A Study to Evaluate Zilebesiran in Japanese Patients With Mild to Moderate Hypertension

A Phase 1/2, Randomized, Double-blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacodynamics, and Pharmacokinetics of Zilebesiran in Japanese Patients With Mild to Moderate Hypertension

The purpose of this study is to evaluate the safety, tolerability, efficacy, pharmacodynamics (PD) and pharmacokinetics (PK) of zilebesiran in Japanese patients with mild to moderate hypertension.

Study Overview

• Status: Completed
• Conditions: Mild to Moderate Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: Zilebesiran

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
    • Clinical Trial Site
  • Osaka, Japan
    • Clinical Trial Site
  • Tokyo, Japan
    • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Must have been born in Japan, and their biological parents and grandparents must have been of Japanese origin
• Has mean systolic office blood pressure (SBP) of >130 and <=165 mmHg by automated office blood pressure measurement, after a minimum of 3 weeks of washout if taking hypertensive medication
• Has 24-hour mean SBP ≥130 mmHg by ambulatory blood pressure monitoring (ABPM), without antihypertensive medication

Exclusion Criteria:

• Has secondary hypertension, symptomatic orthostatic hypotension
• Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2× upper limit of normal (ULN)
• Has elevated serum potassium >5 mmol/L
• Has estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73m^2
• Has received an investigational agent within the last 30 days
• Has Type 1 diabetes mellitus, poorly controlled Type 2 diabetes mellitus or newly diagnosed Type 2 diabetes mellitus
• Has history of intolerance to SC injection(s)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will be administered a single dose of placebo.	Drug: Placebo; Placebo administered by SC injection
Experimental: Zilebesiran; Participants will be administered a single dose of zilebesiran.	Drug: Zilebesiran; Zilebesiran administered by subcutaneous (SC) injection; Other Names: ALN-AGT01

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	An AE is any untoward medical occurrence in a patient or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Serum Angiotensinogen (AGT) at Month 3 and Month 6		Baseline and Month 3 and Month 6
Change From Baseline at Month 3 and Month 6 in 24-hour Mean SBP and DBP Assessed by ABPM		Baseline and Month 3 and Month 6
Change From Baseline at Month 3 and Month 6 in SBP and DBP Assessed by OBP		Baseline and Month 3 and Month 6
Maximum Plasma Concentration (Cmax) of Zilebesiran and Its Metabolite	Cmax is the highest concentration of zilebesiran in the plasma and metabolite after a dose is given.	Predose and 30 minutes, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose.
Time to Maximum Plasma Concentration (Tmax) of Zilebesiran and Its Metabolite	Tmax is the time it takes for zilebesiran to reach the Cmax after administration.	Predose and 30 minutes, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose.
Elimination Half-life (t1/2) of Zilebesiran and Its Metabolite	t½ is the time it takes for the concentration of the drug in the plasma to be reduced by 50%.	Predose and 30 minutes, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose.
Area Under the Curve (AUClast) of Zilebesiran and Its Metabolite	AUClast is the AUC from the time of dosing to the last measurable concentration of the drug.	Predose and 30 minutes, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose.
Pooled Urine PK (fe) of Zilebesiran and Its Metabolite		Predose and 2 to 6, 6 to 12, and 12 to24 hours post-dose.

Collaborators and Investigators

• Sponsor: Alnylam Pharmaceuticals
• Investigators: Study Director: Medical Director, Alnylam Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2024
• Primary Completion (Actual): July 17, 2025
• Study Completion (Actual): July 17, 2025

Study Registration Dates

• First Submitted: May 15, 2024
• First Submitted That Met QC Criteria: May 20, 2024
• First Posted (Actual): May 21, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Hypertension; Hypertensive; siRNA; High blood pressure; AGT; Angiotensinogen
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: ALN-AGT01-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU.

Access to data may be declined where there is likelihood a patient could be identified or other feasibility issue, where there is a potential conflict of interest, a planned business activities or an actual or potential competitive risk. Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Timeframes for data access may vary and can take up to 6 months or more.

Requests for access to data can be submitted via the website www.vivli.org. Questions can also be directed to datasharing@alnylam.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes