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ASTRAAS: A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx in Hypertensive Participants With Uncontrolled Blood Pressure

Sponsor
Ionis Pharmaceuticals, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04714320
Collaborator
(none)
160
Enrollment
50
Locations
2
Arms
17.9
Anticipated Duration (Months)
3.2
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effect of IONIS-AGT-LRx compared to placebo on seated automated office systolic blood pressure (SBP) from baseline to Study Day 85 in uncontrolled hypertensive participants on ≥ 3 antihypertensive medications and to evaluate the effect of IONIS-AGT-LRx on ambulatory blood pressure, seated automated office SBP, seated automated office diastolic blood pressure (DBP), and plasma angiotensinogen (AGT) at each scheduled visit in uncontrolled hypertensive participants on ≥ 3 antihypertensive medications.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This study will be a Phase 2, double-blind, randomized, placebo-controlled study in up to 150 participants. Participants will be randomized in a 2:1 ratio and will receive a once-weekly subcutaneous (SC) treatment with either IONIS-AGT-LRx or matching placebo. The length of participation in the study will be approximately 31 weeks, which includes an up to 6-week screening period, a 12-week treatment period, and a 13-week post-treatment period.

Study Design

Study Type:
Interventional
Actual Enrollment :
160 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Double-Blind, Placebo-Controlled, Phase 2 Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx, an Antisense Inhibitor of Angiotensinogen Production Administered Subcutaneously for 12 Weeks to Hypertensive Patients With Uncontrolled Blood Pressure
Actual Study Start Date :
Mar 4, 2021
Anticipated Primary Completion Date :
Sep 1, 2022
Anticipated Study Completion Date :
Sep 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: IONIS-AGT-LRx

Multiple doses of IONIS-AGT-LRx will be administered subcutaneously once-weekly for 12 weeks.

Drug: IONIS-AGT-LRx
Multiple doses of IONIS-AGT-LRx will be administered by SC injection.
Other Names:
  • ISIS 757456

    		•
    Placebo Comparator: Placebo

    IONIS-AGT-LRx-matching placebo will be administered subcutaneously once-weekly for 12 weeks.

    Drug: Placebo
    IONIS-AGT-LRx-matching placebo will be administered by SC injection.

    Outcome Measures

    Primary Outcome Measures

    1. Change in Seated Automated Office Systolic Blood Pressure (SBP) from Baseline to Study Day 85 [Baseline to Day 85]

    Secondary Outcome Measures

    1. Change from Baseline in plasma AGT to each scheduled, post-baseline visit [Baseline up to Day 169]

    2. Change from Baseline to Study Day 85 in 24-hour mean SBP measured by ambulatory blood pressure monitoring (ABPM) [Baseline to Day 85]

    3. Change from Baseline to Study Day 85 in 24-hour mean Diastolic Blood Pressure (DBP) measured by ABPM [Baseline up to Day 85]

    4. Percentage of participants reaching the goals of seated automated office seated SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and both during the study (excluding participants with a baseline SBP of ≤ 140 mmHg) [Up to Day 169]

    5. Percentage of participants reaching the goals of automated office seated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and both during the study [Baseline up to Day 169]

    6. Change from Baseline on seated automated office SBP to each scheduled, post-Baseline visit [Baseline up to Day 169]

    7. Change from Baseline on seated automated office DBP to each scheduled, post-Baseline visit [Baseline up to Day 169]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Males or females aged 18-80 inclusive and weighing ≥ 50 kilograms (kg) at the time of informed consent

    • Females: must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal

    • Males must be abstinent, surgically sterile or if engaged in sexual relations with a woman of childbearing potential (WOCBP), a highly effective contraceptive method must be used

    • Body mass index (BMI) ≤ 45.0 kilograms per square meter (kg/m^2)

    • At screening, the participant must have been on a stable, maximally tolerated regimen (per Investigator judgement) of 3 or more antihypertensive medications for at least 1 month prior to screening and will be required to maintain this regimen throughout the study. The combination of antihypertensive medications must be in the following categories: a) angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB), b) beta blocker: c) calcium channel blocker d) diuretic, e) alpha-1 blocker f) centrally acting sympatholytic agent or g) direct acting vasodilators (e.g. hydralazine)

    Exclusion Criteria:

    • Clinically significant abnormalities in screening laboratory results, medical history according to Investigator judgment

    • History of secondary hypertension (HTN) including, but not limited to any of the following: renovascular HTN (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, pheochromocytoma, polycystic kidney disease, and drug-induced HTN

    • The use of the following at time of screening and during the course of the study:

    • Other medications for the treatment of HTN (e.g., minoxidil, diazoxide, renin inhibitors)

    • Medications that may cause hyperkalemia unless on a stable dose at least 1 month prior to the screening visit and no known history of hyperkalemia per Investigator judgement

    • Use of oral anticoagulants, unless stable for 4 weeks prior to the first dose of study drug and regular monitoring must be performed per clinical practice during the study unless the participant is receiving vitamin K agonists. If the participant is receiving vitamin K antagonists (e.g., warfarin) international normalized ratio (INR) should be in therapeutic range, as established by the Investigator, for 4 weeks prior to the first dose

