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Neihulizumab (AbGn-168H) in Patients With Steroid-refractory Acute Graft-versus-host Disease

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ClinicalTrials.gov Identifier: NCT03327857
Recruitment Status : Recruiting
First Posted : November 1, 2017
Last Update Posted : October 23, 2018
Sponsor:
Information provided by (Responsible Party):
AbGenomics International, Inc.

Brief Summary:
To establish the pharmacokinetic, pharmacodynamic, safety and efficacy profiles of Neihulizumab in patients with steroid-refractory acute graft-versus-host disease(sr-aGvHD)

Condition or disease Intervention/treatment Phase
Steroid-refractory Acute Graft-versus-Host Disease Biological: AbGn-168H Phase 1

Detailed Description:
This study is a Phase I, single dose, dose-escalation study to study the pharmacokinetics, safety, signs of efficacy, receptor occupancy and pharmacodynamics biomarkers (REG3-alpha and ST2 of Neihulizumab in patients with steroid-refractory acute GvHD. Up to 24 patients will be recruited in 4-9 clinical centers in US.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Neihulizumab (AbGn-168H) in Patients With Steroid-refractory Acute Graft-versus-host Disease (Sr-aGvHD)
Actual Study Start Date : May 31, 2018
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : June 2020


Arm Intervention/treatment
Experimental: AbGn-168H (Neihulizumab)
intravenous doses of AbGn-168H (Neihulizumab)
Biological: AbGn-168H
AbGn-168H (Neihulizumab) is a humanized monoclonal antibody




Primary Outcome Measures :
  1. Area Under the Curve [AUC] [ Time Frame: Days 1, 2, 3, 5, 8,15, 22 and 28 ]
    Including AUC0-t, AUC0-tz, AUC 0-inf

  2. Maximum Plasma Concentration [Cmax] [ Time Frame: Days 1, 2, 3, 5, 8,15, 22 and 28 ]
  3. Time to reach maximum serum concentration [Tmax] [ Time Frame: Days 1, 2, 3, 5, 8,15, 22 and 28 ]
    The amount of time that a drug is present at the maximum concentration in serum

  4. Lambda-z [ Time Frame: Days 1, 2, 3, 5, 8,15, 22 and 28 ]
  5. Half life [t1/2] [ Time Frame: Days 1, 2, 3, 5, 8,15, 22 and 28 ]
  6. Mean Residence Time (MRT) [ Time Frame: Days 1, 2, 3, 5, 8,15, 22 and 28 ]
  7. Volume of distribution [Vz] [ Time Frame: Days 1, 2, 3, 5, 8,15, 22 and 28 ]
  8. Volume of distribution during steady state [Vss] [ Time Frame: Days 1, 2, 3, 5, 8,15, 22 and 28 ]

Secondary Outcome Measures :
  1. Adverse events (AEs) [ Time Frame: Days 1, 2, 3, 5, 8,15, 22 and 28 ]
    AE graded according to CTCAE v4.03, changes in vital signs and physical examination and changes in safety laboratory analysis

