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

Primary Purpose

Acute Graft Versus Host Disease

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

AbGn-168H

About this trial

This is an interventional treatment trial for Acute Graft Versus Host Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Stanford University, School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AbGn-168H

Arm Description

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

Outcomes

Primary Outcome Measures

Adverse events

Grade 3 to 5 adverse events considered at least possibly-related to neihulizumab

Cytokine release syndrome or acute infusion reactions

Grade 3 to 5 cytokine release syndrome or acute infusion reactions

Neutropenia

Grade 4 neutropenia lasting more than 14 days considered at least possibly related to study drug

All-cause mortality

Grade 5 all-cause mortality

Secondary Outcome Measures

Changes in frequency and/or phenotype of aGVHD-associated T-cell clones

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

Treatment response will be estimated by the Kaplan Meier product limit method, with standard confidence limits

Full Information

NCT ID

NCT02436460

First Posted

May 1, 2015

Last Updated

March 28, 2017

Sponsor

AbGenomics B.V Taiwan Branch

1. Study Identification

Unique Protocol Identification Number

NCT02436460

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Terminated

Why Stopped

Re-initiate a new trial per the discussion with FDA

Study Start Date

May 2015 (Actual)

Primary Completion Date

March 2016 (Actual)

Study Completion Date

March 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AbGenomics B.V Taiwan Branch

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Graft Versus Host Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

4 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AbGn-168H

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

AbGn-168H

Other Intervention Name(s)

Neihulizumab

Intervention Description

Humanized monoclonal antibody

Primary Outcome Measure Information:

Title

Adverse events

Description

Grade 3 to 5 adverse events considered at least possibly-related to neihulizumab

Time Frame

On or before study day 52

Title

Cytokine release syndrome or acute infusion reactions

Description

Grade 3 to 5 cytokine release syndrome or acute infusion reactions

Time Frame

Within 24 hours after study drug infusion

Title

Neutropenia

Description

Grade 4 neutropenia lasting more than 14 days considered at least possibly related to study drug

Time Frame

Duration of study

Title

All-cause mortality

Description

Grade 5 all-cause mortality

Time Frame

Within 7 days of infusion

Secondary Outcome Measure Information:

Title

Changes in frequency and/or phenotype of aGVHD-associated T-cell clones

Description

Changes in T cell clonal dynamics will be accomplished by statistical methodology.

Time Frame

At time of diagnosis up to 90 days

Title

GVHD treatment response as measured by the Modified Keystone aGVHD clinical grade scale

Description

Treatment response will be estimated by the Kaplan Meier product limit method, with standard confidence limits

Time Frame

At 90 days after the diagnosis of aGVHD

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Shih-Yao (David) Lin, MD, PhD

Organizational Affiliation

AbGenomics B.V.

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Everett Meyer, MD

Organizational Affiliation

Stanford University Hospitals and Clinics

Official's Role

Principal Investigator

Facility Information:

Facility Name

Stanford University, School of Medicine

City

Stanford

State/Province

California

ZIP/Postal Code

94305

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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