Hypertension
Conditions
Brief summary
The purpose of this study is to evaluate the blood pressure (BP)-lowering efficacy of tonlamarsen in adult participants who, despite taking 2 or more antihypertensive medications, have not achieved their target blood pressure (BP).
Interventions
DRUGTonlamarsen
Tonlamarsen will be administered subcutaneously (SC) every 4 weeks during the randomized part of the study
DRUGPlacebo
Placebo will be administered subcutaneously (SC) 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
Once eligibility is confirmed during screening, there will be two run-in periods (Part A and Part B). Eligible participants will then be randomized to tonlamarsen or placebo (Part C).
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Age 18 to 80, body weight ≥ 50 kg * Has uncontrolled hypertension while receiving between 2 and 5 antihypertensive medications prescribed for hypertension * Has mean office seated systolic blood pressure \> 135 to ≤ 170 mmHg Key
Exclusion criteria
* Has known history of secondary hypertension * Has documented history of poor adherence to antihypertensive medication * Has unstable/underlying known cardiovascular disease * Has abnormal thyroid function with clinical significance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To assess the effect of tonlamarsen on plasma angiotensinogen (AGT) levels | Week 20 | Percent Change from baseline (Week 0) in plasma angiotensinogen (AGT) levels to Week 20 |
| To assess the systolic blood pressure-lowering efficacy of tonlamarsen | Week 20 | Change from baseline (Week 0) in mean office seated systolic blood pressure to Week 20 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the safety and tolerability of tonlamarsen | Week 28 | Incidence and severity of treatment emergent adverse events (TEAEs). Incidence of clinically significant abnormalities in laboratory assessments, ECGs and vital signs. Incidence of: (1) Hyperkalemia, defined as serum potassium \>5.5 mmol/L. (2) Hypotension, defined as systolic blood pressure \<90 mmHg, or systolic blood pressure \<100 mmHg and symptomatic and/or requiring clinical intervention. (3) Renal dysfunction, defined as a decrease of eGFR \>30% from baseline value. (4) Increased proteinuria, defined as UPCR \>0.5 mg/mg from baseline value. |
| To assess the efficacy of tonlamarsen in achieving office seated systolic blood pressure <130 mmHg | Week 20 | Proportion of participants with mean office seated systolic blood pressure \<130 mmHg at Week 20 |
| To assess the systolic blood pressure-lowering efficacy of tonlamarsen | Week 20 | Change from baseline (Week 0) in mean self-assessed home systolic blood pressure through Week 20 |
| To assess the effect of tonlamarsen on severe systolic blood pressure elevations | Week 20 | Proportion of participants with any daily average home systolic blood pressure ≥150 mmHg at Week 20 |
| To assess the diastolic blood pressure-lowering efficacy of tonlamarsen | Week 20 | Change from baseline (Week 0) in mean office seated diastolic blood pressure to Week 20 |
Countries
United States
Outcome results
None listed