HypertensionPhase 1NCT03934307
A Study to Evaluate ALN-AGT01 in Patients With Hypertension
A Phase 1 study testing ALN-AGT01 and Irbesartan in people with Hypertension, run by Alnylam Pharmaceuticals at 3 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hypertension
- What is being tested?
- ALN-AGT01 and Irbesartan
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 124 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- 1 May 2019to 4 Jan 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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/m^2; Part D: Has BMI >35 and ≤50 kg/m^2; Part E: Has BMI ≥18 kg/m^2 and ≤50 kg/m^2
- Has a normal 12-lead electrocardiogram (ECG)
- Is a nonsmoker
Who cannot join
- Has secondary hypertension
- Has orthostatic hypotension
- Has estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73m^2
- Recently received an investigational agent
- Has diabetes mellitus
- Has history of any cardiovascular event
- Has history of intolerance to SC injection(s)
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
Clinical Trial Site
Edinburgh
Clinical Trial Site
London
Clinical Trial Site
Manchester
About this study
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Single Dose and Active Comparator-Controlled Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered ALN-AGT01 in Patients With Hypertension
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.
- Conditions
- Hypertension
- Being tested
- ALN-AGT01, ALN-AGT01-Matching Placebo, Irbesartan, Irbesartan-Matching Placebo
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALN-AGT01Drug
Also called Zilebesiran
ALN-AGT01 will be administered by subcutaneous (SC) injection.
ALN-AGT01-Matching PlaceboDrug
Normal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC.
IrbesartanDrug
Irbesartan will be administered orally.
Irbesartan-Matching PlaceboDrug
Irbesartan-matching placebo will be administered orally.
| Study group | Role | What they receive |
|---|---|---|
| Part A: SAD: ALN-AGT01 | Experimental | Participants will be administered a single dose of ALN-AGT01. Receives: Drug: ALN-AGT01 |
| Part A: SAD: ALN-AGT01-Matching Placebo | Placebo comparator | Participants will be administered a single dose of ALN-AGT01-matching placebo. Receives: Drug: ALN-AGT01-Matching Placebo |
| Part B: SD: ALN-AGT01 | Experimental | Participants with controlled salt intake will be administered a single dose of ALN-AGT01. Receives: Drug: ALN-AGT01 |
| 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. Receives: Drug: ALN-AGT01-Matching Placebo |
| 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. Receives: Drug: ALN-AGT01; Drug: Irbesartan-Matching Placebo |
| Part D: MD: ALN-AGT01-Matching Placebo + Irbesartan | Active comparator | Participants, who are obese, will be administered multiple doses of ALN-AGT01-matching placebo and irbesartan. Receives: Drug: ALN-AGT01-Matching Placebo; Drug: Irbesartan |
| Part E: Open Label: ALN-AGT01 + Irbesartan | Experimental | Participants will be administered a single dose of ALN-AGT01 and multiple doses of irbesartan. Receives: Drug: ALN-AGT01; Drug: Irbesartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Adverse Events (AEs)
Measured: Parts A, B and E: each up to approximately 12 months; Part D: up to approximately 18 months
Secondary outcomes (3)
Change from Baseline in Blood Angiotensinogen (AGT) Level
Measured: 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
Measured: 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
Measured: Parts A, B and E: Up to Day 15; Part D: Up to Day 99
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2019
- Study start1 May 2019
- Primary completion20 Apr 2022
- Study completion4 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by Alnylam PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 124 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03934307
- Sponsor's protocol ID
- ALN-AGT01-001
- Other IDs
- 2019-000129-39, 2019
- Status last verified
- Jan 2023
- First submitted
- 29 Apr 2019
- Last updated
- 17 Jan 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 41388232Lidani 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.
PubMed 40556120Desai 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.
