Kidney Week

Abstract: TH-PO1261

First-in-Human Clinical Trial of CPV-104, a Recombinant Version of Human Complement Factor H: Safety, Tolerability, and Pharmacokinetics for C3 Glomerulopathy

Session Information

• Late-Breaking Research Posters
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Wiesener, Michael Sean, University Hospital Erlangen, Erlangen, Germany

Michael Sean Wiesener, MD, DrMed

• Khullar, Dinesh, Max Super Speciality Hospital Saket, New Delhi, DL, India

Dinesh Khullar, MD, MBBS, DM, FASN

• Jilma, Bernd, Universitatsklinikum AKH Wien, Vienna, Austria

Bernd Jilma, MD

• Zipfel, Peter, Koania, Hamburg, Germany

Peter Zipfel

• Bauer, Martin, One04 Therapeutics, Freiburg, Germany

Martin Bauer, MD, DrMed

• Cochlovius, Björn, One04 Therapeutics, Freiburg, Germany

Björn Cochlovius, PhD

Background

C3 glomerulopathy (C3G) is an ultra-rare, complement-mediated kidney disease characterized by dysregulation of the alternative complement pathway, resulting in glomerular C3 deposition, proteinuria and progressive kidney failure. CPV-104, a full-length recombinant version of human complement factor H, normalized plasma C3 levels and reduced renal C3 deposits in preclinical models (DOI:10.3389/fimmu.2025.1535547). This first-in-human trial evaluated safety, tolerability, and pharmacokinetics (PK) of CPV-104 in healthy volunteers (HVs) and patients with C3G.

Methods

This 2-part, dose-escalation Phase 1 trial evaluated sentinel dosing of CPV-104 in HVs and C3G patients. Part 1 was a randomized, double-blind, placebo-controlled single ascending dose (SAD) study in 21 HVs receiving a single intravenous (IV) dose of CPV-104 (ranging from 1-15 mg/kg) or placebo (29-day follow-up). Part 2 was an open-label, single-arm multiple ascending dose (MAD) study in 12 C3G patients receiving weekly IV CPV-104 doses (3.75 and 7.5 mg/kg; 50-day follow-up) over 4 weeks. The primary objective was to assess the safety and tolerability of CPV-104; secondary objectives included characterization of PK and immunogenicity.

Results

Interim analysis demonstrated that CPV-104 was safe and well-tolerated across all doses in both parts of the study, with no reports of serious/severe adverse drug reactions, deaths, study discontinuations, or anti-drug antibodies (Table 1). Systemic exposure (C_max and AUC) increased dose proportionally with both single and repeated dosing, indicating a linear PK profile. The plasma half-life (t_1/2) of 3-4 days, along with the low accumulation seen at steady state in Part 2, supports the once-weekly dosing regimen.

Conclusion

CPV-104 was generally safe and well tolerated across single and multiple ascending IV doses and demonstrated a favorable PK profile. These findings and the encouraging efficacy trends observed support further clinical development of CPV-104 in C3G and other complement-mediated diseases.

Funding

• Commercial Support – One04 Therapeutics