MyPEAK-1: Study of Safety and Tolerability of TN-201 in Adults With Symptomatic MYBPC3 Mutation-associated HCM

Sponsor

Tenaya Therapeutics (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05836259

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

2.1

Patients Per Site

Patients Per Site Per Month

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Hypertrophic Cardiomyopathy	Genetic: TN-201	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention 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.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)

Primary Purpose:

Treatment

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)

Anticipated Study Start Date :

Jun 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2025

Anticipated Study Completion Date :

Dec 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Dose for Cohort 1 will be 3E13 vg/kg	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.
Experimental: Cohort 2 Dose for Cohort 2 will be 6E13 vg/kg	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.

Arm

Intervention/Treatment

Experimental: Cohort 1

Dose for Cohort 1 will be 3E13 vg/kg

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.

Experimental: Cohort 2

Dose for Cohort 2 will be 6E13 vg/kg

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.

Outcome Measures

Primary Outcome Measures

Number and severity of Adverse Events over the course of the study. [5 Years]
Number of Serious Adverse Events related to study drug. [5 Years]

Secondary Outcome Measures

Change from baseline to Week 52 in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). [52 Weeks]
The score ranges from 0-100, with zero being a worse outcome

Other Outcome Measures

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]
Change from Pre-dose in N-terminal pro B-type natriuretic peptide (NTproBNP), and high-sensitivity cardiac troponin I (hs-cTnI) levels. [5 Years]
Percentage of patients who had a change in New York Heart Association (NYHA) Functional Class from baseline. [5 Years]
Change from baseline peak exercise capacity (pVO2). [5 Years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
2	Mayo Clinic	Rochester	Minnesota	United States	55905
3	Cleveland Clinic	Cleveland	Ohio	United States	44195
4	Oregon Health & Science University	Portland	Oregon	United States	97239
5	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
6	Houston Methodist Hospital	Houston	Texas	United States	77030
7	University of Utah	Salt Lake City	Utah	United States	84132