BAG3 Mutation Associated Dilated Cardiomyopathy, Dilated Cardiomyopathy (DCM)
Conditions
Keywords
AFTX-201, Gene Therapy, AAV, BAG3, Dilated Cardiomyopathy, DCM, ATC-0187
Brief summary
This is a Phase 1/2, open-label, dose-exploration and dose-expansion, clinical trial evaluating the safety, tolerability, pharmacodynamics, and preliminary efficacy of a single intravenous infusion of AFTX-201 in adults with dilated cardiomyopathy caused by a BAG3 gene mutation
Detailed description
Participants will receive a single intravenous infusion of AFTX-201 and will be followed for safety and clinical assessments. The study includes short-term safety monitoring and long-term follow-up for up to 60 months
Interventions
GENETICAFTX-201
AFTX-201 is a gene therapy product consisting of the ATC-0187 capsid containing the BCL2-associated Athanogene 3 (BAG3) transgene. It is administered as a single intravenous infusion
Sponsors
Affinia Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Male or female, 18 to 70 years of age Truncating mutation in BAG3 Dilated cardiomyopathy with left ventricular ejection fraction (LVEF) \< 45% NYHA Class II or III heart failure symptoms NT-proBNP ≥ 300 pg/mL for subjects in sinus rhythm or paced rhythm, or ≥ 600 pg/mL for subjects in atrial fibrillation Willing and able to sign informed consent and comply with study procedures
Exclusion criteria
Prior myocardial infarction, heart transplant, or presence/requirement of a left ventricular assist device (LVAD) IV therapy with positive inotropes, vasodilators, or diuretics for heart failure within 30 days prior to enrollment Positive neutralizing antibodies to ATC-0187 Any condition that, in the investigator's opinion, would place the subject at undue risk or interfere with study participation or interpretation of results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) | Baseline through 12 months | Safety and tolerability of AFTX-201 over 12 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) | Baseline through 12 months | Assessment of the impact of a single IV dose of AFTX-201 on quality of life |
| Number of participants with adverse events during long-term follow-up | Baseline through 60 months | Safety and tolerability of AFTX-201 over 60 months |
| Change from baseline in New York Heart Association (NYHA) functional class | Baseline through 12 months | Assessment of the impact of a single IV dose of AFTX-201 on features of heart failure (HF) including functional classification by New York Heart Association (NYHA) class |
| Change from baseline in pharmacodynamic biomarkers | Baseline through 12 months | Assessment of the extent of AFTX-201 transduction and myocardial BAG3 protein expression after a single IV dose |
| Change from baseline in measurement of cardiac function including left ventricular ejection fraction (LVEF) | Baseline through 12 months | Assessment of the impact of a single IV dose of AFTX-201 on measurement of cardiovascular function |
| Change from baseline in measurement of cardiac function including peak oxygen consumption (pVO2) by cardiopulmonary exercise test (CPET) | Baseline through 12 months | Assessment of the impact of a single IV dose of AFTX-201 on measurement of cardiovascular function |
Countries
Canada, United States
Contacts
CONTACTClinical Trials Information
Outcome results
None listed