Skip to main content
OpenTrials
Recruiting

NCT Number: NCT07511361

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

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Hypertension Acute Severe Hypertension Cardiovascular Diseases Hypertensive Crisis Hypertensive Emergency Hypertensive Urgency Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Western Nephrology and Metabolic Bone Disease, PC - Arvada, Arvada, Colorado, United States

Loading trial locations.

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Tonlamarsen

Drug

Tonlamarsen will be administered subcutaneously (under the skin) every 4 weeks during the randomized part of the study

Placebo

Drug

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

    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

  2. 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

  1. Part A: To assess the safety and tolerability of tonlamarsen compared with placebo

    Time frame: 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

  2. Part A: To assess the feasibility of using AGT levels and systolic blood pressure as efficacy endpoints

    Time frame: Baseline through Week 12

    • Change from baseline in plasma AGT levels and systolic blood pressure
    • Variability in plasma AGT levels and systolic blood pressure

  3. Part B: To assess the safety and tolerability of tonlamarsen compared with placebo

    Time frame: 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

  4. Part B: To evaluate the effect of tonlamarsen on systolic blood pressure measured via daily home blood pressure monitoring

    Time frame: Week 4

    Change in time-averaged systolic blood pressure measured via daily home blood pressure monitoring from Baseline during Week 4

  5. Part B: To evaluate the effect of tonlamarsen on office systolic blood pressure

    Time frame: Week 4

    Change in office systolic blood pressure from Baseline to Week 4

  6. Part B: To assess the PD effect of tonlamarsen on plasma AGT levels

    Time frame: Week 12

    Percent change in plasma AGT levels from Baseline to Week 12

  7. Part B: To evaluate the effect of tonlamarsen on systolic blood pressure measured via daily home blood pressure monitoring

    Time frame: Week 12

    Change in time-averaged systolic blood pressure measured daily via home blood pressure monitoring from Baseline during Week 12

  8. Part B: To evaluate the effect of tonlamarsen on office systolic blood pressure

    Time frame: Week 12

    Change in office systolic blood pressure from Baseline to Week 12

Study contacts

Contact information is provided by the study sponsor or research team.

Kardigan Clinical Study Information Team

CONTACT

[email protected]

+1-877-310-5135

Sponsors and collaborators

Lead sponsor

Kardigan, Inc.

Industry

Registry information

Official study title

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

Acronym: KARDINAL-ASH

Important dates

Study start
2026
Primary completion
2026
Study completion
2027
First posted
Apr 6, 2026
Registry last updated
Jul 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.