Zhang M.,Sanofi S.A. |
Perrin L.,Sanofi S.A. |
Pardo P.,QPS Miami Research Associates Miami
Clinical Pharmacology in Drug Development | Year: 2016
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 tmax ranged from 5.0 to 8.5 days, and t1/2z ranged 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. © American College of Clinical Pharmacology.