Table 2. Sensitivity analysis and evaluation of equivalence of PK parameters between HLX01 and reference rituximaba (375 mg/m2; phase 1b study) .
| Parameters | Patients | N | Dose corrected geometric mean (mg) | Geometric mean ratiob HLX01/reference rituximab (%) (90% CI) | |
| HLX01 | Reference rituximab | ||||
| PK, pharmacokinetic; PKAS, pharmacokinetics analysis set; ADA, anti-drug antibody; AUC0−91 d, area under the plasma concentration-time curve (from time zero to day 91); AUC0−inf, area under the plasma concentration-time curve (from time zero to infinity); 90% CI, 90% confidence interval; Cmax, maximum drug concentration; N, number of subjects in analysis set; a, Reference rituximab was sourced from China (MabThera®; rituximab-CN); b, Determined using WinNonlin analysis; c, Six patients were excluded from the sensitivity analysis due to ADA positivity after baseline; d, Two patients were excluded from the sensitivity analysis due to ADA positivity at consecutive time points; e, Patients with ADA positivity at baseline were included in the sensitivity analysis; f, A patient with extrapolated area as a percentage of total AUC0−inf (% AUCextra) >20% was excluded from the sensitivity analysis of AUC 0–inf; g, Two patients with baseline ADA positivity were included in the sensitivity analysis of AUC0−inf, one patient had % AUCextra >20% and was excluded from the sensitivity analysis of AUC 0−inf. | |||||
| AUC0−91 d
(×105 ng·h/mL) |
PKAS | 81 | 635.3 | 709.3 | 89.6 (80.4−99.8) |
| PKAS excluding patients with ADA positivityc | 75 | 660.2 | 728.7 | 90.6 (81.7−100.5) | |
| PKAS excluding patients with consecutive ADA positivityd | 79 | 649.1 | 715.0 | 90.8 (81.9−100.7) | |
| PKAS and patients with baseline ADA positivitye | 84 | 628.4 | 703.6 | 89.3 (80.3−99.3) | |
| AUC0−inf
(×105 ng·h/mL) |
PKASf | 80 | 667.3 | 767.1 | 87.0 (77.7−97.5) |
| PKAS excluding patients with ADA positivityf | 74 | 694.2 | 791.0 | 87.8 (78.7−97.9) | |
| PKAS excluding patients with consecutive ADA positivityf | 78 | 682.6 | 773.9 | 88.2 (79.1−98.4) | |
| PKAS and patients with baseline ADA positivityf,g | 82 | 660.1 | 767.1 | 86.1 (77.0−96.2) | |
| Cmax
(×105 ng/mL) |
PKAS | 81 | 2.1 | 2.1 | 102.6 (95.2−110.6) |
| PKAS excluding patients with ADA positivityc | 75 | 2.1 | 2.1 | 103.0 (95.1−111.5) | |
| PKAS excluding patients with consecutive ADA positivityd | 79 | 2.1 | 2.1 | 103.3 (95.8−111.5) | |
| PKAS and patients with baseline ADA positivitye | 84 | 2.1 | 2.1 | 101.6 (94.4−109.3) | |