Experimental C3G therapy may reduce protein in urine, early data suggest
Phase 1 findings also showed stable kidney function and good tolerability
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A Phase 1 clinical trial of the experimental therapy CPV-104 showed encouraging early findings in people with C3 glomerulopathy. (Image from iStock)
One04 Therapeutics’ first-in-class experimental therapy CPV-104 showed early signs of reducing protein in the urine in people with C3 glomerulopathy (C3G), while kidney function remained stable, according to interim data from an early-stage clinical trial.
Results from the Phase 1 study (NCT07483827), conducted in Europe, also showed the candidate therapy was generally well tolerated in people with C3G and healthy volunteers. The interim analysis showed that the study met its predefined primary and secondary objectives.
“Meeting primary and secondary study objectives and seeing an early signal of biological activity marks an important milestone for CPV-104,” Björn Cochlovius, PhD, CEO of One04, said in a company press release.
The data were presented in a late-breaking poster at the American Society of Nephrology’s Kidney Week 2026, held last month in Denver, Colorado. The poster was titled “First-in-human clinical trial of CPV-104, a recombinant version of human complement Factor H: safety, tolerability, and pharmacokinetics for C3 glomerulopathy.”
Experimental therapy aims to restore immune system balance
C3G is a rare kidney disease in which an overactive complement system, part of the immune system, damages the glomeruli, the kidney’s tiny filtering units. As kidney damage worsens, symptoms may include blood in the urine (hematuria), protein in the urine (proteinuria), swelling in the face, hands, feet, or legs, and fatigue.
CPV-104 is a lab-made version of human Factor H, a protein that helps regulate the complement system. The therapy is designed to help restore balance to the overactive complement system, with the goal of slowing C3G progression.
CPV-104 was originally developed by eleva GmbH, which separated its operations into two stand-alone companies, Eleva Biologics and One04 Therapeutics, in September 2026. Both remain owned by eleva GmbH, while One04 now owns and is developing CPV-104.
The Phase 1 study has two parts and is being conducted at sites across Europe. In the first part, called single ascending dose (SAD), participants received one intravenous (into-the-vein) dose of CPV-104 or a placebo. Successive groups were given higher doses of CPV-104.
A total of 21 healthy volunteers were enrolled across four dose groups (1, 3.75, 7.5, and 15 mg/kg). All participants in the first group were given CPV-104, while those in the next three groups were randomly assigned to receive CPV-104 or a placebo.
The trial’s second part, called multiple ascending dose (MAD), includes three groups totaling 18 adults with C3G. Participants receive four weekly CPV-104 infusions at doses of 3.75, 7.5, or 15 mg/kg. Dosing in the highest-dose group (15 mg/kg) is ongoing.
An independent safety review committee examined the data before each dose increase and, in the MAD part, before the third and fourth doses.
Early trial findings show good tolerability, signs of activity
The interim analysis was conducted after completion of two of the three planned MAD groups. It met the primary safety goal and secondary goals of assessing the therapy’s tolerability, pharmacokinetics (how the drug moves through the body), and immunogenicity (its ability to trigger an immune response).
CPV-104 was generally well tolerated at single doses up to 15 mg/kg in the SAD portion and weekly doses of 7.5 mg/kg for four weeks in the MAD portion. No serious adverse drug reactions, serious treatment-emergent adverse events, deaths, or treatment discontinuations were reported. No anti-drug antibodies were detected in samples that could be evaluated.
As doses increased, levels of CPV-104 in the body rose roughly in proportion. The drug’s half-life — the time it takes for its level in the body to drop by half — was three to four days. Weekly dosing led to a small buildup of CPV-104 in the body, which the company said supports further study of once-weekly dosing.
Exploratory analyses of the MAD portion showed early signs of reduced protein in the urine (proteinuria) at 7.5 mg/kg, while estimated glomerular filtration rate (eGFR), a measure of how well the kidneys filter blood, remained stable. The MAD portion of the study was open-label and single-arm, meaning researchers and participants knew which treatment was being given, and all patients received CPV-104 rather than a placebo.
The company described these preliminary findings as encouraging and said they support continued evaluation of CPV-104 as a potentially disease-modifying therapy for C3G.
“I am encouraged by the safety and tolerability observations to date and by the early findings on kidney function in patients with C3G,” said Michael Wiesener, MD, senior physician at University Hospital Erlangen in Germany and presenting author of the poster. “This is an early Phase 1 study with a small number of patients and a short treatment period, but these results support continued clinical evaluation of CPV-104.”
