Comparability of Pharmacokinetics, Safety, and Tolerability of Canakinumab Administration With One Injection (200 mg) of Pre‐Filled Syringe or Auto‐Injector Versus Two Injections (150 and 50 mg) of Pre‐Filled Syringe in Healthy Subjects

Abstract

This phase 1, randomized, open‐label, single‐dose, parallel‐group study aimed to describe the pharmacokinetic (PK) comparability and safety of canakinumab administered as a single 200 mg subcutaneous injection via pre‐filled syringes assembled within a needle safety device (PFS‐NSD) by HCP and auto‐injector (AI) by subject self‐administration versus two injections of 150 + 50 mg via PFS‐NSD by HCP. Healthy adults (18–55 years) were allocated to three arms: canakinumab 150 + 50 mg (PFS‐NSD; n = 78), canakinumab 200 mg (AI; n = 76), and canakinumab 200 mg (PFS‐NSD; n = 76). Multiplicity was addressed as two tests were compared with the same reference. Primary PK parameters were comparable across arms. The geometric mean ratios and 95% CI values of AUC _inf , AUC _last , and C _max were within bioequivalence limits of 0.80‐1.25 for both comparisons: (a) canakinumab 200 mg AI versus canakinumab 150 + 50 mg PFS‐NSD and (b) canakinumab 200 mg PFS‐NSD versus canakinumab 150 + 50 mg PFS‐NSD. Median T _max was comparable: 7, 9, and 7 days for canakinumab 150 + 50 mg PFS‐NSD, 200 mg AI, and 200 mg PFS‐NSD, respectively. Exploratory post‐hoc analyses, assessing the impact of pause during the pandemic (N = 131 subjects recruited pre‐pandemic) and evaluating partial AUC _4weeks , suggested similar results. Canakinumab was well‐tolerated, and no treatment‐induced immunogenicity was observed.