Comparison of pharmacokinetics, safety and tolerability of secukinumab administered subcutaneously using different delivery systems in healthy volunteers and in psoriasis patients

Abstract

Aims The aim of the study was to compare the pharmacokinetics (PK), safety and tolerability of secukinumab with different devices for subcutaneous (s.c.) administration of 2 mL. Methods A phase 1 study in healthy subjects with 6 devices to administer 2 mL injection volumes was conducted to evaluate the serum PK, safety and tolerability of secukinumab following single s.c. injection of 300 mg in the abdomen (either side) or in the thigh (either leg). Primary PK endpoints were maximum observed serum concentration and area under the serum concentration–time curve. The impact of device, site and side of injection on serum exposure was evaluated. In a phase 3 study in psoriasis patients, PK of secukinumab was evaluated following multiple s.c. injections of 300 mg by either 2 × 1‐mL prefilled syringe or 1 × 2‐mL prefilled syringe. Results Mean serum concentration–time profiles for administration as 2 × 1 mL injections or as 1 × 2 mL injections were similar. With an injection volume of 2 mL, perceived injection pain was not different from 2 × 1 mL injections. A nonclinically significant difference in PK endpoints was observed between thigh and abdomen. Results with a 2 mL prefilled syringe in a 1‐year phase 3 study in patients confirmed PK results observed in the phase 1 study. Conclusion Collective evidence from both studies demonstrated that 2‐mL injections of secukinumab into the abdomen or thigh using different devices resulted in comparable PK characteristics and were all well tolerated without noticeable local reactions.

Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, and Immunogenicity of the QX002N anti-IL-17 Monoclonal Antibody: A Phase I, Randomized, Double-Blind, Single Ascending Dose Study in Healthy Chinese Volunteers

“…The most frequently reported TEAEs related to drug administration were high bilirubin and aspartate aminotransferase levels, low leukocyte and neutrophils counts, urinary tract infection, and urinary erythrocytes. Most of the TEAEs were associated with infections, consistent with the literature (Gomez et al, 2017;Bruin et al, 2020). However, in our study, the incidence of TEAEs in each category was lower than 15%, as compared to that of similar drugs in the literature (Ellis et al, 2019), in which the incidences of nasopharyngitis and headache were more than 50%, suggesting that the safety of QN002N is better than that of other monoclonal antibodies.…”

Absorption, Distribution, Metabolism, and Excretion of Therapeutic Proteins: Current Industry Practices and Future Perspectives

“…However, for some monoclonal antibodies, statistically significant differences have been observed when comparing injection to the thigh or abdomen (Bittner et al, 2018). Known examples include secukinumab (Bruin et al, 2020), ixekizumab (Talz label), bococizumab (Wang et al, 2017), and mepolizumab ( Ortega et al,201). For golimumab, statistically non-significant differences were observed (Xu et al, 2010).…”

Secukinumab demonstrates efficacy, safety, and tolerability upon administration by 2 ml autoinjector in adult patients with plaque psoriasis: 52‐week results from MATURE, a randomized, placebo‐controlled trial

“…15 Furthermore, an earlier PK comparability study with secukinumab in healthy patients provided evidence for good safety and tolerability with various 2 ml devices. 16 Here we report the efficacy and safety results over a 52-week period from the MATURE study. (last patient, last visit).…”