CellCept® Dose Adjustment Versus Fixed Dose (Standard Care) in Renal Transplant Recipients (MMF)

Phase IV, Open-Label, Multicenter, Randomized Study Comparing Mycophenolate Mofetil (MMF) Dose Adjustment Based on Blood MPA Concentration to Standard Care Treatment With MMF in Renal Transplant Recipients Receiving Tacrolimus

In order to avoid renal transplant rejection, the immune system should be suppressed. After the renal transplant subjects are treated with a combination of two to four different types of immunosuppressive drugs. Theses drugs are very efficient in the prevention of the renal transplant rejection. Still, they can cause side effect.

Research in renal transplant tries to find the best treatment in order to avoid renal rejection on one hand and to reduce as much as possible the undesired adverse and toxicity effects on the other hand.

Therapeutic efficacy and the onset of adverse effects are influenced by levels of mycophenolic acid (MPA, the active metabolite of MMF, CellCept®).

The primary objective of this study is to assess the treatment superiority of CellCept® Dose Adjustment treatment, based on individual MPA concentration value monitored periodically, against treatment with CellCept® Fixed Dose (standard care).

Study Overview

• Status: Unknown
• Conditions: Renal Transplant
• Intervention / Treatment: Drug: Mycophenolate mofetil (CellCept® ); Drug: Mycophenolate mofetil (CellCept® )

Detailed Description

Patient will be randomized into two treatment groups on a 1:1 ratio. Both groups will be treated with the same drugs which is the usual treatment for avoiding renal transplant rejection. In one group the CellCept® dose will be adjusted based on MPA concentration value which will be monitored periodically; and the second group will be treated with CellCept® Fixed Dose (based on the clinical judgment of the treating physician).

• Study Type: Interventional
• Enrollment (Anticipated): 138
• Phase: Phase 4

Contacts and Locations

Study Locations

• Israel
  • Petach Tikvah, Israel
    • Recruiting
    • Rabin Medical Center
    • Contact: Eytan Mor, Prof.; Phone Number: +972-39376528
    • Contact: Alexander Yussim, Dr.; Phone Number: +972-39376452
    • Principal Investigator: Eitan Mor, Prof.
  • Tel Aviv, Israel
    • Recruiting
    • Tel Aviv Sourasky Medical Center
    • Contact: Richard Nakache, MD; Phone Number: 972-3-6974408
    • Contact: Ravit Tvito, RC; Phone Number: 972-508356663
    • Principal Investigator: Richard Nakache, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects, between 18 to 70 years of age at the time of enrollment.
• Patient who received first or second renal transplant.
• Patients who are 0-14 days post transplant.
• Patients capable of understanding the purposes and risks of the study who signed a written informed consent to participate and to comply with the requirements of the study.

Exclusion Criteria:

• Women lactating, pregnant or of childbearing potential not using a reliable contraceptive method before beginning study drug therapy, during therapy and for 4 months following their last dose of the study drug therapy.
• Patients with severe diarrhea or other gastrointestinal disorders that might interfere with their ability to absorb oral medication, including diabetic patients with previously diagnosed diabetic gastroenteropathy.
• Patients with a history of a psychological illness or condition such as to interfere with the patient's ability to understand the requirements of the study.
• Patients with evidence of an active systemic infection requiring the continued use of antibiotics or evidence of an HIV infection, or the presence of a chronic active hepatitis B (HBs-Ag positive) or C.
• Current or historic Panel Reactive Antibody (PRA) >50%
• Positive crossmatch (irrespective of method).
• Cold ischemia time of the graft of more than 30 hours.
• Patients who had received an investigational new drug within the last three months at the time of enrollment.
• Multi-organ recipients (e.g. kidney and pancreas) or previous transplant with any organ other than kidney.
• Patients with any known hypersensitivity to MPA, EC-MPS or other components of the formulation (e.g. lactose).
• Patients with thrombocytopenia (< 75,000/mm3), with an absolute neutrophil count of <1,500/mm3, and/or leukocytopenia (< 2,500/mm3), and/or hemoglobin < 6 g/dL at Screening or Baseline.
• Patients with a history of malignancy within the last five years, except excised squamous or basal cell carcinoma of the skin.
• Previous exposure to EC-MPS.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; Concentration Controlled (CC)group will receive an individually adjusted MMF dosing regimen based on the plasma concentrations of mycophenolic acid (MPA,the active metabolite of mycophenolate mofetil).	Drug: Mycophenolate mofetil (CellCept® ); Concentration Control group: MMF dosage will be adjusted (by addition or subtraction of least 250 mg of MMF twice a day) based on MPA levels (MPA AUC target of 40 mg*h\L) measured on Days 7,14,Months 1,3,6 and 12.; Other Names: MMF; CellCept®; Drug: Mycophenolate mofetil (CellCept® ); Fixed Dose group, MMF dosage will be adjusted based on standard care
ACTIVE_COMPARATOR: 2; Fixed dose (FD) group will receive an a priori set dose of 2mg\day MMF, the recommended dose, with a possible secondary adaptation by the clinician based on criteria of clinical efficacy, toxicity or interactions with other medications.	Drug: Mycophenolate mofetil (CellCept® ); Concentration Control group: MMF dosage will be adjusted (by addition or subtraction of least 250 mg of MMF twice a day) based on MPA levels (MPA AUC target of 40 mg*h\L) measured on Days 7,14,Months 1,3,6 and 12.; Other Names: MMF; CellCept®; Drug: Mycophenolate mofetil (CellCept® ); Fixed Dose group, MMF dosage will be adjusted based on standard care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Primary Endpoint Treatment failure defined as a biopsy proven acute rejection, graft loss, death, MMF discontinuation or lost to follow-up.	During the first 12 months following randomization.

Collaborators and Investigators

• Sponsor: Rabin Medical Center
• Investigators: Principal Investigator: Eytan Mor, Prof., Rabin Medical Center; Principal Investigator: Richard Nakache, Prof., Sorasky Medical Center

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (ANTICIPATED): August 1, 2011
• Study Completion (ANTICIPATED): August 1, 2013

Study Registration Dates

• First Submitted: August 17, 2008
• First Submitted That Met QC Criteria: August 18, 2008
• First Posted (ESTIMATE): August 19, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): March 26, 2010
• Last Update Submitted That Met QC Criteria: March 25, 2010
• Last Verified: December 1, 2008

More Information

Terms related to this study

• Keywords: MMF; Transplant; Renal; MPA; Renal Transplant; Recipients
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid
• Other Study ID Numbers: ML21706