Clinical trial NCT04936035: A Study to Evaluate Efficacy and Safety of ALN-AGT01 in Patients With Mild To-Moderate Hypertension
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertension
Keywords: High blood pressure
Hypertension
Hypertensive
siRNA
Angiotensinogen
AGT
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-06-23
Enrollment: 394
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM
timeFrame: Baseline and Month 3
Secondary outcomes:
measure: Change From Baseline at Month 3 in Mean Sitting Office SBP
timeFrame: Baseline and Month 3
measure: Change From Baseline at Month 6 in 24-hour Mean SBP Assessed by ABPM
timeFrame: Baseline and Month 6
measure: Change From Baseline at Month 6 in Mean Sitting Office SBP
timeFrame: Baseline and Month 6
measure: Percentage of Participants With 24-hour Mean SBP Assessed by ABPM <130 mmHg and/or Reduction of ≥20 mmHg From Baseline Without Additional Antihypertensive Medications at Month 6
timeFrame: Month 6
measure: Change From Baseline at Month 3 in 24-hour Mean DBP Assessed by ABPM
timeFrame: Baseline and Month 3
measure: Change From Baseline at Month 6 in 24-hour Mean DBP Assessed by ABPM
timeFrame: Baseline and Month 6
measure: Change From Baseline at Month 3 in Mean Sitting Office DBP
timeFrame: Baseline and Month 3
measure: Time Adjusted Change From Baseline Through Month 3 in Mean Sitting Office SBP and DBP
timeFrame: Baseline and Month 3
measure: Change From Baseline at Month 6 in Mean Sitting Office DBP
timeFrame: Baseline and Month 6
measure: Time Adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP and DBP Assessed by ABPM
timeFrame: Baseline and Month 6
measure: Time Adjusted Change From Baseline Through Month 6 in Mean Sitting Office SBP and DBP
timeFrame: Baseline and Month 6
measure: Change From Baseline in Daytime/Nighttime Mean SBP and DBP Assessed by ABPM at Each Visit
timeFrame: Baseline, and Months 1, 3 and 6
measure: Percentage Change From Baseline in Serum Angiotensinogen (AGT) Through Month 6
timeFrame: Baseline, Week 2 and Months 1, 2, 3, 4, 5 and 6
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Clinical Trial Site
state: Alabama
city: Tempe
country: United States
facility: Clinical Trial Site
state: Arizona
city: Tempe
country: United States
facility: Clinical Trial Site
state: Arizona
city: Beverly Hills
country: United States
facility: Clinical Trial Site
state: California
city: La Mesa
country: United States
facility: Clinical Trial Site
state: California
city: Los Angeles
country: United States
facility: Clinical Trial Site
state: California
city: S. Gate
country: United States
facility: Clinical Trial Site
state: California
city: San Diego
country: United States
facility: Clinical Trial Site
state: California
city: Vista
country: United States
facility: Clinical Trial Site
state: California
city: Washington
country: United States
facility: Clinical Trial Site
state: District of Columbia
city: Clearwater
country: United States
facility: Clinical Trial Site
state: Florida
city: Coral Gables
country: United States
facility: Clinical Trial Site
state: Florida
city: Fleming Island
country: United States
facility: Clinical Trial Site
state: Florida
city: Hollywood
country: United States
facility: Clinical Trial Site
state: Florida
city: Hollywood
country: United States
facility: Clinical Trial Site
state: Florida
city: Inverness
country: United States
facility: Clinical Trial Site
state: Florida
city: Jacksonville
country: United States
facility: Clinical Trial Site
state: Florida
city: Jacksonville
country: United States
facility: Clinical Trial Site
state: Florida
city: Jacksonville
country: United States
facility: Clinical Trial Site
state: Florida
city: Miami
country: United States
facility: Clinical Trial Site
state: Florida
city: Miami
country: United States
facility: Clinical Trial Site
state: Florida
city: Naples
country: United States
facility: Clinical Trial Site
state: Florida
city: Orlando
country: United States
facility: Clinical Trial Site
state: Florida
city: Acworth
country: United States
facility: Clinical Trial Site
state: Georgia
city: Columbus
country: United States
facility: Clinical Trial Site
state: Georgia
city: Fayetteville
country: United States
facility: Clinical Trial Site
state: Georgia
city: Macon
country: United States
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state: Georgia
city: Champaign
country: United States
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state: Illinois
city: Valparaiso
country: United States
facility: Clinical Trial Site
state: Indiana
city: West Des Moines
country: United States
facility: Clinical Trial Site
state: Iowa
city: Lake Charles
country: United States
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state: Louisiana
city: New Orleans
country: United States
facility: Clinical Trial Site
state: Louisiana
city: Prairieville
country: United States
facility: Clinical Trial Site
state: Louisiana
city: Baltimore
country: United States
facility: Clinical Trial Site
state: Maryland
city: Jackson
country: United States
facility: Clinical Trial Site
state: Mississippi
city: Jefferson City
country: United States
facility: Clinical Trial Site
state: Missouri
city: Las Vegas
country: United States
facility: Clinical Trial Site
state: Nevada
city: Bronx
country: United States
facility: Clinical Trial Site
state: New York
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: Greensboro
country: United States
facility: Clinical Trial Site
state: North Carolina
city: Greensboro
country: United States
facility: Clinical Trial Site
state: North Carolina
city: Medford
country: United States
facility: Clinical Trial Site
state: Oregon
city: Greenville
country: United States
facility: Clinical Trial Site
state: South Carolina
city: Memphis
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Cedar Park
country: United States
facility: Clinical Trial Site
state: Texas
city: Houston
country: United States
facility: Clinical Trial Site
state: Texas
city: Houston
country: United States
facility: Clinical Trial Site
state: Texas
city: Magnolia
country: United States
facility: Clinical Trial Site
state: Texas
city: Pearland
country: United States
facility: Clinical Trial Site
state: Texas
city: San Antonio
country: United States
facility: Clinical Trial Site
state: Texas
city: Stephenville
country: United States
facility: Clinical Trial Site
state: Texas
city: Tomball
country: United States
facility: Clinical Trial Site
state: Texas
city: Waco
country: United States
facility: Clinical Trial Site
state: Texas
city: Burke
country: United States
facility: Clinical Trial Site
state: Virginia
city: Red Deer
country: Canada
facility: Clinical Trial Site
state: Alberta
city: New Minas
country: Canada
facility: Clinical Trial Site
state: Nova Scotia
city: Brampton
country: Canada
facility: Clinical Trial Site
state: Ontario
city: Toronto
country: Canada
facility: Clinical Trial Site
state: Ontario
city: Chicoutimi
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Mirabel
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Montréal
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Quebec City
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Trois-Rivières
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Victoriaville
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Bayamon
country: Puerto Rico
facility: Clinical Trial Site
city: Ponce
country: Puerto Rico
facility: Clinical Trial Site
city: San Juan
country: Puerto Rico
facility: Clinical Trial Site
city: Ivano-Frankivs'k
country: Ukraine
facility: Clinical Trial Site
city: Kharkiv
country: Ukraine
facility: Clinical Trial Site
city: Odesa
country: Ukraine
facility: Clinical Trial Site
city: Úzhgorod
country: Ukraine
facility: Clinical Trial Site
city: Glasgow
country: United Kingdom
facility: Clinical Trial Site
city: Hexham
country: United Kingdom
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
city: Manchester
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References: