A Study to Investigate Tonlamarsen for the Treatment of Adults With Uncontrolled Hypertension (KARDINAL)

A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Monthly Subcutaneous Administration of Tonlamarsen in Participants With Uncontrolled Hypertension (KARDINAL)

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).

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Tonlamarsen; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 206
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group
    • Birmingham, Alabama, United States, 35216
      • Achieve Clinical Research, LLC
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Elite Clinical Studies
    • Tucson, Arizona, United States, 85715
      • Del Sol Research Management, LLC
  • Arkansas
    • Little Rock, Arkansas, United States, 72204
      • Cardiology and Medicine Clinic
  • California
    • Encinitas, California, United States, 92024
      • North Coast Cardiology
    • Lake Forest, California, United States, 92630
      • Orange County Research Center
    • Lincoln, California, United States, 95648
      • Clinical Trials Research
    • Los Angeles, California, United States, 90017
      • American Institute of Research
  • Florida
    • Homestead, Florida, United States, 33033
      • Homestead Associates in Research, Inc.
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research, Inc.
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Agile Clinical Research Trials, LLC
    • Savannah, Georgia, United States, 31406
      • Velocity Clinical Reseach
  • Illinois
    • Chicago, Illinois, United States, 60621
      • Eagle Clinical Research
    • Gurnee, Illinois, United States, 60031
      • Clinical Investigation Specialists, Inc.
    • Morton, Illinois, United States, 61550
      • Koch Family Medicine Clinical Research
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research GI, LLC
    • Monroe, Louisiana, United States, 71201
      • Ima Clinical Research
    • New Orleans, Louisiana, United States, 70115
      • DelRicht Clinical Research - New Orleans
  • Massachusetts
    • Methuen, Massachusetts, United States, 01844
      • ActivMed Practices & Research, LLC
  • Michigan
    • Troy, Michigan, United States, 48085
      • Oakland Medical Research Center
  • Mississippi
    • Olive Branch, Mississippi, United States, 38654
      • Olive Branch Family Medical Center
  • New York
    • Staten Island, New York, United States, 10310
      • Richmond University Medical Center
    • The Bronx, New York, United States, 10455
      • CHEAR Center LLC
  • North Carolina
    • Lenoir, North Carolina, United States, 28645
      • Ima Clinical Research
  • South Carolina
    • Moncks Corner, South Carolina, United States, 29461
      • Clinical Trials of South Carolina
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Health Concepts
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
    • Georgetown, Texas, United States, 78628
      • Advanced Medical Trials, LLC
    • Houston, Texas, United States, 77040
      • Juno Research, LLC
    • Lampasas, Texas, United States, 76550
      • Radiance Clinical Research
    • Missouri City, Texas, United States, 77459
      • Synergy Groups Medical, LLC
    • North Richland Hills, Texas, United States, 76180
      • North Hills Medical Research
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute
  • Virginia
    • Manassas, Virginia, United States, 20110
      • Manassas Clinical Research Center
    • Norfolk, Virginia, United States, 23504
      • York Clinical Research LLC

Participation Criteria

Eligibility Criteria

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

Description

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

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; 1 dose of placebo and 5 doses of active drug will be administered by subcutaneous (SC) injection	Drug: Tonlamarsen; Tonlamarsen will be administered subcutaneously (SC) every 4 weeks during the randomized part of the study
Placebo Comparator: Placebo; 5 doses of placebo and 1 dose of active drug will be administered by subcutaneous (SC) injection	Drug: Placebo; Placebo will be administered subcutaneously (SC) 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 20	Week 20
To assess the systolic blood pressure-lowering efficacy of tonlamarsen	Change from baseline (Week 0) in mean office seated systolic blood pressure to Week 20	Week 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the systolic blood pressure-lowering efficacy of tonlamarsen	Change from baseline (Week 0) in mean self-assessed home systolic blood pressure through Week 20	Week 20
To assess the safety and tolerability of tonlamarsen	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.	Week 28
To assess the efficacy of tonlamarsen in achieving office seated systolic blood pressure <130 mmHg	Proportion of participants with mean office seated systolic blood pressure <130 mmHg at Week 20	Week 20
To assess the effect of tonlamarsen on severe systolic blood pressure elevations	Proportion of participants with any daily average home systolic blood pressure ≥150 mmHg at Week 20	Week 20
To assess the diastolic blood pressure-lowering efficacy of tonlamarsen	Change from baseline (Week 0) in mean office seated diastolic blood pressure to Week 20	Week 20

Collaborators and Investigators

• Sponsor: Kardigan, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2025
• Primary Completion (Actual): January 12, 2026
• Study Completion (Actual): March 17, 2026

Study Registration Dates

• First Submitted: February 12, 2025
• First Submitted That Met QC Criteria: March 3, 2025
• First Posted (Actual): March 7, 2025

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 28, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension
• Other Study ID Numbers: TLA-201

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
• product manufactured in and exported from the U.S.: No