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A Study to Evaluate ALN-AGT01 in Patients With Hypertension

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03934307
Recruitment Status : Completed
First Posted : May 1, 2019
Last Update Posted : January 17, 2023
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals

Study Description
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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.

Condition or disease Intervention/treatment Phase
Hypertension Drug: ALN-AGT01 Drug: ALN-AGT01-Matching Placebo Drug: Irbesartan Drug: Irbesartan-Matching Placebo Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 124 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 1, 2019
Actual Primary Completion Date : April 20, 2022
Actual Study Completion Date : January 4, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Irbesartan

Arms and Interventions
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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 Name: 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 Name: 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 Name: 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 Name: Zilebesiran

Drug: Irbesartan
Irbesartan will be administered orally.


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03934307


Locations
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United Kingdom
Clinical Trial Site
Edinburgh, United Kingdom
Clinical Trial Site
London, United Kingdom
Clinical Trial Site
Manchester, United Kingdom
Sponsors and Collaborators
Alnylam Pharmaceuticals
Investigators
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Study Director: Medical Director Alnylam Pharmaceuticals
More Information
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Responsible Party: Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03934307    
Other Study ID Numbers: ALN-AGT01-001
2019-000129-39 ( EudraCT Number )
First Posted: May 1, 2019    Key Record Dates
Last Update Posted: January 17, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hypertension
Vascular Diseases
Cardiovascular Diseases
Irbesartan
 Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action