Gene Therapy Clinical Study in Adult PKU (pheNIX)

Homology Medicines

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Phenylketonurias; PAH Deficiency

Treatments: Genetic: HMI-102

Study type: Interventional

Funder types: Industry

Identifiers

NCT03952156

HMI-102-101

Details and patient eligibility

About

This is a Phase 1/2, open-label, randomized, concurrently-controlled, dose escalation study to evaluate the safety and efficacy of HMI-102 in adult PKU subjects with PAH deficiency. Participants will receive a single administration of HMI-102 and will be followed for safety and efficacy for 1 year.

Full description

Part 1 of this study will evaluate the safety and efficacy of HMI-102 gene therapy in adult subjects with PKU due to PAH deficiency. Subjects will receive a single dose of HMI-102 administered intravenously. Up to 3 dose levels of HMI-102 may be investigated in this study. At a given dose level, a minimum of 2 subjects will be enrolled and dosed. Dosing of the first two subjects will be staggered. Following evaluation of data from the first 2 subjects in a cohort, a decision can be made to either escalate to the next dose level or expand the cohort at the selected dose level. Additional doses may be added by HMI to investigate intermediate or higher doses.

In Part 2 dose expansion, evaluation of up to 2 dose levels is planned. Subjects will be randomized to receive HMI-102 or a concurrent delayed treatment control arm. Subjects in the delayed treatment control will be eligible to receive HMI-102 after 28 weeks.

Enrollment: 10 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Adults 18-55 years of age at the time of informed consent
• Diagnosis of phenylketonuria (PKU) due to PAH deficiency
• Two plasma Phe values with a concentration of ≥ 600 μmol/L drawn at least 72 hours apart during the screening period and at least one historical value ≥ 600 μmol/L in the preceding 24 months.
• Subject has the ability and willingness to maintain their baseline diet, whether Phe-restricted or unrestricted for the duration of the trial, unless otherwise directed

Key Exclusion Criteria:

• Subjects with PKU that is not due to PAH deficiency
• Presence of anti-AAVHSC15 neutralizing antibodies
• ALT > ULN and AST > ULN
• Alkaline phosphatase > ULN.
• Total bilirubin > ULN, direct bilirubin > ULN
• Serum creatinine >1.5x ULN
• International normalized ratio (INR) > 1.2
• Hematology values outside of the normal range (hemoglobin <11.0 g/dL for males or <10.0 g/dL for females; white blood cells (WBC) <3,000/μL; absolute neutrophils <1500/μL; platelets <100,000/μL)
• Hemoglobin A1c >6.5% or fasting glucose >126 mg/dL
• Any clinically significant abnormal laboratory result at screening, in the opinion of the Investigator
• Contraindication to corticosteroid use or conditions that could worsen in the presence of corticosteroids, as assessed and determined by the investigator
• Previously received gene therapy for the treatment of any condition.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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10 participants in 6 patient groups

Cohort 1

Experimental group

Description:

Dose Level 1 of HMI-102 delivered intravenously one time

Treatment:

Genetic: HMI-102

Genetic: HMI-102

Cohort 2

Experimental group

Description:

Dose Level 2 of HMI-102 delivered intravenously one time

Treatment:

Genetic: HMI-102

Genetic: HMI-102

Cohort 3

Experimental group

Description:

Dose Level 3 of HMI-102 delivered intravenously one time

Treatment:

Genetic: HMI-102

Genetic: HMI-102

Delayed Treatment Control

Experimental group

Description:

Delayed Treatment Control Arm

Treatment:

Genetic: HMI-102

Genetic: HMI-102

Expansion Phase First Dose level

Experimental group

Description:

Expansion Phase First Dose Level of HMI-102 delivered intravenously one time

Treatment:

Genetic: HMI-102

Genetic: HMI-102

Expansion Phase Second Dose level

Experimental group

Description:

Expansion Phase Second Dose Level of HMI-102 delivered intravenously one time

Treatment:

Genetic: HMI-102

Genetic: HMI-102