Ziltivekimab for Heart Failure

(HERMES Trial)

Recruiting in Palo Alto (17 mi)

+1434 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Novo Nordisk A/S

Disqualifiers: Recent MI, Stroke, Unstable angina, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing ziltivekimab to see if it can help people with heart failure and inflammation by reducing inflammation and improving heart function.

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.

What data supports the idea that the drug Ziltivekimab for Heart Failure is an effective treatment?

The available research does not provide specific data supporting the effectiveness of Ziltivekimab for treating heart failure. Instead, it mentions a study where Ziltivekimab was used to reduce inflammation in patients with chronic kidney disease, not heart failure. Other studies focus on different treatments for heart failure, like Anakinra and Celacade, but not Ziltivekimab. Therefore, there is no direct evidence from the provided information that Ziltivekimab is effective for heart failure. ^{1 2 3 4 5}

What safety data is available for Ziltivekimab in heart failure treatment?

The provided research does not contain specific safety data for Ziltivekimab or its other names (COR-001, MEDI-5117, etc.) in the context of heart failure treatment. The articles focus on other treatments and drugs for heart failure, such as omecamtiv mecarbil, anakinra, and vericiguat, but do not mention Ziltivekimab or its associated names. ^{1 6 7 8 9}

Is Ziltivekimab a promising drug for heart failure?

The provided research articles do not contain information about Ziltivekimab or its effectiveness for heart failure. Therefore, we cannot determine if Ziltivekimab is a promising drug for heart failure based on the given data. ^{10 11 12 13 14}

Research Team

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Placebo (Other)
• Ziltivekimab (Monoclonal Antibodies)

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.

Participant Groups

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

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. 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]

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

Broad modulation of tissue responses (immune activation) by celacade may favorably influence pathologic processes associated with heart failure progression. [2007]

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

Interleukin-1 Blockade in Recently Decompensated Systolic Heart Failure: Results From REDHART (Recently Decompensated Heart Failure Anakinra Response Trial). [2018]

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

Optimal Background Pharmacological Therapy for Heart Failure Patients in Clinical Trials: JACC Review Topic of the Week. [2023]

6. India pubmed.ncbi.nlm.nih.gov

Safety and efficacy of omecamtiv mecarbil for heart failure: A systematic review and meta-analysis. [2022]

7. United States 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. [2022]

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

New perspectives and future directions in the treatment of heart failure. [2021]

9. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Recently Approved and Under Investigation Drugs for Treating Patients with Heart Failure. [2021]

10. England 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. [2020]

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

Pharmacokinetic Similarity of ABP 654, an Ustekinumab Biosimilar Candidate: Results from a Randomized, Double-blind Study in Healthy Subjects. [2023]

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

Zarxio (Filgrastim-sndz): The First Biosimilar Approved by the FDA. [2020]

13. United States 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. [2015]

14. England 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. [2022]