CClinicalTrials.gg
CompletedNCT06864104Updated Mar 31, 2026

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

A Phase 2 interventional study of Tonlamarsen and Placebo in Hypertension, sponsored by Kardigan, Inc.. Completed at 39 sites in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-03-31.

Sponsored by Kardigan, Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
206
Allocation
Randomized
Ages
18 Years to 80 Years
Sex
All
01

Study summary

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).

02

Conditions studied

  • Hypertension

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03

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
206 participants (actual)

Study arms

  • Experimental
    Tonlamarsen

    1 dose of placebo and 5 doses of active drug will be administered by subcutaneous (SC) injection

    Drug: Tonlamarsen

  • Placebo comparator
    Placebo

    5 doses of placebo and 1 dose of active drug will be administered by subcutaneous (SC) injection

    Drug: Placebo

Interventions

  • DrugTonlamarsen

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

  • DrugPlacebo

    Placebo will be administered subcutaneously (SC) every 4 weeks during the randomized part of the study

05

What researchers measure

Primary outcomes

  1. 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

    Time frame: Week 20

  2. 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

    Time frame: Week 20

Secondary outcomes

  1. 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.

    Time frame: Week 28

  2. 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

    Time frame: Week 20

  3. 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

    Time frame: Week 20

  4. 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

    Time frame: Week 20

  5. 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

    Time frame: Week 20

06

Study locations

39 sites
  • Pinnacle Research Group
    Anniston, Alabama 36207, United States
  • Achieve Clinical Research, LLC
    Birmingham, Alabama 35216, United States
  • Elite Clinical Studies
    Phoenix, Arizona 85018, United States
  • Del Sol Research Management, LLC
    Tucson, Arizona 85715, United States
  • Cardiology and Medicine Clinic
    Little Rock, Arkansas 72204, United States
  • North Coast Cardiology
    Encinitas, California 92024, United States
  • Orange County Research Center
    Lake Forest, California 92630, United States
  • Clinical Trials Research
    Lincoln, California 95648, United States
  • American Institute of Research
    Los Angeles, California 90017, United States
  • Homestead Associates in Research, Inc.
    Homestead, Florida 33033, United States
  • Jacksonville Center for Clinical Research
    Jacksonville, Florida 32216, United States
  • Suncoast Clinical Research, Inc.
    New Port Richey, Florida 34652, United States
  • Progressive Medical Research
    Port Orange, Florida 32127, United States
  • Agile Clinical Research Trials, LLC
    Atlanta, Georgia 30328, United States
  • Velocity Clinical Reseach
    Savannah, Georgia 31406, United States
  • Eagle Clinical Research
    Chicago, Illinois 60621, United States
  • Clinical Investigation Specialists, Inc.
    Gurnee, Illinois 60031, United States
  • Koch Family Medicine Clinical Research
    Morton, Illinois 61550, United States
  • Tandem Clinical Research GI, LLC
    Marrero, Louisiana 70072, United States
  • IMA Clinical Research
    Monroe, Louisiana 71201, United States
  • DelRicht Clinical Research - New Orleans
    New Orleans, Louisiana 70115, United States
  • ActivMed Practices & Research, LLC
    Methuen, Massachusetts 01844, United States
  • Oakland Medical Research Center
    Troy, Michigan 48085, United States
  • Olive Branch Family Medical Center
    Olive Branch, Mississippi 38654, United States
  • Richmond University Medical Center
    Staten Island, New York 10310, United States
  • CHEAR Center LLC
    The Bronx, New York 10455, United States
  • IMA Clinical Research
    Lenoir, North Carolina 28645, United States
  • Clinical Trials of South Carolina
    Moncks Corner, South Carolina 29461, United States
  • Health Concepts
    Rapid City, South Dakota 57702, United States
  • Holston Medical Group
    Kingsport, Tennessee 37660, United States
  • Central Texas Clinical Research
    Austin, Texas 78705, United States
  • Advanced Medical Trials, LLC
    Georgetown, Texas 78628, United States
  • Juno Research, LLC
    Houston, Texas 77040, United States
  • Radiance Clinical Research
    Lampasas, Texas 76550, United States
  • Synergy Groups Medical, LLC
    Missouri City, Texas 77459, United States
  • North Hills Medical Research
    North Richland Hills, Texas 76180, United States
  • Sun Research Institute
    San Antonio, Texas 78215, United States
  • Manassas Clinical Research Center
    Manassas, Virginia 20110, United States
  • York Clinical Research LLC
    Norfolk, Virginia 23504, United States
07

References and documents

Publications

  • Laffin LJ, Wang Q, Sarraju A, Touyz RM, Schlaich MP, Cohen DL, Mahfoud F, Mitchell LM, Mitchell J, Wolski K, Dennis P, Akere A, Li W, Chen G, Cohen YZ, Kim J, Cooper CG, Ramesan P, Edelberg JM, Nissen SE; KARDINAL Investigators. Efficacy of Tonlamarsen in Patients With Uncontrolled Hypertension: The KARDINAL Phase 2 Randomized Clinical Trial. J Am Coll Cardiol. 2026 May 12;87(18):2508-2520. doi: 10.1016/j.jacc.2026.03.034. Epub 2026 Mar 28. PubMed 41949512 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT06864104
Lead sponsor
Kardigan, Inc.
Responsible party
Sponsor
First posted
Mar 7, 2025
Start date
Apr 10, 2025
Primary completion
Jan 12, 2026
Completion
Mar 17, 2026
Last update
Mar 31, 2026

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Mar 2026. You cannot join it, but the record below documents what was studied.

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