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

Kardigan, Inc.

Status and phase: Enrolling; Phase 2

Conditions: Hypertension; Hypertensive Emergency; Hypertensive Urgency; Acute Severe Hypertension

Treatments: Drug: Placebo; Drug: Tonlamarsen

Study type: Interventional

Funder types: Industry

Identifiers

NCT07511361

TLA-202

Details and patient eligibility

About

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.

Full 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

Enrollment: 140 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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140 participants in 2 patient groups, including a placebo group

Tonlamarsen

Experimental group

Description:

3 doses active drug will be administered by subcutaneous (under the skin) injection (one dose every 4 weeks)

Treatment:

Drug: Tonlamarsen

Placebo

Placebo Comparator group

Description:

3 doses of placebo will be administered by subcutaneous (under the skin) injection (one dose every 4 weeks)

Treatment:

Drug: Placebo