Clinical trial NCT02245412: A Phase 2A Study of ALXN1007 in Participants With Newly Diagnosed Acute Lower Gastrointestinal Graft-Versus-Host Disease
Official title: A Phase 2A Study of ALXN1007 in Subjects With Newly Diagnosed Acute Graft-Versus-Host Disease Involving the Lower Gastrointestinal Tract
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Acute Graft-Versus-Host Disease
GIGVHD
Keywords: GIGVHD
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-09-19
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Overall Acute Graft-Versus-Host Disease (GVHD) Response Rate At Day 28
timeFrame: Day 28
Secondary outcomes:
measure: Pharmacokinetics (PK): Time To Maximum Observed Concentration In Plasma (Tmax) Of IV ALXN1007
timeFrame: Predose up to 72 hours postdose
measure: PK: Maximum Observed Concentration In Plasma (Cmax) Of IV ALXN1007
timeFrame: Predose up to 72 hours postdose
measure: PK: Area Under The Plasma (Or Serum) Concentration Versus Time Curve (AUC) Of IV ALXN1007
timeFrame: Predose up to 72 hours postdose
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Medicine - Hematology, Oncology and Transplantation Office
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Philadelphia
country: United States
facility: Abramson Cancer Perelman Center for Advanced Medicine, University of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Grenoble
country: France
facility: CHU de Grenoble - Hôpital Nord
state: Isere
city: Gironde
country: France
facility: Groupe Hospitalier Sud - Hôpital Haut-Lévêque - Centre François
city: Paris
country: France
facility: Hôpital Saint-Louis
Study officials:
References: