A Study of CellCept (Mycophenolate Mofetil) in Combination Therapy in Liver Transplant Patients.

NCT00545402 | Completed Phase 4 Results

• 1 other identifier: ML21273
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 16

Brief Summary

This 2 arm study will compare the efficacy and safety of two CellCept-containing treatment regimens in de novo liver transplant patients. Patients will be randomized into one of two groups, to receive either CellCept (at a starting dose of 3g/day po, adjusted according to exposure) standard dose tacrolimus and corticosteroids (10-15 mg/kg i.v. on day 0), or fixed dose CellCept 2g/day po, standard dose tacrolimus and corticosteroids (10-15mg/kg i.v. on day 0, then reducing from 20mg to 5mg over 6 months, and discontinuing after 6 months). The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

Conditions

Liver Transplantation

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Treated Biopsy Proven Acute Rejection (BPAR) According to Banff Criteria up to 12 Months Post-Transplant

  Banff criteria required at least 2 of the 3 following features for a histopathological diagnosis of acute rejection: portal inflammation, bile duct inflammation, and venous endothelial inflammation. Each item was graded from 0 to 3 where 0 equals (=) mild, 2 = moderate, and 3 = severe. The sum of the 3 individual scores, from 0 to 9, corresponded to the Rejection Activity Index (RAI). If RAI = 0, 1, or 2, there was no evidence of rejection. If RAI = 3, there was borderline acute rejection. If RAI = 4 or 5, there was mild acute rejection. If RAI = 6 or 7, there was moderate acute rejection. If RAI = 8 or 9, there was severe acute rejection.

  Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12, 28 days after Month 12 or last dose of study treatment, and 6 and 12 months after the last dose of study treatment

Secondary Outcomes (5)

• Percentage of Participants With Graft Loss

  Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12, 28 days after Month 12 or last dose of study treatment, and 6 and 12 months after the last dose of study treatment.

• Graft Survival

  Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12, 28 days after Month 12 or last dose of study treatment, and 6 and 12 months after the last dose of study treatment.

• Overall Survival (OS) at Month 12 - Percentage of Participants With an Event

  Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12

• Overall Survival at Month 12

  Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12

• Percentage of Participants by Graft Histology at 12 Months Post-Transplant - Central Review

  Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12

Study Arms (2)

MMF, Adjusted Dose; Tacrolimus; Corticosteroids

EXPERIMENTAL

Participants received mycophenolate mofetil (MMF) 3 grams per day (g/d), orally (PO), twice per day (BID) with meals from Day 0 to Day 4; the dose was adjusted based on total exposure (AUC) using the Bayesian method with limited sampling strategy on Days 5 and 14, Months 1, 13, 6, 9, and 12. Participants also received tacrolimus adjusted to a target trough level of 8 to (-) 12 nanograms per milliliter (ng/mL) from Day 0 to Month 1; the dose was adjusted to reach a target trough level of 3-8 ng/mL from the end of Month 1 through Month 12. Participants also received corticosteroids 10-15 milligrams per kilogram (mg/kg), intravenously (IV), pre-operation on Day 0.

Drug: Mycophenolate mofetil, adjusted dose; Drug: Tacrolimus; Drug: Corticosteroids, IV

MMF, Standard Dose; Tacrolimus; Corticosteroids

ACTIVE COMPARATOR

Participants received MMF 2 g/d, PO, BID with meals from Day 0 to Month 12. Participants also received tacrolimus adjusted to a target trough level of 8-12 ng/mL from Day 0 to Month 1; the dose was reduced to reach a target trough level of 3-8 ng/mL from the end of Month 1 through Month 12. Participants also received corticosteroids 10-15 mg/kg, IV, pre-operation on Day 0; followed by 20 mg/d, PO, 4 times per day (QDS) from Day 0 through Month 1; 15 mg/d, PO, 3 times per day (TID) from the end of Month 1 through Month 2; 10 mg/d, PO, BID from the end of Month 2 through Month 3; and 5 mg/d once per day from the end of Month 3 through Month 6.

