A Phase 2A Study of ALXN1007 in Participants With Newly Diagnosed Acute Lower Gastrointestinal Graft-Versus-Host Disease

Study Identifier:
ALXN1007-GIGVHD-201
ClinicalTrials.gov Identifier:
NCT02245412
EudraCT Identifier:
N/A
EU CT ID:
N/A
Sponsor:
Alexion Pharmaceuticals, Inc.
Study Contact Information:
N/A
Other

Available Documents

ProtocolStatistical Analysis Plan

Study Details

Medical Condition
  • Acute Graft-Versus-Host Disease
  • Unmapped
Study Drug
  • Biological: ALXN1007 10 mg/kg once weekly
  • Biological: ALXN1007 20 mg/kg once weekly
  • Biological: ALXN1007 20 mg/kg twice weekly
Date
Nov 2014 - Feb 2017
Phase 1
Phase 2
Phase 3
Phase 4
N/A
Patient Requirements
Sex: Female & Male
Age: 18+ years
Requirements Information
Inclusion and Exclusion Criteria
Inclusion Criteria
  • Participants must be males or females age 18 years or older.
  • Participants with Stage 1 to 4 (per the Modified Keystone Grading Schema) acute GVHD of the lower GI tract, without signs of chronic GVHD, at the time of diagnosis, which developed in the first 180 days following allogeneic hematopoietic cell transplantation (HCT) using bone marrow, peripheral blood, or cord blood; or after preplanned donor lymphocyte infusion.
  • Participants are willing to undergo or must have had an endoscopy of the upper and/or lower GI tract and biopsy to confirm GI GVHD.
  • Participants must be receiving systemic corticosteroids.
  • Participants with an absolute neutrophil count (ANC) \>500/microliter (μL) at Screening.
  • Participants and spouse/partner who are of childbearing potential must be using high effective contraception consisting of 2 forms of birth control (at least 1 of which much be barrier method) starting at Screening and continuing through the entire study (for at least 3 months after the last dose of ALXN1007 if study treatment is stopped early or participant withdraws consent).
  • Male participants must not donate sperm during the Screening and Treatment periods, and for at least 3 months after the last dose of ALXN1007.
  • Stage of acute GVHD of the lower GI tract will be determined using the Modified Keystone Grading Schema.
Exclusion Criteria
  • Participants with a body weight \> 140 kg (for Cohorts dosing 20 mg/kg of ALXN1007 and higher only).
  • Participants with signs and symptoms of chronic GVHD.
  • Participants with an active uncontrolled infection.
  • Participants who test positive for Clostridium difficile (C. difficile) at Screening.
  • Participants with relapsed/persistent malignancy requiring rapid immune suppression withdrawal.
  • Participants who received an unplanned (not part of the original transplant therapy plan) donor lymphocyte infusion.
  • Participants who received previous systemic treatment for acute GVHD, except for a maximum of 3 days (72 hours) of 2 mg/kg corticosteroid therapy.
  • Participants with unresolved veno-occlusive disease of the liver.
  • Participants with creatinine clearance \<40 milliliters (mL)/minute at Screening, as calculated by the Cockcroft-Gault formula.
  • Participants known to be infected with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
  • Participants known to have an uncontrolled thyroid disorder.
  • Participants who are pregnant, breast feeding, or sexually active and unwilling to use effective birth control for the duration of the study.
  • Participants who participated in any other investigational drug trial or had exposure to any other investigational agent, device, or procedure \<4 weeks prior to Screening and throughout the entire trial, with the exception of investigational drugs administered prophylactically for cytomegalovirus (CMV) post allogeneic HCT.
Sex
Female & Male
Age
18+ years

Study Details

Medical Condition
  • Acute Graft-Versus-Host Disease
  • Unmapped
Study Drug
  • Biological: ALXN1007 10 mg/kg once weekly
  • Biological: ALXN1007 20 mg/kg once weekly
  • Biological: ALXN1007 20 mg/kg twice weekly
Date
Nov 2014 - Feb 2017
Phase 1
Phase 2
Phase 3
Phase 4
N/A
Patient Requirements
Sex: Female & Male
Age: 18+ years years
Requirements Information
Inclusion and Exclusion Criteria
Inclusion Criteria
  • Participants must be males or females age 18 years or older.
  • Participants with Stage 1 to 4 (per the Modified Keystone Grading Schema) acute GVHD of the lower GI tract, without signs of chronic GVHD, at the time of diagnosis, which developed in the first 180 days following allogeneic hematopoietic cell transplantation (HCT) using bone marrow, peripheral blood, or cord blood; or after preplanned donor lymphocyte infusion.
  • Participants are willing to undergo or must have had an endoscopy of the upper and/or lower GI tract and biopsy to confirm GI GVHD.
  • Participants must be receiving systemic corticosteroids.
  • Participants with an absolute neutrophil count (ANC) \>500/microliter (μL) at Screening.
  • Participants and spouse/partner who are of childbearing potential must be using high effective contraception consisting of 2 forms of birth control (at least 1 of which much be barrier method) starting at Screening and continuing through the entire study (for at least 3 months after the last dose of ALXN1007 if study treatment is stopped early or participant withdraws consent).
  • Male participants must not donate sperm during the Screening and Treatment periods, and for at least 3 months after the last dose of ALXN1007.
  • Stage of acute GVHD of the lower GI tract will be determined using the Modified Keystone Grading Schema.
Exclusion Criteria
  • Participants with a body weight \> 140 kg (for Cohorts dosing 20 mg/kg of ALXN1007 and higher only).
  • Participants with signs and symptoms of chronic GVHD.
  • Participants with an active uncontrolled infection.
  • Participants who test positive for Clostridium difficile (C. difficile) at Screening.
  • Participants with relapsed/persistent malignancy requiring rapid immune suppression withdrawal.
  • Participants who received an unplanned (not part of the original transplant therapy plan) donor lymphocyte infusion.
  • Participants who received previous systemic treatment for acute GVHD, except for a maximum of 3 days (72 hours) of 2 mg/kg corticosteroid therapy.
  • Participants with unresolved veno-occlusive disease of the liver.
  • Participants with creatinine clearance \<40 milliliters (mL)/minute at Screening, as calculated by the Cockcroft-Gault formula.
  • Participants known to be infected with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
  • Participants known to have an uncontrolled thyroid disorder.
  • Participants who are pregnant, breast feeding, or sexually active and unwilling to use effective birth control for the duration of the study.
  • Participants who participated in any other investigational drug trial or had exposure to any other investigational agent, device, or procedure \<4 weeks prior to Screening and throughout the entire trial, with the exception of investigational drugs administered prophylactically for cytomegalovirus (CMV) post allogeneic HCT.

Protocol Summary

The objectives of this trial were to evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics (PK/PD) and efficacy of intravenous (IV) ALXN1007 in participants with acute graft-versus-host disease (GVHD) of the lower gastrointestinal (GI) tract.

Trial Locations

Location
Status
Location
City of Hope
Duarte, California, United States, 91010
Status
N/A
Location
Emory University Hospital
Atlanta, Georgia, United States, 30322
Status
N/A
Location
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Status
N/A
Location
University of Minnesota Medicine - Hematology, Oncology and Transplantation Office
Minneapolis, Minnesota, United States, 55455
Status
N/A
Location
Washington University in St. Louis
St Louis, Missouri, United States, 63110
Status
N/A
Location
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Status
N/A
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