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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03327857
Recruitment Status : Recruiting
First Posted : November 1, 2017
Last Update Posted : March 31, 2022
Information provided by (Responsible Party):
AltruBio Inc.

Brief Summary:
A Phase I study to establish the pharmacokinetics, pharmacodynamics, safety and efficacy profiles of Neihulizumab in patients with steroid-refractory or treatment refractory acute graft-versus-host disease (SR/TR-aGVHD)

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

Detailed Description:
Neihulizumab (AbGn-168H) is an immune checkpoint agonist antibody that regulates T cell homeostasis. The unique mechanism of action provides a natural regulation of T cell homeostasis that induces cell death preferentially in late-stage activated T cells without affecting resting T cells and early-activated T cells. Because pathogenic T cells underlying the inflammatory conditions are usually in late-stage activated state, eliminating this population of cells can potentially result in controlling autoimmune inflammation of T cell associated diseases, such as GvHD.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 37 participants
Allocation: N/A
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) or Treatment-refractory Acute Graft-versus-host Disease (TR-aGVHD)
Actual Study Start Date : May 31, 2018
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : February 2023

Arm Intervention/treatment
Experimental: Neihulizumab (AbGn-168H)
Intravenous doses of Neihulizumab (AbGn-168H)
Biological: Neihulizumab (AbGn-168H)

Single dose phase: Patients will receive single dose of Neihulizumab based on the protocol escalation criteria.

Multiple dose phase: Parients will receive weekly doses of Neihulizumab for 4 weeks.

Primary Outcome Measures :
  1. Pharmacokinetics of Neihulizumab - AUC [ Time Frame: Up to Day 56 ]
    Including AUC0-t, AUC0-tz, AUC 0-inf

  2. Pharmacokinetics of Neihulizumab - Cmax [ Time Frame: Up to Day 56 ]
    Maximum plasma concentration

  3. Pharmacokinetics of Neihulizumab - tmax [ Time Frame: Up to Day 56 ]
    Time to reach Cmax

  4. Pharmacokinetics of Neihulizumab - Lambda-z [ Time Frame: Up to Day 56 ]
    Terminal phase elimination rate constant

  5. Pharmacokinetics of Neihulizumab - t1/2 [ Time Frame: Up to Day 56 ]
    Half life

  6. Pharmacokinetics of Neihulizumab - MRT [ Time Frame: Up to Day 56 ]
    Mean Residence Time

  7. Pharmacokinetics of Neihulizumab - Vz and Vss [ Time Frame: Up to Day 56 ]
    Volume of distribution and volume of distribution at steady state

Secondary Outcome Measures :
  1. Adverse Events (AEs) [ Time Frame: Up to Day 180 ]
    AEs graded according to CTCAE v4.03

  2. To measure the Receptor Occupancy (RO) [ Time Frame: Up to Day 56 ]
    Receptor occupancy will be monitored using a flow cytometry based method

  3. To measure regenerating islet-derived 3-alpha (REG3α) and suppression of tumorigenicity 2 (ST2) as Pharmacodynamics (PD) biomarkers. [ Time Frame: Up to Day 56 ]
    Receptor occupancy will be monitored using a flow cytometry based method

  4. Complete Response (CR) [ Time Frame: Day 28 ]
    To assess the rate of complete response (CR) at Day 28 in patients treated with Neihulizumab

  5. Overall Response Rate (ORR) [ Time Frame: Day 28 ]
    To assess the Overall Response Rate (ORR) at Day 28: CR+PR

  6. Duration of Response [ Time Frame: Up to Day 180 ]
    For subjects with CR at Day 28, duration of response will be assessed according to the time interval from Day 28 to the first occurrence of (1) resumption of Neihulizumab administration or initiation of new systemic treatment for aGvHD or (for patients who have tapered steroids) an increase in corticosteroids to methylprednisolone 2 mg/kg (+/-10%) equivalent or more, or (2) death.

  7. Non Relapse Mortality (NRM) [ Time Frame: Day 180 ]
    Patients will be followed-up for survival for 6 months after the first Neihulizumab treatment

  8. Immunogenicity [ Time Frame: Up to Day 56 ]
    Immunogenicity will be monitored by anti-drug antibody (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:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria (must meet all of the following criteria):

  1. Patients must have clinical aGVHD and pathologic findings consistent with the diagnosis by biopsy of at least 1 involved site, and

