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PhenylketonuriasPhase 1/2pheNIXNCT03952156

Gene Therapy Clinical Study in Adult PKU

A Phase 1/2 study testing HMI-102 in people with Phenylketonurias and PAH Deficiency, run by Homology Medicines, Inc at 13 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 55 years
Conditions the study is for
Phenylketonurias, PAH Deficiency
What is being tested?
HMI-102
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
13 sitesUnited States
Study dates
10 Jun 2019to 1 Aug 2023
Phase
Phase 1/2
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 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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.

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites

  • Emory University Hospital

    Atlanta, Georgia, 30322

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

  • The University of North Carolina At Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Lurie Children's Hospital of Chicago

    Chicago, Illinois, 60611

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75235

  • Kaiser Permanente Los Angeles Medical Center

    Los Angeles, California, 90027

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • UPMC Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15224

  • University of Utah

    Salt Lake City, Utah, 84108

  • University of South Florida

    Tampa, Florida, 33606

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
HMI-102
Keywords
PKU, Phenylketonuria, PAH Deficiency, Hyperphenylalaninemia, Phenylalanine, Adeno Associated Virus, AAVHSC15
Medical subject headings
Phenylketonurias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HMI-102Genetic

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

  • HMI-102Genetic

    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 groups in NCT03952156
Study groupRoleWhat they receive
Cohort 1ExperimentalDose Level 1 of HMI-102 delivered intravenously one time
Receives: Genetic: HMI-102
Cohort 2ExperimentalDose Level 2 of HMI-102 delivered intravenously one time
Receives: Genetic: HMI-102
Cohort 3ExperimentalDose Level 3 of HMI-102 delivered intravenously one time
Receives: Genetic: HMI-102
Delayed Treatment ControlExperimentalDelayed Treatment Control Arm
Receives: Genetic: HMI-102
Expansion Phase First Dose levelExperimentalExpansion Phase First Dose Level of HMI-102 delivered intravenously one time
Receives: Genetic: HMI-102
Expansion Phase Second Dose levelExperimentalExpansion Phase Second Dose Level of HMI-102 delivered intravenously one time
Receives: Genetic: HMI-102

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Escalation Phase)

    Subjects with at least one TEAE or serious TEAE

    Measured: Baseline to Week 52

  2. Change from baseline in clinical laboratory values (Dose Escalation Phase)

    Change in serum chemistry values including liver function tests, hematology, and urinalysis

    Measured: Baseline to Week 52

  3. Change from baseline in 12-lead electrocardiograms (ECGs), vital signs, physical examinations (Dose Escalation Phase)

    Subjects change from baseline in 12-lead electrocardiograms (ECGs), vital signs, physical examinations

    Measured: Baseline to Week 52

  4. Incidence of sustained plasma Phe concentration of ≤360 μmol/L at 28 weeks post dose (Dose Escalation Phase)

    Subjects achieving a sustained plasma Phe concentration ≤360 μmol/L at 28 weeks post dose

    Measured: Week 28

  5. Change from baseline in Plasma Phe Concentration (Dose Escalation Phase)

    Change from baseline in plasma Phe concentration during Weeks 24-28

    Measured: Weeks 24-28

  6. Change from baseline in mean Plasma Phe Concentration (Dose Expansion Phase)

    Change from baseline in mean plasma Phe concentration during Weeks 24-28

    Measured: Weeks 24-28

Secondary outcomes (4)

  1. Incidence of plasma Phe concentration thresholds up to Week 28 post administration of HMI-102 (Dose Expansion Phase)

    Subjects achieving plasma Phe concentration thresholds up to Week 28 post administration of HMI-102

    Measured: Baseline to Week 28

  2. Incidence of plasma Phe concentration thresholds up to Week 52 post administration of HMI-102 (Dose Expansion Phase)

    Subjects achieving plasma Phe concentration thresholds up to Week 52 post administration of HMI-102

    Measured: Baseline to Week 52

  3. Change from baseline in total protein intake at Week 52 post-administration of HMI-102 (Dose Expansion Phase)

    Subject Achieving a change from baseline in total protein intake at Week 52 post-administration of HMI-102

    Measured: Week 52

  4. Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Expansion Phase)

    Subjects with at least one TEAE or serious TEAE

    Measured: Baseline to Week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 May 2019
  2. Study start10 Jun 2019
  3. Primary completion10 Jan 2023
  4. Study completion1 Aug 2023

Why it stopped: Homology Medicines has discontinued the development of this program.

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03952156
Sponsor's protocol ID
HMI-102-101
Acronym
pheNIX
Status last verified
Aug 2023
First submitted
9 May 2019
Last updated
29 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing HMI-102 in people with Phenylketonurias and PAH Deficiency, run by Homology Medicines, Inc at 13 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 4 inclusion and 12 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 29 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 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?

Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Escalation Phase) (time frame: Baseline to Week 52). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03952156.

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 29 Aug 2023.

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