HypertensionPhase 2KARDINAL-ASHNCT07511361
Study of Efficacy and Safety of Tonlamarsen in Participants With a Recent Hospitalization and a Concurrent Episode of Acute Severe Hypertension
A Phase 2 study testing Tonlamarsen in people with Hypertension and Acute Severe Hypertension, run by Kardigan, Inc. at 13 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypertension, Acute Severe Hypertension, Hypertensive Emergency
- 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
- 140 participants
- Where
- 13 sitesUnited States
- Study dates
- 23 Jun 2026to Feb 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
13 sites in 1 country. Contact the study team or a site near you to ask about taking part.
13 sites in 1 country
United States13 sites, 12 recruiting
- Recruiting
Western Nephrology and Metabolic Bone Disease, PC - Arvada
Arvada, Colorado, 80002
Kardigan Clinical Study Information Team, +1-877-310-5135, clinicaltrials@kardigan.bio
- Recruiting
Research Innovations, LLC
Beavercreek, Ohio, 05431
Kardigan Clinical Study Information Team, 1-877-310-5135, clinicaltrials@kardigan.bio
- Recruiting
Chattanooga Research & Medicine CHARM
Chattanooga, Tennessee, 37404
Kardigan Clinical Study Information Team, 1-877-310-5135, clinicaltrials@kardigan.bio
- Recruiting
Eagle Clinical Research
Chicago, Illinois, 60621
Kardigan Clinical Study Information Team, 1-877-310-5135, clinicaltrials@kardigan.bio
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
Kardigan Clinical Study Information Team, 1-877-310-5135, clinicaltrials@kardigan.bio
- Recruiting
Henry Ford Hospital
Detroit, Michigan, 48202
Kardigan Clinical Study Information Team, 1-877-310-5135, clinicaltrials@kardigan.bio
- Recruiting
OnSite Clinical Solutions, LLC
Fort Mill, South Carolina, 29715
Kardigan Clinical Study Information Team, +1-877-310-5135, clinicaltrials@kardigan.bio
- Recruiting
Homestead Associates in Research
Homestead, Florida, 33033
Kardigan Clinical Study Information Team, 1-877-310-5135, clinicaltrials@kardigan.bio
- Recruiting
Laguna Clinical Research Associates
Laredo, Texas, 78041
Kardigan Clinical Study Information Team, 1-877-310-5135, clinicaltrials@kardigan.bio
- Recruiting
Tapia Internal Medicine Clinic
Paris, Texas, 75460
Kardigan Clinical Study Information Team, 1-877-310-5135, clinicaltrials@kardigan.bio
- Recruiting
Progressive Medical Research
Port Orange, Florida, 32127
Kardigan Clinical Study Information Team, +1-877-310-5135, clinicaltrials@kardigan.bio
- Active, not recruiting
Richmond University Medical Center (RUMC)
Staten Island, New York, 10310
- Recruiting
Baylor Scott and White Research Institute - Temple
Temple, Texas, 76502
Kardigan Clinical Study Information Team, 1-877-310-5135, clinicaltrials@kardigan.bio
About this study
Official title: 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.
Read the 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
- Being tested
- Tonlamarsen, Placebo
- Medical subject headings
- Hypertension, Hypertensive Crisis
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 (under the skin) every 4 weeks during the randomized part of the study
PlaceboDrug
Placebo will be administered subcutaneously (under the skin) every 4 weeks during the randomized part of the study
| Study group | Role | What they receive |
|---|---|---|
| Tonlamarsen | Experimental | 3 doses active drug will be administered by subcutaneous (under the skin) injection (one dose every 4 weeks) Receives: Drug: Tonlamarsen |
| Placebo | Placebo comparator | 3 doses of placebo will be administered by subcutaneous (under the skin) injection (one dose every 4 weeks) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Week 4
Secondary outcomes (8)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2026
- Study start23 Jun 2026
- Primary completionDec 2026 (estimated)
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Randomized, Double-Blind, Placebo-Controlled, Multicenter Two-Part study. Once eligibility is confirmed, eligible participants will then be randomized to tonlamarsen or placebo. The randomized treatment period will be followed by a 24-week safety follow-up period.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kardigan, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07511361
- Sponsor's protocol ID
- TLA-202
- Acronym
- KARDINAL-ASH
- Status last verified
- Oct 2026
- First submitted
- 28 Mar 2026
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07511361
- Acronym / sponsor ID
- KARDINAL-ASH / TLA-202
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Kardigan, Inc.Industry (pharma, biotech, devices)
- Study start
- 23 Jun 2026 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Feb 2027 (estimated)
- First posted
- 6 Apr 2026 (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-lowering effect of tonlamarsen in adult participants who were recently hospitalized and concurrently experienced an episode of acute severe hypertension.
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 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
- Randomized, Double-Blind, Placebo-Controlled, Multicenter Two-Part study. Once eligibility is confirmed, eligible participants will then be randomized to tonlamarsen or placebo. The randomized treatment period will be followed by a 24-week safety follow-up period.
| Arm | Type | Receives |
|---|---|---|
| Tonlamarsen | Experimental | Drug: Tonlamarsen3 doses active drug will be administered by subcutaneous (under the skin) injection (one dose every 4 weeks) |
| Placebo | Placebo comparator | Drug: Placebo3 doses of placebo will be administered by subcutaneous (under the skin) injection (one dose every 4 weeks) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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 (7 listed)
- 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
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 (under the skin) every 4 weeks during the randomized part of the study | Drug | Tonlamarsen |
| PlaceboPlacebo will be administered subcutaneously (under the skin) every 4 weeks during the randomized part of the study | Drug | Placebo |
Primary outcome
Part A: To assess variability in clinical and biomarker measures to inform Part B sample-size estimation and study-design assumptions
Time frame: Baseline through Week 12
* Change from baseline in plasma angiotensinogen (AGT) levels and systolic blood pressure * Variability in plasma AGT levels and systolic blood pressure
Part B: To assess the pharmacodynamic (PD) effect of tonlamarsen on plasma AGT levels
Time frame: Week 4
Percent change in plasma AGT levels from Baseline to Week 4
8 secondary outcomes
Part A: To assess the safety and tolerability of tonlamarsen compared with placebo
Time frame: Week 36
Part A: To assess the feasibility of using AGT levels and systolic blood pressure as efficacy endpoints
Time frame: Baseline through Week 12
Part B: To assess the safety and tolerability of tonlamarsen compared with placebo
Time frame: Week 36
Part B: To evaluate the effect of tonlamarsen on systolic blood pressure measured via daily home blood pressure monitoring
Time frame: Week 4
Part B: To evaluate the effect of tonlamarsen on office systolic blood pressure
Time frame: Week 4
Part B: To assess the PD effect of tonlamarsen on plasma AGT levels
Time frame: Week 12
Part B: To evaluate the effect of tonlamarsen on systolic blood pressure measured via daily home blood pressure monitoring
Time frame: Week 12
Part B: To evaluate the effect of tonlamarsen on office systolic blood pressure
Time frame: Week 12
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- Individual participant dataSharing planned: No
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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.
13 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 and Acute Severe Hypertension, run by Kardigan, Inc. at 13 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 4 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kardigan Clinical Study Information Team (+1-877-310-5135, clinicaltrials@kardigan.bio), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: To assess variability in clinical and biomarker measures to inform Part B sample-size estimation and study-design assumptions (time frame: Baseline through Week 12). 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?
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 15 Oct 2026.