CAN106 is safe and well-tolerated in healthy volunteers, according to the results of a phase 1 clinical trial that will be presented at the European Hematology Association’s 2022 annual congress. Moreover, the treatment resulted in a dose-dependent reduction in free C5 and CH50 as well as a complete and sustained complement blockade for up to 4 weeks.

These results may support the further clinical development of CAN106 in complement-mediated conditions such as cold agglutinin disease (CAD).

The randomized, double-blind, placebo-controlled, single-ascending-dose trial evaluated the safety and tolerability as well as pharmacokinetics, pharmacodynamics, and immunogenicity of a single dose of CAN106 in 31 healthy adults, aged 21 to 45 years. 


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Participants received either a placebo or a single dose of intravenous CAN106 at 0.25, 0.75, 2, 4, 8, or 12 mg/kg. The primary outcome measure of the study was the incidence of adverse events. This was assessed overall as well as by intensity, seriousness, type, and relatedness to CAN106.

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Secondary outcome measures were the pharmacokinetics, the pharmacodynamic effects on target engagement and serum hemolytic activity as measured by free C5 and CH50 levels respectively, and the occurrence of antibodies against CAN106.

The results showed that 7 people treated with CAN106 experienced 20 treatment-emergent adverse events. Similarly, 3 people given a placebo also experienced 5 treatment-emergent adverse events. Most of the treatment-emergent adverse events were unrelated to CAN106. They all resolved without causing any negative consequences. 

When the researchers analyzed in more detail patients who received the 2 highest doses of the treatment, they saw that 3 of them experienced 7 treatment-emergent adverse events. Most of these were mild and none were serious. They included a moderate infusion-related reaction, mild dizziness, and a mild increase in ALT, AST, hemoglobin, hematocrit, and red blood cells. These also all resolved without any negative consequences. 

The exposure to CAN106 was linear and proportional to dosage. There was also little variability in exposure between people. The terminal elimination half-life of the treatment was around 32 days. 

Importantly, CAN106 resulted in a dose-dependent reduction in free C5 and CH50 within 24 hours. All people who received the 2 highest doses had more than a 99% decrease in free C5 and more than 90% inhibition of CH50. The CH50 inhibition was sustained for 2 to 4 weeks.

CAN106 is a novel anti-C5 monoclonal antibody developed to bind to C5 under optimal pH conditions. It also has enhanced binding to FcRN, which increases its intracellular recycling and its half-life.

References

Khoo CM, Song X, Wu Q, Cox GF. A phase 1 single arm ascending dose study of CAN106, a long-acting anti-C5 complement monoclonal antibody in clinical development for PNH and other complement-mediated diseases. Poster presented at: 2022 European Hematology Association Annual Congress; June 9-12, 2022; Vienna, Austria and virtual. Poster 822.

Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a single ascending dose (SAD) of CAN106 administered intravenously (IV) in healthy subjects. US National Library of Medicine. Last updated January 19, 2022. Accessed May 18, 2022.