Cardiac Glycogenosis, Cardiomyopathy, Hypertrophic, Wolff-Parkinson-White Syndrome
Conditions
Keywords
AMPK, TfR1, transferrin receptor, ATR 1072, targeted RNA delivery, siRNA, antibody-oligonucleotide conjugate (AOC), glycogen storage disease, PRKAG2 Syndrome, cardiac glycogenosis, cardiomyopathy, PRKAG2, genetic cardiomyopathy, corventis
Brief summary
ATR 1072 is an investigational medicine being studied in adults with PRKAG2 Syndrome. This study will evaluate the safety of ATR 1072 and how the body processes the drug. Researchers will also assess how ATR 1072 affects PRKAG2 activity and measures of heart disease.
Detailed description
ATR 1072 is an antibody-oligonucleotide conjugate (AOC) designed to reduce expression of PRKAG2 through targeted delivery of siRNA to cardiac tissue. This first-in-human, Phase 1/2, open-label, multicenter study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of multiple doses of ATR 1072 in adults with PRKAG2 Syndrome. The study consists of a multiple ascending dose portion (Part A) followed by a dose-expansion cohort at the dose selected in (Part A). After completion of a 48-week treatment period, participants in Parts A and B enter a 42-week extension period followed by a post-treatment follow-up of up to 18 weeks. Approximately 37 participants will be enrolled globally.
Interventions
DRUGATR 1072
ATR 1072 is an investigational therapy that delivers an siRNA to reduce PRKAG2 gene expression. Administered as an intravenous (IV) infusion every 6 weeks (Q6W). Formulated as a sterile liquid for injection.
Sponsors
Atrium Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
None (Open Label)
Intervention model description
Sequential Assignment (MAD escalation followed by expansion)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Adults 18 to 65 years of age. 2. Pathogenic, likely pathogenic, or variant of uncertain significance (VUS) in PRKAG2 confirmed by genetic testing. 3. Clinical manifestations consistent with PRKAG2 Syndrome. 4. Able and willing to comply with study procedures. 5. Able and willing to undergo endomyocardial biopsy procedures (Part A)
Exclusion criteria
1. Pregnancy or breastfeeding. 2. Significant hepatic, renal, hematologic, or cardiovascular abnormalities that may increase study risk. 3. NYHA Class IV heart failure or left ventricular ejection fraction \<45%. 4. Recent clinically significant cardiovascular events or procedures. 5. Prior treatment with prohibited investigational therapies or oligonucleotide therapies within protocol-defined washout periods. 6. Any condition that, in the investigator's
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events (TEAEs) | From first dose through end of study (approximately 48 weeks per participant) | Incidence and severity of treatment-emergent adverse events (TEAEs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in cardiac muscle tissue concentration of ATR 1072 siRNA | Through Week 24 | siRNA content in endomyocardial biopsy samples measured by quantitative bioanalytical methods to characterize cardiac tissue distribution. |
| Plasma pharmacokinetic (PK) parameters of ATR 1072 | Through Week 24 | Peak Plasma Concentration (Cmax) |
| Plasma pharmacokinetic parameters of ATR 1072 | Through week 48 | Area under the plasma concentration versus time curve (AUC) |
Countries
United States
Contacts
CONTACTPatient Recruitment Coordinator
Outcome results
None listed