Gene Therapy Clinical Study in Adult PKU

NCT03952156 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: HMI-102-101
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 13

Brief Summary

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.

Conditions

Phenylketonurias; PAH Deficiency

Keywords

PKU; Phenylketonuria; PAH Deficiency; Hyperphenylalaninemia; Phenylalanine; Adeno Associated Virus; AAVHSC15

Outcome Measures

Primary Outcomes (6)

• Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Escalation Phase)

  Subjects with at least one TEAE or serious TEAE

  Baseline to Week 52

• Change from baseline in clinical laboratory values (Dose Escalation Phase)

  Change in serum chemistry values including liver function tests, hematology, and urinalysis

  Baseline to Week 52

• Change from baseline in 12-lead electrocardiograms (ECGs), vital signs, physical examinations (Dose Escalation Phase)

  Subjects change from baseline in 12-lead electrocardiograms (ECGs), vital signs, physical examinations

  Baseline to Week 52

• Incidence of sustained plasma Phe concentration of ≤360 μmol/L at 28 weeks post dose (Dose Escalation Phase)

  Subjects achieving a sustained plasma Phe concentration ≤360 μmol/L at 28 weeks post dose

  Week 28

• Change from baseline in Plasma Phe Concentration (Dose Escalation Phase)

  Change from baseline in plasma Phe concentration during Weeks 24-28

  Weeks 24-28

• Change from baseline in mean Plasma Phe Concentration (Dose Expansion Phase)

  Change from baseline in mean plasma Phe concentration during Weeks 24-28

  Weeks 24-28

Secondary Outcomes (4)

• Incidence of plasma Phe concentration thresholds up to Week 28 post administration of HMI-102 (Dose Expansion Phase)

  Baseline to Week 28

• Incidence of plasma Phe concentration thresholds up to Week 52 post administration of HMI-102 (Dose Expansion Phase)

  Baseline to Week 52

• Change from baseline in total protein intake at Week 52 post-administration of HMI-102 (Dose Expansion Phase)

  Week 52

• Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Expansion Phase)

  Baseline to Week 52

Other Outcomes (1)

• Phenylketonuria Quality of Life Questionnaire (PKU-QOL)

  Baseline to Week 52

Study Arms (6)

Cohort 1

EXPERIMENTAL

Dose Level 1 of HMI-102 delivered intravenously one time

Genetic: HMI-102

Cohort 2

EXPERIMENTAL

Dose Level 2 of HMI-102 delivered intravenously one time

Genetic: HMI-102

Cohort 3

EXPERIMENTAL

Dose Level 3 of HMI-102 delivered intravenously one time

Genetic: HMI-102

Delayed Treatment Control

EXPERIMENTAL

Delayed Treatment Control Arm

Genetic: HMI-102

Expansion Phase First Dose level

EXPERIMENTAL

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

Genetic: HMI-102

Expansion Phase Second Dose level

EXPERIMENTAL

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

Genetic: HMI-102

Interventions

HMI-102 GENETIC

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

Cohort 1; Cohort 2; Cohort 3; Expansion Phase First Dose level; Expansion Phase Second Dose level

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Homology Medicines, Inc: lead

Study Sites (13)

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, 90027, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

The University of North Carolina At Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

MeSH Terms

Conditions

Phenylketonurias

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Olaf A Bodamer, M.D.

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2019
• First Posted: May 16, 2019
• Study Start: June 10, 2019
• Primary Completion: January 10, 2023
• Study Completion: August 1, 2023
• Last Updated: August 29, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)