PhenylketonuriasPhase 1NCT05222178
Safety and Efficacy of HMI-103 in Participants With Classical PKU Due to PAH Deficiency
A Phase 1 study testing HMI-103 in people with Phenylketonurias and PAH Deficiency, run by Homology Medicines, Inc at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Phenylketonurias, PAH Deficiency, Phenylketonuria
- What is being tested?
- HMI-103
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 2 sitesUnited States
- Study dates
- 3 Jun 2022to 14 Sep 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Clinic for Special Children
Lancaster, Pennsylvania, 17579
The Community Health Clinic
Topeka, Indiana, 46571
About this study
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
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.
Read the 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.
- Conditions
- Phenylketonurias, PAH Deficiency, Phenylketonuria
- Being tested
- HMI-103
- Keywords
- PKU, Gene editing, AAVHSC
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HMI-103Drug
HMI-103 is an AAVHSC15 capsid containing a functional copy of the human PAH gene
| Study group | Role | What they receive |
|---|---|---|
| Low Dose Cohort | Experimental | HMI-103 delivered IV one time Receives: Drug: HMI-103 |
| Intermediate Dose Cohort | Experimental | HMI-103 delivered IV one time Receives: Drug: HMI-103 |
| High Dose Cohort | Experimental | HMI-103 delivered IV one time Receives: Drug: HMI-103 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline to Week 104
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
Measured: Baseline to Weeks 24-32
Secondary outcomes (3)
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
Measured: Baseline to Week 104
To assess durability of response
Incidence of plasma Phe ≤ 360 μmol/L during Weeks 48-52 post-administration of HMI-103
Measured: Weeks 48-52
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
Measured: Baseline to Week 104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2022
- Study start3 Jun 2022
- Primary completion14 Sep 2023
- Study completion14 Sep 2023
Why it stopped: Homology Medicines Inc. has discontinued the development of this program.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PhenylketonuriasStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Dose Escalation
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Homology Medicines, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05222178
- Sponsor's protocol ID
- HMI-103-101
- Status last verified
- Oct 2023
- First submitted
- 21 Dec 2021
- Last updated
- 10 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05222178
- Acronym / sponsor ID
- HMI-103-101
- Conditions
- Phenylketonurias, PAH Deficiency, Phenylketonuria
- Keywords
- PKU, Gene editing, AAVHSC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Homology Medicines Inc. has discontinued the development of this program.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Homology Medicines, IncIndustry (pharma, biotech, devices)
- Study start
- 3 Jun 2022 (actual)
- Primary completion
- 14 Sep 2023 (actual)
- Study completion
- 14 Sep 2023 (actual)
- First posted
- 3 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Dose Escalation
| Arm | Type | Receives |
|---|---|---|
| Low Dose Cohort | Experimental | Drug: HMI-103HMI-103 delivered IV one time |
| Intermediate Dose Cohort | Experimental | Drug: HMI-103HMI-103 delivered IV one time |
| High Dose Cohort | Experimental | Drug: HMI-103HMI-103 delivered IV one time |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HMI-103HMI-103 is an AAVHSC15 capsid containing a functional copy of the human PAH gene | Drug | High Dose Cohort, Intermediate Dose Cohort, Low Dose Cohort |
Primary outcome
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
To evaluate the efficacy of HMI-103 on reduction of plasma Phe concentration at each dose level
Time frame: 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
3 secondary outcomes
To evaluate the effect of HMI-103 on plasma Phe concentration relative to treatment guidelines for PKU
Time frame: Baseline to Week 104
To assess durability of response
Time frame: Weeks 48-52
To assess the changes in dietary protein intake
Time frame: Baseline to Week 104
Results and safety
The study was stopped early (reason given: Homology Medicines Inc. has discontinued the development of this program.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HMI-103 in people with Phenylketonurias and PAH Deficiency, run by Homology Medicines, Inc at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Homology Medicines Inc. has discontinued the development of this program.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2023.