Efficacy and Safety of Everolimus Versus Mycophenolate Mofetil in Liver Transplant Recipients. (MONTBLANC)

Multi-center, Open-label, Randomized Controlled Phase 4 Study to Evaluate the Efficacy and Safety of CertiroBell® Compared With Mycophenolate Mofetil in Primary Living Donor Liver Transplant Recipients.

The purpose of this study is to evaluate the efficacy and safety of CertiroBell® tablet compared with mycophenolate mofetil in primary living donor liver transplant recipients.

Study Overview

• Status: Completed
• Conditions: Liver Transplant
• Intervention / Treatment: Drug: Everolimus Tab.; Drug: Mycophenolate mofetil Tab./Cap.

Detailed Description

This study is multi-center, open-label, randomized controlled phase 4 study to evaluate the efficacy and safety of certirobell® tablet compared with mycophenolate mofetil in primary living donor liver transplant recipients.

On the first visit the patients scheduled to be operated liver transplant in 35 days will be conducted screening. Patients who meet the criteria of this clinical trial will be randomized to CertiroBell or mycophenolate mofetil on the second visit. Each group will take CertiroBell or mycophenolate mofetil and will conduct scheduled tests with 5 additional visits.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 4

Contacts and Locations

Study Locations

• South Korea
  • Seoul, South Korea
    • Severance Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

* Inclusion Criteria:

[Time of screening]

• Patients who have transplanted in primary living donor liver in 35 days or who plan to be transplanted in primary living donor liver.
• Over 20 years old(male or female)
• Agreement with written informed consent

[Time of randomization] - Patients who have transplanted liver within 4 weeks(25 days to 35 days)

* Exclusion Criteria

[Time of screening]

• Patients who have transplanted non-liver organs or have plan to be transplanted non-liver organs.
• Patients with bioartificial liver (cell system)
• Patients who diagnosed with malignant tumor within 5 years [however, who have recovered from skin cancer (squamous cell/basal cell carcinoma) or thyroid cancer, hepatocellular carcinoma without main vessel invasion or extrahepatic metastasis can be enrolled]
• Patients with severe systemic infection
• Women who are pregnant or breast feeding or not agree to the proper use of contraception during the trial
• Participated in other trial within 4 weeks
• In investigator's judgement

[Time of randomization]

• Patients with acute rejection who have been clinically treated after liver transplantation.
• Patients with complication related to the hepatic artery such as hepatic artery thrombosis at the time of randomization.

• At screening

  • WBC <1,500/mm^3 or PLT <30,000/mm^3 or over 3 times upper than normal range of liver function tests(T-bilirubin, AST, ALT) levels
  • Protein/Creatinine ratio(urine test) > 1 or eGFR by MDRD< 30mL/min/1.73m^2 or Total cholesterol > 350mg/dL or triglycerides > 500mg/dL
• Patients taking HCV(hepatitis C virus) Therapeutic Drugs
• Patients who had plasmapheresis within 1 week.
• Patents who had a record of taking mTOR inhibitor before.
• In investigator's judgement

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
Experimental: CertiroBell Tablet; De novo liver transplant recipients will be randomized after liver transplant operation.	Drug: Everolimus Tab.; After first dose 1mg BID(total 2mg daily PO), check the blood concentration of everolimus at each visit and adjust the dose to acheive the blood concentration maintaining at 3~8ng/mL.; Other Names: CertiroBell Tab.
Active Comparator: Mycophenolate mofetil Tablet/Capsule; De novo liver transplant recipients will be randomized after liver transplant operation.	Drug: Mycophenolate mofetil Tab./Cap.; Up to 1.5g BID(total 3g daily), PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of composite efficacy failure	composite efficacy failure include biopsy-confirmed acute rejection, graft loss, death, or follow-up failure	until 24 weeks after taking medicine

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of biopsy-confirmed acute rejection	acute rejection confirmed by result of biopsy(over 4 points of RAI score)	until 24weeks and 48weeks after taking medicine
The pathological results and time of occurrence and method of treatment, result of the treatment of acute rejection confirmed by biopsy(over 4 points of RAI score)	details of acute rejection confirmed by result of biopsy(over 4 points of RAI score)	until 24weeks and 48weeks after taking medicine
Incidence of composite efficacy failure	composite efficacy failure include biopsy-confirmed acute rejection, graft loss, death, or follow-up failure	until 48weeks after taking medicine
Survival rate of patients	Survival rate of patients	until 24weeks and 48weeks after taking medicine
Survival rate of transplanted organ	Survival rate of transplanted organ	until 24weeks and 48weeks after taking medicine
Incidence and recurrence rates of liver cancer	Incidence and recurrence rates of liver cancer	until 24weeks and 48weeks after taking medicine
Incidence and recurrence rates of HCV infection	Incidence and recurrence rates of HCV infection	until 24weeks and 48weeks after taking medicine
Incidence of CMV infection	Incidence of CMV infection	until 24weeks and 48weeks after taking medicine
variation of Serum creatinine, eGFR(estimated glomerular filtration rate) compared to the baseline	eGFR using MDRD(Modification of Diet in Renal Disease) method	at 24 weeks and 48weeks

Collaborators and Investigators

• Sponsor: Chong Kun Dang Pharmaceutical
• Investigators: Study Chair: Dong Jin Joo, M.D., Ph.D., Severance Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2020
• Primary Completion (Actual): July 24, 2024
• Study Completion (Actual): July 24, 2024

Study Registration Dates

• First Submitted: July 10, 2020
• First Submitted That Met QC Criteria: July 10, 2020
• First Posted (Actual): July 15, 2020

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Everolimus; Mycophenolate mofetil; CertiroBell
• Additional Relevant MeSH Terms: Organic Chemicals; Macrolides; Lactones; Sirolimus; Everolimus
• Other Study ID Numbers: B95-02LT1903

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No