  2. Changes in weight (kg) [ Time Frame: Day 1 prior to the infusion and at 30; 60; and 90 minutes after the start of infusion ]
  3. Changes in body temperature (celsius) [ Time Frame: Day 1 prior to the infusion and at 30; 60; and 90 minutes after the start of infusion ]
  4. Changes in heart rate (beats/min) [ Time Frame: Day 1 prior to the infusion and at 30; 60; and 90 minutes after the start of infusion ]
  5. Changes in systolic blood pressure (mmHg) [ Time Frame: Day 1 prior to the infusion and at 30; 60; and 90 minutes after the start of infusion ]
  6. Changes in diastolic blood pressure (mmHg) [ Time Frame: Day 1 prior to the infusion and at 30; 60; and 90 minutes after the start of infusion ]
  7. Changes in respiratory rate (breaths/min) [ Time Frame: Day 1 prior to the infusion and at 30; 60; and 90 minutes after the start of infusion ]
  8. Changes in oxygen saturation (%) [ Time Frame: Day 1 prior to the infusion and at 30; 60; and 90 minutes after the start of infusion ]
  9. Changes in physical examination as assessed by Karnofsky Performance Scale (KPS) [ Time Frame: Day 1 prior to the infusion and at 30; 60; and 90 minutes after the start of infusion ]
  10. Changes in haematocrit (g/dL) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  11. Changes in haemoglobin (g/dL) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  12. Changes in red blood cell count (10^3/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  13. Changes in white blood cell count (10^3/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  14. Changes in platelet count (10^3/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  15. Changes in neutrophil count (10^3/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  16. Changes in eosinophils count (10^3/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  17. Changes in basophils count (10^3/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  18. Changes in monocyte count (10^3/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  19. Changes in lymphocyte count (10^3/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  20. Changes in alanine aminotransferase (μmol/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  21. Changes in aspartate aminotransferase (μmol/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  22. Changes in akaline phosphatase (μmol/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  23. Changes in lactic dehydrogenase (μmol/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  24. Changes in blood glucose (μmol/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  25. Changes in creatinine (μmol/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  26. Changes in blood urea nitrogen (μmol/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  27. Changes in total bilirubin (μmol/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  28. Changes in direct bilirubin (μmol/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  29. Changes in total protein (μmol/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  30. Changes in blood calcium (μmol/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  31. Changes in blood sodium (μmol/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  32. Changes in blood potassium (μmol/L) [ Time Frame: Days 1, 8,15, 22 and 28 ]
    Assessed as part of routine laboratory tests

  33. Receptor Occupancy [ Time Frame: Days 1, 2, 3, 5, 8,15, 22 and 28 ]
    Receptor occupancy will be monitored using a flow cytometry based method

  34. sTNFR1 measurement [ Time Frame: Days 1, 8,15, 22 and 28 ]
  35. ST2 measurement [ Time Frame: Days 1, 8,15, 22 and 28 ]
  36. Skin rash for aGvHD evaluation [ Time Frame: Days 1, 2, 3, 5, 8,15, 22 and 28 ]
  37. Liver grading for aGvHD evaluation [ Time Frame: Days 1, 2, 3, 5, 8,15, 22 and 28 ]
  38. GI track grading for aGvHD evaluation [ Time Frame: Days 1, 2, 3, 5, 8,15, 22 and 28 ]
  39. Immunogenicity [ Time Frame: Days 1 and 28 ]
    Immunogenicity will be monitored by ADA ELISA



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have clinical aGvHD and pathologic findings consistent with the diagnosis by biopsy of at least 1 involved site and treated initially with steroids at prednisone-equivalent doses ≥1 mg/kg/day, and i) worsening of GvHD manifestations across any interval of at least 2 days before tapering of steroid doses has begun, or

    ii) persistence of grade II to IV aGvHD across any interval of at least 7 days without improvement during steroid treatment at any prednisone-equivalent dose >0.4 mg/kg/day or at any lower dose in patients with contraindication to continued treatment at higher steroid doses because of severe steroid-related toxicity (e.g., myopathy), or

    iii) initial response of GvHD manifestations followed by exacerbation of aGvHD across any interval of at least 3 days while tapering glucocorticoid treatment at any prednisone-equivalent dose >0.4 mg/kg/day or at any lower dose in patients with contraindication to continued treatment at higher steroid doses because of severe steroid-related toxicity (e.g., myopathy).

  2. Patients must have erythematous manifestations of cutaneous aGvHD. Characteristics of the rash must indicate active inflammation (red coloration) as distinct from resolving inflammation (brown coloration).
  3. Providers and patients must be willing to defer new systemic or cutaneous topical treatment of aGvHD for at least 36 hours after administration of Neihulizumab.
  4. Patient must give informed consent and sign an approved consent form prior to any study procedures.
  5. Females of childbearing potential must have a negative pregnancy test result before enrollment. Males and females of childbearing potential must agree to use a highly effective method of birth control during the study for at least 30 days after enrollment in the study.

