A Study to Evaluate Efficacy and Safety of ALN-AGT01 in Patients With Mild To-Moderate Hypertension (KARDIA-1)

Alnylam Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Hypertension

Treatments: Drug: ALN-AGT01; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04936035

2021-001248-82 (EudraCT Number)

ALN-AGT01-002

Details and patient eligibility

About

The purpose of this study is to evaluate the effect of ALN-AGT01 on systolic and diastolic blood pressure and to characterize the pharmacodynamic (PD) effects and safety of ALN-AGT01.

Full description

Participants will receive ALN-AGT01 or placebo for the first 6 months of the 12-month double-blind (DB) treatment period. Participants randomized to placebo will be re-randomized at Month 6 to 1 of the 4 initial ALN-AGT01 regimens until the end of the 12-month DB treatment period. Participants randomized to ALN-AGT01 regimens will remain on their originally assigned regimens through remainder of the study.

Enrollment: 394 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Daytime mean SBP ≥135 mmHg and ≤160 mmHg by ABPM, without antihypertensive medication

Exclusion criteria

• Secondary hypertension, orthostatic hypotension
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2× upper limit of normal (ULN)
• Elevated potassium >5 mEq/L
• Estimated glomerular filtration rate (eGFR) of ≤30 mL/min/1.73m^2
• Received an investigational agent within the last 30 days
• Type 1 diabetes mellitus, poorly controlled Type 2 diabetes mellitus, newly diagnosed Type 2 diabetes mellitus
• History of any cardiovascular event within 6 months prior to randomization
• 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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394 participants in 5 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants received zilebesiran matching placebo, subcutaneous (SC) injection, once every 3 months (Q3M), with re-randomization at Month 6 to 1 of the initial 4 zilebesiran regimens. Participants will continue their respective zilebesiran regimen up to Month 12 in the DB period and up to 24 additional months in the DB Extension period. Upon implementation of Amendment 6, the DB Extension period was closed.

Treatment:

Drug: Placebo

Drug: ALN-AGT01

Zilebesiran 150 Milligrams (mg) Once Every 6 Months (Q6M)

Experimental group

Description:

Participants receive zilebesiran, 150 mg, SC injection, Q6M, during the 12-month DB period. Participants will continue receiving the same zilebesiran regimen for up to 24 additional months in the DB Extension period. Participants in this arm will receive a placebo during those dosing visits when they do not receive zilebesiran to maintain the blind. Upon implementation of Amendment 6, the DB Extension period was closed.

Treatment:

Drug: Placebo

Drug: ALN-AGT01

Zilebesiran 300 mg Q6M

Experimental group

Description:

Participants receive zilebesiran, 300 mg, SC injection, Q6M, during the 12-month DB period. Participants will continue receiving the same zilebesiran regimen for up to 24 additional months in the DB Extension period. Participants in this arm will receive a placebo during those dosing visits when they do not receive zilebesiran to maintain the blind. Upon implementation of Amendment 6, the DB Extension period was closed.

Treatment:

Drug: Placebo

Drug: ALN-AGT01

Zilebesiran 300 mg Q3M

Experimental group

Description:

Participants receive zilebesiran, 300 mg, SC injection, Q3M, during the 12-month DB period. Participants continue receiving the same zilebesiran regimen for up to 24 additional months in the DB Extension period. Upon implementation of Amendment 6, the DB Extension period was closed.

Treatment:

Drug: ALN-AGT01

Zilebesiran 600 mg Q6M

Experimental group

Description:

Participants receive zilebesiran, 600 mg, SC injection, Q6M, during the 12-month DB period. Participants will continue receiving the same zilebesiran regimen for up to 24 additional months in the DB Extension period. Participants in this arm will receive a placebo during those dosing visits when they do not receive zilebesiran to maintain the blind. Upon implementation of Amendment 6, the DB Extension period was closed.

Treatment:

Drug: Placebo

Drug: ALN-AGT01