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.
The Sponsor is studying an investigational medication called tonlamarsen to determine if it can help people recently treated for acute severe hypertension (hypertensive emergency and urgency). The purpose of this study is to evaluate how well tonlamarsen works compared to a placebo and to see how safe it is for people following a recent episode of acute severe hypertension. Tonlamarsen is designed to block the body's liver from making a protein called angiotensinogen (AGT), which plays a key role in controlling blood pressure. The main goals of the study are: * To assess the effect of tonlamarsen on the amount of AGT in blood over time * To assess the effect of tonlamarsen on blood pressure * To evaluate the safety and tolerability of tonlamarsen Participants will: * Receive monthly doses of tonlamarsen for approximately 3 months * Visit the clinic about 7 times, including initial evaluation, checkups, tests, and follow-up
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
140
Tonlamarsen will be administered subcutaneously (under the skin) every 4 weeks during the randomized part of the study
Placebo will be administered subcutaneously (under the skin) every 4 weeks during the randomized part of the study
Western Nephrology and Metabolic Bone Disease, PC - Arvada
Arvada, Colorado, United States
RECRUITINGHomestead Associates in Research
Homestead, Florida, United States
RECRUITINGPart 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
Time frame: Baseline through Week 12
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
Time frame: 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
Time frame: Week 36
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
Time frame: Baseline through Week 12
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
Time frame: Week 36
Part B: To evaluate the effect of tonlamarsen on systolic blood pressure measured via daily home blood pressure monitoring
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Progressive Medical Research
Port Orange, Florida, United States
RECRUITINGEagle Clinical Research
Chicago, Illinois, United States
RECRUITINGRichmond University Medical Center (RUMC)
Staten Island, New York, United States
RECRUITINGResearch Innovations, LLC
Beavercreek, Ohio, United States
RECRUITINGOnSite Clinical Solutions, LLC
Fort Mill, South Carolina, United States
RECRUITINGChattanooga Research & Medicine CHARM
Chattanooga, Tennessee, United States
RECRUITINGLaguna Clinical Research Associates
Laredo, Texas, United States
RECRUITINGTapia Internal Medicine Clinic
Paris, Texas, United States
RECRUITING...and 1 more locations
Change in time-averaged systolic blood pressure measured via daily home blood pressure monitoring from Baseline during Week 4
Time frame: Week 4
Part B: To evaluate the effect of tonlamarsen on office systolic blood pressure
Change in office systolic blood pressure from Baseline to Week 4
Time frame: Week 4
Part B: To assess the PD effect of tonlamarsen on plasma AGT levels
Percent change in plasma AGT levels from Baseline to Week 12
Time frame: Week 12
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 daily via home blood pressure monitoring from Baseline during Week 12
Time frame: Week 12
Part B: To evaluate the effect of tonlamarsen on office systolic blood pressure
Change in office systolic blood pressure from Baseline to Week 12
Time frame: Week 12