A Study to Evaluate ALN-AGT01 in Patients With Hypertension
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) effects of subcutaneous (SC) ALN-AGT01 (zilebesiran) in participants with hypertension. The study will be conducted in 4 parts: Part A will be a single ascending dose (SAD) phase in hypertensive participants, Part B will be a single dose (SD) phase in hypertensive participants with controlled salt intake, Part D will be a MD phase in hypertensive participants who are obese, and Part E will be an open-label SD phase with co-administration of irbesartan in hypertensive patients.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Part A: SAD: ALN-AGT01 Participants will be administered a single dose of ALN-AGT01. |
Drug: ALN-AGT01
ALN-AGT01 will be administered by subcutaneous (SC) injection.
Other Names:
|
Placebo Comparator: Part A: SAD: ALN-AGT01-Matching Placebo Participants will be administered a single dose of ALN-AGT01-matching placebo. |
Drug: ALN-AGT01-Matching Placebo
Normal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC.
|
Experimental: Part B: SD: ALN-AGT01 Participants with controlled salt intake will be administered a single dose of ALN-AGT01. |
Drug: ALN-AGT01
ALN-AGT01 will be administered by subcutaneous (SC) injection.
Other Names:
|
Placebo Comparator: Part B: SD: ALN-AGT01-Matching Placebo Participants with controlled salt intake will be administered a single dose of ALN-AGT01-matching placebo. |
Drug: ALN-AGT01-Matching Placebo
Normal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC.
|
Experimental: Part D: MD: ALN-AGT01 + Irbesartan-Matching Placebo Participants, who are obese, will be administered multiple doses of ALN-AGT01 and irbesartan-matching placebo. |
Drug: ALN-AGT01
ALN-AGT01 will be administered by subcutaneous (SC) injection.
Other Names:
Drug: Irbesartan-Matching Placebo
Irbesartan-matching placebo will be administered orally.
|
Active Comparator: Part D: MD: ALN-AGT01-Matching Placebo + Irbesartan Participants, who are obese, will be administered multiple doses of ALN-AGT01-matching placebo and irbesartan. |
Drug: ALN-AGT01-Matching Placebo
Normal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC.
Drug: Irbesartan
Irbesartan will be administered orally.
|
Experimental: Part E: Open Label: ALN-AGT01 + Irbesartan Participants will be administered a single dose of ALN-AGT01 and multiple doses of irbesartan. |
Drug: ALN-AGT01
ALN-AGT01 will be administered by subcutaneous (SC) injection.
Other Names:
Drug: Irbesartan
Irbesartan will be administered orally.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants with Adverse Events (AEs) [Parts A, B and E: each up to approximately 12 months; Part D: up to approximately 18 months]
Secondary Outcome Measures
- Change from Baseline in Blood Angiotensinogen (AGT) Level [Parts A, B and E: each up to approximately 12 months; Part D: up to approximately 18 months]
- Maximum Observed Plasma Concentration (Cmax) of ALN-AGT01 and of Potential Metabolites [Parts A, B and E: Up to Day 15; Part D: Up to Day 99]
- Area Under the Concentration-time Curve (AUC) of ALN-AGT01 and of Potential Metabolites [Parts A, B and E: Up to Day 15; Part D: Up to Day 99]
Eligibility Criteria
Criteria
Inclusion Criteria:
- Has mild to moderate hypertension with mean sitting systolic blood pressure (SBP) of
130 and ≤165 mmHg without hypertensive medication for Parts A, B and D, and >135 and ≤165 mmHg without hypertensive medication for Part E
-
Parts A and B: Has body mass index (BMI) ≥18 and ≤35 kg/m2; Part D: Has BMI >35 and ≤50 kg/m2; Part E: Has BMI ≥18 kg/m2 and ≤50 kg/m2
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Has a normal 12-lead electrocardiogram (ECG)
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Is a nonsmoker
Exclusion Criteria:
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Has secondary hypertension
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Has orthostatic hypotension
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Has estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73m^2
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Recently received an investigational agent
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Has diabetes mellitus
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Has history of any cardiovascular event
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Has history of intolerance to SC injection(s)
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Clinical Trial Site | Edinburgh | United Kingdom | ||
2 | Clinical Trial Site | London | United Kingdom | ||
3 | Clinical Trial Site | Manchester | United Kingdom |
Sponsors and Collaborators
- Alnylam Pharmaceuticals
Investigators
- Study Director: Medical Director, Alnylam Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ALN-AGT01-001
- 2019-000129-39