EZ-2053 in the Prophylaxis of Acute Pulmonary Allograft Rejection

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)

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.

Study Overview

• Status: Completed
• Conditions: Bronchiectasis; Idiopathic Pulmonary Fibrosis; Cystic Fibrosis; Chronic Obstructive Pulmonary; Pulmonary Vascular Disease
• Intervention / Treatment: Biological: EZ-2053; Biological: Placebo; Biological: EZ-2053 5mg/kg

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.

• Study Type: Interventional
• Enrollment (Actual): 223
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia
      • The Alfred Hospital
• Austria
  • Vienna, Austria
    • Medical University of Vienna
• Canada
  • Edmonton, Alberta, Canada
    • University of Alberta
  • Toronto, Canada
    • Toronto General Hospital
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
    • Stanford, California, United States, 94305
      • Stanford University
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospital & Clinics
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Medical Center
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Integris Baptist Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: EZ-2053; Anti-human-T-lymphocyte Immune Globulin, Rabbit (EZ-2053)	Biological: EZ-2053; single IV infusion, 9 mg/kg; Other Names: ATG; Anti-human-T-Lymphocyte Immune Globulin, Rabbit
Placebo Comparator: Placebo; USP 0.9% sodium chloride solution	Biological: Placebo; placebo infusion, single; Other Names: Saline
Active Comparator: EZ-2053 5mg/kg; Anti-human-T-Lymphocyte Immune Globulin, Rabbit	Biological: EZ-2053 5mg/kg; single IV infusion, 5mg/kg; Other Names: ATG; Anti-human-T-Lymphocyte Immune Globulin, Rabbit

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With the Event Death, Graft Loss, Acute Rejection and/or Loss to Follow-up (Whichever Occurred First)	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Death or Graft Loss Post-transplant	12 months
Number of Participants With Acute Rejection	12 months
Number of Participants With Infections and Infestations	12 months
Number of Participants With Severe Adverse Events	12 months
Pulmonary Function Tests, Total Distance Walked 6 Minute Walk Test	12 months
Pulmonary Function Test, Forced Vital Capacity	12 months
Pulmonary Function Test, Forced Expiratory Volume in 1 Second	12 months
Pulmonary Function Test, Forced Expiratory Flow 25-75	12 months

Collaborators and Investigators

• Sponsor: Neovii Biotech
• Investigators: Principal Investigator: Elbert P Trulock III, MD, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: March 8, 2005
• First Submitted That Met QC Criteria: March 8, 2005
• First Posted (Estimate): March 9, 2005

Study Record Updates

• Last Update Posted (Estimate): June 11, 2012
• Last Update Submitted That Met QC Criteria: June 7, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: pulmonary transplantation; Pulmonary Allograft Rejection
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Bronchial Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Bronchiectasis; Vascular Diseases; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Cystic Fibrosis; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin; Antilymphocyte Serum; Immunoglobulin G
• Other Study ID Numbers: EZ-2053-001