Drug: Tacrolimus; Drug: Corticosteroids, IV; Drug: Mycophenolate mofetil, Standard dose; Drug: Corticosteroids, PO

Interventions

Mycophenolate mofetil, adjusted dose DRUG

3 g/d PO BID during meals from Day 0 to Day 4, followed by dose adjustment based on AUC using the Bayesian method with limited sampling strategy on Days 5 and 14, Months 1, 13, 6, 9, and 12.

Also known as: CellCept

MMF, Adjusted Dose; Tacrolimus; Corticosteroids

Tacrolimus DRUG

Target trough level of 8-2 ng/mL from Day 0 to Month 1, adjusted to a target trough level of 3-8 ng/mL from the end of Month 1 through Month 12

MMF, Adjusted Dose; Tacrolimus; Corticosteroids; MMF, Standard Dose; Tacrolimus; Corticosteroids

Corticosteroids, IV DRUG

10-15 mg/kg IV pre-operation on Day 0

Also known as: Solu-Medrol

MMF, Adjusted Dose; Tacrolimus; Corticosteroids; MMF, Standard Dose; Tacrolimus; Corticosteroids

Mycophenolate mofetil, Standard dose DRUG

2 g/d PO BID during meals from Day 0 to Month 12

Also known as: CellCept

MMF, Standard Dose; Tacrolimus; Corticosteroids

Corticosteroids, PO DRUG

20 mg/d QDS from Day 0 through Month 1; 15 mg/day, TID from the end of Month 1 through Month 2; 10 mg/d BID from the end of Month 2 through Month 3; and 5 mg/d once per day from the end of Month 3 through Month 6.

Also known as: Cortancyl

MMF, Standard Dose; Tacrolimus; Corticosteroids

Eligibility Criteria

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

You may qualify if:

• adult patients, \>=18 years of age;
• recipient of a first orthotopic liver transplant.

You may not qualify if:

• history of organ transplants;
• patient receiving a multi-organ transplant;
• calculated creatinine clearance \<=30mL/min before transplant;
• leukocyte count \< 2000/mm3 at randomization;
• history of cancer within past 5 years, except for successfully treated basal cell or squamous cell cancer, or in situ cervical cancer;
• pregnant or breast-feeding females, or females of childbearing age not using effective contraception.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (16)

Unknown Facility

Besançon, 25030, France

Location

Unknown Facility

Bordeaux, 33076, France

Location

Unknown Facility

Caen, 14033, France

Location

Unknown Facility

Clichy, 92118, France

Location

Unknown Facility

Créteil, 94010, France

Location

Unknown Facility

Grenoble, 38043, France

Location

Unknown Facility

Lille, 59037, France

Location

Unknown Facility

Lyon, 69317, France

Location

Unknown Facility

Lyon, 69437, France

Location

Unknown Facility

Marseille, 13385, France

Location

Unknown Facility

Montpellier, 34295, France

Location

Unknown Facility

Nice, 06202, France

Location

Unknown Facility

Paris, 75679, France

Location

Unknown Facility

Rennes, 35033, France

Location

Unknown Facility

Toulouse, 31059, France

Location

Unknown Facility

Villejuif, 94804, France

Location

MeSH Terms

Interventions

Mycophenolic Acid; Tacrolimus; Adrenal Cortex Hormones; Methylprednisolone Hemisuccinate; Prednisone

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Methylprednisolone; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols

Limitations and Caveats

Nonserious adverse events presented in this record include all adverse events reported during the study, not just nonserious events.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffman-LaRoche

genentech@druginfo.com

800-821-8590

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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2007
• First Posted: October 17, 2007
• Study Start: November 1, 2007
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: July 14, 2014
• Results First Posted: July 14, 2014

Record last verified: 2014-06

Locations

FR (16)