A Study of AbGn-168H in Patients With Steroid Refractory Acute Graft-vs-Host Disease After Donor Stem Cell Transplant

Study Overview
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Brief Summary
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This study is to establish the safety, determine if there is an improvement in steroid refractory acute graft-vs-host disease (aGvHD) compared to historical cohorts, and determine the changes of aGvHD-associated T-cell clones in patients with steroid-refractory aGVHD following allogeneic hematopoietic cell transplantation administered AbGn-168H once weekly for 4 weeks.

Detailed Description
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AbGn-168H is a humanized monoclonal antibody. This is a dose escalation study using a modified toxicity probability interval method. AbGn-168H will be administered intravenously (IV) once weekly for four weeks, in patients with steroid refractory aGVHD following hematopoietic cell transplant (HCT). After completion of study treatment, patients are followed up for 90 days.The primary objective of this study is to establish the safety, and the secondary objectives of this study are to determine if there is an improvement in disease response at 3 months after diagnosis of steroid refractory aGVHD compared to historical cohorts and to determine the changes in frequency and/or phenotype of aGVHD-associated T cell clones in response to AbGn-168H therapy.

Official Title
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A Phase Ib Treatment Trial Using AbGn-168H to Treat Steroid Refractory Acute Graft-vs.-Host Disease (aGVHD) in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

Conditions
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Acute Graft Versus Host Disease

Intervention / Treatment
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* Biological: AbGn-168H


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of skin, gut and/or liver steroid-refractory GVHD by clinical assessment of treating physician following allogeneic HCT. Patients who fail to respond to steroids by 7 days are considered steroid-refractory Previously-treated with any conditioning regimen and any GVHD immune suppression prophylaxis and formulation of steroids, except as noted in Exclusion Criteria #2. AbGn-168H (neihulizumab) therapy can begin not more than 14 days after diagnosis of aGvHD Karnofsky Performance Status (KPS) > 50% No evidence of HCT graft failure or multi-organ failure Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Uncontrolled infections not responsive to antimicrobial therapy requiring intensive critical care Progressive malignant disease, including post-transplant lymphoproliferative disease unresponsive to therapy Treatment with investigational GVHD prophylactic agents (eg, CCR5 inhibitors; lenalidomide; and/or bortezomib) within the 7 days prior to the 1st dose of neihulizumab Treatment with other investigational agents within the prior 7 days prior to the 1st dose of AbGn-168H (neihulizumab) CMV PCR > 500 copies/mL or evidence of end-organ damage due to CMV Pregnant or nursing HIV positivity (NOTE: patients positive for hepatitis B or hepatitis C are not excluded, and may be evaluated on a case-by-case basis) Renal clearance CCR < 40 mL/min

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AbGn-168H<br>AbGn-168H will be administered once weekly for four weeks via intravenous infusion. | Biological: AbGn-168H<br>* Humanized monoclonal antibody<br>* Other names: Neihulizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Grade 3 to 5 adverse events considered at least possibly-related to neihulizumab | On or before study day 52 | 
| Cytokine release syndrome or acute infusion reactions | Grade 3 to 5 cytokine release syndrome or acute infusion reactions | Within 24 hours after study drug infusion | 
| Neutropenia | Grade 4 neutropenia lasting more than 14 days considered at least possibly related to study drug | Duration of study | 
| All-cause mortality | Grade 5 all-cause mortality | Within 7 days of infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in frequency and/or phenotype of aGVHD-associated T-cell clones | Changes in T cell clonal dynamics will be accomplished by statistical methodology. | At time of diagnosis up to 90 days | 
| GVHD treatment response as measured by the Modified Keystone aGVHD clinical grade scale | Treatment response will be estimated by the Kaplan Meier product limit method, with standard confidence limits | At 90 days after the diagnosis of aGVHD |