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

NCT ID: NCT02245412

Last Updated: 2019-01-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-14
• Study Completion Date: 2017-02-27

Brief 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.

Detailed 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.

Conditions

Acute Graft-Versus-Host Disease; GIGVHD

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ALXN1007 10 mg/kg once weekly

Cohort 1, the first dosing cohort, received 10 mg/kg ALXN1007 IV once weekly for 8 weeks.

Group Type: EXPERIMENTAL

ALXN1007 10 mg/kg once weekly

Intervention Type: BIOLOGICAL

ALXN1007 is a recombinant humanized monoclonal antibody that binds to complement component C5a and its metabolite C5a desArg.

ALXN1007 20 mg/kg once weekly

Cohort 2 received 20 mg/kg ALXN1007 IV once weekly for 8 weeks. For the first 2 participants enrolled, the first ALXN1007 dose was not to be administered on the same day and a safety and tolerability review was to take place after the second (and prior to the third) ALXN1007 dose for each participant. If the ALXN1007 dose was determined to be sufficiently tolerated by the participant, dosing was to continue for that participant. For any other participants enrolled in the dosing cohort, participants were not to proceed to the third ALXN1007 dose prior to the completion of the safety and tolerability review (of the first 2 doses) for the first 2 participants.

Group Type: EXPERIMENTAL

ALXN1007 20 mg/kg once weekly

Intervention Type: BIOLOGICAL

ALXN1007 is a recombinant humanized monoclonal antibody that binds to complement component C5a and its metabolite C5a desArg.

ALXN1007 20 mg/kg twice weekly

Cohort 3 received 20 mg/kg ALXN1007 IV twice weekly for 8 weeks. For the first 2 participants enrolled, the first ALXN1007 dose was not to be administered on the same day and a safety and tolerability review was to take place after the second (and prior to the third) ALXN1007 dose for each participant. If the ALXN1007 dose was determined to be sufficiently tolerated by the participant, dosing was to continue for that participant. For any other participants enrolled in the dosing cohort, participants were not to proceed to the third ALXN1007 dose prior to the completion of the safety and tolerability review (of the first 2 doses) for the first 2 participants.

Group Type: EXPERIMENTAL

ALXN1007 20 mg/kg twice weekly

Intervention Type: BIOLOGICAL

ALXN1007 is a recombinant humanized monoclonal antibody that binds to complement component C5a and its metabolite C5a desArg.

Interventions

ALXN1007 10 mg/kg once weekly

ALXN1007 is a recombinant humanized monoclonal antibody that binds to complement component C5a and its metabolite C5a desArg.

Intervention Type: BIOLOGICAL

ALXN1007 20 mg/kg once weekly

ALXN1007 is a recombinant humanized monoclonal antibody that binds to complement component C5a and its metabolite C5a desArg.

Intervention Type: BIOLOGICAL

ALXN1007 20 mg/kg twice weekly

ALXN1007 is a recombinant humanized monoclonal antibody that binds to complement component C5a and its metabolite C5a desArg.

Intervention Type: BIOLOGICAL

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

City of Hope

Duarte, California, United States

Emory University Hospital

Atlanta, Georgia, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

University of Minnesota Medicine - Hematology, Oncology and Transplantation Office

Minneapolis, Minnesota, United States

Washington University in St. Louis

St Louis, Missouri, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Abramson Cancer Perelman Center for Advanced Medicine, University of Pennsylvania

Philadelphia, Pennsylvania, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

CHU de Grenoble - Hôpital Nord

Grenoble, Isere, France

Groupe Hospitalier Sud - Hôpital Haut-Lévêque - Centre François

Gironde, , France

Hôpital Saint-Louis

Paris, , France

Countries

United States; France

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ALXN1007-GIGVHD-201

Identifier Type: -

Identifier Source: org_study_id