EZ-2053 in the Prophylaxis of Acute Pulmonary Allograft Rejection

Phase 3

Completed

Conditions: Chronic Obstructive Pulmonary
Idiopathic Pulmonary Fibrosis
Cystic Fibrosis
Bronchiectasis
Pulmonary Vascular Disease

Interventions: Biological: EZ-2053
Biological: Placebo
Biological: EZ-2053 5mg/kg

Registration Number: NCT00105183

Lead Sponsor: Neovii Biotech

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 223

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EZ-2053	EZ-2053	Anti-human-T-lymphocyte Immune Globulin, Rabbit (EZ-2053)
Placebo	Placebo	USP 0.9% sodium chloride solution
EZ-2053 5mg/kg	EZ-2053 5mg/kg	Anti-human-T-Lymphocyte Immune Globulin, Rabbit

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (19): Barnes-Jewish Hospital
🇺🇸
St. Louis, Missouri, United States
University of Pennsylvania Medical Center
🇺🇸
Philadelphia, Pennsylvania, United States
Vanderbilt University
🇺🇸
Nashville, Tennessee, United States
The Alfred Hospital
🇦🇺
Melbourne, Victoria, Australia
Baylor College of Medicine
🇺🇸
Houston, Texas, United States
University of California, San Francisco
🇺🇸
San Francisco, California, United States
Mayo Clinic
🇺🇸
Jacksonville, Florida, United States
Medical University of Vienna
🇦🇹
Vienna, Austria
University of Alberta
🇨🇦
Edmonton, Alberta, Canada
Toronto General Hospital
🇨🇦
Toronto, Canada
Emory University School of Medicine
🇺🇸
Atlanta, Georgia, United States
Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Stanford University
🇺🇸
Stanford, California, United States
University of Iowa Hospital & Clinics
🇺🇸
Iowa City, Iowa, United States
Temple University Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
INTEGRIS Baptist Medical Center
🇺🇸
Oklahoma City, Oklahoma, United States
University of Kentucky Medical Center
🇺🇸
Lexington, Kentucky, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
University of Texas Health Sciences Center
🇺🇸
San Antonio, Texas, United States