Ziltivekimab for Heart Failure

(HERMES Trial)

Recruiting at 1620 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Disqualifiers: Recent MI, Stroke, Unstable angina, 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: 20

Duration: 48 months

5600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether ziltivekimab, a new medication, can improve symptoms for people with heart failure and inflammation. Participants will receive monthly injections of either ziltivekimab or a placebo. Researchers aim to determine if this treatment can enhance symptoms and overall health for those with heart failure. Individuals with heart failure who have faced inflammation-related issues, such as frequent hospital visits for heart problems, might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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

The trial information does not specify if you need to stop your current medications. However, it is common for clinical trials to have specific guidelines about medication use, so it's best to discuss this with the trial coordinators.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ziltivekimab has undergone safety testing in humans. One study found it slightly increased triglyceride levels, a type of fat in the blood, compared to a placebo. This indicates the drug might alter blood fat levels, but these changes are generally small.

Another study found that ziltivekimab significantly reduced inflammation markers related to heart disease without major safety issues, suggesting the treatment is generally well-tolerated.

Overall, ziltivekimab has been tested in people and is considered safe with some manageable side effects. However, consulting a healthcare provider is important to understand how this might apply to individual health needs. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for heart failure, which typically involves medications like ACE inhibitors, beta-blockers, and diuretics, Ziltivekimab is unique due to its specific mechanism of action. Researchers are excited about Ziltivekimab because it targets interleukin-6 (IL-6), a protein involved in inflammation that is thought to play a role in heart failure. This novel approach aims to reduce inflammation more directly than current treatments. Additionally, Ziltivekimab is administered through a convenient monthly subcutaneous injection, which could improve adherence compared to daily oral medications.

What evidence suggests that ziltivekimab might be an effective treatment for heart failure?

In this trial, participants will receive either ziltivekimab or a placebo. Research has shown that ziltivekimab is under study as a treatment for heart failure linked to inflammation. In earlier studies, ziltivekimab reduced inflammation in patients with heart conditions like atherosclerosis, which affects blood flow in the arteries. Reducing inflammation is important because it can lower the risk of heart problems. Initial findings suggest that ziltivekimab might improve outcomes for people with heart failure by targeting this inflammation. While more research is needed, early signs are promising for those with heart failure and inflammation. ^{1 6 7 8 9}

Who Is on the Research Team?

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

This trial is for people with heart failure and inflammation. They must have a certain level of left atrial volume, high levels of C-reactive protein, and meet specific criteria related to heart function documented by echocardiography or hospital visits. It's not for those who've had recent major cardiac events/surgery, planned procedures, specific cardiomyopathies, extremely high blood pressure or abnormal heart rates.

Inclusion Criteria

I have been diagnosed with heart failure and it affects my daily activities.

Your N-terminal-pro-brain natriuretic peptide (NT-proBNP) level needs to be below a certain number if you don't have atrial fibrillation/flutter, and a higher number if you do have atrial fibrillation/flutter.

My heart pumps well, with an LVEF over 40% in the last year.

Exclusion Criteria

Your heart rate is either too fast (above 110 beats per minute) or too slow (below 40 beats per minute) when checked with a special heart test.

I am scheduled for a procedure to improve blood flow to my heart or other areas during the screening period.

My blood pressure is 180 mmHg or higher, or it's 160-179 mmHg and I'm on 3 or more blood pressure medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive once-monthly injections of either ziltivekimab or placebo for up to 4 years

48 months

Up to 20 clinic visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Ziltivekimab

Trial Overview The study tests if Ziltivekimab can treat heart failure with inflammation compared to a placebo. Participants will be randomly assigned to receive either the drug or placebo and monitored up to 4 years through clinic visits and an app that tracks injections and questionnaires.

How Is the Trial Designed?

Group I: Ziltivekimab Experimental Treatment 1 Intervention

Participants will receive ziltivekimab subcutaneous (s.c.) injection once-monthly and added standard of care for up to 4 years.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive ziltivekimab placebo s.c. injection once-monthly and added standard of care for up to 4 years.

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

Published Research Related to This Trial

ABP 654, a proposed biosimilar to ustekinumab, demonstrated pharmacokinetic similarity to both the US and EU versions of ustekinumab in a study involving 238 healthy subjects, indicating it behaves similarly in the body.

