Gene Therapy Clinical Study in Adult PKU (pheNIX)

• ClinicalTrials.gov Identifier: NCT03952156
• Recruitment Status: Recruiting
• First Posted: May 16, 2019
• Last Update Posted: March 2, 2020
• Sponsor: Homology Medicines, Inc
• Information provided by (Responsible Party): Homology Medicines, Inc

Tracking Information

• First Submitted Date: May 9, 2019
• First Posted Date: May 16, 2019
• Last Update Posted Date: March 2, 2020
• Actual Study Start Date: June 10, 2019
• Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 13, 2020)

• Incidence and severity of treatment-emergent adverse events (TEAE) and serious TEAEs [ Time Frame: Baseline to Week 52 ]
  Subjects with at least one TEAE or serious TEAE
• Incidence of sustained plasma Phe concentration of ≤360 μmol/L at 24 weeks post dose [ Time Frame: Baseline to Week 24 ]
  Subjects achieving a sustained plasma Phe concentration ≤360 μmol/L at 24 weeks post dose

Original Primary Outcome Measures (submitted: May 14, 2019)

• Incidence and severity of treatment-emergent adverse events (TEAE) and serious TEAEs [ Time Frame: Baseline to Week 52 ]
  Subjects with at least one TEAE or serious TEAE
• Incidence of sustained reduction in plasma Phe concentration [ Time Frame: Baseline to Week 24 ]
  Subjects achieving a sustained plasma Phe concentration ≤360 μmol/L.

Current Secondary Outcome Measures (submitted: January 13, 2020)

• Plasma Phe Concentration [ Time Frame: Baseline to Week 52 ]
  Change in plasma Phe concentration at 24 weeks
• Incidence of achieving a plasma Phe concentration to ≤360 μmol/L [ Time Frame: Baseline to Week 52 ]
  Subjects achieving plasma Phe concentration ≤360 μmol/L at each time point during the study

Original Secondary Outcome Measures (submitted: May 14, 2019)

• Plasma Phe Concentration [ Time Frame: Baseline to Week 52 ]
  Change in plasma Phe concentration from baseline
• Incidence of achieving a plasma Phe concentration to ≤360 μmol/L [ Time Frame: Baseline to Week 52 ]
  Subjects achieving plasma Phe concentration ≤360 μmol/L at each time point during the study.

Current Other Pre-specified Outcome Measures (submitted: May 14, 2019)

Phenylketonuria Quality of Life Questionnaire (PKU-QOL) [ Time Frame: Baseline to Week 52 ]

Change in PKU-QOL

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Gene Therapy Clinical Study in Adult PKU
• 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
• 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.
• Detailed Description: 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. If the cohort is expanded, additional 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 24 weeks.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Phenylketonurias
• PAH Deficiency

Intervention

Genetic: HMI-102

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

Study Arms

• Experimental: Cohort 1
  Dose Level 1 of HMI-102 delivered intravenously one time
  Intervention: Genetic: HMI-102
• Experimental: Cohort 2
  Dose Level 2 of HMI-102 delivered intravenously one time
  Intervention: Genetic: HMI-102
• Experimental: Cohort 3
  Dose Level 3 of HMI-102 delivered intravenously one time
  Intervention: Genetic: HMI-102
• No Intervention: Delayed Treatment Control
  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.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 14, 2019): 21
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2021
• Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Adults 18-55 years of age at the time of informed consent
• Diagnosis of classic phenylketonuria (PKU) due to PAH deficiency
• Two plasma Phe values with a concentration of ≥ 600 μmol/L drawn at least 48 hours apart during the screening period and at least one historical value ≥ 600 μmol/L in the preceding 12 month.
• Subject has the ability and willingness to maintain their baseline diet, whether Phe-restricted or unrestricted, after administration of HMI-102, unless otherwise directed

Key Exclusion Criteria:

• Subjects with PKU that is not due to PAH deficiency
• Presence of anti-AAVHSC15 neutralizing antibody
• ALT >1.5x ULN and AST >1.5x ULN
• Alkaline phosphatase >1.5x ULN.
• Total bilirubin >1.5x ULN, direct bilirubin ≥ 1.5x ULN
• Serum creatinine >1.5x ULN
• 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 >7.9% or fasting glucose >200 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Steven Glyman, M.D.; 781-819-0967; clinicaltrials@homologymedicines.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03952156
• Other Study ID Numbers: HMI-102-101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Homology Medicines, Inc
• Study Sponsor: Homology Medicines, Inc
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Homology Medicines, Inc
• Verification Date: January 2020