A Study of Itolizumab in Combination With Corticosteroids for the First-Line Treatment of Acute Graft Versus Host Disease (EQUATOR)

Study Overview
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Brief Summary
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This is a multi-center study to compare the efficacy and safety of itolizumab versus placebo as first-line therapy for subjects with Grade III-IV aGVHD or Grade II with LGI involvement, in combination with corticosteroids

Detailed Description
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This study will enroll 200 subjects at approximately 125 sites globally. Subjects will be randomized in a 1:1 ratio to active or placebo and will receive a total of 7 doses administered intravenously approximately every 2 weeks. The study follows the patients for a total of approximately 365 days.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Multicenter Study of Itolizumab in Combination With Corticosteroids for the Initial Treatment of Acute Graft Versus Host Disease

Conditions
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Graft Versus Host Disease, GVHD, Acute-graft-versus-host Disease, Acute GVHD, aGVHD

Intervention / Treatment
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* Biological: Itolizumab
* Drug: EQ001 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is willing and able to provide written informed consent/assent and to comply with all protocol procedures and assessments required for the study. Is age ≥12 years and >40kg at informed consent/assent. Has had an initial allogeneic HSCT for any indication using any graft source, donor source, conditioning regimen intensity or prophylaxis. Has evidence of myeloid engraftment Has a clinical diagnosis of aGVHD Grades III-IV or Grade II with LGI involvement based on Mount Sinai Acute GVHD International Consortium (MAGIC) grading criteria. Began systemic corticosteroid treatment for aGVHD ≤72 hours prior to the start of study drug dosing AND must receive 2 mg/kg/day methylprednisolone or equivalent on Day 1. Exclusion Criteria: Evidence of morphological relapsed, progressive, persistent, or untreated malignancy, with the exception of nonmelanoma skin cancer and in situ ductal carcinoma of the breast. An unplanned donor lymphocyte infusion for persistent or recurrent malignancy after HSCT. Evidence of persistent molecular disease requiring treatment that was not specified prior to HSCT. Evidence of cGVHD or overlap syndrome Use of immunosuppressants other than corticosteroids for the treatment of aGVHD. Use of any systemic corticosteroids of >0.5 mg/kg/day methylprednisolone or equivalent for any indication other than aGVHD within 7 days before the onset of aGVHD.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Itolizumab (EQ001)<br>Itolizumab (EQ001) administered in a blinded fashion by intravenous infusion every 2 weeks for a total of 7 doses. | Biological: Itolizumab<br>* Itolizumab [Bmab600]<br>* Other names: Bmab600;|
| Placebo Comparator: EQ001 Placebo<br>EQ001 Placebo administered in a blinded fashion by intravenous infusion every 2 weeks for a total of 7 doses | Drug: EQ001 Placebo<br>* EQ001 Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The efficacy of itolizumab versus placebo as initial therapy for aGVHD in combination with corticosteroids in achieving early disease response. | Complete response at Day 29 | Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the durability of response to itolizumab versus placebo as initial therapy for aGVHD in combination with corticosteroids. | Durable Complete Response rate from Day 29 through Day 99 | Day 99 | 
| Assess the impact of itolizumab versus placebo on other clinically relevant efficacy measures, | Overall Response Rates at Day 29 | Day 29 |