The study found no significant differences in safety, tolerability, or immunogenicity among ABP 654 and the reference products, suggesting that ABP 654 is a safe alternative for treating chronic inflammatory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Similarity of ABP 654, an Ustekinumab Biosimilar Candidate: Results from a Randomized, Double-blind Study in Healthy Subjects. Chow, V., Mytych, DT., Das, S., et al.[2023]

In a 5-year follow-up of the ENDEAVOR IV trial involving 1440 patients, the Endeavor zotarolimus-eluting stent (E-ZES) showed similar rates of target lesion revascularization and target vessel failure compared to the Taxus paclitaxel-eluting stent (PES), indicating comparable efficacy.

E-ZES was associated with a significantly lower incidence of cardiac death and myocardial infarction, particularly target vessel MI, and had reduced rates of very late stent thrombosis and late MI events compared to PES, suggesting improved long-term safety outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The "final" 5-year follow-up from the ENDEAVOR IV trial comparing a zotarolimus-eluting stent with a paclitaxel-eluting stent. Kirtane, AJ., Leon, MB., Ball, MW., et al.[2015]

Zarxio (filgrastim-sndz) is a biosimilar medication specifically designed to treat severe chronic neutropenia, a condition characterized by low levels of neutrophils, which are crucial for fighting infections.

As a biosimilar, Zarxio is expected to have similar safety and efficacy profiles to the original filgrastim, providing an effective treatment option for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zarxio (Filgrastim-sndz): The First Biosimilar Approved by the FDA. Awad, M., Singh, P., Hilas, O.[2020]

Over the past 30 years, heart failure management has significantly improved, particularly for patients with heart failure and reduced ejection fraction (HFrEF), leading to better quality of life and outcomes.

Ongoing trials are exploring both established and new pharmacological treatments that could enhance therapy for HFrEF and potentially benefit patients with heart failure with preserved ejection fraction (HFpEF) and other heart failure types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New perspectives and future directions in the treatment of heart failure. Pellicori, P., Khan, MJI., Graham, FJ., et al.[2021]

In a study of 75 patients with advanced chronic heart failure, the novel immune modulation therapy Celacade showed a significant reduction in the risk of death and hospitalization compared to placebo, indicating its potential efficacy in managing CHF.

While there was no significant improvement in the 6-minute walk test, more patients treated with Celacade experienced an improvement in their NYHA functional classification, suggesting a positive impact on heart failure symptoms and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Broad modulation of tissue responses (immune activation) by celacade may favorably influence pathologic processes associated with heart failure progression. Torre-Amione, G., Sestier, F., Radovancevic, B., et al.[2007]

MYL-1601D, a biosimilar insulin aspart, demonstrated pharmacokinetic and pharmacodynamic bioequivalence to both the US (Ref-InsAsp-US) and EU (Ref-InsAsp-EU) originator products in a study involving 71 healthy subjects.

The study found that MYL-1601D had a comparable safety profile to the originator products, indicating it is a safe alternative for managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and pharmacodynamic bioequivalence of biosimilar MYL-1601D with US and European insulin aspart in healthy volunteers: A randomized, double-blind, crossover, euglycaemic glucose clamp study. Hövelmann, U., Raiter, Y., Chullikana, A., et al.[2022]

Omecamtiv mecarbil is safe for heart failure patients, showing no increase in death or serious adverse events compared to placebo across eight studies.

The drug may improve heart function by significantly reducing heart rate and potentially enhancing left ventricular ejection fraction and systolic function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of omecamtiv mecarbil for heart failure: A systematic review and meta-analysis. Alqatati, F., Elbahnasawy, M., Bugazia, S., et al.[2022]

In a study of 5050 patients with heart failure, vericiguat did not significantly improve health status outcomes measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) compared to placebo, indicating it may not enhance quality of life despite its use.

However, vericiguat effectively reduced the risk of cardiovascular death or heart failure hospitalization across different baseline health statuses, suggesting it is beneficial for clinical outcomes in heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vericiguat and Health-Related Quality of Life in Patients With Heart Failure With Reduced Ejection Fraction: Insights From the VICTORIA Trial. Butler, J., Stebbins, A., Melenovský, V., et al.[2022]

Sacubitril/valsartan and ivabradine have been recently approved and shown to improve clinical outcomes in patients with heart failure with reduced ejection fraction, addressing a significant health challenge.

