Pharmacokinetics and immunogenicity of T0001, a newly developed anti-TNFα fusion protein, in healthy volunteers.

PURPOSE: T0001 was the first mutant of recombinant fusion protein of human tumor necrosis factor receptor and Fc fragment (rhTNFR:Fc) based on etanercept on a global scale. This study was carried out to investigate the pharmacokinetics (PK) and immunogenicity of T0001 in healthy Chinese volunteers.

METHODS: This study was randomized, with a single ascending dose, and the first-in-human clinical trial of T0001. Healthy Chinese volunteers (n = 56; male: female = 1:1) were randomly assigned to receive a single subcutaneous (sc) injection of 10, 20, 35, 50, 65 or 75 mg of T0001. Blood samples were collected at designated time points after sc injection to assess immunogenicity and pharmacokinetics of T0001.

RESULTS: During the study, no serious adverse events were observed. T0001 was slowly absorbed with a median Tmax of 84 h and slowly eliminated with a T1/2Z of 42.1-58.2 h. In the dose-exposure proportionality analysis, the estimated points for AUC0-∞ and Cmax were 0.87 with a 90% CI of 0.76-0.98 and 0.86 with a 90% CI of 0.74-0.97 respectively. The plasma concentration of free (unbound T0001) plasma TNFα and total (bound and unbound T0001) TNFα both increased significantly after the injection of T0001. Ten out of 56 volunteers (17.9%) tested positive for anti-drug antibodies (ADAs) at a low level.

CONCLUSIONS: T0001 was safe and well-tolerated at doses up to 75 mg. Cmax and AUC0-∞ had an increasing tendency with dose levels, but we could not conclude that T0001 has linear PK properties in this study.