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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-000129-39 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: SAD: ALN-AGT01 | Experimental | Participants will be administered a single dose of ALN-AGT01. |
|
| Part A: SAD: ALN-AGT01-Matching Placebo | Placebo Comparator | Participants will be administered a single dose of ALN-AGT01-matching placebo. |
|
| Part B: SD: ALN-AGT01 | Experimental | Participants with controlled salt intake will be administered a single dose of ALN-AGT01. |
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| Part B: SD: ALN-AGT01-Matching Placebo | Placebo Comparator | Participants with controlled salt intake will be administered a single dose of ALN-AGT01-matching placebo. |
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| Part D: MD: ALN-AGT01 + Irbesartan-Matching Placebo | Experimental | Participants, who are obese, will be administered multiple doses of ALN-AGT01 and irbesartan-matching placebo. |
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| Part D: MD: ALN-AGT01-Matching Placebo + Irbesartan |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ALN-AGT01 | Drug | ALN-AGT01 will be administered by subcutaneous (SC) injection. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Alnylam Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Trial Site | Edinburgh | United Kingdom | ||||
| Clinical Trial Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41388232 | Derived | Badri P, Kolachana K, Duong A, Lasko M, Nandi T, Mehrotra N, Robbie GJ. Platform Assessment of Concentration-QTc Relationship Across GalNAc-siRNA Molecules. Clin Pharmacokinet. 2026 Feb;65(2):293-311. doi: 10.1007/s40262-025-01606-0. Epub 2025 Dec 12. | |
| 40556120 | Derived | Lidani KCF, Trainor PJ, Buscaglia R, Foster K, Jaramillo S, Michael K, Landry AP, Michos ED, Ouyang P, Morgan ES, Tsimikas S, DeFilippis AP. Circulating Levels of Angiotensinogen, Sex Hormones, and Hormone Therapy-The Multi-Ethnic Study of Atherosclerosis (MESA). J Clin Hypertens (Greenwich). 2025 Jun;27(6):e70083. doi: 10.1111/jch.70083. |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000077405 | Irbesartan |
| ID | Term |
|---|---|
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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| Active Comparator |
Participants, who are obese, will be administered multiple doses of ALN-AGT01-matching placebo and irbesartan. |
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| Part E: Open Label: ALN-AGT01 + Irbesartan | Experimental | Participants will be administered a single dose of ALN-AGT01 and multiple doses of irbesartan. |
|
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| ALN-AGT01-Matching Placebo | Drug | Normal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC. |
|
| Irbesartan | Drug | Irbesartan will be administered orally. |
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| Irbesartan-Matching Placebo | Drug | Irbesartan-matching placebo will be administered orally. |
|
| 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 |
| London |
| United Kingdom |
| Clinical Trial Site | Manchester | United Kingdom |
| 37467498 | Derived | Desai AS, Webb DJ, Taubel J, Casey S, Cheng Y, Robbie GJ, Foster D, Huang SA, Rhyee S, Sweetser MT, Bakris GL. Zilebesiran, an RNA Interference Therapeutic Agent for Hypertension. N Engl J Med. 2023 Jul 20;389(3):228-238. doi: 10.1056/NEJMoa2208391. |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D013141 | Spiro Compounds |
| D013777 | Tetrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011083 | Polycyclic Compounds |