Introduction
KJ103, a novel IgG degrading enzyme, has undergone rigorous Phase I clinical trials to evaluate its safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity. These trials, conducted in China and New Zealand, aimed to explore the therapeutic potential of KJ103 in various clinical settings, including gene therapy and organ transplantation.
Study Design and Methodology
Two independent, randomized, blinded, placebo-controlled, single ascending-dose Phase I studies were conducted. The trials enrolled healthy volunteers aged 18-55 years, with a BMI between 18 and 30 kg/m². Participants were administered KJ103 at doses ranging from 0.01 to 0.40 mg/kg, with safety and tolerability as primary endpoints.
Safety and Tolerability
Across both studies, KJ103 demonstrated a favorable safety profile. No dose-limiting toxicities or severe adverse events were reported. The most common adverse event related to KJ103 was elevated alanine aminotransferase (ALT), with no severe infections observed.
Pharmacodynamics and Pharmacokinetics
KJ103 effectively reduced IgG levels in a dose-dependent manner, with significant reductions observed at doses of 0.12 mg/kg and above. The enzyme exhibited rapid distribution and slow elimination, with IgG levels recovering to baseline within 1 to 2 months post-administration.
Immunogenicity
The immunogenicity of KJ103 was low, with pre-existing anti-drug antibodies (ADAs) present in only 33.82% of participants. ADA levels peaked approximately two weeks post-administration and returned to baseline within six months, indicating a transient immune response.
Conclusion
KJ103 has shown promising results in Phase I trials, with excellent safety, tolerability, and efficacy in reducing IgG levels. Its potential applications in gene therapy and organ transplantation are significant, offering a new avenue for treatment ineligibility due to AAV NAbs and complement-mediated immune reactions. Further studies are warranted to explore the full therapeutic potential of KJ103 in clinical settings.