The review highlights various novel drug mechanisms under investigation for heart failure treatment, including targeting inflammatory mediators and specific receptor pathways, which may lead to new therapeutic options in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recently Approved and Under Investigation Drugs for Treating Patients with Heart Failure. Castro-Torres, Y., Katholi, RE.[2021]

In a study of 60 patients with recently decompensated systolic heart failure, treatment with the IL-1 receptor antagonist anakinra for 12 weeks led to a significant improvement in peak aerobic exercise capacity (peak Vo2) compared to baseline, indicating potential benefits of prolonged anti-inflammatory treatment.

While there was a trend towards lower rates of death or rehospitalization for heart failure in the anakinra groups, these differences were not statistically significant, suggesting that further research is needed to confirm the long-term benefits of anakinra in heart failure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-1 Blockade in Recently Decompensated Systolic Heart Failure: Results From REDHART (Recently Decompensated Heart Failure Anakinra Response Trial). Van Tassell, BW., Canada, J., Carbone, S., et al.[2018]

In a study involving 195 healthy participants, FKB327, a biosimilar to adalimumab, showed comparable bioavailability across three delivery methods: prefilled syringe, auto-injector, and vial, indicating that all methods can effectively deliver the medication.

The safety profiles were similar across all groups, with only mild treatment-emergent adverse events reported, and no new safety concerns were identified, suggesting that FKB327 is a safe alternative to the reference product.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1, randomized, open-label, single-dose study to assess the relative bioavailability of a subcutaneous dose of FKB327 when administered using a prefilled syringe, a prefilled auto-injector, or a vial with disposable syringe in healthy subjects. Bush, J., Kawakami, K., Muniz, R.[2020]

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]

The Heart Failure Collaboratory gathered a diverse group of stakeholders to discuss the need for standardizing background therapies in clinical trials for heart failure, particularly for patients with reduced ejection fraction.

The paper emphasizes the importance of establishing a common background therapy to improve the comparability and reliability of results in future heart failure treatment studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal Background Pharmacological Therapy for Heart Failure Patients in Clinical Trials: JACC Review Topic of the Week. Fiuzat, M., Hamo, CE., Butler, J., 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06200207

NCT06200207 | A Research Study Looking Into How ... Heart failure due to infiltrative cardiomyopathy (e.g., sarcoid, amyloid), arrhythmogenic right ventricular cardiomyopathy, Takutsubo cardiomyopathy, genetic ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37211246/

A randomized, double-blind, placebo-controlled, phase 2 trial Background: Despite optimal treatment, a residual inflammatory risk often remains in patients with atherosclerotic cardiovascular disease.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05636176

NCT05636176 | A Research Study to Look at How ... This study will be done to see if ziltivekimab can be used to treat people living with heart failure and inflammation.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1071916423004013

008 HERMES: Effects Of Ziltivekimab Versus Placebo On ... HERMES: Effects Of Ziltivekimab Versus Placebo On Morbidity And Mortality In Patients With Heart Failure With Mildly Reduced Or Preserved Ejection Fraction And ...

5. theglobeandmail.com theglobeandmail.com/investing/markets/stocks/NVO/pressreleases/35744782/novo-nordisks-ziltivekimab-study-a-potential-game-changer-in-heart-failure-treatment/

Novo Nordisk's Ziltivekimab Study: A Potential Game ... The study aims to evaluate the effectiveness of ziltivekimab in treating heart failure patients with systemic inflammation, focusing on reducing ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05021835

ZEUS - A Research Study to Look at How Ziltivekimab ... This study is conducted to see if ziltivekimab reduces the risk of having cardiovascular events (for example heart attack and stroke) in people with ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0914508723001120

Efficacy and safety of interleukin-6 inhibition with ... In the phase 2 RESCUE-2 trial, the IL-6 ligand mAb ziltivekimab significantly reduced inflammatory biomarkers associated with atherosclerosis in Japanese ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05636176

NCT05636176 | A Research Study to Look at How ... This study will be done to see if ziltivekimab can be used to treat people living with heart failure and inflammation.

9. onlinejcf.com onlinejcf.com/article/S1071-9164(23)00401-3/fulltext

HERMES: Effects Of Ziltivekimab Versus Placebo On ... The HERMES trial is an international, multicentre, parallel group, randomized, double-blind, study in patients with HFpEF and HFmrEF.