Comparison of Study Designs for Primary Phase III Trials for Omalizumab Versus Dupilumab for Patients With Chronic Spontaneous Urticaria

Abstract

Introduction

Omalizumab is currently the only biologic approved and recommended as second-line treatment for patients with chronic spontaneous urticaria (CSU). However, clinical trial programs are underway for other biologic treatments such as dupilumab. Given head-to-head trials will not be conducted, consideration of study design may be important.

Methods

Comparison of participants, interventions, outcomes, and results for phase III primary efficacy clinical trials for omalizumab versus dupilumab for patients with CSU. The omalizumab trials were ASTERIA I/II (NCT01287117 and NCT01292473) and the dupilumab trial was LIBERTY-CSU CUPID (NCT04180488) that consisted of Study A, B, and C.

Results

Participants in ASTERIA I/II were 12 to 75 years with a diagnosis of CSU refractory to H1 antihistamines. Participants in LIBERTY-CSU CUPID were 6 to 80 years (Study A and C) or 12 to 80 years (Study B) with a diagnosis of CSU refractory to H1 antihistamines, and Urticaria Activity Score (UAS)7≥16 and Itch Severity Score (ISS)7≥8 during the 7 days before randomization; Study A and C included participants who were omalizumab naïve and Study B included intolerant or incomplete responders to omalizumab. For ASTERIA I and II, the interventions were placebo or omalizumab (75mg, 150mg, 300mg) every 4 weeks for 24 and 12 weeks, respectively. For LIBERY-CSU CUPID, the interventions were placebo or dupilumab (200mg or 300mg, weight based) every 2 weeks for 24 weeks. The primary efficacy outcome for ASTERIA I/II was change from baseline in ISS7 at Week 12. The primary efficacy outcome for LIBERTY-CSU CUPID was change from baseline in ISS7 at Week 24. For the ASTERIA I primary outcome, the change from baseline in ISS7 at Week 12 was -3.6 for placebo and -6.5, -6.7, and ‑9.4 for omalizumab 75mg, 150mg, and 300mg, respectively. For the ASTERIA II primary outcome, the change from baseline in ISS7 at Week 12 was -5.1 for placebo and ‑5.9, ‑8.1, and ‑9.8 for omalizumab 75mg, 150mg, and 300mg, respectively. For the LIBERTY-CSU CUPID Study A primary outcome, the change from baseline in ISS7 at Week 24 was ‑6.0 for placebo and -10.2 for dupilumab. The LIBERTY-CSU CUPID Study B was stopped due to futility based on a pre-specified interim analysis.

Conclusion

Comparing study designs for primary clinical trials for omalizumab and dupilumab for patients with CSU will aid in the comparative analysis and clinical evaluation of final trial results.

Funding: ASTERIA I/II were funded by Genentech Inc. and Novartis Pharma AG.