    1. progressed after 3 days of treatment with methylprednisolone (MP) 2 mg/kg/day equivalent, or
    2. did not improve after 7 days of treatment with MP 2 mg/kg/day equivalent, or
    3. progressed to involve a new organ after treatment with MP 1 mg/kg/day equivalent for skin and upper gastrointestinal (GI) GVHD, or
    4. recurred during or after a steroid taper
  2. For single dose phase: 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. For single dose phase: Providers and patients must be willing to defer new systemic or cutaneous topical treatment of aGVHD for at least 36 hr 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 (may not meet any of the following criteria):

  1. For single dose phase: Prior administration of anti-lymphocyte globulin or anti- thymocyte globulin for treatment of aGVHD.
  2. For multiple dose phase: Has received any systemic treatment in addition to corticosteroids for aGVHD.
  3. Stage 4 lower GI GVHD, defined by the presence of ileus, severe abdominal pain, or overt GI bleeding.
  4. Uncontrolled infections not responding to antimicrobial therapy or requiring intensive critical care or vasopressors.
  5. Evidence of end-organ cytomegalovirus (CMV) or adenovirus infection.
  6. Known to have adenovirus, or Epstein Barr virus (EBV) viremia from screening according to institutional standard practice. Patients receiving appropriate antiviral treatment for CMV, HHV6 or hepatitis viremia are eligible on a case-by-case basis.
  7. HIV infection or a known HIV-related malignancy.
  8. Tuberculosis, history of tuberculosis or a known positive Quantiferon test for tuberculosis.
  9. Unplanned donor lymphocyte infusion (DLI) for residual or relapsed malignancy or mixed chimerism. DLI as part of the planned HCT protocol is allowed.
  10. Known relapsed or progressive malignancy after transplant, posttransplant lymphoproliferative disease or any secondary malignancy diagnosed after HCT.
  11. Absolute neutrophil count (ANC) <1000/mm3.
  12. Total serum bilirubin concentration >3.0 mg/dL UNLESS attributed to GVHD.
  13. Creatinine clearance < 30 mL/min calculated by Cockcroft-Gault equation.
  14. Sodium (Na) concentration < 130 mmol/L.
  15. Karnofsky Performance Status (KPS) or Lansky Performance Status < 20%.
  16. 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.
  17. History of allergy or hypersensitivity to any systemically administered antibody agent or its excipients.
  18. Pregnancy or nursing.
  19. Less than 12 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 identifier (NCT number): NCT03327857

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Contact: Simona Reed, PhD +1 714 215 0224
Contact: Iming Cho, PhD +886 2 2627 2707 ext 412

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United States, California
City of Hope Terminated
Duarte, California, United States, 91010
David Geffen School of Medicine at UCLA Recruiting
Los Angeles, California, United States, 90095
Contact: Courtney Gibbon         
Principal Investigator: Gary Schiller         
United States, Florida
University of Miami - Sylvester Comprehensive Cancer Center Recruiting
Miami, Florida, United States, 33136
Principal Investigator: Trent Wang         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Shantoria Brown    404-778-6547   
Principal Investigator: Edmund Waller         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Michael Gomez    773-834-5314   
Principal Investigator: Satyajit Kosuri         
United States, Indiana
Indiana University Simon Cancer Center Withdrawn
Indianapolis, Indiana, United States, 46202
United States, Kansas
The University of Kansas Cancer Center Recruiting
Westwood, Kansas, United States, 66205
Principal Investigator: Sunil Abhyankar         
United States, Massachusetts
Dana Farber Cancer Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Loan Vuong   
Principal Investigator: Mahasweta Gooptu         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Maggie Kennel    734-232-6816   
Principal Investigator: Sarah Anand, MD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Janine Delage    612-625-8341   
Principal Investigator: Shernan Holtan, MD         
United States, Ohio
University Hospitals Seidman Cancer Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Cancer Information Service Line    800-641-2422      
Principal Investigator: Molly Gallogly         
United States, Tennessee
Vanderbilt-Ingram Cancer Center Withdrawn
Nashville, Tennessee, United States, 37232
United States, Texas
Baylor College of Medicine-Houston Methodist & Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Principal Investigator: LaQuisa Hill         
Sub-Investigator: Brian Friend         
United States, Washington
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109
Contact: Anise Marshall   
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   
Principal Investigator: Sameem Abedin, MD         
Sub-Investigator: Mehdi Hamadani, MD         
Sponsors and Collaborators
AltruBio Inc.
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Study Director: Shih-Yao Lin, MD, PhD AltruBio, Inc. (formerly AbGenomics International)
Principal Investigator: Paul Martin, MD Fred Hutchinson Cancer Center
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Responsible Party: AltruBio Inc. Identifier: NCT03327857    
Other Study ID Numbers: 2017.002.01
First Posted: November 1, 2017    Key Record Dates
Last Update Posted: March 31, 2022
Last Verified: March 2022
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