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Trial record 1 of 3 for:    KARDIA Phase 2
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Zilebesiran as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication (KARDIA-2) (KARDIA-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05103332
Recruitment Status : Recruiting
First Posted : November 2, 2021
Last Update Posted : November 16, 2022
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
Hypertension Drug: Olmesartan Drug: Amlodipine Drug: Indapamide Drug: Placebo Drug: Zilebesiran Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 800 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : November 5, 2021
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : July 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Zilebesiran (Add-on to Olmesartan)
Following a run-in on olmesartan, eligible participants will receive zilebesiran on Day 1 of a 6-month double-blind treatment period as add-on to olmesartan. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period.
Drug: Olmesartan
Olmesartan administered orally

Drug: Zilebesiran
Zilebesiran administered by SC injection
Other Name: ALN-AGT01

Experimental: Placebo (Add-on to Olmesartan)
Following a run-in on olmesartan, eligible participants will receive placebo on Day 1 of a 6-month double-blind treatment period as add-on to olmesartan. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period.
Drug: Olmesartan
Olmesartan administered orally

Drug: Placebo
Placebo administered by subcutaneous (SC) injection

Drug: Zilebesiran
Zilebesiran administered by SC injection
Other Name: ALN-AGT01

Experimental: Zilebesiran (Add-on to Amlodipine)
Following a run-in on amlodipine, eligible participants will receive zilebesiran on Day 1 of a 6-month double-blind treatment period as add-on to amlodipine. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period.
Drug: Amlodipine
Amlodipine administered orally

Drug: Zilebesiran
Zilebesiran administered by SC injection
Other Name: ALN-AGT01

Placebo Comparator: Placebo (Add-on to Amlodipine)
Following a run-in on amlodipine, eligible participants will receive placebo on Day 1 of a 6-month double-blind treatment period as add-on to amlodipine. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period.
Drug: Amlodipine
Amlodipine administered orally

Drug: Placebo
Placebo administered by subcutaneous (SC) injection

Drug: Zilebesiran
Zilebesiran administered by SC injection
Other Name: ALN-AGT01

Placebo Comparator: Zilebesiran (Add-on to Indapamide)
Following a run-in on indapamide, eligible participants will receive zilebesiran on Day 1 of a 6-month double-blind treatment period as add-on to indapamide. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period.
Drug: Indapamide
Indapamide administered orally

Drug: Zilebesiran
Zilebesiran administered by SC injection
Other Name: ALN-AGT01

Placebo Comparator: Placebo (Add-on to Indapamide)
Following a run-in on indapamide, eligible participants will receive placebo on Day 1 of a 6-month double-blind treatment period as add-on to indapamide. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period.
Drug: Indapamide
Indapamide administered orally

Drug: Placebo
Placebo administered by subcutaneous (SC) injection

Drug: Zilebesiran
Zilebesiran administered by SC injection
Other Name: ALN-AGT01




Primary Outcome Measures :
  1. Change from Baseline at Month 3 in 24-Hour Mean Systolic Blood Pressure (SBP) Assessed by Ambulatory Blood Pressure Monitoring (ABPM) [ Time Frame: Baseline and Month 3 ]

Secondary Outcome Measures :
  1. Change from Baseline at Month 3 in Office SBP [ Time Frame: Baseline and Month 3 ]
  2. Time-adjusted Change from Baseline through Month 6 in Office SBP 24-hour Mean SBP, Assessed by ABPM [ Time Frame: Baseline through Month 6 ]
  3. 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 [ Time Frame: Baseline and Month 6 ]
  4. Change in 24-hour Mean SBP and DBP, Assessed by ABPM [ Time Frame: Baseline and Month 6 ]
  5. Change in Office SBP and DBP [ Time Frame: Baseline and Month 6 ]
  6. Change in Daytime and Nighttime Mean SBP and DBP, Assessed by ABPM [ Time Frame: Baseline and Month 6 ]
    Daytime is defined as 6 am to 9:59 pm and nighttime is defined as 10 pm to 5:59 am.

  7. Change from Baseline in Serum Angiotensinogen (AGT) [ Time Frame: Baseline through Month 6 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05103332


Contacts
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Contact: Alnylam Clinical Trial Information Line 1-877-ALNYLAM clinicaltrials@alnylam.com
Contact: Alnylam Clinical Trial Information Line 1-877-256-9526 clinicaltrials@alnylam.com

Locations
Show Show 105 study locations
Sponsors and Collaborators
Alnylam Pharmaceuticals
Investigators
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Study Director: Medical Director Alnylam Pharmaceuticals
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Responsible Party: Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05103332    
Other Study ID Numbers: ALN-AGT01-003
2021-003776-13 ( EudraCT Number )
First Posted: November 2, 2021    Key Record Dates
Last Update Posted: November 16, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alnylam Pharmaceuticals:
High blood pressure
Hypertension
Hypertensive
siRNA
Angiotensinogen
AGT
Additional relevant MeSH terms:
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Hypertension
Vascular Diseases
Cardiovascular Diseases
Amlodipine
Olmesartan
Indapamide
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Vasodilator Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Diuretics
Natriuretic Agents
Sodium Chloride Symporter Inhibitors