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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03327857
Other study ID # 2017.002.01
Secondary ID
Status Completed
Phase Phase 1
First received
Last updated
Start date May 31, 2018
Est. completion date December 31, 2022

Study information

Verified date January 2023
Source AltruBio Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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)


Description:

Neihulizumab (ALTB-168) 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.


Recruitment information / eligibility

Status Completed
Enrollment 37
Est. completion date December 31, 2022
Est. primary completion date September 30, 2022
Accepts healthy volunteers No
Gender All
Age group 12 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms

  • Graft vs Host Disease
  • Steroid-refractory Acute Graft-versus-Host Disease
  • Treatment-refractory Acute Graft-versus-Host Disease

Intervention

Biological:
Neihulizumab (ALTB-168)
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.

Locations

Country Name City State
United States University of Michigan Ann Arbor Michigan
United States Emory University Atlanta Georgia
United States Dana Farber Cancer Center Boston Massachusetts
United States University of Chicago Chicago Illinois
United States University Hospitals Seidman Cancer Center Cleveland Ohio
United States City of Hope Duarte California
United States Baylor College of Medicine-Houston Methodist & Texas Children's Hospital Houston Texas
United States David Geffen School of Medicine at UCLA Los Angeles California
United States University of Miami - Sylvester Comprehensive Cancer Center Miami Florida
United States Medical College of Wisconsin Milwaukee Wisconsin
United States University of Minnesota Minneapolis Minnesota
United States Fred Hutchinson Cancer Research Center Seattle Washington
United States The University of Kansas Cancer Center Westwood Kansas

Sponsors (1)

Lead Sponsor Collaborator
AltruBio Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Pharmacokinetics of Neihulizumab - AUC Including AUC0-t, AUC0-tz, AUC 0-inf Up to Day 56
Primary Pharmacokinetics of Neihulizumab - Cmax Maximum plasma concentration Up to Day 56
Primary Pharmacokinetics of Neihulizumab - tmax Time to reach Cmax Up to Day 56
Primary Pharmacokinetics of Neihulizumab - Lambda-z Terminal phase elimination rate constant Up to Day 56
Primary Pharmacokinetics of Neihulizumab - t1/2 Half life Up to Day 56
Primary Pharmacokinetics of Neihulizumab - MRT Mean Residence Time Up to Day 56
Primary Pharmacokinetics of Neihulizumab - Vz and Vss Volume of distribution and volume of distribution at steady state Up to Day 56
Secondary Adverse Events (AEs) AEs graded according to CTCAE v4.03 Up to Day 180
Secondary To measure the Receptor Occupancy (RO) Receptor occupancy will be monitored using a flow cytometry based method Up to Day 56
Secondary To measure regenerating islet-derived 3-alpha (REG3a) and suppression of tumorigenicity 2 (ST2) as Pharmacodynamics (PD) biomarkers. Receptor occupancy will be monitored using a flow cytometry based method Up to Day 56
Secondary Complete Response (CR) To assess the rate of complete response (CR) at Day 28 in patients treated with Neihulizumab Day 28
Secondary Overall Response Rate (ORR) To assess the Overall Response Rate (ORR) at Day 28: CR+PR Day 28
Secondary Duration of Response 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. Up to Day 180
Secondary Non Relapse Mortality (NRM) Patients will be followed-up for survival for 6 months after the first Neihulizumab treatment Day 180
Secondary Immunogenicity Immunogenicity will be monitored by anti-drug antibody (ADA) ELISA Up to Day 56
See also
  Status Clinical Trial Phase
Recruiting NCT06075706 - Trial of Efficacy and Safety of MC0518 Versus Best Available Therapy in Participants With Steroid-Refractory Acute Graft Versus Host Disease Phase 2
Recruiting NCT04629833 - Treatment Of Steroid-Refractory Acute Graft-versus-host Disease With Mesenchymal Stromal Cells Versus Best Available Therapy Phase 3