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

Phase 1

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
EQ001 Dose Escalation (Part A)	EQ001	Open label EQ001 administered by intravenous infusion every two weeks for a total of 5 doses.
EQ001 (Part B)	EQ001	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.
EQ001 Placebo (Part B)	EQ001 Placebo	Placebo administered in a blinded fashion by intravenous infusion every two weeks for a total of 5 doses.

Primary Outcome Measures

Name	Time	Method
Number of Treatment Emergent Adverse Events	Study Day 85	Number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Overall Response Rate	Study Day 29	Overall Response Rate (ORR) is defined as the number of subjects with a partial response (PR), very good partial response (VGPR), or complete response (CR) who are alive at Day 29. Subjects must not have received new systemic therapy for aGVHD before the Day 29 Visit.

Secondary Outcome Measures

Name	Time	Method
Time to Maximum EQ001serum Concentration, Tmax	Day 337	Time to maximum EQ001 serum concentration, Tmax
Maximum EQ001 Serum Drug Concentration, Cmax	Study Day 337	Maximum EQ001 serum drug concentration, Cmax
Minimum EQ001 Serum Drug Concentration, Cmin	Study Day 337	Minimum EQ001 serum drug concentration prior to next dose, Cmin
Total EQ001 Exposure Across Time, AUC (From Zero to Infinity)	Study Day 337	Total EQ001 exposure across time, AUC (from zero to infinity)
Half Life of EQ001, t1/2	Study Day 337	Half life of EQ001, t1/2
Volume of Distribution of EQ001, Vd	Study Day 337	Volume of distribution of EQ001, Vd
Clearance, Cl	Study Day 337	Clearance, Cl
Inflammatory Markers	Study Day 337	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
CD6 Receptor Expression Levels	Study Day 85	CD6 receptor expression levels - percent of baseline

Locations (16): University of Pittsburgh Cancer Institute
🇺🇸
Pittsburgh, Pennsylvania, United States
University of Florida Health Shands Hospital
🇺🇸
Gainesville, Florida, United States
Dana-Farber Cancer Institute
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Boston, Massachusetts, United States
TriStar Centennial Medical Center (SCRI)
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Nashville, Tennessee, United States
Intermountain Healthcare
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Salt Lake City, Utah, United States
University of Miami - Miller School of Medicine
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Miami, Florida, United States
Emory University Hospital
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Atlanta, Georgia, United States
City of Hope Comprehensive Cancer Center
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Duarte, California, United States
Washington University and Barnes Jewish Heart & Vascular Center
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Saint Louis, Missouri, United States
University of Pennsylvania, Abramson Cancer Center
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Philadelphia, Pennsylvania, United States
Roswell Park Cancer Institute
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Buffalo, New York, United States
Fred Hutchinson Cancer Research Center
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Seattle, Washington, United States
University of North Carolina Lineberger Comprehensive Cancer Center
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Chapel Hill, North Carolina, United States
Oregon Health & Science University
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Portland, Oregon, United States
H. Lee Moffitt Cancer Center & Research Institute
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Tampa, Florida, United States
University of Michigan - C.S. Mott Children's Hospital
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Ann Arbor, Michigan, United States