Clinical trial NCT00105183: EZ-2053 in the Prophylaxis of Acute Pulmonary Allograft Rejection
Official title: A Double-Blind, Placebo-Controlled, Multicenter, Dose-Ranging Study of an Anti-human-T-lymphocyte Immune Globulin (EZ-2053) in the Prophylaxis of Acute Pulmonary Allograft Rejection in Adult Recipients of Primary Pulmonary Allograft(s)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Obstructive Pulmonary
Idiopathic Pulmonary Fibrosis
Cystic Fibrosis
Bronchiectasis
Pulmonary Vascular Disease
Keywords: pulmonary transplantation
Pulmonary Allograft Rejection
Lead sponsor: Neovii Biotech
Sponsor class: INDUSTRY
First posted: 2005-03-09
Enrollment: 223
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the efficacy and safety of the study drug, known as "ATG Fresenius S," which is sometimes called "EZ-2053," to prevent a lung transplant patient's body from rejecting a transplanted lung or lungs.

Detailed description: Patients are generally consented for the study once they go on the lung transplant waiting list and then are re-consented periodically thereafter until they undergo the lung transplant surgery. A pre-surgical assessment consisting of medical history, physical exam, ECG, chest X-Ray, and blood tests are conducted. After lung transplant surgery, patients are assessed for continued eligibility. Within 6-24 hours after the end of surgery, patients are randomized to receive one infusion of study drug or placebo through a central venous catheter. Each day for 5 days following transplant surgery, patients are monitored for transplant rejection, infections, adverse events and laboratory test changes. On post-randomization Days 14, 30, 60, 90, 180, 270 and 365, patients will be monitored for acute transplant rejection, infections and cancer, pulmonary function tests and adverse experiences. Pulmonary biopsies will be performed on post-randomization Days 30, 60, 90, 180 and 365. Blood samples will be drawn during each visit.

Eligibility criteria: Inclusion Criteria:

* Recipient of a primary single or double pulmonary allograft
* Capable of understanding the purposes and risks of the study and has given written informed consent, and agrees to comply with the study requirements
* Women of childbearing potential must have a negative serum pregnancy test within 4 days prior to randomization.

Exclusion Criteria:

* Undergoing second or living donor transplant
* Prior treatment with T-cell depleting agents within the previous 5 years for the purpose of immunosuppression
* Prior plasma exchange and/or treatment with IVIg within the past 5 years
* Pulmonary infection with pan-resistant Pseudomonas or any Burkholderia species
* Known positive blood cultures
* Donor lung ischemia time \> 8 hours for first lung and \> 8 hours for the second lung
* Previously received or is receiving a multi-organ transplant
* Pregnant women, nursing mothers or women of child-bearing potential who are unwilling to use reliable contraception. Effective contraception must be used BEFORE beginning study drug therapy, for the duration of the study and for 6 months following completion of the study
* Active, extra-pulmonary systemic infection requiring the prolonged or chronic use of antimicrobial agents or the presence of a chronic active hepatitis B or C
* Active liver disease (liver function tests greater than or equal to 2 times the upper limit of normal)
* Severe anemia (hemoglobin, \< 6 g/dL), leukopenia (WBC \< 2500/mm3), thrombocytopenia (platelet count \< 80,000/mm3), polycythemia (Hct \> 54% \[male\], Hct \> 49% \[female\]) or clinically significant coagulopathy
* Recipient or donor is seropositive for HIV
* Previous exposure or known contraindication to administration of the study drug or to rabbit proteins
* Current malignancy or a history of malignancy (within the previous 5 years), except non-metastatic basal cell or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix that has been treated successfully
* Unstable cardiovascular disease, or a myocardial infarction within the previous 6 months
* Currently participating in another clinical trial with an investigational agent and/or is taking or has been taking an investigational agent in the 30 days prior to transplant and/or has not recovered from any reversible side effects of prior investigational drug
* Unlikely to comply with visits schedule in the protocol
* Any current history of substance abuse, psychiatric disorder or a condition that, in the opinion of the Investigator, may invalidate communication with the Investigator.

Primary outcomes:
measure: Number of Participants With the Event Death, Graft Loss, Acute Rejection and/or Loss to Follow-up (Whichever Occurred First)
timeFrame: 12 months
Secondary outcomes:
measure: Number of Participants With Death or Graft Loss Post-transplant
timeFrame: 12 months
measure: Number of Participants With Acute Rejection
timeFrame: 12 months
measure: Number of Participants With Infections and Infestations
timeFrame: 12 months
measure: Number of Participants With Severe Adverse Events
timeFrame: 12 months
measure: Pulmonary Function Tests, Total Distance Walked 6 Minute Walk Test
timeFrame: 12 months
measure: Pulmonary Function Test, Forced Vital Capacity
timeFrame: 12 months
measure: Pulmonary Function Test, Forced Expiratory Volume in 1 Second
timeFrame: 12 months
measure: Pulmonary Function Test, Forced Expiratory Flow 25-75
timeFrame: 12 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Hospital & Clinics
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: St. Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Oklahoma City
country: United States
facility: INTEGRIS Baptist Medical Center
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Sciences Center
state: Texas
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Edmonton, Alberta
country: Canada
facility: University of Alberta
city: Toronto
country: Canada
facility: Toronto General Hospital
Study officials:
affiliation: Washington University School of Medicine
name: Elbert P Trulock III, MD
role: PRINCIPAL_INVESTIGATOR
References: