Ziltivekimab for Heart Attack

(ARTEMIS Trial)

Recruiting at 954 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Novo Nordisk A/S

Disqualifiers: Chronic heart failure, Severe kidney impairment, Severe hepatic disease, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The research study is being done to see if ziltivekimab can be used to treat people who were admitted to hospital because of a heart attack. Ziltivekimab might reduce development of heart disease, thereby preventing new heart attacks or strokes. Participants will either get ziltivekimab (active medicine) or placebo (a dummy medicine which has no effect on the body). Which treatment participants get is decided by chance. The chance of getting ziltivekimab or placebo is the same. The participant will need to inject the study medicine into a flat skin surface in there stomach, thigh, or upper arm once every month. Ziltivekimab is not yet approved in any country or region in the world. It is a new medicine that doctors cannot prescribe. The study will last for about 2 years.

Will I have to stop taking my current medications?

The trial information does not specify whether 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 attack?

Research shows that Ziltivekimab, a drug targeting inflammation, significantly reduces inflammation markers in patients at high risk of heart-related issues, which suggests it might help in reducing heart attack risks. ^{1 2 3 4 5}

How is the drug Ziltivekimab unique for treating heart attacks?

Ziltivekimab is unique because it targets interleukin-6 (IL-6), a protein involved in inflammation, which is a different approach compared to traditional heart attack treatments that focus on blood flow and cholesterol. This drug's mechanism of action is similar to other IL-6 inhibitors used in rheumatoid arthritis, suggesting potential benefits in reducing inflammation-related cardiovascular risks. ^{6 7 8 9 10}

Research Team

Clinical Transparency dept. 2834

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

This trial is for adults who've been hospitalized with a heart attack. They should be able to join the study soon after their hospital stay and have had certain types of heart attacks (STEMI or NSTEMI). People with previous heart issues, diabetes, kidney disease, stroke, carotid disease, or multivessel coronary artery disease can also join.

Inclusion Criteria

I have a history of heart issues, diabetes, kidney disease, stroke, or artery disease.

I had a heart attack with specific ECG changes or troponin levels.

I was hospitalized for a heart attack confirmed by a special heart test.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an initial loading dose of ziltivekimab or placebo subcutaneously, followed by monthly injections for up to 2 years

up to 2 years

Monthly visits for injections

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ziltivekimab (Monoclonal Antibodies)

Trial Overview The ARTEMIS study tests if Ziltivekimab can prevent further heart problems in people who've had a heart attack compared to a placebo. Participants are randomly given either Ziltivekimab or placebo in equal chances over about two years.

Participant Groups

Group I: Ziltivekimab Experimental Treatment 1 Intervention

Participants will receive an initial loading dose of ziltivekimab Dose 1 subcutaneously (s.c.) as early as possible after invasive procedure, and latest within 36 hours of hospitalisation for ST-elevation myocardial infarction (STEMI) and within 48 hours of hospitalisation for non-ST-elevation myocardial infarction (NSTEMI), followed by ziltivekimab Dose 2 s.c. once-monthly during the treatment period (estimated up to 2 years) added to standard of care.

Group II: Placebo ziltivekimab Experimental Treatment 1 Intervention

Participants will receive placebo matched to ziltivekimab at an initial loading dose subcutaneously (s.c.) as early as possible after invasive procedure, and latest within 36 hours of hospitalisation for STEMI and latest within 48 hours of hospitalisation for NSTEMI, followed by placebo matched to ziltivekimab s.c. once-monthly during the treatment period (estimated up to 2 years) added to standard of care.

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

Duke Clinical Research Institute

Collaborator

Trials

69

Recruited

242,000+

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]

Anakinra, an interleukin-1 blocker, significantly reduces systemic inflammation and the incidence of heart failure events in patients with STEMI, regardless of how quickly it is administered after reperfusion, as shown in a study of 139 patients.

The treatment was effective in both groups analyzed based on the timing of administration, demonstrating a reduction in C-reactive protein levels and a lower combined rate of death or new onset heart failure, indicating its efficacy in managing acute inflammatory responses in heart conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and Pharmacological Implications of Time to Treatment with Interleukin-1 Blockade in ST-Segment Elevation Myocardial Infarction. Del Buono, MG., Damonte, JI., Moroni, F., et al.[2023]

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 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 1862 patients with STEMI, prehospital administration of ticagrelor did not significantly improve coronary reperfusion compared to in-hospital treatment, indicating that timing of administration may not impact this aspect of care.

