Safety and Efficacy of HMI-103, a Gene Editing Development Candidate in Adults With Classical PKU Due to PAH Deficiency
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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. Following evaluation of data from the first 3 participants in a cohort, the DMC will decide to escalate to the next dose level or expand the cohort at the selected dose level.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Low Dose Cohort Low dose of HMI-103 delivered intravenously one time |
Drug: HMI-103
HMI-103 is an AAVHSC15 vector containing a functional copy of the human PAH gene
|
| Experimental: Intermediate Dose Cohort Intermediate dose of HMI-103 delivered intravenously one time |
Drug: HMI-103
HMI-103 is an AAVHSC15 vector containing a functional copy of the human PAH gene
|
| Experimental: High Dose Cohort High Dose of HMI-103 delivered intravenously one time |
Drug: HMI-103
HMI-103 is an AAVHSC15 vector containing a functional copy of the human PAH gene
|
Outcome Measures
Primary Outcome Measures
- To determine incidence and severity of Treatment Emergent Adverse Events and adverse events of special interest of a single administration of HMI-103 [Baseline to Week 104]
Incidence and severity of TEAEs Incidence and severity of adverse events of special interest (AESIs)
- To evaluate the efficacy of HMI-103 on reduction of plasma Phe concentration at each dose level [Baseline to Weeks 24-32]
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 [Baseline to Week 104]
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 [Weeks 48-52]
Incidence of plasma Phe ≤ 360 μmol/L during Weeks 48-52 post-administration of HMI-103
- To assess the changes in dietary protein intake [Baseline to Week 104]
Change from baseline in natural and total protein intake (g/day) at each timepoint post-administration of HMI-103
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Adults 18-55 years of age at the time of informed consent
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Diagnosis of classical phenylketonuria (PKU) due to PAH deficiency
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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.
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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.
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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
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Participants who are well controlled on a Phe-restricted diet.
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Hemoglobin A1c >6.5% or fasting glucose >126 mg/dL
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Liver function tests > ULN
-
International normalized ratio (INR) > 1.2
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Hematology values outside of the normal range
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Previously received gene therapy for the treatment of any condition.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Spectrum Health Butterworth Hospital | Grand Rapids | Michigan | United States | 49503 |
| 2 | John R. Oishei Children's Hospital | Buffalo | New York | United States | 14203 |
| 3 | UPMC Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania | United States | 15224 |
| 4 | University of Texas Southwestern Medical Center at Dallas | Dallas | Texas | United States | 75390 |
Sponsors and Collaborators
- Homology Medicines, Inc
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HMI-103-101