AzTrials
AzTrials

Chronic Heart Failure With Reduced Ejection FractionPhase 2ASTRAAS-HFNCT04836182

A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx in Participants With Chronic Heart Failure With Reduced Ejection Fraction

A Phase 2 study testing IONIS-AGT-LRx in people with Chronic Heart Failure With Reduced Ejection Fraction, run by Ionis Pharmaceuticals, Inc. at 19 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate the effect of IONIS-AGT-LRX weekly subcutaneous (SC) injection on plasma angiotensinogen (AGT) concentration from Baseline to Study Day 85 (Week 13) and to evaluate the effect of IONIS-AGT-LRx weekly SC injection on plasma AGT concentration and N-terminal prohormone of B-type… Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
IONIS-AGT-LRx
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
72 participants
Where
19 sitesin 3 countries
Study dates
8 Jun 2021to 11 Jan 2023
Phase
Phase 2
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 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Females must be non-pregnant and non-lactating and of non- childbearing potential.
  • Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential (WOCBP), she must be willing to use a highly effective contraceptive method
  • Screening NT-proBNP ≥ 600 picograms per milliliter (pg/mL) and less than (<) 8500 pg/mL
  • Established diagnosis of heart failure (HF) with reduced systolic function for at least 6 months prior to the screening visit (left ventricular ejection fraction, [LVEF] ≤ 40%
  • New York Heart Association class I-III
  • Participants should receive background standard of care for HFrEF. Therapy should have been individually optimized and stable for ≥ 4 weeks before randomization and include:
Show all 9Show fewer
  • An angiotensin-converting-enzyme inhibitor (ACEi), or angiotensin II receptor blockers (ARBs) or sacubitril/valsartan (mandatory)
  • A beta-blocker (unless contraindicated or not tolerated)
  • A mineralocorticoid receptor antagonist (MRA, unless contraindicated or not tolerated)

Who cannot join

  • HF due to restrictive cardiomyopathy, active myocarditis, chemotherapy, hypertrophic cardiomyopathy, primary cardiac valve disease, non-compaction cardiomyopathy, or takotsubo cardiomyopathy.
  • Acute decompensated HF requiring intravenous (IV) diuretics, IV inotropes or IV vasodilators with discharge date within 30 days of screening or acute mechanical support (e.g., intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device) with discharge date within 90 days of screening.
  • Symptomatic hypotension or systolic blood pressure (SBP) ≤ 90 millimeters of mercury (mmHg) at screening.
  • Uncontrolled hypertension (HTN) (SBP > 160 mmHg or diastolic blood pressure (BP) > 100 mmHg) prior to screening.
  • Heart transplant, and/or Left Ventricular Assist Device (LVAD) prior to screening or anticipated heart transplant or LVAD during the study.
  • Implantation of a cardiac resynchronization therapy device (CRT) within 3 months prior screening or intent to implant a CRT within 3 months after screening.
Show all 22Show fewer
  • Acute coronary syndrome, unstable angina, stroke, transient ischemic attack (TIA), coronary revascularization, cardiac device implantation, cardiac valve repair, carotid or other major surgery within 3 months of screening.
  • Coronary, valve or carotid artery disease likely to require surgical or percutaneous intervention within the 3 months after screening.
  • Severe pulmonary disease with any of the following:
  • Requirement of continuous (home) oxygen or
  • Known diagnosis of severe chronic obstructive pulmonary disease (as defined by the American Thoracic Society/European Respiratory Society) or severe restrictive lung disease, in the opinion of the investigator.
  • Screening laboratory results as follows, or any other clinically significant abnormalities in screening laboratory values that would render a participant unsuitable for inclusion in the opinion of the investigator.
  • Alanine aminotransferase/aspartate aminotransferase (ALT/AST) > 2.0 × upper limit of normal (ULN).
  • Total bilirubin ≥ 1.5 × ULN (participants with total bilirubin ≥ 1.5 × ULN may be allowed on study if indirect bilirubin only is elevated, ALT/AST is not greater than the ULN, and known to have Gilbert's disease).
  • Platelets < 100,000/millimeter^3 (mm^3).
  • Urine protein creatinine ratio (UPCR) ≥ 500 milligrams per gram (mg/g).
  • Hemoglobin A1c (HbA1c) > 9.5% or uncontrolled diabetes per investigator judgement.
  • Estimated glomerular filtration rate (eGFR) < 30 milliliters/ minute /1.73 m^2 (mL/min/1.73 meter^2) at screening.
  • Abnormal thyroid function tests with clinical significance per investigator judgement.
  • Serum potassium > 5.1 millimoles per liter (mmol/L) at screening.
  • Requirement of treatment with both ACEi and ARBs.
  • Previous history of intolerance to ACEi or ARBs or history of hyperkalemia.

Trial locations and contacts

19 sites in 3 countries.

