Safety and Efficacy of HMI-103 in Participants With Classical PKU Due to PAH Deficiency
Primary Purpose
Phenylketonurias, PAH Deficiency, Phenylketonuria
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
HMI-103
Sponsored by
About this trial
This is an interventional treatment trial for Phenylketonurias focused on measuring PKU, Gene editing, AAVHSC
Eligibility Criteria
Inclusion Criteria:
- Adults 18-55 years of age at the time of informed consent
- Diagnosis of classical phenylketonuria (PKU) due to PAH deficiency
- Four baseline plasma Phe values with a concentration of ≥ 600 μmol/L and at least one historical value ≥ 600 μmol/L in the preceding 24 months.
- Participants must have uncontrolled classical PKU disease (despite Phe-restricted dietary management) in the judgment of the investigator and confirmed by the independent DMC at the end of the Screening period.
- Participant has the ability and willingness to maintain their baseline diet, for the duration of the trial, unless otherwise directed
Exclusion Criteria:
- Subjects with PKU that is not due to PAH deficiency
- Presence of anti-AAVHSC15 neutralizing antibodies
- Participants who are well controlled on a Phe-restricted diet.
- Hemoglobin A1c >6.5% or fasting glucose >126 mg/dL
- Liver function tests > ULN
- International normalized ratio (INR) > 1.2
- Hematology values outside of the normal range
- Previously received gene therapy for the treatment of any condition.
Sites / Locations
- The Community Health Clinic
- Clinic for Special Children
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Low Dose Cohort
Intermediate Dose Cohort
High Dose Cohort
Arm Description
HMI-103 delivered IV one time
HMI-103 delivered IV one time
HMI-103 delivered IV one time
Outcomes
Primary Outcome Measures
To measure incidence and severity of Treatment Emergent Adverse Events (TEAEs) and adverse events of special interest (AESIs) of a single administration of HMI-103
To evaluate the efficacy of HMI-103 on reduction of plasma Phe concentration at each dose level
Mean percent change from baseline at Weeks 24-32 in plasma Phe concentration within each dose cohort post-administration of HMI-103
Secondary Outcome Measures
To evaluate the effect of HMI-103 on plasma Phe concentration relative to treatment guidelines for PKU
Incidence of plasma Phe of ≤ 360 μmol/L within each dose cohort at each timepoint post-administration of HMI-103
To assess durability of response
Incidence of plasma Phe ≤ 360 μmol/L during Weeks 48-52 post-administration of HMI-103
To assess the changes in dietary protein intake
Change from baseline in natural and total protein intake (g/day) at each timepoint post-administration of HMI-103
Full Information
NCT ID
NCT05222178
First Posted
December 21, 2021
Last Updated
October 5, 2023
Sponsor
Homology Medicines, Inc
1. Study Identification
Unique Protocol Identification Number
NCT05222178
Brief Title
Safety and Efficacy of HMI-103 in Participants With Classical PKU Due to PAH Deficiency
Official Title
A Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety and Efficacy of HMI-103 Administered Intravenously in Adult Participants With Classical PKU Due to PAH Deficiency
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Terminated
Why Stopped
Homology Medicines Inc. has discontinued the development of this program.
Study Start Date
June 3, 2022 (Actual)
Primary Completion Date
September 14, 2023 (Actual)
Study Completion Date
September 14, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Homology Medicines, Inc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is an open-label, sequential ascending dose-escalation, Phase 1 study to evaluate the safety and efficacy of a single intravenous (I.V.) administration of HMI-103, a gene editing development candidate, in adult participants aged 18 to 55 years, inclusive, with classical PKU due to PAH deficiency who have uncontrolled disease despite Phe restricted dietary management.
Detailed Description
This is an open-label, sequential ascending dose-escalation, Phase 1 study to evaluate the safety and efficacy of a single intravenous administration of HMI-103, a gene editing development candidate, in adult participants aged 18 to 55 years, inclusive, with classical PKU due to PAH deficiency who have uncontrolled disease despite Phe-restricted dietary management. Up to 3 dose levels of HMI-103 may be investigated. At a given dose level, 3 participants are planned to be enrolled and dosed. Participant dosing will be staggered.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Phenylketonurias, PAH Deficiency, Phenylketonuria
Keywords
PKU, Gene editing, AAVHSC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Dose Escalation
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low Dose Cohort
Arm Type
Experimental
Arm Description
HMI-103 delivered IV one time
Arm Title
Intermediate Dose Cohort
Arm Type
Experimental
Arm Description
HMI-103 delivered IV one time
Arm Title
High Dose Cohort
Arm Type
Experimental
Arm Description
HMI-103 delivered IV one time
Intervention Type
Drug
Intervention Name(s)
HMI-103
Intervention Description
HMI-103 is an AAVHSC15 capsid containing a functional copy of the human PAH gene
Primary Outcome Measure Information:
Title
To measure incidence and severity of Treatment Emergent Adverse Events (TEAEs) and adverse events of special interest (AESIs) of a single administration of HMI-103
Time Frame
Baseline to Week 104
Title
To evaluate the efficacy of HMI-103 on reduction of plasma Phe concentration at each dose level
Description
Mean percent change from baseline at Weeks 24-32 in plasma Phe concentration within each dose cohort post-administration of HMI-103
Time Frame
Baseline to Weeks 24-32
Secondary Outcome Measure Information:
Title
To evaluate the effect of HMI-103 on plasma Phe concentration relative to treatment guidelines for PKU
Description
Incidence of plasma Phe of ≤ 360 μmol/L within each dose cohort at each timepoint post-administration of HMI-103
Time Frame
Baseline to Week 104
Title
To assess durability of response
Description
Incidence of plasma Phe ≤ 360 μmol/L during Weeks 48-52 post-administration of HMI-103
Time Frame
Weeks 48-52
Title
To assess the changes in dietary protein intake
Description
Change from baseline in natural and total protein intake (g/day) at each timepoint post-administration of HMI-103
Time Frame
Baseline to Week 104
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adults 18-55 years of age at the time of informed consent
Diagnosis of classical phenylketonuria (PKU) due to PAH deficiency
Four baseline plasma Phe values with a concentration of ≥ 600 μmol/L and at least one historical value ≥ 600 μmol/L in the preceding 24 months.
Participants must have uncontrolled classical PKU disease (despite Phe-restricted dietary management) in the judgment of the investigator and confirmed by the independent DMC at the end of the Screening period.
Participant has the ability and willingness to maintain their baseline diet, for the duration of the trial, unless otherwise directed
Exclusion Criteria:
Subjects with PKU that is not due to PAH deficiency
Presence of anti-AAVHSC15 neutralizing antibodies
Participants who are well controlled on a Phe-restricted diet.
Hemoglobin A1c >6.5% or fasting glucose >126 mg/dL
Liver function tests > ULN
International normalized ratio (INR) > 1.2
Hematology values outside of the normal range
Previously received gene therapy for the treatment of any condition.
Facility Information:
Facility Name
The Community Health Clinic
City
Topeka
State/Province
Indiana
ZIP/Postal Code
46571
Country
United States
Facility Name
Clinic for Special Children
City
Lancaster
State/Province
Pennsylvania
ZIP/Postal Code
17579
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy of HMI-103 in Participants With Classical PKU Due to PAH Deficiency
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