Back to resultsGene Therapy Clinical Study in Adult PKU (pheNIX)
Primary Purpose
Phenylketonurias, PAH Deficiency
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
HMI-102
HMI-102
Sponsored by
About this trial
This is an interventional treatment trial for Phenylketonurias focused on measuring PKU, Phenylketonuria, PAH Deficiency, Hyperphenylalaninemia, Phenylalanine, Adeno Associated Virus, AAVHSC15
Eligibility Criteria
Key Inclusion Criteria:
- 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
Key Exclusion Criteria:
- 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
- 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.
Sites / Locations
- Kaiser Permanente Los Angeles Medical Center
- Children's Hospital of Orange County
- University of South Florida
- Emory University Hospital
- Lurie Children's Hospital of Chicago
- Boston Children's Hospital
- Icahn School of Medicine at Mount Sinai
- The University of North Carolina At Chapel Hill
- Nationwide Children's Hospital
- Children's Hospital of Philadelphia
- UPMC Children's Hospital of Pittsburgh
- University of Texas Southwestern Medical Center
- University of Utah
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Cohort 3
Delayed Treatment Control
Expansion Phase First Dose level
Expansion Phase Second Dose level
Arm Description
Dose Level 1 of HMI-102 delivered intravenously one time
Dose Level 2 of HMI-102 delivered intravenously one time
Dose Level 3 of HMI-102 delivered intravenously one time
Delayed Treatment Control Arm
Expansion Phase First Dose Level of HMI-102 delivered intravenously one time
Expansion Phase Second Dose Level of HMI-102 delivered intravenously one time
Outcomes
Primary Outcome Measures
Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Escalation Phase)
Subjects with at least one TEAE or serious TEAE
Change from baseline in clinical laboratory values (Dose Escalation Phase)
Change in serum chemistry values including liver function tests, hematology, and urinalysis
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
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
Change from baseline in Plasma Phe Concentration (Dose Escalation Phase)
Change from baseline in plasma Phe concentration during Weeks 24-28
Change from baseline in mean Plasma Phe Concentration (Dose Expansion Phase)
Change from baseline in mean plasma Phe concentration during Weeks 24-28
Secondary Outcome Measures
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
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
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
Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Expansion Phase)
Subjects with at least one TEAE or serious TEAE
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03952156
Brief Title
Gene Therapy Clinical Study in Adult PKU
Acronym
pheNIX
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Terminated
Why Stopped
Homology Medicines has discontinued the development of this program.
Study Start Date
June 10, 2019 (Actual)
Primary Completion Date
January 10, 2023 (Actual)
Study Completion Date
August 1, 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 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Phenylketonurias, PAH Deficiency
Keywords
PKU, Phenylketonuria, PAH Deficiency, Hyperphenylalaninemia, Phenylalanine, Adeno Associated Virus, AAVHSC15
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Dose Level 1 of HMI-102 delivered intravenously one time
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Dose Level 2 of HMI-102 delivered intravenously one time
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
Dose Level 3 of HMI-102 delivered intravenously one time
Arm Title
Delayed Treatment Control
Arm Type
Experimental
Arm Description
Delayed Treatment Control Arm
Arm Title
Expansion Phase First Dose level
Arm Type
Experimental
Arm Description
Expansion Phase First Dose Level of HMI-102 delivered intravenously one time
Arm Title
Expansion Phase Second Dose level
Arm Type
Experimental
Arm Description
Expansion Phase Second Dose Level of HMI-102 delivered intravenously one time
Intervention Type
Genetic
Intervention Name(s)
HMI-102
Intervention Description
HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene
Intervention Type
Genetic
Intervention Name(s)
HMI-102
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Escalation Phase)
Description
Subjects with at least one TEAE or serious TEAE
Time Frame
Baseline to Week 52
Title
Change from baseline in clinical laboratory values (Dose Escalation Phase)
Description
Change in serum chemistry values including liver function tests, hematology, and urinalysis
Time Frame
Baseline to Week 52
Title
Change from baseline in 12-lead electrocardiograms (ECGs), vital signs, physical examinations (Dose Escalation Phase)
Description
Subjects change from baseline in 12-lead electrocardiograms (ECGs), vital signs, physical examinations
Time Frame
Baseline to Week 52
Title
Incidence of sustained plasma Phe concentration of ≤360 μmol/L at 28 weeks post dose (Dose Escalation Phase)
Description
Subjects achieving a sustained plasma Phe concentration ≤360 μmol/L at 28 weeks post dose
Time Frame
Week 28
Title
Change from baseline in Plasma Phe Concentration (Dose Escalation Phase)
Description
Change from baseline in plasma Phe concentration during Weeks 24-28
Time Frame
Weeks 24-28
Title
Change from baseline in mean Plasma Phe Concentration (Dose Expansion Phase)
Description
Change from baseline in mean plasma Phe concentration during Weeks 24-28
Time Frame
Weeks 24-28
Secondary Outcome Measure Information:
Title
Incidence of plasma Phe concentration thresholds up to Week 28 post administration of HMI-102 (Dose Expansion Phase)
Description
Subjects achieving plasma Phe concentration thresholds up to Week 28 post administration of HMI-102
Time Frame
Baseline to Week 28
Title
Incidence of plasma Phe concentration thresholds up to Week 52 post administration of HMI-102 (Dose Expansion Phase)
Description
Subjects achieving plasma Phe concentration thresholds up to Week 52 post administration of HMI-102
Time Frame
Baseline to Week 52
Title
Change from baseline in total protein intake at Week 52 post-administration of HMI-102 (Dose Expansion Phase)
Description
Subject Achieving a change from baseline in total protein intake at Week 52 post-administration of HMI-102
Time Frame
Week 52
Title
Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Expansion Phase)
Description
Subjects with at least one TEAE or serious TEAE
Time Frame
Baseline to Week 52
Other Pre-specified Outcome Measures:
Title
Phenylketonuria Quality of Life Questionnaire (PKU-QOL)
Description
Change in PKU-QOL
Time Frame
Baseline to Week 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
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
Key Exclusion Criteria:
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
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olaf A Bodamer, M.D.
Organizational Affiliation
Boston Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kaiser Permanente Los Angeles Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Children's Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
Emory University Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
The University of North Carolina At Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
UPMC Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84108
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Gene Therapy Clinical Study in Adult PKU
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