A Preview of the Ziltevekimab ZEUS Clinical Trial

Data derived from the CANTOS trial, in which canakinumab was assessed to treat patients with atherosclerotic disease and kidney dysfunction, has opened a new lane of assessment into patients with the comorbid disease.

In the second segment of an interview with HCPLive during the American College of Cardiology (ACC) 2022 Scientific Sessions in Washington, DC, study author Paul M. Ridker, MD, of Brigham and Women’s Hospital and Harvard Medical School, discussed the details of the new ZEUS trial—in which clinicians will assess a new clinical agent, ziltevekimab, for lowering atherosclerotic inflammatory biomarker.

“It’s only launching around the world right now,” Ridker, the ZEUS trial co-author, said. “It’ll ultimately be in about 16-17 countries—we’re in the middle of country launches as we speak—investigators are just getting used to the protocol.”

On the basis of CANTOS outcomes showing a heightened priority of treating residual inflammation over residual hypertension in patients with atherosclerosis and chronic kidney disease (CKD), the ZEUS trial patient population will include such patients who are on full-dose statins and report a high sensitivity-grade CRP score at baseline.

Patients will receive 15 mg ziltevekimab subcutaneously once-monthly or placebo, plus standard of care. Ridker and colleagues are seeking a primary endpoint of standard major adverse cardiovascular event (MACE) outcomes, plus “fascinating” secondary endpoints including speed of declining GFR and renal endpoints.

“Launching a clinical trial during COVID is kind of complicated,” Ridker said. “We’re all kind of exhausted, and what we’re discovering is we need clinicians and coordinators to dig deep and (realize) this is really important. Our patients with CKD are at high risk.”

Ridker also discussed the increasing marriages between specialties in cardiovascular-based outcome clinical trials. As he noted, it’s standard practice at Harvard to emphasize pathophysiology processes.

“We teach inflammation, we teach coagulation, which affects all organs,” Ridker explained. “And I think it’s going to be much more common as we move into the future that there will be these large clinical trials that might be focused on Part A, but is very aware of Part B.”

Case in point: he noted that CANTOS considered outcomes relevant to lung cancer biomarkers—and now canakinumab is being investigated for such a treatment indication.

“We have diabetologists we work with very close,” Ridker said. “I have rheumatologists I work with closely, because an inflammatory disease is going to affect many different organs, and we need to figure out a way to work together."