A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Two-Part Study to Evaluate the Efficacy and Safety of Tonlamarsen in Participants With a Recent Hospitalization and a Concurrent Episode of Acute Severe Hypertension
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 140
- Locations
- 13
- Primary Endpoint
- Part A: To assess variability in clinical and biomarker measures to inform Part B sample-size estimation and study-design assumptions
Study Overview
Brief Summary
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.
Detailed Description
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:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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
- •History of and/or obvious clinical signs or symptoms of cirrhosis or other significant liver disease
- •Alanine aminotransferase or aspartate aminotransferase >2 x upper limit of normal
- •Most recent hospitalization was for non-cardiovascular or non-renal conditions
Arms & Interventions
Placebo
3 doses of placebo will be administered by subcutaneous (under the skin) injection (one dose every 4 weeks)
Intervention: Placebo (Drug)
Tonlamarsen
3 doses active drug will be administered by subcutaneous (under the skin) injection (one dose every 4 weeks)
Intervention: Tonlamarsen (Drug)
Outcomes
Primary Outcomes
Part A: To assess variability in clinical and biomarker measures to inform Part B sample-size estimation and study-design assumptions
Time Frame: Baseline through Week 12
* 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
Time Frame: Week 4
Percent change in plasma AGT levels from Baseline to Week 4
Secondary Outcomes
- Part A: To assess the safety and tolerability of tonlamarsen compared with placebo(Week 36)
- Part A: To assess the feasibility of using AGT levels and systolic blood pressure as efficacy endpoints(Baseline through Week 12)
- Part B: To assess the safety and tolerability of tonlamarsen compared with placebo(Week 36)
- Part B: To evaluate the effect of tonlamarsen on systolic blood pressure measured via daily home blood pressure monitoring(Week 4)
- Part B: To evaluate the effect of tonlamarsen on office systolic blood pressure(Week 4)
- Part B: To assess the PD effect of tonlamarsen on plasma AGT levels(Week 12)
- Part B: To evaluate the effect of tonlamarsen on systolic blood pressure measured via daily home blood pressure monitoring(Week 12)
- Part B: To evaluate the effect of tonlamarsen on office systolic blood pressure(Week 12)