HypertensionPhase 2NCT06864104
A Study to Investigate Tonlamarsen for the Treatment of Adults With Uncontrolled Hypertension (KARDINAL)
A Phase 2 study testing Tonlamarsen in people with Hypertension, run by Kardigan, Inc. at 39 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hypertension
- What is being tested?
- Tonlamarsen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 206 participants
- Where
- 39 sitesUnited States
- Study dates
- 10 Apr 2025to 17 Mar 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
39 sites in 1 country.
39 sites in 1 country
United States39 sites
Pinnacle Research Group
Anniston, Alabama, 36207
Agile Clinical Research Trials, LLC
Atlanta, Georgia, 30328
Central Texas Clinical Research
Austin, Texas, 78705
Achieve Clinical Research, LLC
Birmingham, Alabama, 35216
Eagle Clinical Research
Chicago, Illinois, 60621
North Coast Cardiology
Encinitas, California, 92024
Advanced Medical Trials, LLC
Georgetown, Texas, 78628
Clinical Investigation Specialists, Inc.
Gurnee, Illinois, 60031
Homestead Associates in Research, Inc.
Homestead, Florida, 33033
Juno Research, LLC
Houston, Texas, 77040
Jacksonville Center for Clinical Research
Jacksonville, Florida, 32216
Holston Medical Group
Kingsport, Tennessee, 37660
Orange County Research Center
Lake Forest, California, 92630
Radiance Clinical Research
Lampasas, Texas, 76550
IMA Clinical Research
Lenoir, North Carolina, 28645
Clinical Trials Research
Lincoln, California, 95648
Cardiology and Medicine Clinic
Little Rock, Arkansas, 72204
American Institute of Research
Los Angeles, California, 90017
Manassas Clinical Research Center
Manassas, Virginia, 20110
Tandem Clinical Research GI, LLC
Marrero, Louisiana, 70072
ActivMed Practices & Research, LLC
Methuen, Massachusetts, 01844
Synergy Groups Medical, LLC
Missouri City, Texas, 77459
Clinical Trials of South Carolina
Moncks Corner, South Carolina, 29461
IMA Clinical Research
Monroe, Louisiana, 71201
Koch Family Medicine Clinical Research
Morton, Illinois, 61550
DelRicht Clinical Research - New Orleans
New Orleans, Louisiana, 70115
Suncoast Clinical Research, Inc.
New Port Richey, Florida, 34652
York Clinical Research LLC
Norfolk, Virginia, 23504
North Hills Medical Research
North Richland Hills, Texas, 76180
Olive Branch Family Medical Center
Olive Branch, Mississippi, 38654
Elite Clinical Studies
Phoenix, Arizona, 85018
Progressive Medical Research
Port Orange, Florida, 32127
Health Concepts
Rapid City, South Dakota, 57702
Sun Research Institute
San Antonio, Texas, 78215
Velocity Clinical Reseach
Savannah, Georgia, 31406
Richmond University Medical Center
Staten Island, New York, 10310
CHEAR Center LLC
The Bronx, New York, 10455
Oakland Medical Research Center
Troy, Michigan, 48085
Del Sol Research Management, LLC
Tucson, Arizona, 85715
About this study
Official title: 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).
- Conditions
- Hypertension
- Being tested
- Tonlamarsen, Placebo
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TonlamarsenDrug
Tonlamarsen will be administered subcutaneously (SC) every 4 weeks during the randomized part of the study
PlaceboDrug
Placebo will be administered subcutaneously (SC) every 4 weeks during the randomized part of the study
| Study group | Role | What they receive |
|---|---|---|
| Tonlamarsen | Experimental | 1 dose of placebo and 5 doses of active drug will be administered by subcutaneous (SC) injection Receives: Drug: Tonlamarsen |
| Placebo | Placebo comparator | 5 doses of placebo and 1 dose of active drug will be administered by subcutaneous (SC) injection Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Week 20
Secondary outcomes (5)
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.
Measured: 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
Measured: Week 20
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
Measured: 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
Measured: 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
Measured: Week 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2025
- Study start10 Apr 2025
- Primary completion12 Jan 2026
- Study completion17 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Once eligibility is confirmed during screening, there will be two run-in periods (Part A and Part B). Eligible participants will then be randomized to tonlamarsen or placebo (Part C).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 206 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kardigan, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06864104
- Sponsor's protocol ID
- TLA-201
- Status last verified
- Mar 2026
- First submitted
- 12 Feb 2025
- Last updated
- 31 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT06864104
- Acronym / sponsor ID
- TLA-201
- Conditions
- Hypertension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 206 participants (actual)
- Lead sponsor
- Kardigan, Inc.Industry (pharma, biotech, devices)
- Study start
- 10 Apr 2025 (actual)
- Primary completion
- 12 Jan 2026 (actual)
- Study completion
- 17 Mar 2026 (actual)
- First posted
- 7 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Once eligibility is confirmed during screening, there will be two run-in periods (Part A and Part B). Eligible participants will then be randomized to tonlamarsen or placebo (Part C).
| Arm | Type | Receives |
|---|---|---|
| Tonlamarsen | Experimental | Drug: Tonlamarsen1 dose of placebo and 5 doses of active drug will be administered by subcutaneous (SC) injection |
| Placebo | Placebo comparator | Drug: Placebo5 doses of placebo and 1 dose of active drug will be administered by subcutaneous (SC) injection |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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 (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TonlamarsenTonlamarsen will be administered subcutaneously (SC) every 4 weeks during the randomized part of the study | Drug | Tonlamarsen |
| PlaceboPlacebo will be administered subcutaneously (SC) every 4 weeks during the randomized part of the study | Drug | Placebo |
Primary outcome
To assess the effect of tonlamarsen on plasma angiotensinogen (AGT) levels
Time frame: Week 20
Percent Change from baseline (Week 0) in plasma angiotensinogen (AGT) levels to Week 20
To assess the systolic blood pressure-lowering efficacy of tonlamarsen
Time frame: Week 20
Change from baseline (Week 0) in mean office seated systolic blood pressure to Week 20
5 secondary outcomes
To assess the safety and tolerability of tonlamarsen
Time frame: Week 28
To assess the efficacy of tonlamarsen in achieving office seated systolic blood pressure <130 mmHg
Time frame: Week 20
To assess the systolic blood pressure-lowering efficacy of tonlamarsen
Time frame: Week 20
To assess the effect of tonlamarsen on severe systolic blood pressure elevations
Time frame: Week 20
To assess the diastolic blood pressure-lowering efficacy of tonlamarsen
Time frame: Week 20
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2026.
- Derived from this study: PubMed 41949512Laffin 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.
- Individual participant dataSharing planned: No
Related trials for Hypertension
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Enrolling by invitation
Testing Implementation Strategies to Support Clinic Fidelity to an Outpatient Hypertension Bundle
Pregnancy Related, Hypertension
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
39 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tonlamarsen in people with Hypertension, run by Kardigan, Inc. at 39 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the effect of tonlamarsen on plasma angiotensinogen (AGT) levels (time frame: Week 20). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06864104, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2026.