Ziltivekimab for Heart Failure and Inflammation

(ATHENA Trial)

Recruiting at 293 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Disqualifiers: Recent MI, Stroke, Hypertension, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 12

Duration: 12 months

680 Participants Needed

Trial Summary

What is the purpose of this trial?

The study is being done to see if ziltivekimab can be used to treat participants living with heart failure and inflammation. Participants will either get ziltivekimab (active medicine) or placebo (inactive substance that looks like the study medicine but does not contain any medicine). The treatment participants get is decided by chance. Participant's chance of getting ziltivekimab or placebo is the same. Ziltivekimab is not yet approved in any country or region in the world. It is a new medicine that doctors cannot prescribe. The study is expected to last for up to 1 year and 4 months.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug Ziltivekimab for heart failure and inflammation?

Research shows that Ziltivekimab, which targets inflammation, significantly reduced inflammation markers in patients with atherosclerotic cardiovascular disease and chronic kidney disease. While this suggests potential benefits for heart failure, direct evidence for heart failure outcomes is not yet available. ^{1 2 3 4 5}

Is Ziltivekimab safe for humans?

Ziltivekimab has been tested in clinical trials for conditions like atherosclerotic cardiovascular disease and chronic kidney disease, showing it can reduce inflammation markers. These studies suggest it is generally safe for humans, but as with any treatment, there may be risks, and it's important to discuss these with a healthcare provider. ^{1 3 6 7 8}

How is the drug Ziltivekimab different from other heart failure treatments?

Ziltivekimab is unique because it targets the interleukin-6 ligand, a specific part of the immune system involved in inflammation, which is not a common approach in current heart failure treatments. This makes it potentially effective in reducing inflammation-related risks in heart failure, unlike traditional treatments that focus on other mechanisms. ^{1 2 3 4 5}

Research Team

Clinical Transparency dept. 2834

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

This trial is for individuals with heart failure and inflammation. Participants should not have any other conditions that could interfere with the study or pose a risk to their health.

Inclusion Criteria

Structural heart disease and/or functional heart disease documented by echocardiography within 12 months prior to or at screening (visit 1) showing specific criteria

E/e' (mean septal and lateral) greater than or equal to 10

Serum high-sensitivity C-reactive protein (hs-CRP) greater than or equal to 2 milligrams per liter (mg/L) at screening (visit 1)

Exclusion Criteria

I have heart failure not caused by common heart diseases.

I haven't had a heart attack, stroke, severe chest pain, mini-stroke, or been hospitalized for heart failure in the last 30 days.

I am scheduled for a heart device placement or a procedure to correct heart rhythm issues.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ziltivekimab or placebo administered subcutaneously once-monthly for 12 months

12 months

12 visits (in-person, monthly)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ziltivekimab

Trial Overview The study tests Ziltivekimab, an experimental medication, against a placebo in treating heart failure and inflammation. Patients are randomly assigned to receive either the real drug or placebo, with equal chances of receiving either.

Participant Groups

Group I: Ziltivekimab Active Control 1 Intervention

Participants will receive ziltivekimab administered subcutaneously (s.c.) once-monthly and added to standard of care for 12 months.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive placebo matched to ziltivekimab administered s.c. once-monthly and added to standard of care for 12 months.

Who Is Running the Clinical Trial?

Novo Nordisk A/S

Lead Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Findings from Research

In a 12-week phase 2 trial involving Japanese patients with chronic kidney disease, ziltivekimab significantly reduced inflammatory markers, with median hsCRP levels decreasing by 96.2% in the 15 mg group and 93.4% in the 30 mg group compared to placebo.

Ziltivekimab was well tolerated, showing no adverse effects on cholesterol ratios, although there was a small increase in triglyceride levels, indicating its potential as a safe treatment option for patients at high atherosclerotic risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of interleukin-6 inhibition with ziltivekimab in patients at high risk of atherosclerotic events in Japan (RESCUE-2): A randomized, double-blind, placebo-controlled, phase 2 trial. Wada, Y., Jensen, C., Meyer, ASP., et al.[2023]

In a study involving 10,061 patients with a history of myocardial infarction, the interleukin-1β inhibitor canakinumab showed a dose-dependent reduction in hospitalizations for heart failure (HHF) and heart failure-related mortality, particularly at the 300 mg dose.

Patients receiving canakinumab had a lower risk of HHF and related mortality compared to placebo, suggesting that targeting inflammation may be beneficial in managing heart failure in patients with elevated inflammatory markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-Inflammatory Therapy With Canakinumab for the Prevention of Hospitalization for Heart Failure. Everett, BM., Cornel, JH., Lainscak, M., et al.[2019]

In a subanalysis of the RESCUE trial involving 264 adults with chronic kidney disease (CKD) stage 3-5, treatment with ziltivekimab significantly increased hemoglobin levels after 12 weeks compared to placebo, indicating its potential efficacy in managing anemia associated with CKD.

