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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Randomized, Double-blind, Placebo-Controlled, Dose-Ranging Multicenter Study to Evaluate the Efficacy and Safety of ALN-AGT01 in Patients With Mild-to-Moderate Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Placebo
* Drug: ALN-AGT01


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALN-AGT01 Dose Regimen 1<br>Multiple doses of ALN-AGT01 administered by subcutaneous (SC) injection during the 12-month DB treatment period. | Drug: ALN-AGT01<br>* ALN-AGT01 administered by SC injection<br>|
| Experimental: ALN-AGT01 Dose Regimen 2<br>Multiple doses of ALN-AGT01 administered by SC injection during the 12-month DB treatment period. | Drug: ALN-AGT01<br>* ALN-AGT01 administered by SC injection<br>|
| Experimental: ALN-AGT01 Dose Regimen 3<br>Multiple doses of ALN-AGT01 administered by SC injection during the 12-month DB treatment period. | Drug: ALN-AGT01<br>* ALN-AGT01 administered by SC injection<br>|
| Experimental: ALN-AGT01 Dose Regimen 4<br>Multiple doses of ALN-AGT01 administered by SC injection during the 12-month DB treatment period. | Drug: ALN-AGT01<br>* ALN-AGT01 administered by SC injection<br>|
| Placebo Comparator: Placebo + ALN-AGT01<br>Multiple doses of placebo administered by SC injection during the first 6 months of 12-month DB treatment period, followed by multiple doses of ALN-AGT01 administered by SC injection during the last 6 months of the 12-month DB treatment period. | Drug: Placebo<br>* Placebo administered by SC injection<br>Drug: ALN-AGT01<br>* ALN-AGT01 administered by SC injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline at Month 3 in 24-hour Mean Systolic Blood Pressure (SBP) Assessed by Ambulatory Blood Pressure Monitoring (ABPM) |  | Baseline and Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline at Month 3 in Office SBP |  | Baseline and Month 3 | 
| Change from Baseline at Month 6 in 24-hour Mean SBP Assessed by ABPM |  | Baseline through Month 6 | 
| Change from Baseline at Month 6 in Office SBP |  | Baseline through Month 6 | 
| Proportion of Patients with 24-hour Mean SBP Assessed by ABPM <130 mmHg and/or Reduction ≥20 mmHg without Additional Antihypertensive Medications at Month 6 |  | Baseline through Month 6 | 
| Time-adjusted Change from Baseline in 24-hour Mean SBP and Diastolic Blood Pressure (DBP), Assessed by ABPM |  | Baseline through Month 6 | 
| Change from Baseline in 24-hour mean DBP, Assessed by ABPM |  | Baseline through Month 6 | 
| Change from Baseline in Office SBP and DBP |  | Baseline through Month 6 | 
| Change in Serum Angiotensinogen (AGT) |  | Baseline through Month 6 | 
| Change from Baseline in Daytime and Nighttime SBP and DBP by ABPM (Including Dipping Pattern) |  | Baseline through Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High blood pressure, Hypertension, Hypertensive, siRNA, Angiotensinogen, AGT