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

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ClinicalTrials.gov Identifier: NCT04714320
Recruitment Status : Recruiting
First Posted : January 19, 2021
Last Update Posted : October 21, 2021
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE January 14, 2021
First Posted Date  ICMJE January 19, 2021
Last Update Posted Date October 21, 2021
Actual Study Start Date  ICMJE March 4, 2021
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 14, 2021)
Change in Systolic Blood Pressure (SBP) from Baseline to Study Day 85 [ Time Frame: Baseline to Day 85 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 14, 2021)
  • Change from Baseline in plasma AGT to each scheduled, post-baseline visit [ Time Frame: Baseline up to Day 169 ]
  • Change from Baseline to Study Day 85 in 24-hour mean Diastolic Blood Pressure (DBP) measured by ambulatory blood pressure monitoring (ABPM) [ Time Frame: Baseline up to Day 85 ]
  • Percentage of participants reaching the goals of seated automated office seated SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and both during the study [ Time Frame: Up to Day 169 ]
  • Percentage of participants reaching the goals of automated office seated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and both during the study [ Time Frame: Baseline up to Day 169 ]
  • Change from Baseline on seated automated office SBP to each scheduled, post-Baseline visit [ Time Frame: Baseline up to Day 169 ]
  • Change from Baseline on seated automated office DBP to each scheduled, post-Baseline visit [ Time Frame: Baseline up to Day 169 ]
  • Change from Baseline to Study Day 85 in 24-hour mean SBP measured by ABPM [ Time Frame: Baseline to Day 85 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx in Hypertensive Participants With Uncontrolled Blood Pressure
Official Title  ICMJE 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
Brief Summary The purpose of this study is to evaluate the effect of IONIS-AGT-LRx compared to placebo on 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 SBP, diastolic blood pressure (DBP) and plasma angiotensinogen (AGT) at each scheduled visit in uncontrolled hypertensive participants on ≥ 3 antihypertensive medications.
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 29 weeks, which includes an up to 4-week screening period, a 12-week treatment period, and a 13-week post-treatment period.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Hypertension
Intervention  ICMJE
  • Drug: IONIS-AGT-LRx
    Multiple doses of IONIS-AGT-LRx will be administered by SC injection.
    Other Name: ISIS 757456
  • Drug: Placebo
    IONIS-AGT-LRx-matching placebo will be administered by SC injection.
Study Arms  ICMJE
  • Experimental: IONIS-AGT-LRx
    Multiple doses of IONIS-AGT-LRx will be administered subcutaneously once-weekly for 12 weeks.
    Intervention: Drug: IONIS-AGT-LRx
  • Placebo Comparator: Placebo
    IONIS-AGT-LRx-matching placebo will be administered subcutaneously once-weekly for 12 weeks.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 14, 2021)
150
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2022
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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) non-potassium sparing 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 (e.g., cyclosporine or tacrolimus, pentamidine, trimethoprim-sulfamethoxazole, all heparins)
    • 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)
    • Potassium sparing diuretics (e.g., eplerenone, spironolactone, amiloride, triamterene)
  • 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
    • 12-lead electrocardiogram (ECG) demonstrating a QT interval (corrected using Fridericia's formula [QTcF]) ˃ 450 milliseconds (msec) in males and ˃ 470 msec in females at screening, or a history or evidence of long QT syndrome
    • 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
  • Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1
  • Participant works nighttime shifts (e.g., 11 PM to 7 AM)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ionis Pharmaceuticals (844) 414-1754 ionisNCT04714320study@clinicaltrialmedia.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04714320
Other Study ID Numbers  ICMJE ISIS 757456-CS4
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Ionis Pharmaceuticals, Inc.
Study Sponsor  ICMJE Ionis Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Ionis Pharmaceuticals, Inc.
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP