We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy of HMI-103, a Gene Editing Development Candidate in Adults With Classical PKU Due to PAH Deficiency

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05222178
Recruitment Status : Recruiting
First Posted : February 3, 2022
Last Update Posted : March 10, 2023
Sponsor:
Information provided by (Responsible Party):
Homology Medicines, Inc

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
Phenylketonurias PAH Deficiency Phenylketonuria Drug: HMI-103 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose Escalation
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 3, 2022
Estimated Primary Completion Date : June 2026
Estimated Study Completion Date : June 2028


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




Primary Outcome Measures :
  1. To determine incidence and severity of Treatment Emergent Adverse Events and adverse events of special interest of a single administration of HMI-103 [ Time Frame: Baseline to Week 104 ]
    • Incidence and severity of TEAEs
    • Incidence and severity of adverse events of special interest (AESIs)

  2. 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


Secondary Outcome Measures :
  1. To evaluate the effect of HMI-103 on plasma Phe concentration relative to treatment guidelines for PKU [ Time Frame: Baseline to Week 104 ]
    Incidence of plasma Phe of ≤ 360 μmol/L within each dose cohort at each timepoint post-administration of HMI-103

  2. To assess durability of response [ Time Frame: Weeks 48-52 ]
    Incidence of plasma Phe ≤ 360 μmol/L during Weeks 48-52 post-administration of HMI-103

  3. To assess the changes in dietary protein intake [ Time Frame: Baseline to Week 104 ]
    Change from baseline in natural and total protein intake (g/day) at each timepoint post-administration of HMI-103



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05222178


Contacts
Layout table for location contacts
Contact: Julie Jordan, M.D. 781-819-0967 clinicaltrials@homologymedicines.com

Locations
Layout table for location information
United States, California
Children's Health of Orange County (CHOC) Recruiting
Orange, California, United States, 92868
Contact: Harriet Chang    714-509-3344    hchang1@choc.org   
Principal Investigator: Richard Chang, MD         
United States, Colorado
Children's Hospital Colorado - Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
Contact: Kristine Lima    720-777-9257    kristine.lima@childrenscolorado.org   
Principal Investigator: Janet Thomas, MD         
United States, Connecticut
Yale University School of Medicine - Yale Genetics Recruiting
New Haven, Connecticut, United States, 06511
Contact: Michele Jasne    203-785-4945    michele.jasne@yale.edu   
Principal Investigator: Michele Spencer-Manzon, MD         
United States, Indiana
Indiana University School of Medicine University Hospital Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Susan Romie    317-278-6650    sromie@iu.edu   
Principal Investigator: Melissa Lah, MD         
United States, Michigan
Spectrum Health Butterworth Hospital Recruiting
Grand Rapids, Michigan, United States, 49503
Contact: Robert Conway, MD         
Contact: Nikki Soules    616-486-2064    nicole.soules@helendevoschildrens.org   
United States, New Jersey
Atlantic Health - Morristown Medical Center Recruiting
Morristown, New Jersey, United States, 07960
Contact: Christina Flores    973-971-7634    Christina.Flora@atlantichealth.org   
Principal Investigator: Darius Adams, MD         
United States, New York
John R. Oishei Children's Hospital Active, not recruiting
Buffalo, New York, United States, 14203
United States, Pennsylvania
Clinic for Special Children Recruiting
Lancaster, Pennsylvania, United States, 17579
Contact: Karlla Brigatti    717-687-9407    kbrigatti@clinicforspecialchildren.org   
Principal Investigator: Kevin Strauss, MD         
UPMC Children's Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Gerard Vockley, MD         
Contact: Jennifer Baker    412-692-6378    Jennifer.Baker@chp.edu   
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Kristen Roberts    615-322-4356    kristen.l.roberts@vumc.org   
Contact: Leanna Melton    615-343-6761    leeanna.melton@vumc.org   
Principal Investigator: John Phillips, MD         
United States, Texas
University of Texas Southwestern Medical Center at Dallas Recruiting
Dallas, Texas, United States, 75390
Contact: Markey McNutt, MD, PhD         
Contact: Kellyn Pollard    (214) 645-7415    Kellyn.Pollard@utsouthwestern.edu   
Sponsors and Collaborators
Homology Medicines, Inc
Layout table for additonal information
Responsible Party: Homology Medicines, Inc
ClinicalTrials.gov Identifier: NCT05222178    
Other Study ID Numbers: HMI-103-101
First Posted: February 3, 2022    Key Record Dates
Last Update Posted: March 10, 2023
Last Verified: March 2023

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Homology Medicines, Inc:
PKU
Gene editing
AAVHSC
Additional relevant MeSH terms:
Layout table for MeSH terms
Phenylketonurias
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases