The purpose of this study is to evaluate the blood pressure-lowering effect of tonlamarsen in adult participants who were recently hospitalized and concurrently experienced an episode of acute severe hypertension.
Age 18 or older, body weight ≥ 50 kg with BMI ≤45.0 kg/m2
Ready for discharge or recently discharged from the hospital to home (within the past 7 days) during which evaluation and/or treatment of acute severe hypertension (documented SBP ≥ 180 mmHg and/or DBP ≥ 110 mmHg) occurred, as measured by a healthcare provider (HCP) within the 24 hours preceding hospitalization or during the initial 24 hours of hospitalization
At Screening and Randomization visit, average resting office systolic blood pressure ≥ 145 mmHg
Presence of established cardiovascular or renal disease
Has known history of secondary hypertension
Any malignancy requiring treatment within 5 years (except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated)
Has abnormal thyroid function with clinical significance
Recent hospitalization for stroke, myocardial infarction or coronary revascularization within 30 days prior to screening
Parallel
Tonlamarsen
DrugTonlamarsen will be administered subcutaneously (under the skin) every 4 weeks during the randomized part of the study
Placebo
DrugPlacebo will be administered subcutaneously (under the skin) every 4 weeks during the randomized part of the study
Part A: To assess variability in clinical and biomarker measures to inform Part B sample-size estimation and study-design assumptions
* Change from baseline in plasma angiotensinogen (AGT) levels and systolic blood pressure * Variability in plasma AGT levels and systolic blood pressure
Part B: To assess the pharmacodynamic (PD) effect of tonlamarsen on plasma AGT levels
Percent change in plasma AGT levels from Baseline to Week 4
Part A: To assess the safety and tolerability of tonlamarsen compared with placebo
* Incidence and severity of treatment emergent adverse events (TEAEs), including serious adverse events (SAEs) and adverse events of special interest (AESIs) * Incidence of clinically significant abnormalities in laboratory assessments, physical examinations, 12-lead electrocardiograms, and vital signs
Part A: To assess the feasibility of using AGT levels and systolic blood pressure as efficacy endpoints
* Change from baseline in plasma AGT levels and systolic blood pressure * Variability in plasma AGT levels and systolic blood pressure
Part B: To assess the safety and tolerability of tonlamarsen compared with placebo
* Incidence and severity of treatment emergent adverse events (TEAEs), including serious adverse events (SAEs) and adverse events of special interest (AESIs) * Incidence of clinically significant abnormalities in laboratory assessments, physical examinations, 12-lead electrocardiograms, and vital signs
Part B: To evaluate the effect of tonlamarsen on systolic blood pressure measured via daily home blood pressure monitoring
Change in time-averaged systolic blood pressure measured via daily home blood pressure monitoring from Baseline during Week 4
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