A Study to Evaluate the Safety, Tolerability, PK, PD, and Clinical Activity of EQ001 in Subjects With aGVHD

Study Overview
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Brief Summary
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This is a multi-center study to evaluate the safety, tolerability, PK, PD, and clinical activity of EQ001 in subjects with Acute Graft Versus Host Disease (aGVHD).

Detailed Description
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The study will enroll approximately 100 subjects in two (2) parts: Part A is an open label study and will enroll approximately 40 evaluable subjects with aGVHD across 4 cohorts. The total number of patients will depend on the number of dose escalations necessary to enable a decision to be made on the recommended dose to take forward into Part B of the study. The planned dose escalation will start with cohort 1, where subjects will receive EQ001 administered intravenously every two weeks for a total of 5 doses. Part B is a randomized, double-blind, placebo-controlled study and will enroll approximately 60 additional subjects, randomized in a 2:1 ratio to either active treatment EQ001 (40) or placebo (20). Subjects will receive either EQ001 or placebo administered intravenously every two weeks for a total of 5 doses.

Official Title
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A Phase 1b/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of EQ001 in Subjects With Newly Diagnosed Acute Graft Versus Host Disease

Conditions
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Acute-graft-versus-host Disease, aGVHD, GVHD, GVHD, Acute

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject at least 18 years of age for Part A, and at least 12 years of age for Part B. Recipients of allogeneic hematopoietic stem cell transplantation (alloHSCT) using myeloablative or non myeloablative conditioning regimens. Have a clinical diagnosis of acute GVHD requiring systemic immune suppressive therapy. Deemed by the investigator to be likely to comply with the planned procedure as required by the protocol for the duration of the study Exclusion Criteria: Presence of morphologic relapsed primary malignancy, treatment for relapse after alloHSCT was performed, or requirement for rapid immunosuppressive treatment withdrawal for early malignancy relapse. Evidence of graft failure based on cytopenia(s), and as determined by the investigator. Evidence of post-transplant lymphoproliferative disease. Any prior therapy for acute GVHD, except for alloHSCT prophylaxis regimens or systemically administered corticosteroids. As determined by the investigator, any medical, psychiatric, or other condition or circumstance that is likely to negatively affect: the subject's participation in this clinical study, the subject's safety, or the reliability of the study data.

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: Sequential Assignment
Interventional Model Description: Part A is an open label 3+3 dose escalation Part B is blinded and randomized 2:1
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EQ001 Dose Escalation (Part A)<br>Open label EQ001 administered by intravenous infusion every two weeks for a total of 5 doses. | Biological: EQ001<br>* Itolizumab [Bmab 600])<br>* Other names: Itolizumab;|
| Experimental: EQ001 (Part B)<br>EQ001 administered in a blinded fashion using the optimal dose selected from Part A by intravenous infusion every two weeks for a total of 5 doses. | Biological: EQ001<br>* Itolizumab [Bmab 600])<br>* Other names: Itolizumab;|
| Placebo Comparator: EQ001 Placebo (Part B)<br>Placebo administered in a blinded fashion by intravenous infusion every two weeks for a total of 5 doses. | Biological: EQ001 Placebo<br>* EQ001 Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Events | Number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. | Study Day 85 | 
| Change from baseline in aGVHD organ stages and overall clinical grading, aGVHD-AI | Clinical activity will be assessed by change from baseline in aGVHD organ stages and overall clinical grading, aGVHD-AI, concomitant medication usage and disease progression assessments | Study Day 337 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to maximum EQ001serum concentration, Tmax | Time to maximum EQ001 serum concentration, Tmax | Study Day 337 | 
| Maximum EQ001 serum drug concentration, Cmax | Maximum EQ001 serum drug concentration, Cmax | Study Day 337 | 
| Minimum EQ001 serum drug concentration, Cmin | Minimum EQ001 serum drug concentration prior to next dose, Cmin | Study Day 337 | 
| Total EQ001 exposure across time, AUC (from zero to infinity) | Total EQ001 exposure across time, AUC (from zero to infinity) | Study Day 337 | 
| Half life of EQ001, t1/2 | Half life of EQ001, t1/2 | Study Day 337 | 
| Volume of distribution of EQ001, Vd | Volume of distribution of EQ001, Vd | Study Day 337 | 
| Clearance, Cl | Clearance, Cl | Study Day 337 | 
| Inflammatory Markers | Including but not limited to: IL-1β, IL-2, IL-6, IL-17, IL-21, IL-22, IL-23, IFN-γ, and TGF-β, C-reactive protein | Study Day 337 | 
| CD6 receptor expression levels | CD6 receptor expression levels | Study Day 337 |