Efficacy and Safety of ATG-Fresenius Following a Renal Transplantation, Without Corticosteroids (IBERICA)

Prospective, Randomized, Multi-center, Open Label, Phase III Study to Evaluate the Efficacy and Safety of Immunosuppression Following a Heart-beating Cadaveric Renal Transplantation Based on the Use of Rabbit Anti-T-lymphocyte Serum, Tacrolimus and Mycophenolate, Free of Concomitant Corticosteroids From the Start of Immunosuppression

The main objective of the study is the assessment of the overall graft rejection rate (acute, chronic and subclinical) between a treatment with ATG-Fresenius administered in addition to standard treatment consisting of CellCept® or Myfortic®/TAC and without corticosteroids and a treatment consisting of CellCept® or Myfortic®/TAC and corticosteroids during the first year after renal transplantation.

Study Overview

• Status: Terminated
• Conditions: Renal Transplant Rejection
• Intervention / Treatment: Drug: ATG-Fresenius S

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• Portugal
  • Carnaxide, Portugal, 2799-523
    • Centro Hospitalar de Lisboa Ocidental
  • Coimbra, Portugal, 3000-075
    • Hospitais da universidade de Coimbra
  • Lisboa, Portugal, 1069-166
    • Hospital de Curry Cabral
  • Porto, Portugal, 4090-001
    • Hospital Geral de Santo António, SA
• Spain
  • A Coruña, Spain, 15006
    • Hospital Universitario Juan Canalejo
  • Barcelona, Spain, 08036
    • Hospital Universitari Clinic I Provincial
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28007
    • Hosptial Gregorio Maranon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Signed and dated informed consent form,
• End-stage renal disease,
• Candidates for a first transplantation,
• Re-transplant patients are eligible if a graft loss after transplantation was NOT due to immunological reasons,
• Availability of a heart-beating cadaveric donor up to 70 years of age with a cold ischemia time shorter than 36 hours,
• Male or female patients between 18 to 75 years of age inclusive,
• Patients able to comply with all study related requirements,
• Patients able to receive oral medication,
• Women of childbearing age with a safe contraceptive method throughout the study.

Exclusion Criteria

• Women who are pregnant or breast feeding,
• Known Human Immunodeficiency Virus,
• Hepatitis B Virus or Hepatitis C Virus infection,
• Severe actual viral, bacterial or fungal infection not adequately controlled,
• Patients with anamnestically known hypersensitivity to rabbit immunoglobulin antibodies or positive rabbit immunoglobulin skin test or known allergies to any component of the immunosuppressive drugs per protocol,
• Patients at high immunological risk defined as current PRA > 25% or historical PRA > 50%,
• Patients receiving pre-transplant immunosuppressive treatment, including corticosteroids,
• Patients with current or history of malignancies (exception basal cell carcinoma or squamous cell carcinoma in remission),
• Patients with previous transplantation except 1st graft loss due to surgical complications,
• Patients receiving combined transplantation,
• Patients with major organ dysfunctions,
• Serious psychiatric or psychological disorders,
• Pre-transplant thrombocytopenia: < 50,000 thrombocytes/µl, Pre-transplant leukopenia: < 2,000 leukocytes/µl,
• Unable or unwilling to comply fully with the protocol,
• Participation in another study of an investigational medicinal product concurrently or within the last 30 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Study Group; immunosuppressive treatment consisting of ATG-Fresenius/TAC/MMF or Myfortic	Drug: ATG-Fresenius S; Dosage: Single high-dose of 9 mg/kg pre-operatively, followed by 3 mg/kg/d at day +2 and +4. ATG-Fresenius treatment at Days 0, +2, and +4 is mandatory. (In case of persisting DGF, the treatment is left to the discretion of the investigator. Treatment options include the continuation of ATG-Fresenius treatment with 3 mg/kg/d at Day +6 and if deemed necessary also at Day +8 - but without corticosteroids).
No Intervention: Control Group; immunosuppressive treatment consisting of TAC, MMF or Myfortic, and corticosteroids.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoint is the incidence of biopsy-proven acute allograft rejection after 12 months, including all types of rejections like: • acute rejection • chronic rejection • subclinical rejection	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Time of onset, histological severity and incidence of steroid resistance of acute and chronic rejections	1 year
Incidence and duration of initial DGF	1 year
Renal function	1 year
Patient and Graft survival	1 year
Safety endpoints are the incidence of AEs/SAEs and ADRs	1 year

Collaborators and Investigators

• Sponsor: Neovii Biotech
• Collaborators: Eurotrials Brasil Consultores Cientificos Ltda; Recerca Clínica S.L.; PsyConsult
• Investigators: Principal Investigator: Manuel Rengel, Dr, Hosptial Gregorio Maranon, Madrid, Spain

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: March 21, 2011
• First Submitted That Met QC Criteria: March 28, 2011
• First Posted (Estimate): March 29, 2011

Study Record Updates

• Last Update Posted (Estimate): May 1, 2015
• Last Update Submitted That Met QC Criteria: April 30, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: kidney transplantation; acute rejection; chronic rejection; renal transplantation; subclinical rejection; steroid-free
• Other Study ID Numbers: AP-AS-24-ES