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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Hypertrophic Cardiomyopathy

Intervention / Treatment
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* Genetic: TN-201


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional 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)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Dose for Cohort 1 will be 3E13 vg/kg | Genetic: TN-201<br>* 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.<br>|
| Experimental: Cohort 2<br>Dose for Cohort 2 will be 6E13 vg/kg | Genetic: TN-201<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Genetic HCM, Hypertrophic Cardiomyopathy (HCM), Myosin Binding Protein C3 (MYBPC3), Nonobstructive HCM, Familial HCM, Adenoassociated Virus (AAV), Gene Therapy