Trial Overview

The EQUATE study was a Phase 1b trial to evaluate the safety and clinical efficacy of itolizumab for front-line treatment in patients who present with aGVHD. The study was an open-label dose escalation study in adult patients who present with high risk aGVHD who typically respond poorly to steroids. Patients in this study received up to a total of 5 doses of itolizumab, administered bi-weekly over the course of 10 weeks. The Phase 1b data was presented to the FDA to inform the path forward for the aGVHD program, and the company is now enrolling the Phase 3 EQUATOR study.

The Phase 3, randomized, double-blind, placebo-controlled multicenter study will compare the efficacy and safety of IV administered itolizumab versus placebo (randomized 1:1) as a first-line therapy in up to 200 adult and adolescent patients with Grade III-IV aGVHD, or Grade II aGVHD with lower GI involvement, in combination with high doses of corticosteroids, the current standard of care. The primary study endpoint is complete response rate at Day 29; key secondary endpoints include overall response rate at Day 29 and durability of complete response rate from Day 29 through Day 99.

Per the study protocol, patients must receive itolizumab within 3-days of the first administration of high-dose corticosteroids with a treatment period from Days 1-99, and a follow-up period from Days 100-365. Approximately 200 eligible subjects who receive 2 mg/kg methylprednisolone or equivalent on Day 1 will be randomized in a 1:1 ratio to the following two treatment groups:

• Group A: Itolizumab, 1.6 mg/kg initial dose followed by 6 doses of 0.8 mg/kg once every 2 weeks (q2w), plus systemic corticosteroids (100 subjects)
• Group B: Placebo, 7 doses q2w, plus systemic corticosteroids (100 subjects)

An independent data monitoring committee regularly reviews safety data, and an interim analysis for both futility and efficacy was conducted after approximately 100 subjects had completed Day 29 assessments.