A Study to Evaluate Efficacy and Safety of ALN-AGT01 in Patients With Mild To-Moderate Hypertension (KARDIA-1) (KARDIA-1)
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| ClinicalTrials.gov Identifier: NCT04936035 |
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Recruitment Status :
Active, not recruiting
First Posted : June 23, 2021
Last Update Posted : April 19, 2024
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Sponsor:
Alnylam Pharmaceuticals
Information provided by (Responsible Party):
Alnylam Pharmaceuticals
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hypertension | Drug: Placebo Drug: ALN-AGT01 | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 394 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, Dose-Ranging Multicenter Study to Evaluate the Efficacy and Safety of ALN-AGT01 in Patients With Mild-to-Moderate Hypertension |
| Actual Study Start Date : | July 7, 2021 |
| Actual Primary Completion Date : | April 4, 2023 |
| Estimated Study Completion Date : | December 4, 2024 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Hypertension
MedlinePlus related topics:
High Blood Pressure
| Arm | Intervention/treatment |
|---|---|
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Experimental: ALN-AGT01 Dose Regimen 1
Multiple doses of ALN-AGT01 administered by subcutaneous (SC) injection during the 12-month DB treatment period.
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Drug: ALN-AGT01
ALN-AGT01 administered by SC injection
Other Name: Zilebesiran |
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Experimental: ALN-AGT01 Dose Regimen 2
Multiple doses of ALN-AGT01 administered by SC injection during the 12-month DB treatment period.
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Drug: ALN-AGT01
ALN-AGT01 administered by SC injection
Other Name: Zilebesiran |
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Experimental: ALN-AGT01 Dose Regimen 3
Multiple doses of ALN-AGT01 administered by SC injection during the 12-month DB treatment period.
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Drug: ALN-AGT01
ALN-AGT01 administered by SC injection
Other Name: Zilebesiran |
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Experimental: ALN-AGT01 Dose Regimen 4
Multiple doses of ALN-AGT01 administered by SC injection during the 12-month DB treatment period.
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Drug: ALN-AGT01
ALN-AGT01 administered by SC injection
Other Name: Zilebesiran |
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Placebo Comparator: Placebo + ALN-AGT01
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.
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Drug: Placebo
Placebo administered by SC injection Drug: ALN-AGT01 ALN-AGT01 administered by SC injection
Other Name: Zilebesiran |
Primary Outcome Measures :
- 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 :
- Change from Baseline at Month 3 in Office SBP [ Time Frame: Baseline and Month 3 ]
- Change from Baseline at Month 6 in 24-hour Mean SBP Assessed by ABPM [ Time Frame: Baseline through Month 6 ]
- Change from Baseline at Month 6 in Office SBP [ Time Frame: 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 [ Time Frame: Baseline through Month 6 ]
- Time-adjusted Change from Baseline in 24-hour Mean SBP and Diastolic Blood Pressure (DBP), Assessed by ABPM [ Time Frame: Baseline through Month 6 ]
- Change from Baseline in 24-hour mean DBP, Assessed by ABPM [ Time Frame: Baseline through Month 6 ]
- Change from Baseline in Office SBP and DBP [ Time Frame: Baseline through Month 6 ]
- Change in Serum Angiotensinogen (AGT) [ Time Frame: Baseline through Month 6 ]
- Change from Baseline in Daytime and Nighttime SBP and DBP by ABPM (Including Dipping Pattern) [ 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:
- 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)
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): NCT04936035
Locations
Show 107 study locations
Sponsors and Collaborators
Alnylam Pharmaceuticals
Investigators
| Study Director: | Medical Director | Alnylam Pharmaceuticals |
| Responsible Party: | Alnylam Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT04936035 |
| Other Study ID Numbers: |
ALN-AGT01-002 2021-001248-82 ( EudraCT Number ) |
| First Posted: | June 23, 2021 Key Record Dates |
| Last Update Posted: | April 19, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU. Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Requests for access to data can be submitted via the website www.vivli.org. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Alnylam Pharmaceuticals:
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High blood pressure Hypertension Hypertensive |
siRNA Angiotensinogen AGT |
Additional relevant MeSH terms:
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Hypertension Vascular Diseases Cardiovascular Diseases |