Clinical Trials/NCT03934307

NCT03934307CompletedPhase 1

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

Alnylam Pharmaceuticals1 site in 1 country124 target enrollmentStarted: May 1, 2019Last updated: January 17, 2023

Conditions

Interventions

Trial Snapshot

Phase: Phase 1
Status: Completed
Sponsor
Enrollment: 124
Locations: 1
Primary Endpoint: Number of Participants with Adverse Events (AEs)

Study Overview Study Design Eligibility Criteria Arms & Interventions Outcomes Investigators Sites Records & Identifiers Similar Trials

Study Overview

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.

Study Design

Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel
Primary Purpose: Treatment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Eligibility Criteria

Ages: 18 Years to 65 Years (Adult, Older Adult)
Sex: All
Accepts Healthy Volunteers: No

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)

Arms & Interventions

Part A: SAD: ALN-AGT01

Experimental

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

Intervention: ALN-AGT01 (Drug)

Part A: SAD: ALN-AGT01-Matching Placebo

Placebo Comparator

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

Intervention: ALN-AGT01-Matching Placebo (Drug)

Part B: SD: ALN-AGT01

Experimental

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

Intervention: ALN-AGT01 (Drug)

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.

Intervention: ALN-AGT01-Matching Placebo (Drug)

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.

Intervention: ALN-AGT01 (Drug)

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.

Intervention: Irbesartan-Matching Placebo (Drug)

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.

Intervention: ALN-AGT01-Matching Placebo (Drug)

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.

Intervention: Irbesartan (Drug)

Part E: Open Label: ALN-AGT01 + Irbesartan

Experimental

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

Intervention: ALN-AGT01 (Drug)

Part E: Open Label: ALN-AGT01 + Irbesartan

Experimental

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

Intervention: Irbesartan (Drug)

Outcomes

Primary Outcomes

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 Outcomes

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)
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)

Investigators

Sponsor

Alnylam Pharmaceuticals

Sponsor Class

Industry

Responsible Party

Sponsor

Study Sites (1)

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