19 sites in 3 countries

United States10 sites

  • North Texas Research Associates

    Allen, Texas, 75013

  • The Lindner Center for Research and Education at The Christ Hospital

    Cincinnati, Ohio, 45219

  • Nature Coast Clinical Research - Crystal River

    Crystal River, Florida, 34429

  • New Generation of Medical Research

    Hialeah, Florida, 33016

  • Arkansas Cardiology

    Little Rock, Arkansas, 72205

  • York Clinical Research LLC

    Norfolk, Virginia, 23510

  • South Oklahoma Heart Research

    Oklahoma City, Oklahoma, 73135

  • Newton Clinical Research

    Oklahoma City, Oklahoma, 73159

  • St. Louis Heart and Vascular Cardiology

    St Louis, Missouri, 63136

  • Michigan Heart

    Ypsilanti, Michigan, 48197

Other trials in United States

Poland7 sites

  • Specjalistyczna Praktyka Lekarska

    Krakow, 30-082

  • Samodzielny Publiczny ZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego

    Lodz, 92-213

  • Indywidualna Specjalistyczna Praktyka Lekarska

    Lodz, 94-255

  • AKA-MED Centrum Spólka z Ograniczona Odpowiedzialnoscia

    Ruda Śląska, 41-710

  • NZOZ Pro Cordis Sopockie Centrum Badan Kardiologicznych

    Sopot, 81-717

  • Centrum Chorob Serca w USK

    Wroclaw, 50-556

  • 4 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny ZOZ we Wroclawiu

    Wroclaw, 50-981

Other trials in Poland

Hungary2 sites

  • Semmelweis Egyetem - Varosmajori Sziv es Ergyogyaszati Klinika

    Budapest, H-1122

  • Kardiologiai Maganrendeles es Klinikai Vizsgalohely

    Orosháza, 5900

Other trials in Hungary

About this study

Official title: A Double-Blind, Placebo-Controlled, Randomized, Multicenter, Phase 2 Study Assessing the Safety, Tolerability and Efficacy of IONIS-AGT-LRx, an Antisense Inhibitor of Angiotensinogen Production, Administered Subcutaneously Over 12 Weeks in Patients With Chronic Heart Failure With Reduced Ejection Fraction

The purpose of this study is to evaluate the effect of IONIS-AGT-LRX weekly subcutaneous (SC) injection on plasma angiotensinogen (AGT) concentration from Baseline to Study Day 85 (Week 13) and to evaluate the effect of IONIS-AGT-LRx weekly SC injection on plasma AGT concentration and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) levels at each scheduled visit in chronic heart failure participants with reduced ejection fraction (HFrEF).

Read the detailed description

This study will be a Phase 2, double-blind, randomized, placebo-controlled study in up to 72 participants. Participants will be randomized in a 2:1 ratio to either IONIS-AGT-LRX or matching placebo and receive a once-weekly SC treatment. The length of participation in the study will be approximately 35 weeks, which includes an up to 10-week screening period, a 12-week treatment period, and a 13-week post-treatment period.

Being tested
IONIS-AGT-LRx, Placebo
Keywords
Heart Failure, AGT, NT-proBNP
Medical subject headings
Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IONIS-AGT-LRxDrug

    Also called ISIS 757456

    Multiple doses of IONIS-AGT-LRx will be administered by SC injection.

  • PlaceboDrug

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

Study groups in NCT04836182
Study groupRoleWhat they receive
IONIS-AGT-LRxExperimentalIONIS-AGT-LRX by subcutaneous injection once-weekly
Receives: Drug: IONIS-AGT-LRx
PlaceboPlacebo comparatorMatching placebo by subcutaneous injection once-weekly
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percent Change in Plasma AGT Concentration From Baseline to Study Day 85

    Measured: Baseline to Day 85

Secondary outcomes (6)

  1. Absolute Level of Plasma AGT

    Measured: Baseline to Day 169

  2. Change in Plasma AGT From Baseline to Each Scheduled, Post-Baseline Visit

    Measured: Baseline to Day 169

  3. Percent Change in Plasma AGT From Baseline to Each Scheduled, Post-Baseline Visit

    Measured: Baseline to Day 169

  4. Absolute Level of NT-proBNP

    Measured: Baseline to Day 169

  5. Change in NT-proBNP From Baseline to Each Scheduled, Post-Baseline Visit

    Measured: Baseline to Day 169

  6. Percent Change from Baseline in NT-proBNP to Each Scheduled, Post-Baseline Visit

    Measured: Baseline to Day 169

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Apr 2021
  2. Study start8 Jun 2021
  3. Primary completion19 Oct 2022
  4. Study completion11 Jan 2023

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
72 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04836182
Sponsor's protocol ID
ISIS 757456-CS5
Other IDs
2020-005878-10
Acronym
ASTRAAS-HF
Status last verified
Sep 2023
First submitted
5 Apr 2021
Last updated
11 Sep 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IONIS-AGT-LRx in people with Chronic Heart Failure With Reduced Ejection Fraction, run by Ionis Pharmaceuticals, Inc. at 19 sites in 3 countries.

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 9 inclusion and 22 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 11 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States, Poland, Hungary. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Percent Change in Plasma AGT Concentration From Baseline to Study Day 85 (time frame: Baseline to Day 85). 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 NCT04836182.

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 11 Sep 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in