Study of Efficacy and Safety of Tonlamarsen in Participants With Acute Severe Hypertension Recently Discharged From the Hospital (KARDINAL-ASH)

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Tonlamarsen in Participants With Acute Severe Hypertension Recently Discharged From the Hospital

The purpose of this study is to evaluate the blood pressure-lowering effect of tonlamarsen in adult participants who were recently discharged from the hospital, after treatment for acute severe hypertension.

Study Overview

• Status: Recruiting
• Conditions: Hypertension; Acute Severe Hypertension
• Intervention / Treatment: Drug: Tonlamarsen; Drug: Placebo

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 6 times, including initial evaluation, checkups, tests, and follow-up

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kardigan Clinical Study Information Team; Phone Number: +1-877-310-5135; Email: clinicaltrials@kardigan.bio

Study Locations

• United States
  • Colorado
    • Arvada, Colorado, United States, 80002
      • Not yet recruiting
      • Western Nephrology and Metabolic Bone Disease, PC - Arvada
      • Contact: Kardigan Clinical Study Information Team; Phone Number: 877-310-5135; Email: clinicaltrials@kardigan.bio
  • Florida
    • Homestead, Florida, United States, 33033
      • Recruiting
      • Homestead Associates in Research
      • Contact: Kardigan Clinical Study Information Team; Phone Number: 877-310-5135; Email: clinicaltrials@kardigan.bio
    • Port Orange, Florida, United States, 32127
      • Recruiting
      • Progressive Medical Research
      • Contact: Kardigan Clinical Study Information Team; Phone Number: 877-310-5135; Email: clinicaltrials@kardigan.bio
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Not yet recruiting
      • Chattanooga Research & Medicine CHARM
      • Contact: Kardigan Clinical Study Information Team; Phone Number: 877-310-5135; Email: clinicaltrials@kardigan.bio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Age 18 or older, body weight ≥ 50 kg
• Recently discharged from the hospital to home within the past 3 days during which evaluation and/or treatment of acute severe hypertension (documented systolic blood pressure >180 mmHg and/or diastolic >110 mmHg) occurred, as measured by a healthcare provider within the 24 hours preceding hospitalization or during the initial 24 hours of hospitalization
• At Screening and Randomization visit, average systolic blood pressure > 145 mmHg
• Presence of established cardiovascular or renal comorbidities

Key Exclusion Criteria:

• Has known history of secondary hypertension
• Any malignancy requiring treatment within 5 years
• Has abnormal thyroid function with clinical significance
• Recent hospitalization for stroke, type 1 myocardial infarction or coronary revascularization within 3 months prior to the first on-study visit
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tonlamarsen; 3 doses active drug will be administered by subcutaneous (under the skin) injection (one dose every 4 weeks)	Drug: Tonlamarsen; Tonlamarsen will be administered subcutaneously (under the skin) every 4 weeks during the randomized part of the study
Placebo Comparator: Placebo; 3 doses of placebo will be administered by subcutaneous (under the skin) injection (one dose every 4 weeks)	Drug: Placebo; Placebo will be administered subcutaneously (under the skin) every 4 weeks during the randomized part of the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the effect of tonlamarsen on plasma angiotensinogen (AGT) levels	Percent Change from baseline (Week 0) in plasma angiotensinogen (AGT) levels to Week 12	Week 12
To assess the systolic blood pressure-lowering effect of tonlamarsen	Change from baseline (Week 0) in mean office seated systolic blood pressure to Week 12	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the safety and tolerability of tonlamarsen compared with placebo	Incidence and severity of treatment emergent adverse events (TEAEs) Incidence of clinically significant abnormalities in laboratory assessments, physical examinations, 12-lead electrocardiograms, and vital signs	Week 20
To evaluate the effect of tonlamarsen on systolic blood pressure measured via daily home blood pressure monitoring	Change in time-averaged SBP measured via daily home BP monitoring The percentage of days with daily average self-assessed home SBP>150 mmHg	Week 12

Collaborators and Investigators

• Sponsor: Kardigan, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): April 20, 2026
• Primary Completion (Estimated): December 29, 2026
• Study Completion (Estimated): February 23, 2027

Study Registration Dates

• First Submitted: March 28, 2026
• First Submitted That Met QC Criteria: March 28, 2026
• First Posted (Actual): April 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension
• Other Study ID Numbers: TLA-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No