Clinical trial NCT05103332: Zilebesiran as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication (KARDIA-2)
Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Zilebesiran Used as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication
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: 2021-11-02
Enrollment: 672
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 zilebesiran on systolic and diastolic blood pressure and to characterize the pharmacodynamic (PD) effects and safety of zilebesiran as add-on therapy.


Eligibility criteria: Inclusion Criteria:

* Office SBP at Screening as follows:

  1. ≥155 mmHg and ≤180 mmHg for patients with untreated hypertension
  2. ≥145 mmHg and ≤180 mmHg for patients on antihypertensive medications
* 24-hour mean SBP ≥130 mmHg and ≤160 mmHg by ABPM after at least 4 weeks of run-in

Exclusion Criteria:

* Secondary hypertension, orthostatic hypotension
* Elevated potassium \>5 milliequivalents per liter (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, or laboratory evidence of diabetes during screening without known diagnosis of diabetes
* 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 Systolic Blood Pressure (SBP) Assessed by Ambulatory Blood Pressure Monitoring (ABPM)
timeFrame: Baseline and Month 3
Secondary outcomes:
measure: Change from Baseline at Month 3 in Office SBP
timeFrame: Baseline and Month 3
measure: Time-adjusted Change from Baseline through Month 6 in Office SBP and 24-hour Mean SBP, Assessed by ABPM
timeFrame: Baseline through Month 6
measure: Proportion of Patients with 24-hour Mean SBP Assessed by ABPM <130 mmHg and/or Reduction from Baseline ≥ 20 mmHg without Escape Antihypertensive Medication at Month 6
timeFrame: Baseline and Month 6
measure: Change in 24-hour Mean SBP and Diastolic Blood Pressure (DBP), Assessed by ABPM
timeFrame: Baseline and Month 6
measure: Change in Office SBP and DBP
timeFrame: Baseline and Month 6
measure: Change in Daytime and Nighttime Mean SBP and DBP, Assessed by ABPM
timeFrame: Baseline and Month 6
measure: Change from Baseline in Serum Angiotensinogen (AGT)
timeFrame: Baseline through Month 6
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Clinical Trial Site
state: Arizona
city: Tempe
country: United States
facility: Clinical Trial Site
state: Arizona
city: Tempe
country: United States
facility: Clinical Trial Site
state: Arizona
city: Bell Gardens
country: United States
facility: Clinical Trial Site
state: California
city: Beverly Hills
country: United States
facility: Clinical Trials Site
state: California
city: Canoga Park
country: United States
facility: Clinical Trial Site
state: California
city: Carlsbad
country: United States
facility: Clinical Trial Site
state: California
city: Encinitas
country: United States
facility: Clinical Trial Site
state: California
city: Garden Grove
country: United States
facility: Clinical Trial Site
state: California
city: Hollywood
country: United States
facility: Clinical Trial Site
state: California
city: Huntington Beach
country: United States
facility: Clinical Trial Site
state: California
city: Irvine
country: United States
facility: Clinical Trial Site
state: California
city: Long Beach
country: United States
facility: Clinical Trial Site
state: California
city: Los Angeles
country: United States
facility: Clinical Trial Site
state: California
city: Mission Hills
country: United States
facility: Clinical Trial Site
state: California
city: Oceanside
country: United States
facility: Clinical Trial Site
state: California
city: Panorama City
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: Santa Clarita
country: United States
facility: Clinical Trial Site
state: California
city: Tustin
country: United States
facility: Clinical Trial Site
state: California
city: Upland
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: Coconut Creek
country: United States
facility: Clinical Trial Site
state: Florida
city: Coral Gables
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: Miami
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: 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: Orlando
country: United States
facility: Clinical Trial Site
state: Florida
city: Pembroke Pines
country: United States
facility: Clinical Trial Site
state: Florida
city: Tampa
country: United States
