A Study to Evaluate ALN-AGT01 in Patients With Hypertension

Sponsor
Alnylam Pharmaceuticals (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03934307
Collaborator
(none)
124
3
7
48
41.3
0.9

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

Study Type:
Interventional
Actual Enrollment :
124 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
May 1, 2019
Actual Primary Completion Date :
Apr 20, 2022
Anticipated Study Completion Date :
May 1, 2023

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:
  • Zilebesiran
  • 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:
  • Zilebesiran
  • 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:
  • Zilebesiran
  • 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:
  • Zilebesiran
  • Drug: Irbesartan
    Irbesartan will be administered orally.

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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]

    2. 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]

    3. 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

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    • Has a normal 12-lead electrocardiogram (ECG)

    • Is a nonsmoker

    Exclusion Criteria:
    • 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)

    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.
    Responsible Party:
    Alnylam Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT03934307
    Other Study ID Numbers:
    • ALN-AGT01-001
    • 2019-000129-39
    First Posted:
    May 1, 2019
    Last Update Posted:
    Aug 9, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 9, 2022