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

NCT03327857 | Completed Phase 1 FDA Drug

• 1 other identifier: 2017.002.01
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 13

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)

Conditions

Steroid-refractory Acute Graft-versus-Host Disease; Treatment-refractory Acute Graft-versus-Host Disease

Outcome Measures

Primary Outcomes (7)

• Pharmacokinetics of Neihulizumab - AUC

  Including AUC0-t, AUC0-tz, AUC 0-inf

  Up to Day 56

• Pharmacokinetics of Neihulizumab - Cmax

  Maximum plasma concentration

  Up to Day 56

• Pharmacokinetics of Neihulizumab - tmax

  Time to reach Cmax

  Up to Day 56

• Pharmacokinetics of Neihulizumab - Lambda-z

  Terminal phase elimination rate constant

  Up to Day 56

• Pharmacokinetics of Neihulizumab - t1/2

  Half life

  Up to Day 56

• Pharmacokinetics of Neihulizumab - MRT

  Mean Residence Time

  Up to Day 56

• Pharmacokinetics of Neihulizumab - Vz and Vss

  Volume of distribution and volume of distribution at steady state

  Up to Day 56

Secondary Outcomes (8)

• Adverse Events (AEs)

  Up to Day 180

• To measure the Receptor Occupancy (RO)

  Up to Day 56

• To measure regenerating islet-derived 3-alpha (REG3α) and suppression of tumorigenicity 2 (ST2) as Pharmacodynamics (PD) biomarkers.

  Up to Day 56

• Complete Response (CR)

  Day 28

• Overall Response Rate (ORR)

  Day 28

Study Arms (1)

Neihulizumab (ALTB-168)

EXPERIMENTAL

Intravenous doses of Neihulizumab (ALTB-168)

Biological: Neihulizumab (ALTB-168)

Interventions

Neihulizumab (ALTB-168) BIOLOGICAL

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.

Neihulizumab (ALTB-168)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have clinical aGVHD and pathologic findings consistent with the diagnosis by biopsy of at least 1 involved site, and
• progressed after 3 days of treatment with methylprednisolone (MP) 2 mg/kg/day equivalent, or
• did not improve after 7 days of treatment with MP 2 mg/kg/day equivalent, or
• progressed to involve a new organ after treatment with MP 1 mg/kg/day equivalent for skin and upper gastrointestinal (GI) GVHD, or
• recurred during or after a steroid taper
• 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).
• 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.
• Patient must give informed consent and sign an approved consent form prior to any study procedures.
• 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.

You may not qualify if:

• For single dose phase: Prior administration of anti-lymphocyte globulin or anti- thymocyte globulin for treatment of aGVHD.
• For multiple dose phase: Has received any systemic treatment in addition to corticosteroids for aGVHD.
• Stage 4 lower GI GVHD, defined by the presence of ileus, severe abdominal pain, or overt GI bleeding.
• Uncontrolled infections not responding to antimicrobial therapy or requiring intensive critical care or vasopressors.
• Evidence of end-organ cytomegalovirus (CMV) or adenovirus infection.
• 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.
• HIV infection or a known HIV-related malignancy.
• Tuberculosis, history of tuberculosis or a known positive Quantiferon test for tuberculosis.
• Unplanned donor lymphocyte infusion (DLI) for residual or relapsed malignancy or mixed chimerism. DLI as part of the planned HCT protocol is allowed.
• Known relapsed or progressive malignancy after transplant, posttransplant lymphoproliferative disease or any secondary malignancy diagnosed after HCT.
• Absolute neutrophil count (ANC) \<1000/mm3.
• Total serum bilirubin concentration \>3.0 mg/dL UNLESS attributed to GVHD.
• Creatinine clearance \< 30 mL/min calculated by Cockcroft-Gault equation.
• Sodium (Na) concentration \< 130 mmol/L.
• Karnofsky Performance Status (KPS) or Lansky Performance Status \< 20%.

Sponsors & Collaborators

• AltruBio Inc.: lead

Study Sites (13)

City of Hope

Duarte, California, 91010, United States

Location

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

The University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Dana Farber Cancer Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University Hospitals Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

Baylor College of Medicine-Houston Methodist & Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Study Officials

• Shih-Yao Lin, MD, PhD

  AltruBio, Inc. (formerly AbGenomics International)

  STUDY DIRECTOR

• Paul Martin, MD

  Fred Hutchinson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2017
• First Posted: November 1, 2017
• Study Start: May 31, 2018
• Primary Completion: September 30, 2022
• Study Completion: December 31, 2022
• Last Updated: January 19, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)