facility: Clinical Trial Site
state: Florida
city: Winter Haven
country: United States
facility: Clinical Trial Site
state: Florida
city: Winter Park
country: United States
facility: Clinical Trial Site
state: Florida
city: Acworth
country: United States
facility: Clinical Trial Site
state: Georgia
city: Canton
country: United States
facility: Clinical Trial Site
state: Georgia
city: Columbus
country: United States
facility: Clinical Trial Site
state: Georgia
city: Savannah
country: United States
facility: Clinical Trial Site
state: Georgia
city: Louisville
country: United States
facility: Clinical Trial Site
state: Kentucky
city: New Orleans
country: United States
facility: Clinical Trial Site
state: Louisiana
city: Southgate
country: United States
facility: Clinical Trial Site
state: Michigan
city: Jackson
country: United States
facility: Clinical Trial Site
state: Mississippi
city: Hazelwood
country: United States
facility: Clinical Trial Site
state: Missouri
city: Jefferson City
country: United States
facility: Clinical Trial Site
state: Missouri
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: Monroe
country: United States
facility: Clinical Trial Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Clinical Trial site
state: North Carolina
city: Norman
country: United States
facility: Clinical Trial Site
state: Oklahoma
city: Little River
country: United States
facility: Clinical Trial Site
state: South Carolina
city: Memphis
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Amarillo
country: United States
facility: Clinical Trial Site
state: Texas
city: Coppell
country: United States
facility: Clinical Trial Site
state: Texas
city: Dallas
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: Lake Jackson
country: United States
facility: Clinical Trial Site
state: Texas
city: Plano
country: United States
facility: Clinical Trial Site
state: Texas
city: Sherman
country: United States
facility: Clinical Trial Site
state: Texas
city: Splendora
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: Kenosha
country: United States
facility: Clinical Trial Site
state: Wisconsin
city: Brampton
country: Canada
facility: Clinical Trial Site
state: Ontario
city: Concord
country: Canada
facility: Clinical Trial Site
state: Ontario
city: London
country: Canada
facility: Clinical Trial Site
state: Ontario
city: Toronto
country: Canada
facility: Clinical Trial Site
state: Ontario
city: Winnipeg
country: Canada
facility: Clinical Trial Site
state: Ontario
city: Chicoutimi
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Lévis
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Pointe-Claire
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Québec
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Trois-Rivières
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Québec
country: Canada
facility: Clinical Trial Site
city: Tartu
country: Estonia
facility: Clinical Trial Site
city: Frankfurt
country: Germany
facility: Clinical Trial Site
city: Riga
country: Latvia
facility: Clinical Trial Site
city: Kaunas
country: Lithuania
facility: Clinical Trial Site
city: Vilnius
country: Lithuania
facility: Clinical Trial Site
city: Czestochowa
country: Poland
facility: Clinical Trial Site
city: Gdańsk
country: Poland
facility: Clinical Trial Site
city: Katowice
country: Poland
facility: Clinical Trial Site
city: Staszów
country: Poland
facility: Clinical Trial Site
city: Warszawa
country: Poland
facility: Clinical Trial Site
city: Wrocław
country: Poland
facility: Clinical Trial Site
city: Bellshill
country: United Kingdom
facility: Clinical Trial Site
state: Lanarkshire
city: Carshalton
country: United Kingdom
facility: Clinical Trial Site
city: Edinburgh
country: United Kingdom
facility: Clinical Trial Site
city: Fowey
country: United Kingdom
facility: Clinical Trial Site
city: Glasgow
country: United Kingdom
facility: Clinical Trial Site
city: Lancashire Preston
country: United Kingdom
facility: Clinical Trial Site
city: Liskeard
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
city: Newquay
country: United Kingdom
facility: Clinical Trial Site
city: Plymouth
country: United Kingdom
facility: Clinical Trial Site
city: Sheffield
country: United Kingdom
facility: Clinical Trial Site
city: Torpoint
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References: