Ziltivekimab for Heart Attack

(ARTEMIS Trial)

Recruiting at 1143 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: Unknown

Duration: up to 2 years

10000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether ziltivekimab can benefit individuals hospitalized due to a heart attack. The researchers aim to determine if the medication can reduce the risk of future heart attacks or strokes. Participants will receive either ziltivekimab or a placebo (a dummy treatment) and will inject the medication once a month for about two years. Ideal candidates include those who have experienced a heart attack, possibly with diabetes, kidney issues, or previous strokes, and are not currently on fibrinolytic therapy (clot-busting drugs). As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking heart attack prevention.

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.

Is there any evidence suggesting that ziltivekimab is likely to be safe for humans?

Research has shown that ziltivekimab is under study for its potential to aid those who have experienced a heart attack. Early results suggest that participants generally tolerate ziltivekimab well. Although specific side effects have not been detailed, the treatment's progression to a later phase of clinical trials indicates promising earlier safety results. This phase typically focuses on confirming the treatment's efficacy and safety in a larger group. While ziltivekimab is not yet approved for any condition, its ongoing clinical trials are a positive sign for its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for heart attacks, which usually include medications like aspirin, beta-blockers, and statins, Ziltivekimab targets inflammation specifically by acting on a protein called interleukin-6 (IL-6). This novel approach could offer benefits beyond traditional therapies by potentially reducing inflammation more effectively, which is a key factor in heart attack recovery. Researchers are excited about Ziltivekimab because it is administered as a once-monthly injection, making it more convenient and potentially improving patient adherence compared to daily pills. Additionally, its ability to be administered shortly after a heart attack might help to improve outcomes right from the start of treatment.

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

Research has shown that ziltivekimab, which participants in this trial may receive, might help people who have had a heart attack. This medicine blocks a protein in the body that causes inflammation, a factor linked to heart issues. Early findings suggest that reducing inflammation can lower the risk of another heart attack or stroke. Although ziltivekimab is not yet approved for use, initial studies are promising for managing heart health after a heart attack. Further research is underway to confirm these benefits. ^{1 3 6 7 8}

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 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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Ziltivekimab

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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 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 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 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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06118281

ARTEMIS - A Research Study to Look at How Ziltivekimab ... 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.

2. trialx.com trialx.com/clinical-trials/listings/296264/artemis-a-research-study-to-look-at-how-ziltivekimab-works-compared-to-placebo-in-people-with-a-heart-attack/

ARTEMIS - A Research Study to Look at How Ziltivekimab ... Clinical trial for Cardiovascular Risk | Acute Myocardial Infarction ... Ziltivekimab Works Compared to Placebo in People With a Heart Attack.

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

NCT05636176 | A Research Study to Look at How ... ... myocardial infarction [MI] or heart failure [HF] hospitalisation). ... Heart Diseases. Cardiovascular Diseases. Heart Failure. ziltivekimab. Plan for ...

4. healthpartners.com healthpartners.com/institute/research/studies/artemis-effects-of-ziltivekimab-versus-placebo-on-cardiovascular-outcomes-in-patients-with-acute-myocardial-infarction/

ARTEMIS - Effects of ziltivekimab versus placebo on ... ARTEMIS – Effects of ziltivekimab versus placebo on cardiovascular outcomes in patients with acute myocardial infarction. Success!,Accepting participants ...

5. withpower.com withpower.com/trial/phase-3-heart-failure-5-2024-0ba15

Ziltivekimab for Heart Attack (ARTEMIS Trial) What data supports the effectiveness of the drug Ziltivekimab for heart attack? ... Prehospital ticagrelor in ST-segment elevation myocardial infarction.

6. novonordisk-trials.com novonordisk-trials.com/trials-conditions/all-trials-v2/EX6018-4979.html

ARTEMIS - A Research Study to Look at How Ziltivekimab ... ARTEMIS - A Research Study to Look at How Ziltivekimab Works Compared to Placebo in People With a Heart Attack ... Acute Myocardial Infarction (AMI) ...

7. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT06118281

ARTEMIS - A Research Study to Look at How Ziltivekimab ... 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.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8861265/

From RESCUE to ZEUS: will interleukin-6 inhibition with ... All of these findings, and others, support the likelihood that lowering IL-6 activity will reduce incidence rates not just of myocardial ...