Evaluation of Thymoglobulin Induction and Reduced Doses of Calcineurin Inhibitors on Liver Transplant Rejection

NCT00117689 | Completed Phase 2

• 1 other identifier: Thymo102700103
• Study Type: interventional
• Target: 75
• Locations: 2 countries
• Sites: 16

Brief Summary

This study involves the use of a drug called Thymoglobulin, which is approved in the US to treat kidney transplant rejection and in Canada to treat and prevent kidney transplant rejection. This study will evaluate the effect of Thymoglobulin induction therapy and reduced doses of calcineurin inhibitors on the incidence of liver rejection and will provide a basis for future evaluations of Thymoglobulin as an immunosuppressive agent to help decrease the incidence of liver transplant rejection. Subjects meeting all inclusion and exclusion criteria are eligible to participate in this study. Approximately 75 study subjects from up to 18 transplant centers in the United States and Canada will be enrolled in this 12-month study.

Conditions

Liver Dysfunction; Rejection, Transplant; Transplantation, Liver

Keywords

Anti-T cell antibodies; Primary Liver Transplantation and Renal Dysfunction; Liver Transplant Rejection; Induction Therapy with reduction of Calcineurin inhibitors; Primary Liver Transplantation; Primary Transplant Rejection; Transplantation, Liver; Rejection, Transplant

Outcome Measures

Primary Outcomes (1)

• Freedom from biopsy-proven acute rejection (including humoral rejection)

  6 months

Secondary Outcomes (2)

• Explore the impact of Thymoglobulin on kidney function after transplant

  6 months

• Explore the impact of Thymoglobulin on the prevention of liver transplant rejection, transplanted liver loss, death, and safety of Thymoglobulin after transplant.

  12 months

Study Arms (2)

1

EXPERIMENTAL

Standard (tacrolimus based standard therapy without induction)

Biological: Thymoglobulin; Drug: Tacrolimus; Drug: Mycophenolate Mofetil

2 Standard of Care

ACTIVE COMPARATOR

Thymoglobulin with tacrolimus and corticosteroid sparing maintenance therapy

Drug: Corticosteroid; Drug: Tacrolimus; Drug: Mycophenolate Mofetil

Interventions

Thymoglobulin BIOLOGICAL

Antibody inductions with tacrolimus and corticosteroid sparing maintenance therapy

Also known as: [Anti-thymocyte Globulin (rabbit)]

1

Corticosteroid DRUG

For a minimum of 3 months

2 Standard of Care

Tacrolimus DRUG

Between Day 3 the last dose of Thymoglobulin

1; 2 Standard of Care

Mycophenolate Mofetil DRUG

for at least 1 month posttransplant

1; 2 Standard of Care

Eligibility Criteria

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

You may qualify if:

• Primary liver transplant recipient with Model for End-Stage Liver Disease (MELD) criteria documentation
• Serum creatinine \> 1.5mg/dL at the time of transplant, or based on the value used to calculate the most recent pre-operative MELD Score for liver allocation
• Ages greater than or equal to 18 years
• If female, must not be lactating; must have a negative serum beta-human chorionic gonadotropin (HCG) test within 7 days prior to Study Day 0 (Day of Transplant); and must agree to practice an acceptable and reliable form of contraception during the study
• Signed informed consent

You may not qualify if:

• Living donor or multiple organ transplants
• Prior solid organ or bone marrow transplant recipient
• Fulminant hepatic failure
• Status 1 transplants
• ABO incompatible transplants
• Transplants utilizing livers from non heart-beating donors
• Liver transplant candidates with \> 6 weeks of analysis
• Donor with positive serology for hepatitis B surface antigen (HBsAg)
• Evidence of human immunodeficiency virus (HIV)
• Autoimmune hepatitis
• History of chronic steroid or immunosuppressant use in the 90 days prior to transplant, except for inhaled corticosteroids to treat asthma
• Recipient of investigational therapy within 90 days prior to transplant procedure
• Known contraindication to administration of rabbit anti-thymocyte globulin
• Acute viral illness
• History of malignancy within 5 years, with the exception of adequately treated localized squamous or basal cell carcinoma of the skin without evidence of recurrence, and/or hepatocellular carcinoma

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (16)

University of Alabama, Birmingham

Birmingham, Alabama, 35294, United States

Location

USC University Hospital

Los Angeles, California, 90033, United States

Location

University of California, San Fransisco Hospital

San Francisco, California, 94143, United States

Location

University of Colorado Hospital and Health Sciences Center

Denver, Colorado, 80262, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Fairview University Medical Center

Minneapolis, Minnesota, 55455, United States

Location

Washington University Medical Center

St Louis, Missouri, 63110, United States

Location

University of Nebraska

Omaha, Nebraska, 68198, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

University of Texas Health Science Center at San Antonio, University Hospital

San Antonio, Texas, 78229, United States

Location

VCU Medical Center

Richmond, Virginia, 23298, United States

Location

Toronto University Hospital - UHN

Toronto, Ontario, M5G 2N2, Canada

Location

Royal Victoria Hospital

Montreal, Quebec, H3A 1A1, Canada

Location

Related Links

• US FDA Approved Full Prescribing Information for Thymoglobulin®

MeSH Terms

Conditions

Liver Diseases; Rejection, Psychology; Renal Insufficiency

Interventions

thymoglobulin; Antilymphocyte Serum; Adrenal Cortex Hormones; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Digestive System Diseases; Social Behavior; Behavior; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2005
• First Posted: July 8, 2005
• Study Start: April 1, 2005
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: March 18, 2015

Record last verified: 2015-03

Locations

CA (2); US (14)