Ziltivekimab also led to significant improvements in iron homeostasis, including increased serum iron levels and transferrin saturation, with no major safety concerns reported, suggesting it could be a safe option for anemia management in patients with systemic inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Ziltivekimab on Determinants of Hemoglobin in Patients with CKD Stage 3-5: An Analysis of a Randomized Trial (RESCUE). Pergola, PE., Davidson, M., Jensen, C., et al.[2023]

A phase II clinical trial is underway to evaluate the efficacy of anakinra, an IL-1 receptor antagonist, in improving peak oxygen consumption in 102 patients with acute decompensated heart failure and systemic inflammation over 24 weeks.

The trial aims to provide insights into how anakinra affects not only exercise capacity but also other heart function parameters and quality of life, potentially offering a novel treatment strategy for heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of interleukin-1 blockade in recently decompensated heart failure (REDHART2): a randomized, double blind, placebo controlled, single center, phase 2 study. Van Tassell, B., Mihalick, V., Thomas, G., et al.[2023]

In a study of 30 patients with acute decompensated heart failure (ADHF), treatment with anakinra significantly reduced inflammatory marker C-reactive protein (CRP) levels by 61% within 72 hours, compared to only a 6% reduction in the placebo group.

Anakinra was well tolerated by patients, suggesting it is a safe option for targeting inflammation in ADHF, but further research is needed to see if this reduction in inflammation leads to better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-1 Blockade in Acute Decompensated Heart Failure: A Randomized, Double-Blinded, Placebo-Controlled Pilot Study. Van Tassell, BW., Abouzaki, NA., Oddi Erdle, C., et al.[2018]

Sarilumab, a monoclonal antibody that blocks IL-6 signaling, demonstrated a stable long-term safety profile in patients with rheumatoid arthritis over an average exposure of 2.8 years for combination therapy and 1.7 years for monotherapy, involving a total of 2887 and 471 patients respectively.

The incidence rates of serious adverse events and serious infections were relatively low, with no increase in adverse events over time, indicating that sarilumab is a safe treatment option for rheumatoid arthritis when used alone or with other disease-modifying drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety of sarilumab in rheumatoid arthritis: an integrated analysis with up to 7 years' follow-up. Fleischmann, R., Genovese, MC., Lin, Y., et al.[2020]

In a phase 2 trial involving 264 participants with chronic kidney disease and elevated high-sensitivity CRP, ziltivekimab significantly reduced high-sensitivity CRP levels by up to 92% compared to only 4% in the placebo group, demonstrating its efficacy in lowering inflammation related to atherosclerosis.

Ziltivekimab was well tolerated with no serious adverse effects reported, indicating a favorable safety profile for patients at high cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): a double-blind, randomised, placebo-controlled, phase 2 trial. Ridker, PM., Devalaraja, M., Baeres, FMM., et al.[2022]

In a study of 274 patients with active rheumatoid arthritis (RA) who were already on stable methotrexate therapy, canakinumab 150 mg administered subcutaneously every 4 weeks significantly improved patient responses compared to placebo, with 26.5% of patients meeting the American College of Rheumatology 50 criteria.

Canakinumab was well-tolerated, showing no significant safety concerns, particularly regarding infections, and had minimal injection-site reactions, indicating it may be a safe addition to existing RA treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the human anti-IL-1β monoclonal antibody canakinumab in rheumatoid arthritis: results of a 12-week, Phase II, dose-finding study. Alten, R., Gomez-Reino, J., Durez, P., et al.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of interleukin-6 inhibition with ziltivekimab in patients at high risk of atherosclerotic events in Japan (RESCUE-2): A randomized, double-blind, placebo-controlled, phase 2 trial. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Anti-Inflammatory Therapy With Canakinumab for the Prevention of Hospitalization for Heart Failure. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Effect of Ziltivekimab on Determinants of Hemoglobin in Patients with CKD Stage 3-5: An Analysis of a Randomized Trial (RESCUE). [2023]

4. England pubmed.ncbi.nlm.nih.gov

Rationale and design of interleukin-1 blockade in recently decompensated heart failure (REDHART2): a randomized, double blind, placebo controlled, single center, phase 2 study. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Interleukin-1 Blockade in Acute Decompensated Heart Failure: A Randomized, Double-Blinded, Placebo-Controlled Pilot Study. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Long-term safety of sarilumab in rheumatoid arthritis: an integrated analysis with up to 7 years' follow-up. [2020]

7. England pubmed.ncbi.nlm.nih.gov

IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): a double-blind, randomised, placebo-controlled, phase 2 trial. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the human anti-IL-1β monoclonal antibody canakinumab in rheumatoid arthritis: results of a 12-week, Phase II, dose-finding study. [2021]