RESUMO
Background: ASLAN004 is a fully human monoclonal antibody that binds to IL-13Ra1 with high affinity and inhibits IL-4 and IL-13 signaling via the Type 2 cytokine receptor, an important target in atopic dermatitis (AD). Objective: To evaluate the emerging safety, tolerability, and efficacy of ASLAN004 in a multipleascending dose escalation phase in patients with moderate to severe AD. Methods: Twenty-five adult patients with moderate to severe AD were recruited from the US, Australia and Singapore and randomized 3:1 in three cohorts to receive once weekly 200, 400 or 600mg of subcutaneous ASLAN004 or matching placebo over eight weeks, with a 12-week recovery period. An interim data readout was conducted after Cohorts 1-3 completed eight weeks of treatment to evaluate various clinical endpoints in a limited number of patients before conducting an expansion cohort (Cohort 4, results reported elsewhere). Endpoints in the interim analysis include change from baseline in Eczema Area Severity Index (EASI) score at week 8 and safety assessments including local tolerability and incidence of adverse events (AEs). [NCT04090229] Results: Three of 25 patients randomized into Cohorts 1-3 discontinued due to restrictions imposed in response to the COVID-19 pandemic. 18 of the remaining 22 patients in the planned interim data readout completed at least 29 days of dosing and assessment and were evaluable for efficacy. The mean ± SD (n=18) baseline scores were 32.5±11.8 for EASI and 44% had severe Investigator Global Assessment (IGA) scores. At Week 8, mean reductions in EASI from baseline were 50 percent, 74 percent and 76 percent for the 200mg (n=4), 400 mg (n=6) and 600 mg (n=3) ASLAN004 dose groups respectively, compared with 42 percent (n=5) for placebo. Mean reductions of peak pruritus from baseline to Week 8 were 34 percent, 48 percent and 39 percent for 200mg (n=4), 400mg (n=6) and 600mg (n=2) ASLAN004 dose groups respectively, compared with 16% for placebo (n=5). Other secondary endpoints were also improved for ASLAN004 compared with placebo (EASI-50, EASI- 75, results reported elsewhere). The proportion of patients with AEs and treatment-emergent adverse events (TEAEs) were similar across ASLAN004 treatment and placebo arms. There were no TEAEs leading to discontinuation in the ASLAN004 treatment groups. Conclusion: ASLAN004 was well tolerated, with 400mg and 600mg showing promising eicacy in adults with moderate to severe AD.