AB0285 RANDOMIZED, OPEN-LABEL, SINGLE-DOSE, PARALLEL-GROUP PHARMACOKINETIC STUDY OF PF-06410293, AN ADALIMUMAB BIOSIMILAR, BY SUBCUTANEOUS DOSING USING A PREFILLED SYRINGE OR A PREFILLED PEN IN HEALTHY SUBJECTS

Abstract

Background:Similarity in efficacy, safety, and immunogenicity (IMG) of PF-06410293 (ADL-PF), an adalimumab (ADL) biosimilar, and reference ADL sourced from the European Union (ADL-EU), by subcutaneous (SC) injection using a prefilled syringe (PFS), have been demonstrated in a randomised controlled trial in patients with rheumatoid arthritis (RA) (NCT02480153).Objectives:To determine if the pharmacokinetics (PK), safety and tolerability of ADL-PF were similar following a single SC dose by prefilled pen (PFP) or PFS in healthy subjects (NCT02572245).Methods:In this phase 1, 2-arm study, healthy subjects, aged 18–55 years, were randomised (1:1) to receive ADL-PF (40 mg, SC) in the lower abdomen or upper anterior thigh by PFS or PFP. Primary endpoints were maximum observed serum concentration (Cmax) and area under the serum concentration–time profile from time 0–2 weeks after dosing (AUC0-2wk). Safety, including injection-site reactions (ISRs), and secondary PK endpoints, were also assessed. Bioequivalence between ADL-PF administered by PFS or PFP device was demonstrated if the 90% confidence intervals (CIs) for the test/reference ratios of AUC0-2wkand Cmaxfell within the 80.00–125.00% pre-specified margin.Results:A total of 164 subjects, stratified by body weight were randomised and assigned to treatment; ADL-PF PFS (n=81) and PFP (n=83). Baseline characteristics were comparable between treatment arms. 163 subjects were included in the primary PK analysis. The concentration–time profiles were comparable between the ADL-PF PFS and PFP treatment arms, and were characterized by an increase in serum drug concentrations, with the Cmaxachieved at approximately 6-7 days, followed by a multi-phasic decline in drug concentrations. The 90% CIs for test/reference ratios of the geometric means for the primary PK parameters fell within the pre-specified margin (Table). In total, 50 and 51 treatment-emergent adverse events (AEs) were reported in 31 (38.3%) and 29 subjects (34.9%), respectively, in the ADL-PF PFS and PFP groups. One subject experienced an unrelated serious AE in the ADL-PF PFS group. Injection-site pain was similar between treatment arms at all time points, and for the 2 injection-site locations. IMG testing was limited to subjects experiencing an ISR and/or rash AE, and a matched control group, with 11 (11/15; 73.3%) and 7 (7/15; 46.7%) subjects, respectively, testing anti-drug antibody (ADA)-positive. Amongst ADA-positive subjects, a majority (12/18) also tested positive for neutralising ADAs (7/11 [63.6%] and 5/7 [71.4%] subjects, respectively).Conclusion:This study demonstrated that the PK of ADL-PF was comparable following SC administration using either a PFS or PFP device. ADL-PF by PFS or PFP injection was well tolerated by healthy subjects, with the distribution of AEs, including ISRs, being similar between treatment arms.Table.Summary of Statistical Comparisons of PK Exposure Parameters between Test and Reference Treatments (PK Analysis Set)PK parameter (units)Adjusted geometric meansRatioa,b90% CIfor ratiobADL-PF PFP (test)ADL-PF PFS (reference)Cmax(μg/mL)4.454.13107.7499.16–117.06AUC0-2wk(μg•hr/mL)11501100104.8995.76–114.89AUCT(μg•hr/mL)2040210097.2386.75 – 108.98AUC0-inf(μg•hr/mL)22002150102.2791.12 – 114.78Tmax(hr)c142 (45.4, 336)166 (47.7, 674)a(test/reference) of adjusted means.bRatios and 90% CIs are expressed as percentages.cMedian (range).ADL-PF, PF-06410293; AUC, area under the serum concentration–time profile; AUC0-2wk, AUC from time 0–2 weeks after dosing; AUCinf, AUC from time 0 extrapolated to infinity; AUCT, AUC from time 0 to the time point of the last quantifiable concentration; Cmax, maximum observed serum concentration; CI, confidence interval; h, hour(s); PK, pharmacokinetic(s); PFP, prefilled pen; PFS, prefilled syringe; Tmax, time of maximum serum concentration.Acknowledgments:Medical writing support was provided by Iain McDonald of Engage Scientific Solutions. The study was funded by Pfizer.Disclosure of Interests:Donna Cox Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Daniel Alvarez Shareholder of: Pfizer, Employee of: Pfizer, Amy Bock Shareholder of: Pfizer, Employee of: Pfizer, Carol Cronenberger Shareholder of: Pfizer, Employee of: Pfizer