IONIS-AGT-LRx for Heart Failure

(ASTRAAS-HF Trial)

No longer recruiting at 33 trial locations

Overseen By Ionis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ionis Pharmaceuticals, Inc.

Must be taking: ACEi, ARBs, Beta-blockers, MRAs

Disqualifiers: Severe pulmonary disease, Uncontrolled diabetes, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called IONIS-AGT-LRx for individuals with chronic heart failure and reduced ejection fraction, meaning their heart doesn't pump blood effectively. The researchers aim to determine if the treatment can safely improve heart function by monitoring specific blood markers over time. Participants will receive either the new treatment or a placebo (a harmless, inactive substance) through weekly injections. Candidates may qualify for this trial if they have been diagnosed with heart failure with reduced pumping ability for at least six months and are already on stable heart failure medication. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires participants to continue their current heart failure medications, including an ACE inhibitor, ARB, or sacubitril/valsartan, a beta-blocker, and a mineralocorticoid receptor antagonist, unless they are not tolerated. Your current medications should be stable for at least 4 weeks before joining the study.

Is there any evidence suggesting that IONIS-AGT-LRx is likely to be safe for humans?

Research has shown that IONIS-AGT-LRx is generally safe and well-tolerated. In earlier studies, participants who took IONIS-AGT-LRx did not experience serious side effects, such as significant drops in blood pressure or kidney issues. Most side effects were minor, such as redness or swelling at the injection site, affecting about one in six participants. These studies help researchers better understand the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for heart failure?

Unlike the standard treatments for chronic heart failure with reduced ejection fraction, which often include medications like beta-blockers or ACE inhibitors, IONIS-AGT-LRx is unique because it targets the production of angiotensinogen, a protein involved in blood pressure regulation. This treatment is delivered through a once-weekly subcutaneous injection, which can be more convenient than daily oral medications. Researchers are excited about IONIS-AGT-LRx because its novel mechanism of action offers a new way to potentially improve heart function by directly reducing the levels of angiotensinogen, aiming to address the underlying causes of heart failure more effectively.

What evidence suggests that IONIS-AGT-LRx might be an effective treatment for chronic heart failure with reduced ejection fraction?

Research has shown that IONIS-AGT-LRx, the investigational treatment in this trial, can significantly lower levels of a protein called angiotensinogen (AGT), which relates to blood pressure and heart health. In previous studies, patients who received IONIS-AGT-LRx experienced a noticeable drop in AGT levels compared to those who received a placebo. This treatment also reduced systolic blood pressure, the pressure in blood vessels when the heart beats. Lowering AGT and blood pressure may improve heart function in people with chronic heart failure with reduced ejection fraction (HFrEF), potentially enhancing overall heart health. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Inclusion Criteria

Females must be non-pregnant and non-lactating and of non- childbearing potential.

An angiotensin-converting-enzyme inhibitor (ACEi), or angiotensin II receptor blockers (ARBs) or sacubitril/valsartan (mandatory)

A beta-blocker (unless contraindicated or not tolerated)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 10 weeks

Treatment

Participants receive IONIS-AGT-LRx or placebo via subcutaneous injection once-weekly

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

13 weeks

What Are the Treatments Tested in This Trial?

Interventions

• IONIS-AGT-LRx

How Is the Trial Designed?

Group I: IONIS-AGT-LRx Experimental Treatment 1 Intervention

IONIS-AGT-LRX by subcutaneous injection once-weekly

Group II: Placebo Placebo Group 1 Intervention

Matching placebo by subcutaneous injection once-weekly

Who Is Running the Clinical Trial?

Ionis Pharmaceuticals, Inc.

Lead Sponsor

Trials

151

Recruited

27,800+

Dr. Brett P. Monia

Ionis Pharmaceuticals, Inc.

Chief Executive Officer since 2020

PhD in Pharmacology from the University of Pennsylvania, BSc in Molecular Biology and Analytical Chemistry from Stockton State College

Dr. Eric Bastings

Ionis Pharmaceuticals, Inc.

Chief Medical Officer

MD

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8246029/

Antisense Inhibition of Angiotensinogen With IONIS-AGT-LRx After 8 weeks of dosing, at day 57, a significant absolute reduction in mean AGT levels was noted in the IONIS-AGT-LRx group compared with the placebo group (− ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04714320

NCT04714320 | A Study to Assess the Safety, Tolerability ... The purpose of this study was to evaluate the effect of IONIS-AGT-LRx compared to placebo on seated automated office systolic blood pressure (SBP) from ...

3. ahajournals.org ahajournals.org/doi/10.1161/HYPERTENSIONAHA.122.19430?doi=10.1161/HYPERTENSIONAHA.122.19430

A Focus on RNA-Based Therapeutics | Hypertension Patients were randomized to receive 80 mg of IONIS-AGT-LRX or placebo and all received a loading dose (80 mg) on day 3, followed by 80-mg weekly subcutaneous ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03714776?tab=results

A Study to Assess the Safety, Tolerability and Efficacy of ... A type of clinical study in which participants are identified as belonging to study groups and are assessed for biomedical or health outcomes. Participants may ...

5. ctv.veeva.com ctv.veeva.com/study/a-study-to-assess-the-safety-tolerability-and-efficacy-of-ionis-agt-lrx-in-hypertensive-participant

A Study to Assess the Safety, Tolerability and Efficacy of IONIS ... The purpose of this study was to evaluate the effect of IONIS-AGT-LRx compared to placebo on seated automated office systolic blood pressure (SBP)

6. jacc.org jacc.org/doi/abs/10.1016/j.jacbts.2021.04.004

Antisense Inhibition of Angiotensinogen With IONIS-AGT-L ... IONIS-AGT-L Rx significantly reduced AGT levels compared with placebo in all 3 studies. Although not powered for this endpoint, trends were noted in blood ...

7. unsw.edu.au unsw.edu.au/newsroom/news/2024/07/injectables-high-blood-pressure-in-the-workds-could-they-mean-no-more-daily-pills

Injectables for high blood pressure are in the works. Could ... The most common side effects are minor reactions such as redness or swelling at the injection site in about one in six people. A small ...