A Study to Evaluate ALN-AGT01 RVR in Adult Patients With Mild to Moderate Hypertension Pretreated With Zilebesiran

A Phase 2, Randomized, Double-blind, Placebo-controlled, Single Dose Study of the Efficacy, Pharmacodynamics, and Safety of ALN-AGT01 RVR in Adult Patients With Mild to Moderate Hypertension Pretreated With Zilebesiran

The purpose of this study is to evaluate the efficacy, pharmacodynamics (PD), and safety of ALN-AGT01 RVR in participants with mild to moderate hypertension pretreated with zilebesiran.

Study Overview

• Status: Recruiting
• Conditions: Hypertension
• Intervention / Treatment: Drug: ALN-AGT01 RVR; Drug: Placebo; Drug: Zilebesiran

Detailed Description

This study will be conducted in 2 parts:

• Part A: Single dose (SD), dose-ranging part in adults with mild to moderate hypertension.
• Part B: SD in adults with mild to moderate hypertension.

• Study Type: Interventional
• Enrollment (Estimated): 93
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alnylam Clinical Trial Information Line; Phone Number: 1-877-ALNYLAM; Email: clinicaltrials@alnylam.com
• Study Contact Backup: Name: Alnylam Clinical Trial Information Line; Phone Number: 1-877-256-9526; Email: clinicaltrials@alnylam.com

Study Locations

• United States
  • California
    • Lake Forest, California, United States, 92630
      • Recruiting
      • Clinical Trial Site
  • Florida
    • Tampa, Florida, United States, 33602
      • Recruiting
      • Clinical Trial Site
  • Georgia
    • Savannah, Georgia, United States, 31401
      • Recruiting
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

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

Description

Part A: Inclusion Criteria

• Is an adult participant with a mean seated office systolic blood pressure (SBP) of at least 130 mmHg and no more than than 170 mmHg
• Either not taking antihypertensive medication or on stable therapy with up to 2 antihypertensive medications

Part B: Inclusion Criteria

• Is an adult participant with a mean seated office SBP of at least 140 mmHg and no more than 170 mmHg
• Has discontinued all prior antihypertensive medication other than a calcium channel blocker (CCB) and/or thiazide/thiazide-like diuretic (if taking) for at least 3 weeks

Both Parts: Exclusion Criteria

• Has known secondary hypertension or serum potassium more than 5 mmol/L
• Has an estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73m^2

Note: other protocol defined inclusion / exclusion criteria apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALN-AGT1 RVR; Participants will be administered a single dose of zilebesiran followed by a single dose of ALN-AGT01 RVR.	Drug: ALN-AGT01 RVR; ALN-AGT01 RVR will be administered subcutaneously (SC); Drug: Zilebesiran; Zilebesiran will be administered SC
Placebo Comparator: Placebo; Participants will be administered a single dose of zilebesiran followed by a single dose of placebo.	Drug: Placebo; Placebo will be administered SC; Drug: Zilebesiran; Zilebesiran will be administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part A: Percentage recovery from baseline in serum AGT	Up to Day 4
Part B: Percentage recovery from baseline in mean seated office SBP	At Day 4 and Day 7

Secondary Outcome Measures

Outcome Measure	Time Frame
Both Parts: Frequency of Adverse Events (AEs)	Up to 10 months
Part A: Percentage recovery from baseline in serum AGT	Up to Day 7
Part B: Percentage recovery from baseline in serum AGT	At Day 4 and Day 7
Part B: Change from baseline in mean seated office SBP	At Day 4 and Day 7

Collaborators and Investigators

• Sponsor: Alnylam Pharmaceuticals
• Collaborators: Hoffmann-La Roche
• Investigators: Study Director: Medical Director, Alnylam Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: April 22, 2026
• First Submitted That Met QC Criteria: April 22, 2026
• First Posted (Actual): April 28, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: RNAi therapeutic; oligonucleotide; Reversir; Zilebesiran; ALN-AGT01
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension
• Other Study ID Numbers: ALN-AGT01 RVR-002

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