Study of Efficacy and Safety of Tonlamarsen in Participants With a Recent Hospitalization and a Concurrent Episode of Acute Severe Hypertension (KARDINAL-ASH)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hypertension; Hypertensive Urgency; Hypertensive Emergency; 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 7 times, including initial evaluation, checkups, tests, and follow-up

• Study Type: Interventional
• Enrollment (Estimated): 140
• 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
      • Recruiting
      • Western Nephrology and Metabolic Bone Disease, PC - Arvada
      • Contact: Kardigan Clinical Study Information Team; Phone Number: +1-877-310-5135; Email: clinicaltrials@kardigan.bio
  • Florida
    • Homestead, Florida, United States, 33033
      • Recruiting
      • Homestead Associates in Research
      • Contact: Kardigan Clinical Study Information Team; Phone Number: 1-877-310-5135; Email: clinicaltrials@kardigan.bio
    • Port Orange, Florida, United States, 32127
      • Recruiting
      • Progressive Medical Research
      • Contact: Kardigan Clinical Study Information Team; Phone Number: +1-877-310-5135; Email: clinicaltrials@kardigan.bio
  • New York
    • Staten Island, New York, United States, 10310
      • Recruiting
      • Richmond University Medical Center (RUMC)
      • Contact: Kardigan Clinical Study Information Team; Phone Number: 1-877-310-5135; Email: clinicaltrials@kardigan.bio
  • Ohio
    • Beavercreek, Ohio, United States, 05431
      • Recruiting
      • Research Innovations, LLC
      • Contact: Kardigan Clinical Study Information Team; Phone Number: 1-877-310-5135; Email: clinicaltrials@kardigan.bio
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Recruiting
      • Chattanooga Research & Medicine CHARM
      • Contact: Kardigan Clinical Study Information Team; Phone Number: 1-877-310-5135; Email: clinicaltrials@kardigan.bio
  • Texas
    • Laredo, Texas, United States, 78041
      • Recruiting
      • Laguna Clinical Research Associates
      • Contact: Kardigan Clinical Study Information Team; Phone Number: 1-877-310-5135; Email: clinicaltrials@kardigan.bio
    • Temple, Texas, United States, 76502
      • Recruiting
      • Baylor Scott and White Research Institute - Temple
      • Contact: Kardigan Clinical Study Information Team; Phone Number: 1-877-310-5135; 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 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

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
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	Baseline through Week 12
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	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Week 36
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	Baseline through Week 12
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	Week 36
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	Week 4
Part B: To evaluate the effect of tonlamarsen on office systolic blood pressure	Change in office systolic blood pressure from Baseline to Week 4	Week 4
Part B: To assess the PD effect of tonlamarsen on plasma AGT levels	Percent change in plasma AGT levels from Baseline to Week 12	Week 12
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	Week 12
Part B: To evaluate the effect of tonlamarsen on office systolic blood pressure	Change in office systolic blood pressure from Baseline to Week 12	Week 12

Collaborators and Investigators

• Sponsor: Kardigan, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): February 1, 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): July 1, 2026
• Last Update Submitted That Met QC Criteria: June 29, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertensive Crisis; 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