Premium
Randomized, controlled study of bleselumab (ASKP1240) pharmacokinetics and safety in patients with moderate‐to‐severe plaque psoriasis
Author(s) -
Anil Kumar Mysore S.,
Papp Kim,
Tainaka Ryo,
Valluri Udaya,
Wang Xuegong,
Zhu Tong,
Schwabe Christian
Publication year - 2018
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2130
Subject(s) - medicine , pharmacokinetics , tolerability , placebo , psoriasis area and severity index , area under the curve , psoriasis , adverse effect , body surface area , gastroenterology , randomized controlled trial , urology , pharmacology , anesthesia , immunology , pathology , alternative medicine
This study evaluated the pharmacokinetics (PK), efficacy, safety, and tolerability of bleselumab – a fully‐human anti‐CD40 monoclonal recombinant IgG4. Patients with moderate‐to‐severe psoriasis were randomized on day 1 to receive bleselumab or placebo on days 1, 15 and 29 in a dose‐escalation of bleselumab at 0.1, 0.3, 1.0 or 3.0 mg/kg. The safety‐analysis set (SAF) and full‐analysis set (FAS) included all patients who received bleselumab or placebo, and the PK‐analysis set (PKAS) included patients in the SAF with ≥1 quantifiable serum bleselumab concentration. Serial blood samples were collected after each dose, and the bleselumab serum concentration was measured. After each dose, the area‐under‐the‐concentration–time curve over 336 hours (AUC 336 ) and the maximum serum concentration (C max ), and dose proportionality of AUC 336 and C max were determined. The psoriasis area and severity index (PASI) score, the physician static global assessment (PSGA) score, the percentage body surface area (%BSA) affected with psoriasis, adverse events and laboratory parameters were assessed. Sixty patients were randomized and included in the SAF/FAS (bleselumab, n = 49; placebo, n = 11); 48 formed the PKAS. Bleselumab C max and AUC 336 were more than dose proportional in the range 0.1–3.0 mg/kg, suggesting nonlinear PK after single/multiple doses. No clinically significant infusion reactions, cytokine‐release syndrome, or thromboembolic events were reported. Bleselumab did not improve the PASI scores, PSGA scores, or %BSA versus placebo. Transient elevation of alanine aminotransferase and aspartate aminotransferase levels by >3 × upper limit of normal were observed in four (8.2%) and two (4.1%) patients, respectively, in the 1.0 or 3.0 mg/kg groups. Patients with liver function test increases had no concurrent changes in bilirubin. Bleselumab demonstrated nonlinear PK after single and multiple doses, with few adverse reactions.