MMF, Daclizumab and Corticosteroids as Mainstay Immunosuppression in Renal Transplant Patients

Kidney Transplantation Clinical Trial

Official title:

Evaluating Safety and Efficacy of MMF, Daclizumab and Corticosteroids as Mainstay Immunosuppression in Combination With Low-Dose CsA, Tac or Sir in Comparison to Current Standard Immunosuppression (MMF, CsA and Corticosteroids) in Renal Tx

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00231764
• Other study ID #: SYMPHONY
• Status: Completed
• Phase: Phase 4
• First received: September 30, 2005
• Last updated: April 22, 2008
• Start date: November 2002
• Est. completion date: February 2008

Study information

• Verified date: April 2008
• Source: Ekberg, Henrik, M.D.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationAustria: Federal Ministry for Health and WomenBelgium: Ministere de la Protection de la Consommation, de la Santé Publique et de l'EnvironnementBrazil: National Health Surveillance AgencyCanada: Health Canada, Health Products and Food Branch, Biologics and Genetic Therapies DirectorateCzech Republic: State Institute for Drug ControlGermany: Paul-Ehrlich-InstitutGreece: National Drug Organization (EOF).Israel: Israeli Health Ministry Pharmaceutical AdministrationPoland: Urzad Rejestracji Produktów Leczniczych, Wyrobów Leczniczych i Produktów Biobójczych (Office for Registration of Medicinal Products, Medical Devices and Biocides)Spain: Ministerio de Sanidad y Consumo, Subdirección General de Medicamentos de uso HumanoSweden: Medical Products AgencyTurkey: Ministry of HealthUK: North Wales Health Authority
• Study type: Interventional

Clinical Trial Summary

To determine the renal function, as expressed by the glomerular filtration rate at 12 months, in renal transplant recipients receiving mycophenolate mofetil, daclizumab, and corticosteroids as mainstay immunosuppression in combination with low-dose cyclosporine, tacrolimus, or sirolimus, and compare it to that of renal transplant recipients receiving standard immunosuppression with mycophenolate mofetil, normal dose cyclosporine and corticosteroids.

Description:

The purpose of the SYMPHONY study is to compare four different immunosuppressive regimens. They are each given for one year. The following four combinations are tested in four groups of patients:

• Group A: Cyclosporine in a normal dosage, mycophenolate mofetil (MMF) and corticosteroids

• Group B: Daclizumab in the first two months after transplantation, cyclosporine in a lower dosage compared to group A, mycophenolate mofetil (MMF) and corticosteroids

• Group C: Daclizumab in the first two months after transplantation, tacrolimus in low dosage, mycophenolate mofetil (MMF) and corticosteroids

• Group D: Daclizumab in the first two months after transplantation, sirolimus in a low dosage, mycophenolate mofetil (MMF) and corticosteroids.

All drugs of the four immunosuppressive regimes are approved by the Health Authorities in the participating country for use in kidney transplantation. The regimen administered to the patients in Group A represents a standard treatment, currently given with success to many transplant patients in a number of countries in the world. The treatments in Groups B, C and D are experimental in the sense that either the doses administered are lower than the ones used before and/or the combination of drugs is experimental. Nevertheless, there are results of scientific studies indicating that they are all effective alternatives and that they might have advantages compared to the standard immunosuppressive regimen, in particular as far as their safety (side effects, long-term toxicity) is concerned. However, from the previous clinical experience, it is not yet clear which regimen offers the most advantages for the patients. To find this out, in SYMPHONY the four regimens are administered to the four groups of patients (A-D) and the results in the different groups will be compared.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1760
• Est. completion date: February 2008
• Est. primary completion date: May 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Male or female patients between 18 - 75 years

• Recipients of single-organ renal primary allograft or second renal transplants (provided that the previous graft was not lost from acute rejection within the first year) from living or cadaver donors

• Patients who provide written informed consent.

Exclusion Criteria:

• PRA > 20% within 6 months prior to enrollment

• Cold ischemia time > 30 hours

• Previous treatment with daclizumab

• History of malignancy (except localized skin cancer)

• Active peptic ulcer disease.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

Drug:
• daclizumab

Locations

Country	Name	City	State
n/a

Sponsors (9)

Lead Sponsor

Collaborator

Ekberg, Henrik, M.D.

Hoffmann-La Roche, Prof. Flavio Vincenti, San Francisco, USA (Ass. Steering Committee Member), Prof. Josep Grinyo, Barcelona, Spain (Ass. Steering Committee Member), Prof. Philip Halloran, Edmonton, Canada (sponsor), Prof. Pierre Daloze, Montréal, Canada (Steering Committee Member), Prof. Thomas C. Pearson, Atlanta, USA (Steering Committee Member), Prof. Ulrich Frei, Berlin, Germany (Steering Committee Member), Prof. Yves Vanrenterghem, Leuven, Belgium (Steering Committee Member)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	GFR calculated from the serum creatinine with the Cockcroft-Gault formula at 12 months posttransplantation
Secondary	Acute rejection rate at 6 and 12 months, patient and graft survival rates at 12 months
Secondary	Treatment failure during the first twelve months
Secondary	Time to first acute rejection
Secondary	Patient and graft survival at 6 and 12 months posttransplant
Secondary	Calculated GFR using the Cockcroft-Gault formula during the study and measured GFR at month 12
Secondary	Incidence of Delayed Graft Function (DGF)
Secondary	Safety Parameters:
Secondary	Clinical assessments, vital signs, laboratory analyses, adverse events, opportunistic infections, malignancies, and deaths
Secondary	Incidence of failure to achieve primary closure of transplant surgical wound at 2 weeks
Secondary	Incidence of lymphocele requiring intervention in the first 6 months posttransplant