A Study to Evaluate the Efficacy and Safety of Zenapax in Combination With CellCept, Cyclosporine, and Corticosteroids in Patients Undergoing Cardiac Transplantation

NCT00048165 | Completed Phase 4 Results

• 1 other identifier: NR15880
• Study Type: interventional
• Target: 434
• Locations: 4 countries
• Sites: 30

Brief Summary

The purpose of the study is to compare the number of randomized participants in each treatment group who experience an acute rejection episode in the first 6 months after undergoing cardiac transplantation.

Conditions

Heart Transplantation

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Developed Acute Rejection Episode Within 6 Months Post-Transplant

  The acute rejection episode was a composite end-point of acute rejection and treatment failure within 6 months post-transplant (PT). Participants with acute rejection included participants with a biopsy histology of International Society of Heart and Lung Transplant (ISHLT) Grade IIIA, IIIB, or IV and participants with hemodynamic compromise (HDC) who were treated for acute rejection (whether or not a biopsy was done and regardless of the grade of the biopsy). Participants who had treatment failure included participants who died within 6 months of transplantation before experiencing acute rejection or who were re-transplanted within 6 months of the primary transplantation and who did not experience an acute rejection or who were lost to follow-up.

  Up to 6 months PT

Secondary Outcomes (13)

• Number of Participants Who Developed Acute Rejection Episode Within the 12 Months PT

  Up to 12 months PT

• Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT

  Within 6 months and 12 months PT

• Number of Participant Who Died Within 6 Months 12 Months and 3 Years PT

  At 6 months, 12 months , 3 years PT

• Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT

  Within 6 months and 12 months PT

• Median Time to First Acute Rejection Episode Within the First 6 Months and 12 Months PT

  Within 6 months and 12 months PT

Study Arms (2)

Daclizumab

EXPERIMENTAL

Daclizumab will be administered as a intravenous dose of 1 milligrams per kilogram \[mg/kg\] on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\], cyclosporine 1-4 mg/kg IV or 2-6 mg/kg, and 500-1000 mg IV methylprednisolone peri operative switch to oral at 0.5-1 mg/kg/day followed by tapering.

Drug: Daclizumab; Drug: Methylprednisolone; Drug: Mycophenolate mofetil; Drug: cyclosporine

Placebo

PLACEBO COMPARATOR

Matching placebo will be administered on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\], cyclosporine 1-4 mg/kg IV or 2-6 mg/kg orally, and 500-1000 mg IV methylprednisolone peri-op switch to oral at 0.5-1 mg/kg/day followed by tapering.

Drug: Methylprednisolone; Drug: Mycophenolate mofetil; Drug: Placebo; Drug: cyclosporine

Interventions

Daclizumab DRUG

Daclizumab will be administered as 1 mg/kg IV within 12 hours post-op (Day 1), and Days 8, 22, 36 and 50.

Also known as: Zenapax

Daclizumab

Methylprednisolone DRUG

Methylprednisolone will be administered as 500-1000 mg IV and peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering till 0.0-0.15 mg/kg/day (up to 365 days).

Daclizumab; Placebo

Mycophenolate mofetil DRUG

Mycophenolate mofetil will be administered as 1.5 grams bid begun post-op, either IV or orally as required up to 365 days.

Daclizumab; Placebo

Placebo DRUG

Matching placebo will be administered on Days 1, 8, 22, 36, and 50.

Placebo

cyclosporine DRUG

Cyclosporine will be administered as 1-4 mg/kg IV or 2-6 mg/kg orally up to 365 days.

Daclizumab; Placebo

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be undergoing their first cardiac allograft transplant
• Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to transplantation
• Women of childbearing potential must use two reliable forms of contraception simultaneously. Effective contraception must be used before beginning study drug therapy, and for 4 months following discontinuation of study drug therapy
• Participants and/or their guardians must be willing and be capable of understanding risks and comply with the purpose of the study

You may not qualify if:

• Previous organ transplants
• Participants receiving multiple organs
• Participants requiring ventricular assist device (VAD) upon completion of transplantation surgery
• Women lactating, pregnant or of childbearing potential not using, or who are unwilling to use two reliable forms of contraception simultaneously during the study
• History of a psychological illness or condition which would interfere with the participant's ability to understand the requirements of the study
• White blood count =\<2500/mm\^3, platelets =\<50,000/mm\^3 or hemoglobin =\<6 g/dL
• HIV-1, the presence of positive HBsAg, or chronic active hepatitis C
• Active peptic ulcer disease
• Severe diarrhea or other gastrointestinal disorders which might interfere with their ability to absorb oral medication
• Malignancies within the past 5 years, excluding skin carcinoma that have been adequately treated
• Participants who have received within the past 30 days or require concomitant treatment with other investigational drugs or immunosuppressive medications that are prohibited for this study
• Inability to start microemulsion form of cyclosporine within 72 hours

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (30)

Unknown Facility

Birmingham, Alabama, 35294-0006, United States

Location

Unknown Facility

Los Angeles, California, 90095, United States

Location

Unknown Facility

Tampa, Florida, 33606, United States

Location

Unknown Facility

Louisville, Kentucky, 40202, United States

Location

Unknown Facility

Baltimore, Maryland, 21287, United States

Location

Unknown Facility

Boston, Massachusetts, 02111, United States

Location

Unknown Facility

Boston, Massachusetts, 02115, United States

Location

Unknown Facility

Ann Arbor, Michigan, 48109-0366, United States

Location

Unknown Facility

Minneapolis, Minnesota, 55455, United States

Location

Unknown Facility

Albuquerque, New Mexico, 87106, United States

Location

Unknown Facility

New York, New York, 10032, United States

Location

Unknown Facility

Durham, North Carolina, 27710, United States

Location

Unknown Facility

Cincinnati, Ohio, 45267-0542, United States

Location

Unknown Facility

Cleveland, Ohio, 44195, United States

Location

Unknown Facility

Portland, Oregon, 97201, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, 19104, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, 19140, United States

Location

Unknown Facility

Pittsburgh, Pennsylvania, 15213-2582, United States

Location

Unknown Facility

Charleston, South Carolina, 29425-2221, United States

Location

Unknown Facility

Dallas, Texas, 75230, United States

Location

Unknown Facility

Dallas, Texas, 75246, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

Salt Lake City, Utah, 84132, United States

Location

Unknown Facility

Madison, Wisconsin, 53792, United States

Location

Unknown Facility

Milwaukee, Wisconsin, 53215, United States

Location

Unknown Facility

London, Ontario, N6A 5A5, Canada

Location

Unknown Facility

Ottawa, Ontario, K1Y 4W7, Canada

Location

Unknown Facility

Frankfurt am Main, 60590, Germany

Location

Unknown Facility

Hanover, 30625, Germany

Location

Unknown Facility

Gothenburg, 41345, Sweden

Location

MeSH Terms

Interventions

Daclizumab; Methylprednisolone; Mycophenolic Acid; Cyclosporine

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Peptides

Results Point of Contact

• Title: Roche Trial Information Hotline
• Organization: F. Hoffmann-La Roche AG

global.trial_information@roche.com

+41 616878333

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2002
• First Posted: October 25, 2002
• Study Start: August 1, 1999
• Primary Completion: August 1, 2002
• Study Completion: August 1, 2002
• Last Updated: June 13, 2016
• Results First Posted: June 13, 2016

Record last verified: 2016-05

Locations

DE (2); SE (1); CA (2); US (25)