Study of EZ-2053 in the Prophylaxis of Acute Pulmonary Allograft Rejection - Full Text View

Sponsored by:	Fresenius Biotech GmbH
Information provided by:	Fresenius Biotech GmbH
ClinicalTrials.gov Identifier:	NCT00105183

Purpose

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.

Condition	Intervention	Phase
Graft Rejection Lung Transplantation	Biological: Placebo Biological: Anti-T-Lymphocyte Immune Globulin, Rabbit	Phase III

MedlinePlus related topics: Lung Transplantation

Drug Information available for: Immunoglobulins Globulin, Immune

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Double-Blind, Placebo-Controlled, Multicenter, Dose-Ranging Study of an Anti-T-Lymphocyte Immune Globulin (EZ-2053) in the Prophylaxis of Acute Pulmonary Allograft Rejection in Adult Recipients of Primary Pulmonary Allograft(s)

Further study details as provided by Fresenius Biotech GmbH:

Primary Outcome Measures:

Rate of efficacy post-transplant [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Incidence of death or re-transplant [ Time Frame: 6, 24, and 36 months ] [ Designated as safety issue: Yes ]
Incidence, frequency and severity of biopsy-proven acute allograft rejection [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Incidence and frequency of steroid-resistant allograft rejection [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]
Incidence and frequency of Bronchiolitis Obliterans Syndrome [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
Incidence of infections and malignancies [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
Incidence and severity of adverse experiences [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
Changes in laboratory values [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	240
Study Start Date:	January 2005
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Standard dose EZ-2053	Biological: Anti-T-Lymphocyte Immune Globulin, Rabbit single IV infusion, 9 mg/kg
2: Active Comparator Low dose EZ-2053	Biological: Anti-T-Lymphocyte Immune Globulin, Rabbit single IV infusion, 5 mg/kg
3: Placebo Comparator Placebo	Biological: Placebo placebo infusion, single

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 as 9mg/kg, 5mg/kg 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, 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 during Year 1. During Years 2 and 3, patients will have visits on Days 545, 730, 910 and 1095 for monitoring of transplant rejection, infections and cancer.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00105183

Contacts

Contact: Terry Burns

(781) 699-4631

theresa.burns@fresenius-biotech.com

Locations

United States, California
University of California, San Francisco	Recruiting
San Francisco, California, United States, 94143
Contact: Tina Mattucci tina.mattucci@ucsf.edu
Principal Investigator: Charles Hoopes, MD
Stanford University	Recruiting
Stanford, California, United States, 94305
Contact: Kim Bonnett 650-736-8083 kbonnett@stanford.edu
Contact: Susan Jacobs (650) 725-8082 ssjpulm@stanford.edu
Principal Investigator: Gundeep Dhillon, MD
United States, Florida
Mayo Clinic	Recruiting
Jacksonville, Florida, United States, 32224
Contact: Pam Oldano, RN 904-953-7499 oldano.pamela@mayo.edu
Principal Investigator: Cesar Keller, MD
United States, Georgia
Emory University School of Medicine	Active, not recruiting
Atlanta, Georgia, United States, 30322
United States, Iowa
University of Iowa Hospital & Clinics	Recruiting
Iowa City, Iowa, United States, 52242
Contact: Kathleen Lilli 319-356-0575 kathleen-lilli@uiowa.edu
Principal Investigator: Julia Klesney-Tait, MD
United States, Kentucky
University of Kentucky Medical Center	Recruiting
Lexington, Kentucky, United States, 40536
Contact: Connie Dampier 859-323-1781 dampier@emailuky.edu
Principal Investigator: Timothy Mullett, MD
United States, Missouri
Barnes-Jewish Hospital	Recruiting
St. Louis, Missouri, United States, 63110
Contact: Aviva Aloush 314-747-1931 alousha@wudosis.wustl.edu
Principal Investigator: Elbert Trulock, MD
United States, Ohio
Cleveland Clinic	Recruiting
Cleveland, Ohio, United States, 44195
Contact: Ramona Ramachandran 216-636-2487 ramachr@ccf.org
Principal Investigator: Marie Budev, D.O., MPH
United States, Oklahoma
INTEGRIS Baptist Medical Center	Active, not recruiting
Oklahoma City, Oklahoma, United States, 73112
United States, Pennsylvania
University of Pennsylvania Medical Center	Active, not recruiting
Philadelphia, Pennsylvania, United States, 19104
Temple University Hospital	Active, not recruiting
Philadelphia, Pennsylvania, United States, 19140
United States, Tennessee
Vanderbilt University	Active, not recruiting
Nashville, Tennessee, United States, 37232
United States, Texas
University of Texas Health Sciences Center	Active, not recruiting
San Antonio, Texas, United States, 78229
Baylor College of Medicine	Recruiting
Houston, Texas, United States, 77030
Contact: Diana (Quan) Lin 713-798-1204 quanl@bcm.tmc.edu
Principal Investigator: Harish Seethamraju, MD
Australia, Victoria
The Alfred Hospital	Recruiting
Melbourne, Victoria, Australia
Contact: Bronwyn Levvey 61 3 9276 3829 b.levvey@alfred.org.au
Principal Investigator: Gregory Snell, MD
Austria
Medical University of Vienna	Recruiting
Vienna, Austria
Contact: Julian Marschalek 43 69910301857 julian.marschalek@meduniwien.ac.at
Contact: Hannelore Goff 43-1-40400-7989
Principal Investigator: Peter Jaksch, MD
Canada
Toronto General Hospital	Recruiting
Toronto, Canada
Contact: Sassan Azad 416-340-4800 ext 6224 sassan.azad@uhn.on.ca
Principal Investigator: Shaf Keshavjee, MD
University of Alberta	Not yet recruiting
Edmonton, Alberta, Canada
Contact: Patricia Lo 780-407-7320 pslo@ualberta.ca
Principal Investigator: John Mullen, MD

Sponsors and Collaborators

Fresenius Biotech GmbH

Investigators

Study Director:

Claudio Carini, MD

Fresenius Biotech NA

More Information

Responsible Party:	Fresenius Biotech North America ( Terry Burns/Clinical Project Manager )
Study ID Numbers:	EZ-2053-001
Study First Received:	March 8, 2005
Last Updated:	January 15, 2009
ClinicalTrials.gov Identifier:	NCT00105183
Health Authority:	United States: Food and Drug Administration; Canada: Health Canada; Australia: Department of Health and Ageing Therapeutic Goods Administration; Austria: Agency for Health and Food Safety

Keywords provided by Fresenius Biotech GmbH:

pulmonary transplantation
Pulmonary Allograft Rejection

Study placed in the following topic categories:

Antilymphocyte Serum
Antibodies
Immunoglobulins

Additional relevant MeSH terms:

Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009