A multi-center, open-label, randomized, parallel-controlled phase II study comparing pharmacokinetic, pharmacodynamics and safety of ripertamab (SCT400) to rituximab (MabThera) in patients with CD20-positive B-cell non-Hodgkin lymphoma.

OBJECTIVE

This multi-center, open-label, randomized, parallel-controlled phase II study aimed to compare the pharmacokinetics (PK), pharmacodynamics (PD) and safety profile of ripertamab (SCT400), a recombinant anti-CD20 monoclonal antibody, to rituximab (MabThera) in patients with CD20-positive B-cell non-Hodgkin lymphoma (NHL).

METHODS

Patients with CD20-positive B-cell NHL who achieved complete remission or unconfirmed complete remission after standard treatment were randomly assigned at a 1:1 ratio to receive a single dose of ripertamab (375 mg/m) or rituximab (MabThera, 375 mg/m). PK was evaluated using area under the concentration-time curve (AUC) from time 0 to d 85 (AUC), AUC from time 0 to week 1 (AUC), AUC from time 0 to week 2 (AUC), AUC from time 0 to week 3 (AUC), AUC from time 0 to week 8 (AUC), maximum serum concentration (C), terminal half-life (T), time to maximum serum concentration (T) and clearance (CL). Bioequivalence was confirmed if the 90% confidence interval (90% CI) of the geometric mean ratio of ripertamab/rituximab was within the pre-defined bioequivalence range of 80.0%-125.0%. PD, immunogenicity, and safety were also evaluated.

RESULTS

From December 30, 2014 to November 24, 2015, a total of 84 patients were randomized (ripertamab, n=42; rituximab, n=42) and the PK analysis was performed on 76 patients (ripertamab, n=38; rituximab, n=38). The geometric mean ratios of ripertamab/rituximab for AUC, AUC, and C were 96.1% (90% CI: 87.6%-105.5%), 95.9% (90% CI: 86.5%-106.4%) and 97.4% (90% CI: 91.6%-103.6%), respectively. All PK parameters met the pre-defined bioequivalence range of 80.0%-125.0%. For PD and safety evaluation, there was no statistical difference in peripheral CD19-positive B-cell counts and CD20-positive B-cell counts at each visit, and no difference in the incidence of anti-drug antibodies was observed between the two groups. The incidences of treatment-emergent adverse events and treatment-related adverse events were also comparable between the two groups.

CONCLUSIONS

In this study, the PK, PD, immunogenicity, and safety profile of ripertamab (SCT400) were similar to rituximab (MabThera) in Chinese patients with CD20-positive B-cell NHL.