Pharmacokinetics and Pharmacodynamics of JNJ-55920839, an Antibody Targeting Interferon α/ω, in Healthy Subjects and Subjects with Mild-to-Moderate Systemic Lupus Erythematosus

• Published in: Clinical drug investigation Vol. 40; no. 12; pp. 1127 - 1136
• Main Authors: Yao, Zhenling, Loggia, Laura, Fink, Damien, Chevrier, Marc, Marciniak, Stanley, Sharma, Amarnath, Xu, Zhenhua
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.12.2020; Springer Nature B.V
• Subjects: Administration, Intravenous; Adult; Adults; Antibodies; Antibodies, Monoclonal, Humanized - pharmacokinetics; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; Area Under Curve; Biological Availability; Double-Blind Method; Drug dosages; Enrollments; Female; Females; Healthy Volunteers; Humans; Immunoglobulins; Infusions, Intravenous; Injections, Subcutaneous; Interferon; Interferon-alpha - antagonists & inhibitors; Internal Medicine; Lupus; Lupus Erythematosus, Systemic - drug therapy; Male; Medicine; Medicine & Public Health; Middle Aged; Original Research Article; Pharmacodynamics; Pharmacokinetics; Pharmacology/Toxicology; Pharmacotherapy; Placebos; Serology
• ISSN: 1173-2563; 1179-1918; 1179-1918
• DOI: 10.1007/s40261-020-00978-4

Background The interferon (IFN) pathway has been correlated with clinical and serological markers of disease activity in patients with systemic lupus erythematosus (SLE). Objective The pharmacokinetics and pharmacodynamics of JNJ-55920839, a fully human immunoglobulin G1κ antibody targeting IFNα/ω, were investigated. Methods In a double-blind, first-in-human study, Part A enrolled 48 healthy adults who received a single dose of placebo/JNJ-55920839 between 0.3 and 15 mg/kg intravenous (IV) or at 1 mg/kg subcutaneous (SC). Part B enrolled 26 adults with SLE who received placebo or JNJ-55920839 10 mg/kg IV 6 times biweekly. Pharmacokinetic parameters were calculated by noncompartmental analysis (NCA) and estimated by nonlinear mixed-effects modeling. Results JNJ-55920839 pharmacokinetics following a single IV infusion exhibited a biphasic disposition in healthy subjects. Maximum plasma concentration ( C max ) and area under the concentration-time curve values increased dose-proportionally. Mean clearance (CL) after a single IV infusion ranged between 2.28 and 3.09 mL/kg/day. Absolute bioavailability after a single SC injection was ≥ 80.0%. Mean terminal elimination half-life ( t 1/2 ) was similar after IV (20.7 to 24.6 days) and SC administration (22.6 days). Steady state of JNJ-55920839 was achieved 6 weeks after multiple 10 mg/kg IV doses in subjects with SLE. Mean steady-state CL and t 1/2 were 4.73 mL/kg/day and 14.8 days, respectively. A linear 2-compartment population pharmacokinetic model with 1st-order absorption and elimination adequately characterized the pharmacokinetics; parameters were consistent with NCA estimates. Higher CL was estimated in subjects with SLE compared with healthy subjects, after correcting for body weight. A trend of increased total IFNα/ω levels was observed after treatment with JNJ-55920839. Conclusion Pharmacokinetic and pharmacodynamic analyses of the data from this study demonstrated that there was biphasic disposition in both healthy subjects and subjects with SLE, CL was faster in subjects with SLE, and increases in total IFNα/ω levels were observed in both healthy subjects and subjects with SLE after treatment with JNJ-55920839, thus further development is supported. The study is registered at ClinicalTrials.gov NCT02609789.