Study of Safety and Tolerability of TN-201 in Adults With Symptomatic MYBPC3 Mutation-associated HCM (MyPEAK-1)
Primary Purpose
Hypertrophic Cardiomyopathy
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
TN-201
Sponsored by
About this trial
This is an interventional treatment trial for Hypertrophic Cardiomyopathy focused on measuring Hypertrophic Cardiomyopathy (HCM), Myosin Binding Protein C3 (MYBPC3), Nonobstructive HCM, Genetic HCM, Familial HCM, Adenoassociated Virus (AAV), Gene Therapy
Eligibility Criteria
Inclusion Criteria: MYBPC3 mutation Nonobstructive Hypertrophic Cardiomyopathy Left Ventricular Ejection Fraction ≥50% Functioning Implantable Cardiac Defibrillator NYHA Functional Class II or III symptoms NT-proBNP ≥300pg/ml Exclusion Criteria: High AAV9 neutralizing antibody titer
Sites / Locations
- UC San Diego Altman Clinical and Translational Research Institute - Center for Clinical Research
- University of California San Francisco
- Emory University
- Brigham and Women's Hospital
- Mayo Clinic
- University of Cincinnati Health Physicians - Clifton
- Cleveland ClinicRecruiting
- Oregon Health & Science University
- Hospital of the University of Pennsylvania
- University of Pittsburgh Medical Center
- Houston Methodist Hospital
- University of Utah
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Arm Description
Dose for Cohort 1 will be 3E13 vg/kg
Dose for Cohort 2 will be 6E13 vg/kg
Outcomes
Primary Outcome Measures
Number and severity of Adverse Events over the course of the study.
Number of Serious Adverse Events related to study drug.
Secondary Outcome Measures
Change from baseline to Week 52 in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS).
The score ranges from 0-100, with zero being a worse outcome
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05836259
Brief Title
Study of Safety and Tolerability of TN-201 in Adults With Symptomatic MYBPC3 Mutation-associated HCM
Acronym
MyPEAK-1
Official Title
First-in-Human, Open-Label, Safety, Tolerability, Dose-Finding, Pharmacodynamic and Cardiac Transgene Expression Study of TN-201, a Recombinant Adenoassociated Virus Serotype 9 (AAV9) Containing Myosin Binding Protein C Transgene, in Adults With MYBPC3 Mutation-Associated Hypertrophic Cardiomyopathy (HCM)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 2023 (Anticipated)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2029 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tenaya Therapeutics
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 first-in-human, non-randomized, open-label study designed to evaluate the safety, tolerability, and pharmacodynamics (PD) of TN-201 in adult patients with symptomatic MYBPC3 mutation-associated nonobstructive hypertrophic cardiomyopathy (nHCM).
Detailed Description
The study will consist of 2 escalating dose cohorts. The study will enroll at least 6 and as many as 15 patients. All patients will receive active drug. The study will follow patients for 5 years following a single dose of TN-201.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertrophic Cardiomyopathy
Keywords
Hypertrophic Cardiomyopathy (HCM), Myosin Binding Protein C3 (MYBPC3), Nonobstructive HCM, Genetic HCM, Familial HCM, Adenoassociated Virus (AAV), Gene Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
This is a first-in-human, non-randomized, open label Phase 1b study. The study will consist of 2 escalating dose cohorts. The study will enroll at least 6 and as many as 15 patients. All patients will receive active drug.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Dose for Cohort 1 will be 3E13 vg/kg
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Dose for Cohort 2 will be 6E13 vg/kg
Intervention Type
Genetic
Intervention Name(s)
TN-201
Intervention Description
TN-201 is a recombinant adeno-associated virus serotype 9 (AAV9) containing Myosin Binding Protein C (MYBPC3) transgene. It is a single (one-time) intravenous dose.
Primary Outcome Measure Information:
Title
Number and severity of Adverse Events over the course of the study.
Time Frame
5 Years
Title
Number of Serious Adverse Events related to study drug.
Time Frame
5 Years
Secondary Outcome Measure Information:
Title
Change from baseline to Week 52 in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS).
Description
The score ranges from 0-100, with zero being a worse outcome
Time Frame
52 Weeks
Other Pre-specified Outcome Measures:
Title
Expression levels of vector genomes and transgene messenger ribonucleic acid (mRNA) and MyBP-C protein in right ventricular (RV) septal biopsy samples at Week 8 and Week 52.
Time Frame
52 Weeks
Title
Change from Pre-dose in N-terminal pro B-type natriuretic peptide (NTproBNP), and high-sensitivity cardiac troponin I (hs-cTnI) levels.
Time Frame
5 Years
Title
Percentage of patients who had a change in New York Heart Association (NYHA) Functional Class from baseline.
Time Frame
5 Years
Title
Change from baseline peak exercise capacity (pVO2).
Time Frame
5 Years
Title
Change from baseline in echocardiography measurement of left ventricular mass index (g/m^2).
Time Frame
5 Years
Title
Change from baseline in echocardiography measurement of e/e' ratio.
Time Frame
5 Years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
MYBPC3 mutation
Nonobstructive Hypertrophic Cardiomyopathy
Left Ventricular Ejection Fraction ≥50%
Functioning Implantable Cardiac Defibrillator
NYHA Functional Class II or III symptoms
NT-proBNP ≥300pg/ml
Exclusion Criteria:
High AAV9 neutralizing antibody titer
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Laura Robertson, M.D.
Phone
650-416-1186
Email
lrobertson@tenayathera.com
First Name & Middle Initial & Last Name or Official Title & Degree
LaTanya Tomlinson, RN, MHSA
Phone
650-825-6990
Email
clinical.trials@tenayathera.com
Facility Information:
Facility Name
UC San Diego Altman Clinical and Translational Research Institute - Center for Clinical Research
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94117
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
University of Cincinnati Health Physicians - Clifton
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Houston Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Individual Site Status
Not yet recruiting
12. IPD Sharing Statement
Learn more about this trial
Study of Safety and Tolerability of TN-201 in Adults With Symptomatic MYBPC3 Mutation-associated HCM
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