    • Chronic administration of NSAIDs or COX-2 inhibitors (except aspirin for cardiovascular disease provided the total daily dose does not exceed 325 mg)

    • History of bleeding diathesis, coagulopathy, immune thrombocytopenic purpura (ITP), thrombotic cytopenic purpura (TTP), or any qualitative or quantitative platelet defect

    • Unstable/underlying known cardiovascular disease defined as:

    • Any history of congestive heart failure (New York Heart Association [NYHA] Class III-IV)

    • Any history of previous myocardial infarction, coronary revascularization, unstable or stable angina pectoris ˂ 1 year prior to screening

    • Any hemodynamically unstable atrial or ventricular arrhythmias

    • Significant uncorrected valvular heart disease

    • Any history of stroke or transient ischemic attack < 1 year prior to screening

    • A cardiac valve repair, cardiac device implantation, and/or a hospitalization for heart failure within 3 months of screening

    • Participant works nighttime shifts (e.g., 11 PM to 7 AM)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Pinnacle Research Group Anniston Alabama United States 36207
    2 Central Research Associates, Inc. Birmingham Alabama United States 35205
    3 Achieve Clinical Research, LLC Birmingham Alabama United States 35216
    4 Cahaba Research, Inc. Pelham Alabama United States 35124
    5 Syed Research Consultants LLC Sheffield Alabama United States 35660
    6 Cardiology and Medicine Clinic Little Rock Arkansas United States 72204
    7 Advanced Research Center Anaheim California United States 92805
    8 National Research Institute - Huntington Park Huntington Park California United States 90255
    9 RESPIRE Research La Mesa California United States 91942
    10 Clinical Trials Research Lincoln California United States 95648
    11 Catalina Research Institute Montclair California United States 91763
    12 San Fernando Valley Health Institute Van Nuys California United States 91405
    13 Creekside Endocrine Associates, PC Denver Colorado United States 80246
    14 Chase Medical Research LLC Waterbury Connecticut United States 06708
    15 ALL Medical Research, LLC Cooper City Florida United States 33024
    16 Nature Coast Clinical Research - Crystal River Crystal River Florida United States 34429
    17 East Coast Institute for Research Jacksonville Florida United States 32216
    18 Canvas Clinical Research Lake Worth Florida United States 33467
    19 AMPM Research Clinic Miami Gardens Florida United States 33169
    20 Allied Biomedical Research Institute, Inc. Miami Florida United States 33155
    21 Advanced Research Institute Inc New Port Richey Florida United States 34653
    22 Ocala Research Institute Ocala Florida United States 34471
    23 Progressive Medical Research Port Orange Florida United States 32124
    24 Gwinnett Research Institute Buford Georgia United States 30519
    25 Sandhill Research, LLC Decatur Georgia United States 30030
    26 Georgia Institute for Clinical Research Marietta Georgia United States 30060
    27 Eagle Clinical Research Chicago Illinois United States 60621
    28 Clinical Investigation Specialists, Inc. - Wauconda Wauconda Illinois United States 60084
    29 The Research Group of Lexington, LLC Lexington Kentucky United States 40503
    30 Louisiana Heart Center Slidell Louisiana United States 70458
    31 Clinical Trials of America, LLC - Monroe, LA West Monroe Louisiana United States 71291
    32 BioPharm Clinical Research Caro Michigan United States 48723
    33 Palm Research Center, Inc. Las Vegas Nevada United States 89148
    34 NY Scientific Brooklyn New York United States 11235
    35 Summit Research Group, LLC Stow Ohio United States 44224
    36 Conrad Clinical Research Edmond Oklahoma United States 73013
    37 South Oklahoma Heart Research Oklahoma City Oklahoma United States 73135
    38 Health Concepts Research Rapid City South Dakota United States 57702
    39 Chattanooga Research & Medicine, PLLC Chattanooga Tennessee United States 37404
    40 Holston Medical Group Kingsport Tennessee United States 37660
    41 North Texas Research Associates Allen Texas United States 75013
    42 Juno Research, LL Houston Texas United States 77040
    43 Protenium Clinical Research, LLC Hurst Texas United States 76054
    44 Laguna Clinical Research Associates Laredo Texas United States 78041
    45 Kalo Clinical Research Salt Lake City Utah United States 84102
    46 Manassas Clinical Research Center Manassas Virginia United States 20110
    47 York Clinical Research LLC Norfolk Virginia United States 23510
    48 TPMG Clinical Research Williamsburg Virginia United States 23188
    49 Ecogene-21 Chicoutimi Quebec Canada G7H 7K9
    50 CardioVasc HR Saint-Jean-sur-Richelieu Quebec Canada J3A 1J2

    Sponsors and Collaborators

    • Ionis Pharmaceuticals, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Ionis Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT04714320
    Other Study ID Numbers:
    • ISIS 757456-CS4
    First Posted:
    Jan 19, 2021
    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:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Ionis Pharmaceuticals, Inc.
    Hypertension
    Hypertensive
    AGT
    Angiotensinogen
    Blood Pressure
    Additional relevant MeSH terms:
    Hypertension

    Study Results

    No Results Posted as of Aug 9, 2022