Study of Safety and Tolerability of TN-201 in Adults With Symptomatic MYBPC3 Mutation-associated HCM

Hypertrophic Cardiomyopathy Clinical Trial

— 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05836259
• Other study ID #: TN-201-0009
• Status: Recruiting
• Phase: Phase 1
• Start date: August 10, 2023
• Est. completion date: December 2029

Study information

• Verified date: May 2024
• Source: Tenaya Therapeutics
• Contact: Laura Robertson, M.D.
• Phone: 650-416-1186
• Email: lrobertson[@]tenayathera.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 2029
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Hypertrophic
• Hypertrophic Cardiomyopathy
• Hypertrophy

Intervention

Genetic:
• TN-201
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.

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	University of Cincinnati Health Physicians - Clifton	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Houston Methodist Hospital	Houston	Texas
United States	UC San Diego Altman Clinical and Translational Research Institute - Center for Clinical Research	La Jolla	California
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Utah	Salt Lake City	Utah
United States	University of California San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Tenaya Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.		52 Weeks
Other	Change from Pre-dose in N-terminal pro B-type natriuretic peptide (NTproBNP), and high-sensitivity cardiac troponin I (hs-cTnI) levels.		5 Years
Other	Percentage of patients who had a change in New York Heart Association (NYHA) Functional Class from baseline.		5 Years
Other	Change from baseline peak exercise capacity (pVO2).		5 Years
Other	Change from baseline in echocardiography measurement of left ventricular mass index (g/m^2).		5 Years
Other	Change from baseline in echocardiography measurement of e/e' ratio.		5 Years
Primary	Number and severity of Adverse Events over the course of the study.		5 Years
Primary	Number of Serious Adverse Events related to study drug.		5 Years
Secondary	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	52 Weeks