EZ-2053 in the Prophylaxis of Acute Pulmonary Allograft Rejection

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

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

Intervention / Treatment
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* Biological: Placebo
* Biological: EZ-2053
* Biological: EZ-2053 5mg/kg


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pulmonary transplantation, Pulmonary Allograft Rejection