Clinical trial NCT05836259: Multi-center, Open-label, Single-ascending Dose Study of Safety and Tolerability of TN-201 in Adults With Symptomatic MYBPC3 Mutation-associated HCM
Official title: First-in-Human, Open-Label, Safety, Tolerability, Dose-Finding, Pharmacodynamic and Cardiac Transgene Expression Study of TN-201, a Recombinant Adeno-associated Virus Serotype 9 (AAV9) Containing Myosin Binding Protein C Transgene, in Adults With MYBPC3 Mutation-associated Hypertrophic Cardiomyopathy (HCM)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Hypertrophic Cardiomyopathy
Keywords: Hypertrophic Cardiomyopathy (HCM)
Myosin Binding Protein C3 (MYBPC3)
Nonobstructive HCM
Genetic HCM
Familial HCM
Adenoassociated Virus (AAV)
Gene Therapy
Obstructive HCM
nHCM
oHCM
Lead sponsor: Tenaya Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-05-01
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This is a first-in-human, non-randomized, open label Phase 1b/2 study. The study will consist of 2 escalating dose cohorts. The study will enroll at least 6 and as many as 30 patients. All patients will receive active drug.
Primary purpose: TREATMENT

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 hypertrophic cardiomyopathy (HCM) caused by mutations in the MYBPC3 gene.

Detailed description: The study will consist of 2 escalating dose cohorts (groups). The study will enroll at least 6 and as many as 30 patients. All patients will receive active drug (TN-201 Gene Therapy). The study will follow patients for 5 years following a single dose of TN-201.

Eligibility criteria: Inclusion Criteria:

* MYBPC3 mutation
* Hypertrophic Cardiomyopathy (obstructive and nonobstructive)
* Left Ventricular Ejection Fraction ≥45%
* NYHA Functional Class II or III symptoms
* NT-proBNP ≥160pg/ml

Exclusion Criteria:

* High AAV9 neutralizing antibody titer

Primary outcomes:
measure: Number and severity of Adverse Events over the course of the study.
timeFrame: 5 Years
measure: Number of Serious Adverse Events related to study drug.
timeFrame: 5 Years
Secondary outcomes:
measure: Change from baseline to Week 52 in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS).
timeFrame: 52 Weeks
Other outcomes:
measure: Expression levels of vector genomes and transgene messenger ribonucleic acid (mRNA) and MyBP-C protein in right ventricular (RV) septal biopsy samples at Pre-Treatment, Week 26, and Week 52.
timeFrame: 52 Weeks
measure: Change from Pre-Treatment period in N-terminal pro B-type natriuretic peptide (NTproBNP), and high-sensitivity cardiac troponin I (hs-cTnI) levels.
timeFrame: 5 Years
measure: Percentage of patients who had a change in New York Heart Association (NYHA) Functional Class from baseline.
timeFrame: 5 Years
measure: Change from baseline in echocardiography measurements of indexed left atrial and left ventricular (LV) volumes.
timeFrame: 5 Years
measure: Change from baseline in echocardiography measurements of LV mass.
timeFrame: 5 Years
measure: Change from baseline in echocardiography measurements of maximal LV wall thickness.
timeFrame: 5 Years
measure: Change from baseline in echocardiography measurements of global longitudinal strain.
timeFrame: 5 Years
measure: Change from baseline in 6MWT distance.
timeFrame: 5 Years
measure: Change from baseline peak exercise capacity (pVO2).
timeFrame: 5 Years
Locations:
city: La Jolla
country: United States
facility: UC San Diego Altman Clinical and Translational Research Institute - Center for Clinical Research
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Cincinnati
country: United States
facility: The Christ Hospital Physicians - The Ohio Heart and Vascular Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
Study officials:
References: