A Study to Evaluate ALN-AGT01 in Patients With Hypertension

Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03934307
• Other study ID #: ALN-AGT01-001
• Secondary ID: 2019-000129-39
• Status: Completed
• Phase: Phase 1
• Start date: May 1, 2019
• Est. completion date: January 4, 2023

Study information

• Verified date: January 2023
• Source: Alnylam Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: January 4, 2023
• Est. primary completion date: April 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• ALN-AGT01
ALN-AGT01 will be administered by subcutaneous (SC) injection.
• ALN-AGT01-Matching Placebo
Normal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC.
• Irbesartan
Irbesartan will be administered orally.
• Irbesartan-Matching Placebo
Irbesartan-matching placebo will be administered orally.

Locations

Country	Name	City	State
United Kingdom	Clinical Trial Site	Edinburgh
United Kingdom	Clinical Trial Site	London
United Kingdom	Clinical Trial Site	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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