EZ-2053 in the Prophylaxis of Acute Pulmonary Allograft Rejection

NCT00105183 | Completed Phase 3 Results DMC

• 1 other identifier: EZ-2053-001
• Study Type: interventional
• Target: 223
• Locations: 3 countries
• Sites: 18

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.

Conditions

Chronic Obstructive Pulmonary; Idiopathic Pulmonary Fibrosis; Cystic Fibrosis; Bronchiectasis; Pulmonary Vascular Disease

Keywords

pulmonary transplantation; Pulmonary Allograft Rejection

Outcome Measures

Primary Outcomes (1)

• Number of Participants With the Event Death, Graft Loss, Acute Rejection and/or Loss to Follow-up (Whichever Occurred First)

  12 months

Secondary Outcomes (8)

• 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

Study Arms (3)

EZ-2053

ACTIVE COMPARATOR

Anti-human-T-lymphocyte Immune Globulin, Rabbit (EZ-2053)

Biological: EZ-2053

Placebo

PLACEBO COMPARATOR

USP 0.9% sodium chloride solution

Biological: Placebo

EZ-2053 5mg/kg

ACTIVE COMPARATOR

Anti-human-T-Lymphocyte Immune Globulin, Rabbit

Biological: EZ-2053 5mg/kg

Interventions

Placebo BIOLOGICAL

placebo infusion, single

Also known as: Saline

Placebo

EZ-2053 BIOLOGICAL

single IV infusion, 9 mg/kg

Also known as: ATG, Anti-human-T-Lymphocyte Immune Globulin, Rabbit

EZ-2053

EZ-2053 5mg/kg BIOLOGICAL

single IV infusion, 5mg/kg

Also known as: ATG, Anti-human-T-Lymphocyte Immune Globulin, Rabbit

EZ-2053 5mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Neovii Biotech: lead

Study Sites (19)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

University of Iowa Hospital & Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kentucky Medical Center

Lexington, Kentucky, 40536, United States

Location

Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

INTEGRIS Baptist Medical Center

Oklahoma City, Oklahoma, 73112, United States

Location

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Texas Health Sciences Center

San Antonio, Texas, 78229, United States

Location

The Alfred Hospital

Melbourne, Victoria, Australia

Location

Medical University of Vienna

Vienna, Austria

Location

University of Alberta

Edmonton, Alberta, Canada

Location

Toronto General Hospital

Toronto, Canada

Location

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Cystic Fibrosis; Bronchiectasis

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Pancreatic Diseases; Digestive System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Bronchial Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

Interim analysis: Dropped 5mg/kg arm. Study was insufficiently powered \& focus shifted to safety endpoints. Eliminated some secondary endpoints eg. steroid resistant\&antibody treated rejection,CNI\&antiproliferative agent, bronchiolitis obliterans.

Results Point of Contact

• Title: Regulatory Affairs
• Organization: Fresenius Biotech

anne.kuan@fresenius-biotech.com

781 699 4618

Study Officials

• Elbert P Trulock III, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2005
• First Posted: March 9, 2005
• Study Start: January 1, 2005
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2011
• Last Updated: June 11, 2012
• Results First Posted: June 8, 2012

Record last verified: 2012-06

Locations

US (15); CA (2); AU (1)