NCT03934307

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
124

participants targeted

Target at P75+ for phase_1 hypertension

Timeline
Completed

Started May 2019

Longer than P75 for phase_1 hypertension

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 29, 2019

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 1, 2019

Completed
Same day until next milestone

Study Start

First participant enrolled

May 1, 2019

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 20, 2022

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 4, 2023

Completed
Last Updated

January 17, 2023

Status Verified

January 1, 2023

Enrollment Period

3 years

First QC Date

April 29, 2019

Last Update Submit

January 13, 2023

Conditions

Hypertension

Outcome Measures

Primary Outcomes (1)

  • Number of Participants with Adverse Events (AEs)

    Parts A, B and E: each up to approximately 12 months; Part D: up to approximately 18 months

Secondary Outcomes (3)

  • Change from Baseline in Blood Angiotensinogen (AGT) Level

    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

    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

    Parts A, B and E: Up to Day 15; Part D: Up to Day 99

Study Arms (7)

Part A: SAD: ALN-AGT01

EXPERIMENTAL

Participants will be administered a single dose of ALN-AGT01.

Drug: ALN-AGT01

Part A: SAD: ALN-AGT01-Matching Placebo

PLACEBO COMPARATOR

Participants will be administered a single dose of ALN-AGT01-matching placebo.

Drug: ALN-AGT01-Matching Placebo

Part B: SD: ALN-AGT01

EXPERIMENTAL

Participants with controlled salt intake will be administered a single dose of ALN-AGT01.

Drug: ALN-AGT01

Part B: SD: ALN-AGT01-Matching Placebo

PLACEBO COMPARATOR

Participants with controlled salt intake will be administered a single dose of ALN-AGT01-matching placebo.

Drug: ALN-AGT01-Matching Placebo

Part D: MD: ALN-AGT01 + Irbesartan-Matching Placebo

EXPERIMENTAL

Participants, who are obese, will be administered multiple doses of ALN-AGT01 and irbesartan-matching placebo.

Drug: ALN-AGT01Drug: Irbesartan-Matching Placebo

Part D: MD: ALN-AGT01-Matching Placebo + Irbesartan

ACTIVE COMPARATOR

Participants, who are obese, will be administered multiple doses of ALN-AGT01-matching placebo and irbesartan.

Drug: ALN-AGT01-Matching PlaceboDrug: Irbesartan

Part E: Open Label: ALN-AGT01 + Irbesartan

EXPERIMENTAL

Participants will be administered a single dose of ALN-AGT01 and multiple doses of irbesartan.

Drug: ALN-AGT01Drug: Irbesartan

Interventions

ALN-AGT01DRUG

ALN-AGT01 will be administered by subcutaneous (SC) injection.

Also known as: Zilebesiran
Part A: SAD: ALN-AGT01Part B: SD: ALN-AGT01Part D: MD: ALN-AGT01 + Irbesartan-Matching PlaceboPart E: Open Label: ALN-AGT01 + Irbesartan
ALN-AGT01-Matching PlaceboDRUG

Normal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC.

Part A: SAD: ALN-AGT01-Matching PlaceboPart B: SD: ALN-AGT01-Matching PlaceboPart D: MD: ALN-AGT01-Matching Placebo + Irbesartan
IrbesartanDRUG

Irbesartan will be administered orally.

Part D: MD: ALN-AGT01-Matching Placebo + IrbesartanPart E: Open Label: ALN-AGT01 + Irbesartan
Irbesartan-Matching PlaceboDRUG

Irbesartan-matching placebo will be administered orally.

Part D: MD: ALN-AGT01 + Irbesartan-Matching Placebo

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Clinical Trial Site

Edinburgh, United Kingdom

Location

Clinical Trial Site

London, United Kingdom

Location

Clinical Trial Site

Manchester, United Kingdom

Location

Related Publications (2)

  • Badri P, Kolachana K, Duong A, Lasko M, Nandi T, Mehrotra N, Robbie GJ. Platform Assessment of Concentration-QTc Relationship Across GalNAc-siRNA Molecules. Clin Pharmacokinet. 2025 Dec 12. doi: 10.1007/s40262-025-01606-0. Online ahead of print.

    PMID: 41388232DERIVED

  • Desai AS, Webb DJ, Taubel J, Casey S, Cheng Y, Robbie GJ, Foster D, Huang SA, Rhyee S, Sweetser MT, Bakris GL. Zilebesiran, an RNA Interference Therapeutic Agent for Hypertension. N Engl J Med. 2023 Jul 20;389(3):228-238. doi: 10.1056/NEJMoa2208391.

    PMID: 37467498DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

Irbesartan

Condition Hierarchy (Ancestors)

Vascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

Biphenyl CompoundsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsSpiro CompoundsTetrazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPolycyclic Compounds

Study Officials

  • Medical Director

    Alnylam Pharmaceuticals

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 29, 2019

First Posted

May 1, 2019

Study Start

May 1, 2019

Primary Completion

April 20, 2022

Study Completion

January 4, 2023

Last Updated

January 17, 2023

Record last verified: 2023-01

Data Sharing

IPD Sharing
Will not share

Locations

GB(3)