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

Acute Graft-Versus-Host Disease Clinical Trial

— GIGVHD  

Official title:

A Phase 2A Study of ALXN1007 in Subjects With Newly Diagnosed Acute Graft-Versus-Host Disease Involving the Lower Gastrointestinal Tract

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02245412
• Other study ID #: ALXN1007-GIGVHD-201
• Status: Terminated
• Phase: Phase 2
• Start date: November 14, 2014
• Est. completion date: February 27, 2017

Study information

• Verified date: December 2018
• Source: Alexion Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This was a Phase 2A open-label, non-randomized study to evaluate the safety, tolerability, PK/PD, and efficacy of ALXN1007 (a C5a inhibitor) in up to 36 participants with newly diagnosed acute GVHD of the lower GI tract. All participants meeting the inclusion and exclusion criteria for the study were to receive ALXN1007 over an 8 week treatment period. Participants in Cohort 1, the first dosing cohort, were to receive 10 milligrams/kilogram (mg/kg) ALXN1007 administered IV once weekly for 8 weeks. Participants in Cohort 2 were to receive 20 mg/kg ALXN1007 IV once weekly for 8 weeks. Participants in Cohort 3 were to receive 20 mg/kg ALXN1007 IV twice weekly for 8 weeks. All doses of ALXN1007 were to be administered as a continuous IV infusion.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: February 27, 2017
• Est. primary completion date: February 27, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Graft-Versus-Host Disease
• GIGVHD
• Graft vs Host Disease

Intervention

Biological:
• ALXN1007 10 mg/kg once weekly
ALXN1007 is a recombinant humanized monoclonal antibody that binds to complement component C5a and its metabolite C5a desArg.
• ALXN1007 20 mg/kg once weekly
ALXN1007 is a recombinant humanized monoclonal antibody that binds to complement component C5a and its metabolite C5a desArg.
• ALXN1007 20 mg/kg twice weekly
ALXN1007 is a recombinant humanized monoclonal antibody that binds to complement component C5a and its metabolite C5a desArg.

Locations

Country	Name	City	State
France	Groupe Hospitalier Sud - Hôpital Haut-Lévêque - Centre François	Gironde
France	CHU de Grenoble - Hôpital Nord	Grenoble	Isere
France	Hôpital Saint-Louis	Paris
United States	Emory University Hospital	Atlanta	Georgia
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Minnesota Medicine - Hematology, Oncology and Transplantation Office	Minneapolis	Minnesota
United States	Abramson Cancer Perelman Center for Advanced Medicine, University of Pennsylvania	Philadelphia	Pennsylvania
United States	Washington University in St. Louis	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals

Countries where clinical trial is conducted

United States,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Acute Graft-Versus-Host Disease (GVHD) Response Rate At Day 28	The number of participants with overall acute GVHD response was determined at Day 28. Acute Overall GVHD is defined as improvement from diagnosis in any organ by at least 1 stage, without progression in any other organ, and with no additional therapy being administered. Acute GVHD staging included skin, liver, and GI assessments, which were to be performed using the Modified Keystone Grading Schema. Deaths were considered nonresponders; otherwise last postbaseline values were carried forward for imputation of missing responses. Modified Keystone Grading Schema: Skin - Stages 0 = No Rash, 1 = Rash <25% body surface area (BSA), 2 = 25% to 50% BSA, 3 = >50% BSA, 4 = bullae, desquamation; Lower GI Tract (stool volume over 24 hours) - Stages 0 = <500 mL, 1 = 500 to 1000 mL, 2 = 1001 to 1500 mL, 3 = >1500 mL, 4 = severe abdominal pain +/- ileus, frank blood, or melena; Liver (bilirubin levels) - Stages 0 = =2 mg/dL, 1 = 2.1 to 3 mg/dL, 2 = 3.1 to 6 mg/dL, 3 = 6.1 to 15 mg/dL, 4 = >15 mg/dL.	Day 28
Secondary	Pharmacokinetics (PK): Time To Maximum Observed Concentration In Plasma (Tmax) Of IV ALXN1007	The Tmax of ALXN1007 was measured on Treatment Days 1, 28, and 49, from blood samples collected at time points relative to the dosing of ALXN1007. PK assessments were to have been measured from Baseline, Treatment Days 7, 14, 21, 28, 35, 42, 49, 56, and Follow-up Days 86, 180, and Early Termination (ET).; Due to the early termination of the study and the clinical development of the ALXN1007 program, a number of PK analyses were not completed. PK data for the 20 mg/kg ALXN1007 once weekly dosing group and the 20 mg/kg ALXN1007 twice weekly dosing group are not available.	Predose up to 72 hours postdose
Secondary	PK: Maximum Observed Concentration In Plasma (Cmax) Of IV ALXN1007	The Cmax of ALXN1007 was measured on Treatment Days 1, 28, and 49, from blood samples collected at time points relative to the dosing of ALXN1007. PK assessments were to have been measured from Baseline, Treatment Days 7, 14, 21, 28, 35, 42, 49, 56, and Follow-up Days 86, 180, and Early Termination (ET).; Due to the early termination of the study and the clinical development of the ALXN1007 program, a number of PK analyses were not completed. PK data for the 20 mg/kg ALXN1007 once weekly dosing group and the 20 mg/kg ALXN1007 twice weekly dosing group are not available.	Predose up to 72 hours postdose
Secondary	PK: Area Under The Plasma (Or Serum) Concentration Versus Time Curve (AUC) Of IV ALXN1007	The AUC of ALXN1007 was measured on Treatment Days 1, 28, and 49, from blood samples collected at time points relative to the dosing of ALXN1007. PK assessments were to have been measured from Baseline, Treatment Days 7, 14, 21, 28, 35, 42, 49, 56, and Follow-up Days 86, 180, and Early Termination (ET).; Due to the early termination of the study and the clinical development of the ALXN1007 program, a number of PK analyses were not completed. PK data for the 20 mg/kg ALXN1007 once weekly dosing group and the 20 mg/kg ALXN1007 twice weekly dosing group are not available.	Predose up to 72 hours postdose