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Kidney Week

Abstract: TH-PO1158

CER-001, an Engineered High-Density Lipoprotein, Shows Beneficial Pleiotropic Effects in Patients with Sepsis in RACERS: A Phase 2A Randomized Control Trial

Session Information

  • Late-Breaking Posters
    November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 102 AKI: Clinical, Outcomes, and Trials

Authors

  • Fiorentino, Marco, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • Stasi, Alessandra, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • Franzin, Rossana, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • Gesualdo, Loreto, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
Background

The cytokine storm, an excessive immune response in sepsis, leads to acute kidney injury (AKI) and multi-organ failure. Our recent research highlighted the diverse properties of HDL, including LPS scavenging, anti-inflammatory effects, and preservation of endothelial integrity in an LPS-induced AKI swine model. Subsequently, we investigated the effects of CER-001, an apoA-I-containing engineered HDL, in a Phase 2a clinical trial.

Methods

We conducted an open-label, randomized, dose-ranging trial (RACERS study, N° EUDRACT 2020-004202-60) in 20 septic patients with intra-abdominal infection or urosepsis. Patients were randomized to receive standard of care (SOC; n=5) or SOC + CER-001 (5 mg/kg BID, 10 mg/kg BID, or 20 mg/kg BID; n=5 per group) on days 1, 2, 3, and 6. The primary outcomes were safety and efficacy in preventing AKI onset and/or progression, while secondary outcomes included changes in inflammatory and endothelial dysfunction markers.

Results

Patients were enrolled from the ICU and Nephrology Unit during the early phase of sepsis (median time from hospital admission: 2 days). CER-001 treatment was well tolerated, and no serious adverse events were attributed to its use. Rapid normalization of apoA-I levels with CER-001 was associated with significant and sustained LPS removal (p<0.05 on days 3, 6 and 9) and subsequent immunomodulation. CER-001 treatment led to rapid and significant decreases in pro-inflammatory cytokines (e.g., IL-6, IL-8, TNF-α, MCP-1), endothelial dysfunction markers (sVCAM, sICAM) and mortality biomarker (sTREM-1), resulting in improved clinical outcomes regardless of sepsis type or severity. CER-001-treated patients had a reduced risk of developing or progressing to severe AKI and, in a subset of critically ill patients, a shorter ICU stay and decreased need for organ support.

Conclusion

CER-001 replicates the beneficial pleiotropic effects of natural HDL by scavenging LPS, reducing inflammation, and protecting the endothelium. Therefore, CER-001 represents a promising therapeutic strategy for sepsis management, improving outcomes and mitigating the cytokine storm and associated organ damage often observed in our patients.

Funding

  • Commercial Support – Abionyx Pharma SA