, 37232


Texas, United States

University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, united States, 75390

Study start:
Jun. 3, 2022
9 participants
Gene editing method:
Proprietary nuclease-free gene-editing method
Type of edit:
Gene replacement. The company's nuclease-free gene-editing technology harnesses the body's natural DNA repair process of homologous recombination to replace mutated PAH gene with a functional copy, including a liver-specific promoter to maximise its long-term expression.
Phenylalanine hydroxylase (PAH)
Delivery method:
Adeno-associated virus (AAV) - In-vivo
IND Enabling Pre-clinical
Phase I Safety
Phase II Safety and Dosing
Phase III Safety and Efficacy

Status: Active recruiting


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. Following evaluation of data from the first 3 participants in a cohort, the DMC will decide to escalate to the next dose level or expand the cohort at the selected dose level.

Last updated: Dec. 19, 2023
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