However, prehospital treatment was associated with lower rates of definite stent thrombosis within the first 30 days, suggesting a potential safety benefit without increasing major bleeding events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prehospital ticagrelor in ST-segment elevation myocardial infarction. Montalescot, G., van 't Hof, AW., Lapostolle, F., et al.[2022]

In a study of 18,754 rheumatoid arthritis patients over a median follow-up of 4 years, biologic DMARDs like TNF inhibitors and abatacept were linked to a reduced risk of cardiovascular disease compared to conventional DMARDs.

Higher exposure to glucocorticoids increased cardiovascular risk, while the use of methotrexate, especially at higher doses, was associated with a lower risk of cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Risk of Cardiovascular Events Associated With Disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis. Ozen, G., Pedro, S., Michaud, K.[2021]

A network meta-analysis of 19 studies found that tocilizumab (TCZ) has comparable cardiovascular safety to other biological disease-modifying antirheumatic drugs (bDMARD), with no significant differences in major adverse cardiovascular outcomes (MACE) when compared to treatments like abatacept (ABA) and rituximab (RTX).

While TCZ was associated with increased cholesterol levels, it showed a lower risk of myocardial infarction compared to abatacept, indicating that TCZ is a safe option for rheumatoid arthritis patients regarding cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular safety of tocilizumab: A systematic review and network meta-analysis. Castagné, B., Viprey, M., Martin, J., et al.[2023]

In a study involving 357 rheumatoid arthritis patients, the IL-6 receptor blocker tocilizumab did not show a significant advantage over placebo in reducing cardiac biomarkers NT-proBNP and hsTnT after 24 weeks, suggesting it may not provide rapid cardiovascular benefits.

Both treatment groups experienced a decrease in NT-proBNP and hsTnT, but the reduction in hsTnT was actually greater in the placebo group, indicating that while tocilizumab is effective for RA, its impact on cardiovascular risk markers may not be as beneficial as expected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of IL-6 receptor blockade on high-sensitivity troponin T and NT-proBNP in rheumatoid arthritis. Welsh, P., Tuckwell, K., McInnes, IB., et al.[2022]

In a study of 8689 rheumatoid arthritis patients across Hong Kong, Taiwan, and Korea, interleukin-6 inhibitors (IL-6i) and Janus Kinase inhibitors (JAKi) showed no significant increase in cardiovascular events compared to tumor necrosis factor inhibitors (TNFi).

The pooled analysis indicated that both IL-6i and JAKi have a similar cardiovascular safety profile to TNFi, suggesting that these newer treatments do not pose additional cardiovascular risks for patients with rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular risk in rheumatoid arthritis patients treated with targeted synthetic and biological disease-modifying antirheumatic drugs: A multi-centre cohort study. Tong, X., Shen, CY., Jeon, HL., et al.[2023]

In a study of 1732 rheumatoid arthritis patients over 6431 patient-years, the use of Janus kinase inhibitors (JAKis) did not show a significant increase in major adverse cardiovascular events (MACEs) or cancer compared to tumor necrosis factor inhibitors (TNFis).

However, patients using JAKis experienced a higher rate of non-serious infections, particularly herpes zoster, with an incidence of 16.3 per 100 patient-years compared to 9.9 per 100 patient-years for TNFi users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of the JAK and TNF inhibitors in rheumatoid arthritis: real world data from the Hong Kong Biologics Registry. Mok, CC., So, H., Yim, CW., et al.[2023]

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

Clinical and Pharmacological Implications of Time to Treatment with Interleukin-1 Blockade in ST-Segment Elevation Myocardial Infarction. [2023]

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

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

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

Prehospital ticagrelor in ST-segment elevation myocardial infarction. [2022]

6. Canada pubmed.ncbi.nlm.nih.gov

The Risk of Cardiovascular Events Associated With Disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis. [2021]

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

Cardiovascular safety of tocilizumab: A systematic review and network meta-analysis. [2023]

8. Ireland pubmed.ncbi.nlm.nih.gov

Effect of IL-6 receptor blockade on high-sensitivity troponin T and NT-proBNP in rheumatoid arthritis. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Cardiovascular risk in rheumatoid arthritis patients treated with targeted synthetic and biological disease-modifying antirheumatic drugs: A multi-centre cohort study. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Safety of the JAK and TNF inhibitors in rheumatoid arthritis: real world data from the Hong Kong Biologics Registry. [2023]