pheNIX: Gene Therapy Clinical Study in Adult PKU

Sponsor

Homology Medicines, Inc (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03952156

Collaborator

(none)

Enrollment

Locations

Arms

50.7

Anticipated Duration (Months)

2.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Phenylketonurias PAH Deficiency	Genetic: HMI-102 Genetic: HMI-102	Phase 1/Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

28 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 10, 2019

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Dose Level 1 of HMI-102 delivered intravenously one time	Genetic: HMI-102 HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene
Experimental: Cohort 2 Dose Level 2 of HMI-102 delivered intravenously one time	Genetic: HMI-102 HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene
Experimental: Cohort 3 Dose Level 3 of HMI-102 delivered intravenously one time	Genetic: HMI-102 HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene
Experimental: Delayed Treatment Control Delayed Treatment Control Arm	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.
Experimental: Expansion Phase First Dose level Expansion Phase First Dose Level of HMI-102 delivered intravenously one time	Genetic: HMI-102 HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene
Experimental: Expansion Phase Second Dose level Expansion Phase Second Dose Level of HMI-102 delivered intravenously one time	Genetic: HMI-102 HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene

Outcome Measures

Primary Outcome Measures

Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Escalation Phase) [Baseline to Week 52]
Subjects with at least one TEAE or serious TEAE
Change from baseline in clinical laboratory values (Dose Escalation Phase) [Baseline to Week 52]
Change in serum chemistry values including liver function tests, hematology, and urinalysis
Change from baseline in 12-lead electrocardiograms (ECGs), vital signs, physical examinations (Dose Escalation Phase) [Baseline to Week 52]
Subjects change from baseline in 12-lead electrocardiograms (ECGs), vital signs, physical examinations
Incidence of sustained plasma Phe concentration of ≤360 μmol/L at 28 weeks post dose (Dose Escalation Phase) [Week 28]
Subjects achieving a sustained plasma Phe concentration ≤360 μmol/L at 28 weeks post dose
Change from baseline in Plasma Phe Concentration (Dose Escalation Phase) [Weeks 24-28]
Change from baseline in plasma Phe concentration during Weeks 24-28
Change from baseline in mean Plasma Phe Concentration (Dose Expansion Phase) [Weeks 24-28]
Change from baseline in mean plasma Phe concentration during Weeks 24-28

Secondary Outcome Measures

Incidence of plasma Phe concentration thresholds up to Week 28 post administration of HMI-102 (Dose Expansion Phase) [Baseline to Week 28]
Subjects achieving plasma Phe concentration thresholds up to Week 28 post administration of HMI-102
Incidence of plasma Phe concentration thresholds up to Week 52 post administration of HMI-102 (Dose Expansion Phase) [Baseline to Week 52]
Subjects achieving plasma Phe concentration thresholds up to Week 52 post administration of HMI-102
Change from baseline in total protein intake at Week 52 post-administration of HMI-102 (Dose Expansion Phase) [Week 52]
Subject Achieving a change from baseline in total protein intake at Week 52 post-administration of HMI-102
Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Expansion Phase) [Baseline to Week 52]
Subjects with at least one TEAE or serious TEAE

Other Outcome Measures

Phenylketonuria Quality of Life Questionnaire (PKU-QOL) [Baseline to Week 52]
Change in PKU-QOL

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
2	Children's Hospital of Orange County	Orange	California	United States	92868
3	University of South Florida	Tampa	Florida	United States	33606
4	Emory University Hospital	Atlanta	Georgia	United States	30322
5	Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
6	Boston Children's Hospital	Boston	Massachusetts	United States	02115
7	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
8	The University of North Carolina At Chapel Hill	Chapel Hill	North Carolina	United States	27599
9	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
10	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
11	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15224
12	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75235
13	University of Utah	Salt Lake City	Utah	United States	84108