065: Pharmacokinetics of Subcutaneous Itepekimab Injection With an Autoinjector Device or Prefilled Syringe

Statement of Purpose: Itepekimab (SAR440340/REGN3500), a human IgG 4 monoclonal antibody against IL-33 demonstrated reduction in exacerbation rate and improvement in lung function in former smokers with chronic obstructive pulmonary disease (COPD). This study was designed to assess and compare the pharmacokinetics (PK) of itepekimab, administered by 2 different devices, autoinjector device (AI) vs a prefilled syringe (PFS), in healthy participants.

Description of Methods & Materials: In this Phase 1, parallel-design, single-center study, 90 healthy male and female participants (age: 18–65 years; weight: 50–100 kg) were randomized 1:1 to receive a single 300 mg subcutaneous (SC) dose of itepekimab either via AI or PFS. The randomization was stratified by 3 weight categories ( < 70 kg, ≥70 to < 80 kg and ≥80 kg) and 3 injection sites (abdomen, thigh and arm). Blood samples for measurement of concentrations of itepekimab and assessment of immunogenicity were collected at pre-dose (Day 1) and during a follow-up period including an end of study visit (Day 2–Day 141). The PK parameters were calculated, using noncompartmental methods from serum concentrations obtained after single dose administration. PK parameters were summarized using descriptive statistics for each treatment group. For maximum plasma concentration observed (C_max), area under curve from dosing to the time of the last measured concentration (AUC_last) and area under curve extrapolated to infinity (AUC), point estimates of the geometric mean ratio of the AI relative to PFS were provided with 90% confidence intervals (CI). Safety and tolerability were also assessed and compared between the treatment groups.

Data & Results: Following the itepekimab administration, systemic exposure was similar for both AI and PFS groups (Figure 1). The geometric mean treatment ratios (AI [test] vs PFS [reference]) with 90% CIs were 1.01 (0.92 to 1.11) for C_max, 1.06 (0.98 to 1.14) for AUC_last, and 1.04 (0.96 to 1.13) for AUC. The mean systemic exposure of itepekimab decreased with an increase in body weight, but the estimates were similar between the two device groups within each body weight category. PK parameter estimates for itepekimab were similar between the two device groups for each injection site location. Itepekimab administration by both devices was well tolerated, and there were no serious adverse events, or severe treatment-emergent adverse events experienced during the study. No participants had treatment-emergent anti-drug antibody (ADA) response or treatment-boosted ADA response.

Interpretation, Conclusion or Significance: Systemic exposure of itepekimab 300 mg was comparable when administered via the AI or PFS devices, in healthy participants. A single-dose administration of itepekimab via both the devices was well tolerated in healthy participants.

Disclosures: Christine Xu, Kong Xin, Allison Butler, Helene Goulaouic and Vanaja Kanamaluru are employees of Sanofi and may hold stock and/or stock options in the company. Matthew P. Kosloski and Michael C Nivens are employees of Regeneron Pharmaceuticals Inc, and may hold stock and/or stock options in the company.