Bioequivalence, safety and immunogenicity of BI 695501, an adalimumab biosimilar candidate, compared with the reference biologic in a randomized, double-blind, active comparator phase I clinical study (VOLTAIRE®-PK) in healthy subjects

Background: This Phase I study (VOLTAIRE (R)-PK) aimed to evaluate three-way pharmacokinetic similarity (bioequivalence), safety, and immunogenicity of BI 695501 (a Humira (R) [adalimumab] biosimilar candidate) compared with US-and EU-approved Humira in healthy male subjects. Methods: Subjects (N = 327) were randomized 1: 1: 1 to receive one 40-mg subcutaneous dose of BI 695501, US-or EU-approved Humira; safety was assessed for 70 days. Bioequivalence was evaluated using the average bioequivalence method to test if the 90% confidence intervals (CIs) of the geometric means (BI 695501 vs US-and EU-approved Humira) for the primary end points were within prespecified acceptance ranges (80-125%). Immunogenicity was assessed using a sensitive bridging method. Results: Bioequivalence between BI 695501 and US-and EU-approved Humira was demonstrated with the 90% CIs of the ratios of all primary end points: Cmax, AUC0-inf, pred and AUC0-tz being within the prespecified acceptance ranges of 80-125%. Concentration vs time profiles were similar as were the time course and frequency of immunogenic responses. All study drugs showed similar safety and tolerability results. Conclusions: Three-way bioequivalence of BI 695501 to US-and EU-approved Humira was demonstrated; safety and immunogenicity results of the three study drugs were also similar.