Acute Severe Hypertension, Hypertension, Hypertensive Emergency, Hypertensive Urgency
Conditions
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: * Receive monthly doses of tonlamarsen for approximately 3 months * Visit the clinic about 7 times, including initial evaluation, checkups, tests, and follow-up
Interventions
DRUGTonlamarsen
Tonlamarsen will be administered subcutaneously (under the skin) every 4 weeks during the randomized part of the study
DRUGPlacebo
Placebo will be administered subcutaneously (under the skin) every 4 weeks during the randomized part of the study
Sponsors
Kardigan, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized, Double-Blind, Placebo-Controlled, Multicenter Two-Part study. Once eligibility is confirmed, eligible participants will then be randomized to tonlamarsen or placebo. The randomized treatment period will be followed by a 24-week safety follow-up period.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key 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 Key
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: To assess variability in clinical and biomarker measures to inform Part B sample-size estimation and study-design assumptions | 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 | Week 4 | Percent change in plasma AGT levels from Baseline to Week 4 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: To assess the safety and tolerability of tonlamarsen compared with placebo | Week 36 | * 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 | Baseline through Week 12 | * 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 | Week 36 | * 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 | Week 4 | Change in time-averaged systolic blood pressure measured via daily home blood pressure monitoring from Baseline during Week 4 |
| Part B: To evaluate the effect of tonlamarsen on office systolic blood pressure | Week 4 | Change in office systolic blood pressure from Baseline to Week 4 |
| Part B: To assess the PD effect of tonlamarsen on plasma AGT levels | Week 12 | Percent change in plasma AGT levels from Baseline to Week 12 |
Countries
United States
Contacts
CONTACTKardigan Clinical Study Information Team
Outcome results
None listed