Study of Efficacy and Safety of Tonlamarsen in Participants With a Recent Hospitalization and a Concurrent Episode of Acute Severe Hypertension

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• Hypertension 6,681
• Hypertensive Crisis 35

Eligibility criteria

Study arms

• Experimental
  Tonlamarsen

  3 doses active drug will be administered by subcutaneous (under the skin) injection (one dose every 4 weeks)

  Drug: Tonlamarsen

• Placebo comparator
  Placebo

  3 doses of placebo will be administered by subcutaneous (under the skin) injection (one dose every 4 weeks)

  Drug: Placebo

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

Primary outcomes

1. 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

   Time frame: Baseline through Week 12

2. 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

Secondary outcomes

1. 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

2. 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

3. 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

4. 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

   Time frame: Week 4

5. 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

6. 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

7. 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

8. 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

Individual participant data

Plan to share: No