PubMed 37467498
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Randomized, Double-Blind, Placebo-Controlled Single Dose and Active Comparator-Controlled Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered ALN-AGT01 in Patients With Hypertension
- ClinicalTrials.gov ID
- NCT03934307
- Acronym / sponsor ID
- ALN-AGT01-001
- Conditions
- Hypertension
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 124 participants (actual)
- Lead sponsor
- Alnylam PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 1 May 2019 (actual)
- Primary completion
- 20 Apr 2022 (actual)
- Study completion
- 4 Jan 2023 (actual)
- First posted
- 1 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Part A: SAD: ALN-AGT01 | Experimental | Drug: ALN-AGT01Participants will be administered a single dose of ALN-AGT01. |
| Part A: SAD: ALN-AGT01-Matching Placebo | Placebo comparator | Drug: ALN-AGT01-Matching PlaceboParticipants will be administered a single dose of ALN-AGT01-matching placebo. |
| Part B: SD: ALN-AGT01 | Experimental | Drug: ALN-AGT01Participants with controlled salt intake will be administered a single dose of ALN-AGT01. |
| Part B: SD: ALN-AGT01-Matching Placebo | Placebo comparator | Drug: ALN-AGT01-Matching PlaceboParticipants with controlled salt intake will be administered a single dose of ALN-AGT01-matching placebo. |
| Part D: MD: ALN-AGT01 + Irbesartan-Matching Placebo | Experimental | Drug: ALN-AGT01, Drug: Irbesartan-Matching PlaceboParticipants, who are obese, will be administered multiple doses of ALN-AGT01 and irbesartan-matching placebo. |
| Part D: MD: ALN-AGT01-Matching Placebo + Irbesartan | Active comparator | Drug: ALN-AGT01-Matching Placebo, Drug: IrbesartanParticipants, who are obese, will be administered multiple doses of ALN-AGT01-matching placebo and irbesartan. |
| Part E: Open Label: ALN-AGT01 + Irbesartan | Experimental | Drug: ALN-AGT01, Drug: IrbesartanParticipants will be administered a single dose of ALN-AGT01 and multiple doses of irbesartan. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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/m^2; Part D: Has BMI >35 and ≤50 kg/m^2; Part E: Has BMI ≥18 kg/m^2 and ≤50 kg/m^2
- Has a normal 12-lead electrocardiogram (ECG)
- Is a nonsmoker
Key exclusion criteria (7 listed)
- Has secondary hypertension
- Has orthostatic hypotension
- Has estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73m^2
- Recently received an investigational agent
- Has diabetes mellitus
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ALN-AGT01Also: ZilebesiranALN-AGT01 will be administered by subcutaneous (SC) injection. | Drug | Part A: SAD: ALN-AGT01, Part B: SD: ALN-AGT01, Part D: MD: ALN-AGT01 + Irbesartan-Matching Placebo, Part E: Open Label: ALN-AGT01 + Irbesartan |
| ALN-AGT01-Matching PlaceboNormal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC. | Drug | Part A: SAD: ALN-AGT01-Matching Placebo, Part B: SD: ALN-AGT01-Matching Placebo, Part D: MD: ALN-AGT01-Matching Placebo + Irbesartan |
| IrbesartanIrbesartan will be administered orally. | Drug | Part D: MD: ALN-AGT01-Matching Placebo + Irbesartan, Part E: Open Label: ALN-AGT01 + Irbesartan |
| Irbesartan-Matching PlaceboIrbesartan-matching placebo will be administered orally. | Drug | Part D: MD: ALN-AGT01 + Irbesartan-Matching Placebo |
Primary outcome
Number of Participants with Adverse Events (AEs)
Time frame: Parts A, B and E: each up to approximately 12 months; Part D: up to approximately 18 months
3 secondary outcomes
Change from Baseline in Blood Angiotensinogen (AGT) Level
Time frame: 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
Time frame: 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
Time frame: Parts A, B and E: Up to Day 15; Part D: Up to Day 99
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2023.
- Derived from this study: PubMed 41388232Badri 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.
- Derived from this study: PubMed 40556120Lidani 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.
- Derived from this study: PubMed 37467498Desai 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Alnylam Pharmaceuticals
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ALN-AGT01 and Irbesartan in people with Hypertension, run by Alnylam Pharmaceuticals at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Adverse Events (AEs) (time frame: Parts A, B and E: each up to approximately 12 months; Part D: up to approximately 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03934307, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2023.