Exclusion Criteria:

  1. Uncontrolled infections not responding to antimicrobial therapy or requiring intensive critical care or vasopressors
  2. Evidence of end-organ Cytomegalovirus (CMV) infection
  3. Patients known to have CMV, adenovirus, human herpes virus 6 (HHV6), Epstein Barr virus (EBV) or any hepatitis viremia from screening according to institutional standard practice
  4. HIV infection or a known HIV-related malignancy.
  5. Tuberculosis, history of tuberculosis or a known positive Quantiferon test for tuberculosis
  6. Unplanned donor lymphocyte infusion (DLI) for residual or relapsed malignancy or mixed chimerism. DLI as part of the planned HCT protocol is allowed.
  7. Known relapsed or progressive malignancy after transplant, post-transplant lymphoproliferative disease or any secondary malignancy diagnosed after HCT
  8. Absolute neutrophil count (ANC) <1000/mm3
  9. Total serum bilirubin concentration >3.0 mg/dL UNLESS attributed to GvHD
  10. Creatinine clearance < 40 mL/min calculated by Cockcroft-Gault equation.
  11. Ileus, abdominal pain, extensive denudation of intestinal mucosa or stage 4 GI GvHD.
  12. Karnofsky Performance Status (KPS) <50%
  13. Intensive care unit (ICU) care, life expectancy of less than 28 days, ongoing or unresolved hepatic sinusoidal obstruction syndrome, unstable hemodynamics, or evidence of current or previous clinically significant disease, medical condition or finding (including vital signs and ECG) that in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data
  14. History of allergy or hypersensitivity to any systemically administered antibody agent or its excipients
  15. Pregnancy or nursing
  16. Prior treatment with anti-lymphocyte globulin or anti-thymocyte globulin
  17. Patients <18 years of age

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03327857


Contacts
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Contact: Hazel Cheng, PhD +1 949 786 0390 hazel.cheng@abgenomics.com
Contact: Irene Cheng, PhD +886 2 2627 2707 ext 311 irene.cheng@abgenomics.com

Locations
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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Roxanne Garcia       roxgarcia@coh.org   
Contact: Golnaz Namdar    626-218-0061    gnamdar@coh.org   
Principal Investigator: Haris Ali         
United States, Georgia
Emory University Not yet recruiting
Atlanta, Georgia, United States, 30322
Contact: Shantoria Mayes    404-778-6547    shantoria.mayes@emory.edu   
Principal Investigator: Edmund Waller         
United States, Illinois
University of Chicago Not yet recruiting
Chicago, Illinois, United States, 60637
Principal Investigator: Michael Bishop         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Lynne Bischoff    734-615-5939    lloisros@med.umich.edu   
Principal Investigator: Sarah Anand, MD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Amy Hays    612-626-0461    hays0024@umn.edu   
Principal Investigator: Shernan Holtan, MD         
United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Delia Darst    615-343-7190    delia.h.darst@vumc.org   
Principal Investigator: Madan Jagasia, MD         
United States, Washington
Fred Hutchinson Recruiting
Seattle, Washington, United States, 98109
Contact: Lisa Grimm    206-667-2353    lgrimm@fredhutch.org   
Principal Investigator: Paul Martin, MD         
Sub-Investigator: Marco Mielcarek         
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Kaylee Meisinger    414-805-8926    kmeisinger@mcw.edu   
Principal Investigator: Sameem Abedin, MD         
Sub-Investigator: Mehdi Hamadani, MD         
Sponsors and Collaborators
AbGenomics International, Inc.
Investigators
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Study Director: Shih-Yao Lin, MD, PhD AbGenomics International, Inc.
Principal Investigator: Paul Martin, MD Fred Hutchinson Cancer Research Center

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Responsible Party: AbGenomics International, Inc.
ClinicalTrials.gov Identifier: NCT03327857     History of Changes
Other Study ID Numbers: 2017.002.01
First Posted: November 1, 2017    Key Record Dates
Last Update Posted: October 23, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases