A Study to Evaluate ALN-AGT01 in Patients With Hypertension

Alnylam Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Hypertension

Treatments: Drug: Irbesartan; Drug: ALN-AGT01-Matching Placebo; Drug: ALN-AGT01; Drug: Irbesartan-Matching Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03934307

ALN-AGT01-001

2019-000129-39 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 124 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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124 participants in 7 patient groups, including a placebo group

Part A: SAD: ALN-AGT01

Experimental group

Description:

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

Treatment:

Drug: ALN-AGT01

Part A: SAD: ALN-AGT01-Matching Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: ALN-AGT01-Matching Placebo

Part B: SD: ALN-AGT01

Experimental group

Description:

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

Treatment:

Drug: ALN-AGT01

Part B: SD: ALN-AGT01-Matching Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: ALN-AGT01-Matching Placebo

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

Experimental group

Description:

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

Treatment:

Drug: Irbesartan-Matching Placebo

Drug: ALN-AGT01

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

Active Comparator group

Description:

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

Treatment:

Drug: Irbesartan

Drug: ALN-AGT01-Matching Placebo

Part E: Open Label: ALN-AGT01 + Irbesartan

Experimental group

Description:

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

Treatment:

Drug: Irbesartan

Drug: ALN-AGT01