Zilebesiran as an adjunct therapy in patients with high cardiovascular risk and hypertension not adequately controlled by standard antihypertensive medications (KARDIA-3)

Zusammenfassung der Studie

KARDIA-3 is a study to evaluate a new treatment called Zilebesiran, administered as a subcutaneous injection. It targets adults with high risk of heart disease and hypertension that has not been well controlled with 2 to 4 common antihypertensive medications. The primary aim of the study is to determine whether Zilebesiran can lower blood pressure better than a placebo after 3 months. The placebo contains no active ingredient. The study also examines how well Zilebesiran works over a period of up to 6 months and its effects on blood pressure. Zilebesiran works in a novel way to lower blood pressure by targeting a protein in the liver. In this study, we investigate how effective and safe Zilebesiran is. Participants are assigned to one of two groups, Cohort A and Cohort B, based on their kidney health status. The goal is to find a better method for controlling blood pressure and reducing the risk of heart disease.

(BASEC)

Untersuchte Intervention

Zilebesiran is administered as an adjunct therapy via subcutaneous injection in patients with established cardiovascular disease or high cardiovascular risk with uncontrolled hypertension despite treatment with 2 to 4 standard antihypertensive medications. Hypertension is a common problem affecting up to 45% of adults and poses a significant risk for heart disease. Despite numerous treatment options, controlling blood pressure remains a challenge, partly because patients do not take their medications. Zilebesiran, a novel treatment in development, utilizes a natural process called RNA, short for ribonucleic acid, a vital molecule in our cells. It acts as a messenger that receives instructions from our DNA and uses them to produce proteins. RNAi therapeutics target a specific RNA and degrade it before the instructions can be processed. In this way, RNAi therapeutics reduce the production of certain proteins. Zilebesiran targets a protein called angiotensinogen (AGT), produced by the liver. While AGT is a normal protein, excess AGT is believed to contribute to hypertension and various other diseases. This new approach aims to effectively lower blood pressure and reduce the risk of heart disease. In this study, each participant receives a unique code. After agreeing to participate in the study, they receive this code through a special system. If the participant meets all study requirements, they are randomly assigned either a single dose of the study drug Zilebesiran at varying doses or a single dose of a placebo without active ingredients. Zilebesiran Participants receive a single dose of Zilebesiran on the first day of the 6-month treatment period. Before participating in the study, they should have taken the same dose of 2 to 4 antihypertensive medications for at least 30 days, and they should maintain this dose throughout the study. The estimated total duration of the study for each patient is up to 14 months, which includes up to 45 days of screening, the 6-month treatment period, and a 6-month safety observation. Placebo Participants receive a single dose of placebo on the first day of the 6-month treatment period. They must have taken the same amount of 2 to 4 antihypertensive medications for at least 30 days before the study begins and should maintain this dose during the study. The estimated total duration of the study for each patient is up to 14 months, which includes up to 45 days of screening, the 6-month treatment period, and a 6-month safety observation. Zilebesiran is administered as a subcutaneous injection in doses of 150, 300, or 600 mg. Previous studies have shown that Zilebesiran effectively lowers blood pressure and AGT, a protein associated with blood pressure control, while demonstrating good safety. For this study, doses of 300 and 600 mg were chosen because they significantly lower blood pressure and are safe. For patients with advanced kidney issues, a lower dose of 150 mg is also being tested to ensure safety and efficacy. During the study, the doctors, the staff at the trial center (except for the pharmacist who prepares the medications), and the patients do not know who receives the actual study drug and who receives a placebo. This is to ensure the fairness of the study. Some staff members of the research facility and the company developing the drug will also know who receives what, but they will only share this information after analyzing the main results of the study. The administration of the drug is carried out by the study physician or under their supervision and according to strict guidelines to maintain the integrity of the study. Patients can decide at any time and without providing reasons to withdraw from part of the study or to leave the study entirely, without it affecting their future medical care. The study physician or the company conducting the study may also decide to end a patient's participation if they believe it is in the patient's best interest.

(BASEC)

Untersuchte Krankheit(en)

Hypertension

(BASEC)

Sponsor

Alnylam Pharmaceuticals, Inc., Cambridge PPD Switzerland GmbH c/o Dufour Treuhand AG, Basel

(BASEC)

Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)

Ethikkommission Nordwest- und Zentralschweiz EKNZ

(BASEC)

Datum der Bewilligung durch die Ethikkommission

15.05.2024

(BASEC)

Ergebnisse der Studie