EZ-2053 in the Prophylaxis of Acute Pulmonary Allograft Rejection

Cystic Fibrosis Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00105183
• Other study ID #: EZ-2053-001
• Status: Completed
• Phase: Phase 3
• First received: March 8, 2005
• Last updated: June 7, 2012
• Start date: January 2005
• Est. completion date: January 2011

Study information

• Verified date: June 2012
• Source: Neovii Biotech
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaAustralia: Department of Health and Ageing Therapeutic Goods AdministrationAustria: Agency for Health and Food Safety
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 223
• Est. completion date: January 2011
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Bronchiectasis
• Chronic Obstructive Pulmonary
• Cystic Fibrosis
• Fibrosis
• Idiopathic Interstitial Pneumonias
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis
• Pulmonary Vascular Disease
• Vascular Diseases

Intervention

Biological:
• Placebo
placebo infusion, single
• EZ-2053
single IV infusion, 9 mg/kg
• EZ-2053 5mg/kg
single IV infusion, 5mg/kg

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Neovii Biotech

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With the Event Death, Graft Loss, Acute Rejection and/or Loss to Follow-up (Whichever Occurred First)		12 months	Yes
Secondary	Number of Participants With Death or Graft Loss Post-transplant		12 months	Yes
Secondary	Number of Participants With Acute Rejection		12 months	Yes
Secondary	Number of Participants With Infections and Infestations		12 months	Yes
Secondary	Number of Participants With Severe Adverse Events		12 months	Yes
Secondary	Pulmonary Function Tests, Total Distance Walked 6 Minute Walk Test		12 months	Yes
Secondary	Pulmonary Function Test, Forced Vital Capacity		12 months	Yes
Secondary	Pulmonary Function Test, Forced Expiratory Volume in 1 Second		12 months	Yes
Secondary	Pulmonary Function Test, Forced Expiratory Flow 25-75		12 months	Yes