Kidney Week

Abstract: PUB044

Design of a Phase 3 Cardiovascular Outcomes Trial of the Anti-Interleukin-6 Antibody Clazakizumab in Patients with ESKD on Dialysis (POSIBIL6ESKD)

Session Information

• Publication Only

Category: Cardiovascular-Kidney-Metabolic Health

• 602 Cardiovascular-Kidney-Metabolic Health: Clinical

Authors

• Chertow, Glenn M., Stanford University School of Medicine, Stanford, California, United States

Glenn M. Chertow, MD, MPH, FASN

• Fedorov, Viktor, CSL Behring LLC, King of Prussia, Pennsylvania, United States

Viktor Fedorov, MD

• Felker, Gary Michael, Duke University Duke Clinical Research Institute, Durham, North Carolina, United States

Gary Michael Felker, MD

• Heise, Mark A., CSL Behring LLC, King of Prussia, Pennsylvania, United States

Mark A. Heise, PhD

• Velkoska, Elena, CSL Behring LLC, King of Prussia, Pennsylvania, United States

Elena Velkoska, PhD

• Alperovich Lehrer, Gabriela, CSL Behring LLC, King of Prussia, Pennsylvania, United States

Gabriela Alperovich Lehrer, MD, PhD

• Fellstrom, Bengt C., Uppsala universitet Medicinska fakulteten, Uppsala, Uppsala County, Sweden

Bengt C. Fellstrom, MD, PhD

• Charytan, David M., New York University Grossman School of Medicine, New York, New York, United States

David M. Charytan, MD, MS, MSc

• Worden, Joshua N., CSL Behring LLC, King of Prussia, Pennsylvania, United States

Joshua N. Worden, MS

• Gibson, C. Michael, Harvard Medical School, Boston, Massachusetts, United States

C. Michael Gibson, MD, MS

• Goodman, Shaun G., Canadian Heart Research Centre, North York, Ontario, Canada

Shaun G. Goodman, MD, MSc

• Jardine, Meg, NHMRC Clinical Trials Centre, Camperdown, New South Wales, Australia

Meg Jardine, MBBS, PhD

• Levin, Adeera, The University of British Columbia, Vancouver, British Columbia, Canada

Adeera Levin, MD

• Lokhnygina, Yuliya, Duke University Duke Clinical Research Institute, Durham, North Carolina, United States

Yuliya Lokhnygina, MSc, PhD

• Mehran, Roxana, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Roxana Mehran

• Stenvinkel, Peter, Karolinska Institutet, Stockholm, Stockholm County, Sweden

Peter Stenvinkel, MD, PhD

• Wang, Angela Yee-Moon, Singapore General Hospital, Singapore, Singapore

Angela Yee-Moon Wang, MD, PhD

• Wheeler, David C., University College London, London, England, United Kingdom

David C. Wheeler, MD

• Zoccali, Carmine, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli, Reggio Calabria, Calabria , Italy

Carmine Zoccali, MD, DrMed, FASN

• Ridker, Paul M., Harvard Medical School, Boston, Massachusetts, United States

Paul M. Ridker, MD, MPH

• Mahaffey, Kenneth W., Stanford University School of Medicine, Stanford, California, United States

Kenneth W. Mahaffey, MD

• Wolf, Myles, Weill Cornell Medicine, New York, New York, United States

Myles Wolf, MD, MS, MSc

Background

Patients with end-stage kidney disease (ESKD) undergoing maintenance dialysis experience a disproportionately high burden of cardiovascular (CV) morbidity and mortality, with few effective treatment or secondary prevention options currently available. Systemic inflammation, driven in part by interleukin 6 (IL-6), is strongly associated with adverse CV outcomes in ESKD. Clazakizumab is a humanized monoclonal antibody targeting the IL-6 cytokine and is currently in development for the reduction of CV risk in patients on maintenance dialysis.

Methods

POSIBIL₆ESKD is a global, multicenter, randomized, double-blind, placebo-controlled, event-driven CV outcomes trial. Adults with ESKD on maintenance dialysis (hemodialysis or peritoneal dialysis) for ≥12 weeks, with established atherosclerotic CV disease or diabetes mellitus and evidence of systemic inflammation (hs-CRP ≥ 2.0 mg/L), are randomized 1:1 to receive clazakizumab 5 mg or placebo intravenously every 4 weeks, in addition to standard of care. The Phase 3 dose was selected based on efficacy, safety and population pharmacokinetics and pharmacodynamic model data from the previously published Phase 2b dose-finding study (Nat Med 2024).

Approximately 2,190 participants are planned for enrolment and will be treated until accrual of a prespecified number (878) of adjudicated primary events. The primary endpoint is time to first occurrence of myocardial infarction or CV death. Key secondary endpoints include composites and individual components of CV death, myocardial infarction, ischemic stroke, heart failure hospitalization, and all-cause mortality, as well as total hospitalization burden. CV events are adjudicated by an independent, blinded clinical events committee. Safety assessments include treatment-emergent adverse events, serious adverse events, and selected laboratory parameters, with oversight by an independent data monitoring committee.

Results

Not Applicable

Conclusion

This Phase 3 trial is designed to evaluate whether targeted IL-6 inhibition with clazakizumab reduces major adverse CV events in a high-risk dialysis population. The event-driven design, large sample size, and comprehensive endpoint adjudication aim to provide evidence on the efficacy and safety of anti-inflammatory therapy for CV risk reduction in patients with ESKD on dialysis.

Funding

• Commercial Support – CSL Behring LLC