A Study to Evaluate ALN-AGT01 in Patients With Hypertension

January 13, 2023 updated by: Alnylam Pharmaceuticals

A Phase 1, Randomized, Double-Blind, Placebo-Controlled Single Dose and Active Comparator-Controlled Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered ALN-AGT01 in Patients With Hypertension

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) effects of subcutaneous (SC) ALN-AGT01 (zilebesiran) in participants with hypertension. The study will be conducted in 4 parts: Part A will be a single ascending dose (SAD) phase in hypertensive participants, Part B will be a single dose (SD) phase in hypertensive participants with controlled salt intake, Part D will be a MD phase in hypertensive participants who are obese, and Part E will be an open-label SD phase with co-administration of irbesartan in hypertensive patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

124

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Edinburgh, United Kingdom
        • Clinical Trial Site
      • London, United Kingdom
        • Clinical Trial Site
      • Manchester, United Kingdom
        • Clinical Trial Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Has mild to moderate hypertension with mean sitting systolic blood pressure (SBP) of >130 and ≤165 mmHg without hypertensive medication for Parts A, B and D, and >135 and ≤165 mmHg without hypertensive medication for Part E
  • Parts A and B: Has body mass index (BMI) ≥18 and ≤35 kg/m^2; Part D: Has BMI >35 and ≤50 kg/m^2; Part E: Has BMI ≥18 kg/m^2 and ≤50 kg/m^2
  • Has a normal 12-lead electrocardiogram (ECG)
  • Is a nonsmoker

Exclusion Criteria:

  • Has secondary hypertension
  • Has orthostatic hypotension
  • Has estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73m^2
  • Recently received an investigational agent
  • Has diabetes mellitus
  • Has history of any cardiovascular event
  • Has history of intolerance to SC injection(s)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A: SAD: ALN-AGT01
Participants will be administered a single dose of ALN-AGT01.
Drug: ALN-AGT01
ALN-AGT01 will be administered by subcutaneous (SC) injection.
Other Names:
  • Zilebesiran
Placebo Comparator: Part A: SAD: ALN-AGT01-Matching Placebo
Participants will be administered a single dose of ALN-AGT01-matching placebo.
Drug: ALN-AGT01-Matching Placebo
Normal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC.
Experimental: Part B: SD: ALN-AGT01
Participants with controlled salt intake will be administered a single dose of ALN-AGT01.
Drug: ALN-AGT01
ALN-AGT01 will be administered by subcutaneous (SC) injection.
Other Names:
  • Zilebesiran
Placebo Comparator: Part B: SD: ALN-AGT01-Matching Placebo
Participants with controlled salt intake will be administered a single dose of ALN-AGT01-matching placebo.
Drug: ALN-AGT01-Matching Placebo
Normal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC.
Experimental: Part D: MD: ALN-AGT01 + Irbesartan-Matching Placebo
Participants, who are obese, will be administered multiple doses of ALN-AGT01 and irbesartan-matching placebo.
Drug: ALN-AGT01
ALN-AGT01 will be administered by subcutaneous (SC) injection.
Other Names:
  • Zilebesiran
Drug: Irbesartan-Matching Placebo
Irbesartan-matching placebo will be administered orally.
Active Comparator: Part D: MD: ALN-AGT01-Matching Placebo + Irbesartan
Participants, who are obese, will be administered multiple doses of ALN-AGT01-matching placebo and irbesartan.
Drug: ALN-AGT01-Matching Placebo
Normal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC.
Drug: Irbesartan
Irbesartan will be administered orally.
Experimental: Part E: Open Label: ALN-AGT01 + Irbesartan
Participants will be administered a single dose of ALN-AGT01 and multiple doses of irbesartan.
Drug: ALN-AGT01
ALN-AGT01 will be administered by subcutaneous (SC) injection.
Other Names:
  • Zilebesiran
Drug: Irbesartan
Irbesartan will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of Participants with Adverse Events (AEs)
Time Frame: Parts A, B and E: each up to approximately 12 months; Part D: up to approximately 18 months
Parts A, B and E: each up to approximately 12 months; Part D: up to approximately 18 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Change from Baseline in Blood Angiotensinogen (AGT) Level
Time Frame: Parts A, B and E: each up to approximately 12 months; Part D: up to approximately 18 months
Parts A, B and E: each up to approximately 12 months; Part D: up to approximately 18 months
Maximum Observed Plasma Concentration (Cmax) of ALN-AGT01 and of Potential Metabolites
Time Frame: Parts A, B and E: Up to Day 15; Part D: Up to Day 99
Parts A, B and E: Up to Day 15; Part D: Up to Day 99
Area Under the Concentration-time Curve (AUC) of ALN-AGT01 and of Potential Metabolites
Time Frame: Parts A, B and E: Up to Day 15; Part D: Up to Day 99
Parts A, B and E: Up to Day 15; Part D: Up to Day 99

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alnylam Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2019

Primary Completion (Actual)

April 20, 2022

Study Completion (Actual)

January 4, 2023

Study Registration Dates

First Submitted

April 29, 2019

First Submitted That Met QC Criteria

April 29, 2019

First Posted (Actual)

May 1, 2019

Study Record Updates

Last Update Posted (Estimate)

January 16, 2023

Last Update Submitted That Met QC Criteria

January 13, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALN-AGT01-001
  • 2019-000129-39 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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