Gene Therapy Clinical Study in Adult PKU

NCT ID: NCT03952156

Last Updated: 2023-08-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-10

Study Completion Date

2023-08-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Phenylketonurias PAH Deficiency

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1

Dose Level 1 of HMI-102 delivered intravenously one time

Group Type EXPERIMENTAL

HMI-102

Intervention Type GENETIC

HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene

Cohort 2

Dose Level 2 of HMI-102 delivered intravenously one time

Group Type EXPERIMENTAL

HMI-102

Intervention Type GENETIC

HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene

Cohort 3

Dose Level 3 of HMI-102 delivered intravenously one time

Group Type EXPERIMENTAL

HMI-102

Intervention Type GENETIC

HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene

Delayed Treatment Control

Delayed Treatment Control Arm

Group Type EXPERIMENTAL

HMI-102

Intervention Type GENETIC

Control subjects will generally have the same assessments as treated subjects.

Control subjects will undergo pre-baseline procedures to confirm that they are eligible to receive treatment with HMI-102. Once eligible control subjects are dosed with HMI-102, they will initiate the same post-dose procedures as subjects who received HMI-102.

Expansion Phase First Dose level

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

Group Type EXPERIMENTAL

HMI-102

Intervention Type GENETIC

HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene

Expansion Phase Second Dose level

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

Group Type EXPERIMENTAL

HMI-102

Intervention Type GENETIC

HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene

Interventions

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HMI-102

HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene

Intervention Type GENETIC

HMI-102

Control subjects will generally have the same assessments as treated subjects.

Control subjects will undergo pre-baseline procedures to confirm that they are eligible to receive treatment with HMI-102. Once eligible control subjects are dosed with HMI-102, they will initiate the same post-dose procedures as subjects who received HMI-102.

Intervention Type GENETIC

Eligibility Criteria

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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

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Homology Medicines, Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Olaf A Bodamer, M.D.

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Locations

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Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

University of South Florida

Tampa, Florida, United States

Site Status

Emory University Hospital

Atlanta, Georgia, United States

Site Status

Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status

The University of North Carolina At Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Countries

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United States

Other Identifiers

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HMI-102-101

Identifier Type: -

Identifier Source: org_study_id

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