A randomized phase I pharmacokinetic trial comparing the potential biosimilar adalimumab (CinnoRA®) with the reference product (Humira®) in healthy volunteers.

Background: CinnoRA® (CinnaGen, Iran) is a biosimilar candidate for the reference adalimumab, Humira® (AbbVie, USA). This study aimed to compare the pharmacokinetics, safety, and tolerability of these products in healthy participants.Research design and methods: In this phase-I, randomized, double-blind trial, 74 healthy adult volunteers were randomized in a 1:1 ratio to receive a single 40 mg subcutaneous injection of CinnoRA® or Humira®. Serum concentrations of adalimumab were analyzed using a validated enzyme-linked immunosorbent assay and were evaluated by non-compartmental methods. Pharmacokinetic equivalence between groups was determined using the standard equivalence margins of 0.80 to 1.25.Results: The baseline characteristics were similar between study groups. Mean values of area under the serum concentration-time curve from time zero to infinity (AUCinf) and maximum serum concentration (Cmax) were similar in study groups and the 90% confidence intervals for the geometric mean ratios of AUCinf and Cmax were within the prespecified equivalence margins. There were no deaths and the total number of treatment-related adverse events was not statistically different between groups (p-value = 0.19).Conclusions: The results clearly showed the pharmacokinetic similarity of the biosimilar adalimumab to the originator. CinnoRA® was safe and well-tolerated in healthy volunteers, with no significant differences in safety from the reference product.Trial Registration: The trial is registered at ClinicalTrials.gov (# NCT03273192).