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Gene Therapy Clinical Study in Adult PKU (pheNIX)

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ClinicalTrials.gov Identifier: NCT03952156
Recruitment Status : Recruiting
First Posted : May 16, 2019
Last Update Posted : March 26, 2021
Sponsor:
Information provided by (Responsible Party):
Homology Medicines, Inc

Tracking Information
First Submitted Date  ICMJE May 9, 2019
First Posted Date  ICMJE May 16, 2019
Last Update Posted Date March 26, 2021
Actual Study Start Date  ICMJE June 10, 2019
Estimated Primary Completion Date June 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 23, 2021)
  • Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Escalation Phase) [ Time Frame: Baseline to Week 52 ]
    Subjects with at least one TEAE or serious TEAE
  • Change from baseline in clinical laboratory values (Dose Escalation Phase) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Weeks 24-28 ]
    Change from baseline in mean plasma Phe concentration during Weeks 24-28
Original Primary Outcome Measures  ICMJE
 (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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 23, 2021)
  • Incidence of plasma Phe concentration thresholds up to Week 28 post administration of HMI-102 (Dose Expansion Phase) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Baseline to Week 52 ]
    Subjects with at least one TEAE or serious TEAE
Original Secondary Outcome Measures  ICMJE
 (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  ICMJE Gene Therapy Clinical Study in Adult PKU
Official Title  ICMJE 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

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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Phenylketonurias
  • PAH Deficiency
Intervention  ICMJE
  • Genetic: HMI-102
    HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene
  • 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.

Study Arms  ICMJE
  • 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
  • Experimental: Delayed Treatment Control
    Delayed Treatment Control Arm
    Intervention: Genetic: HMI-102
  • Experimental: Expansion Phase First Dose level
    Expansion Phase First Dose Level of HMI-102 delivered intravenously one time
    Intervention: Genetic: HMI-102
  • Experimental: Expansion Phase Second Dose level
    Expansion Phase Second Dose Level of HMI-102 delivered intravenously one time
    Intervention: Genetic: HMI-102
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 23, 2021)
28
Original Estimated Enrollment  ICMJE
 (submitted: May 14, 2019)
21
Estimated Study Completion Date  ICMJE September 2023
Estimated Primary Completion Date June 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jan Iles, M.D. 781-819-0967 clinicaltrials@homologymedicines.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03952156
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Responsible Party Homology Medicines, Inc
Study Sponsor  ICMJE Homology Medicines, Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Olaf A Bodamer, M.D. Boston Children's Hospital
PRS Account Homology Medicines, Inc
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP