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

Phase 1

Terminated

• Conditions: Acute Graft Versus Host Disease
• Interventions: Biological: AbGn-168H

• Registration Number: NCT02436460
• Lead Sponsor: AbGenomics B.V Taiwan Branch

Brief Summary

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

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.

Study Timeline

• Study Start: 2015-05
• Study First Submitted: 2015-05-01
• Study First Submitted QC: 2015-05-01
• Study First Posted: 2015-05-06
• Primary Completion: 2016-03
• Study Completion: 2016-03
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-28
• Last Update Posted: 2017-03-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 4

Inclusion Criteria

1. 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
2. Previously-treated with any conditioning regimen and any GVHD immune suppression prophylaxis and formulation of steroids, except as noted in Exclusion Criteria #2.
3. AbGn-168H (neihulizumab) therapy can begin not more than 14 days after diagnosis of aGvHD
4. Karnofsky Performance Status (KPS) > 50%
5. No evidence of HCT graft failure or multi-organ failure
6. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

1. Uncontrolled infections not responsive to antimicrobial therapy requiring intensive critical care
2. Progressive malignant disease, including post-transplant lymphoproliferative disease unresponsive to therapy
3. Treatment with investigational GVHD prophylactic agents (eg, CCR5 inhibitors; lenalidomide; and/or bortezomib) within the 7 days prior to the 1st dose of neihulizumab
4. Treatment with other investigational agents within the prior 7 days prior to the 1st dose of AbGn-168H (neihulizumab)
5. CMV PCR > 500 copies/mL or evidence of end-organ damage due to CMV
6. Pregnant or nursing
7. HIV positivity (NOTE: patients positive for hepatitis B or hepatitis C are not excluded, and may be evaluated on a case-by-case basis)
8. Renal clearance CCR < 40 mL/min

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AbGn-168H	AbGn-168H	AbGn-168H will be administered once weekly for four weeks via intravenous infusion.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Stanford University, School of Medicine; 🇺🇸 Stanford, California, United States