title: A Randomized Phase 1 Study to Assess the Safety and Pharmacokinetics of the Subcutaneously Injected Anti-LIGHT Antibody, SAR252067.
abstract: LIGHT, a member of the tumor necrosis factor superfamily, is potentially involved in mucosal inflammation associated with inflammatory bowel disease. The safety and pharmacokinetics of the fully human monoclonal anti-LIGHT antibody, SAR252067, was evaluated in healthy volunteers in a phase 1 study as a potential treatment for diseases related to LIGHT-mediated mucosal inflammation. This double-blind, randomized, placebo-controlled, sequential ascending single-dose, single-center, 16-week study randomized 48 subjects to a single subcutaneous dose of SAR252067 (40, 120, 300, 600, 900, or 1200 mg) or placebo. Safety assessments included adverse events (AEs), injection-site reactions, and antidrug antibody (ADA) titer. Pharmacokinetic end points were serum parameters of SAR252067 (Cmax, AUC0-∞, tmax, t1/2z). Serum-soluble LIGHT concentrations were also determined. Safety analyses included all 48 participants; pharmacokinetic analyses included 36 subjects who received SAR252067. No serious AEs were reported, and no dose-effect relationship was apparent. Injection-site reactions were minimal. ADAs were not clinically relevant. SAR252067 exposure increased in a near-dose-proportional manner, median tmaxranged from 5.0 to 8.5 days, and t1/2zranged from 18.0 to 27.0 days. Serum-soluble LIGHT significantly increased after SAR252067 administration with the 40-mg dose only. SAR252067 had a good safety profile, was well tolerated in healthy humans, and displayed a predictable pharmacokinetic profile.
authors.affiliation: Sanofi, Bridgewater, NJ, USA.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Biostatistics Department, Sanofi-Aventis Recherche Développement, Montpellier, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Perrin
authors.affiliation: QPS Miami Research Associates, Miami, FL, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Pardo
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D019540:Area Under Curve; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C000626305:SAR252067; C505914:TNFSF14 protein, human; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14
keywords: LIGHT; SAR252067; inflammatory bowel disease; monoclonal antibody; pharmacokinetics