Gene Therapy Clinical Study in Adult PKU

Phenylketonurias Clinical Trial

— pheNIX  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03952156
• Other study ID #: HMI-102-101
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: June 10, 2019
• Est. completion date: August 1, 2023

Study information

• Verified date: August 2023
• Source: Homology Medicines, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: August 1, 2023
• Est. primary completion date: January 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• PAH Deficiency
• Phenylketonurias

Intervention

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

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia
United States	Boston Children's Hospital	Boston	Massachusetts
United States	The University of North Carolina At Chapel Hill	Chapel Hill	North Carolina
United States	Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of Utah	Salt Lake City	Utah
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Homology Medicines, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Phenylketonuria Quality of Life Questionnaire (PKU-QOL)	Change in PKU-QOL	Baseline to Week 52
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Change from baseline in Plasma Phe Concentration (Dose Escalation Phase)	Change from baseline in plasma Phe concentration during Weeks 24-28	Weeks 24-28
Primary	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	Incidence of plasma Phe concentration thresholds up to Week 28 post administration of HMI-102 (Dose Expansion Phase)	Subjects achieving plasma Phe concentration thresholds up to Week 28 post administration of HMI-102	Baseline to Week 28
Secondary	Incidence of plasma Phe concentration thresholds up to Week 52 post administration of HMI-102 (Dose Expansion Phase)	Subjects achieving plasma Phe concentration thresholds up to Week 52 post administration of HMI-102	Baseline to Week 52
Secondary	Change from baseline in total protein intake at Week 52 post-administration of HMI-102 (Dose Expansion Phase)	Subject Achieving a change from baseline in total protein intake at Week 52 post-administration of HMI-102	Week 52
Secondary	Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Expansion Phase)	Subjects with at least one TEAE or serious TEAE	Baseline to Week 52