Neihulizumab (ALTB-168) in Patients With Steroid-refractory Acute Graft-versus-host Disease or Treatment-refractory Acute Graft-versus-host Disease
- Conditions
- Treatment-refractory Acute Graft-versus-Host DiseaseSteroid-refractory Acute Graft-versus-Host Disease
- Interventions
- Biological: Neihulizumab (ALTB-168)
- Registration Number
- NCT03327857
- Lead Sponsor
- 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)
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 37
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Neihulizumab (ALTB-168) Neihulizumab (ALTB-168) Intravenous doses of Neihulizumab (ALTB-168)
- Primary Outcome Measures
Name Time Method Pharmacokinetics of Neihulizumab - t1/2 Up to Day 56 Half life
Pharmacokinetics of Neihulizumab - tmax Up to Day 56 Time to reach Cmax
Pharmacokinetics of Neihulizumab - Lambda-z Up to Day 56 Terminal phase elimination rate constant
Pharmacokinetics of Neihulizumab - AUC Up to Day 56 Including AUC0-t, AUC0-tz, AUC 0-inf
Pharmacokinetics of Neihulizumab - Cmax Up to Day 56 Maximum plasma concentration
Pharmacokinetics of Neihulizumab - MRT Up to Day 56 Mean Residence Time
Pharmacokinetics of Neihulizumab - Vz and Vss Up to Day 56 Volume of distribution and volume of distribution at steady state
- Secondary Outcome Measures
Name Time Method To measure the Receptor Occupancy (RO) Up to Day 56 Receptor occupancy will be monitored using a flow cytometry based method
Overall Response Rate (ORR) Day 28 To assess the Overall Response Rate (ORR) at Day 28: CR+PR
Immunogenicity Up to Day 56 Immunogenicity will be monitored by anti-drug antibody (ADA) ELISA
Adverse Events (AEs) Up to Day 180 AEs graded according to CTCAE v4.03
To measure regenerating islet-derived 3-alpha (REG3α) and suppression of tumorigenicity 2 (ST2) as Pharmacodynamics (PD) biomarkers. Up to Day 56 Receptor occupancy will be monitored using a flow cytometry based method
Complete Response (CR) Day 28 To assess the rate of complete response (CR) at Day 28 in patients treated with Neihulizumab
Duration of Response 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.
Non Relapse Mortality (NRM) Day 180 Patients will be followed-up for survival for 6 months after the first Neihulizumab treatment
Trial Locations
- Locations (13)
David Geffen School of Medicine at UCLA
🇺🇸Los Angeles, California, United States
Baylor College of Medicine-Houston Methodist & Texas Children's Hospital
🇺🇸Houston, Texas, United States
University of Miami - Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
The University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
University Hospitals Seidman Cancer Center
🇺🇸Cleveland, Ohio, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Dana Farber Cancer Center
🇺🇸Boston, Massachusetts, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
City of Hope
🇺🇸Duarte, California, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States