A National Multi-center Randomized, Open Label Study to Evaluate Efficacy and Safety of Everolimus With EC-MPS Compared to Standard Treatment Combination Tacrolimus and EC-MPS in de Novo Liver Transplant Recipients

NCT01625377 | Completed Phase 3 Results DMC

• 2 other identifiers: CRAD001HFR022012-000137-39
• Study Type: interventional
• Target: 188
• Locations: 1 country
• Sites: 14

Brief Summary

The aims of the study was to evaluate the safety and efficacy of early introduction one month post-transplantation of everolimus associated to EC-MPS with tacrolimus discontinuation in de novo liver transplant recipients and to evaluate if it leads to a better renal function 6 month post-transplantation compared to standard treatment associating tacrolimus and EC-MPS. The renal function was estimated by glomerular filtration rate.

Conditions

Liver Transplantation

Keywords

Everolimus,; liver transplantation,; early introduction,; renal function

Outcome Measures

Primary Outcomes (1)

• Change From Baseline (Randomization) in Renal Function

  Change in renal function was measured by change in glomerular filtration rate (GFR). GFR calculated using the abbreviated modification of diet in renal disease (aMDRD) formula. GFR in mL/min/1.73m\^2 for men of non-black ethnicity: 186 \* \[C/88\]\^-1.154 \* \[A\]\^-0.023\*G\*R ; C = serum creatinine (in μmol/L); A = Age (in years). G = 0.742 when the patient is a women; Otherwise G=1 R= 1.21 when the patient was of black ethnicity; Otherwise R = 1 Baseline was Day 28 visit.

  Baseline, Week 24

Secondary Outcomes (12)

• Number of Patients With Treatment Failures

  At week 12 and week 24

• Number of Patients With Treated or Not Treated Biopsy Proven Acute Rejection (BPAR)

  at 12 week and 24 week

• Number of Patients Reported With Different Categories of Severity of BPAR According to Banff Classification

  at 12 week and 24 week

• Number of Patients With Treated or Untreated BPAR With RAI Score Greater Than 3

  At 24 weeks

• Number of Patients With Death or Graft Loss

  at week 24

Study Arms (2)

Tacrolimus

ACTIVE COMPARATOR

From transplantation to randomization: Basiliximab (40mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids. From randomization to month 6 : tacrolimus (C0 6-10 ng/ml) + mycophenolic acid 1440 mg/d ± oral corticosteroids

Drug: tacrolimus; Drug: Basiliximab; Drug: Mycophenolic Acid; Drug: Corticosteroids

Everolimus (RAD001)

EXPERIMENTAL

From transplantation to randomization: Basiliximab (40mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids. From randomization to month 6 : everolimus (recommended starting dose of 2 mg/day, then adjusted to achieve the target 6 ≤ C0 ≤ 10 ng/mL, until W24) + mycophenolic acid 1440 mg/d ± oral corticosteroids. The dose of tacrolimus was reduced by 50% twice: at the introduction of everolimus and at week 8 post-transplantation. Tacrolimus had to be finally discontinued in week 12 post-transplantation (by week 16 at the latest).

Drug: tacrolimus; Drug: everolimus; Drug: Basiliximab; Drug: Mycophenolic Acid; Drug: Corticosteroids

Interventions

tacrolimus DRUG

Arm 1 : tacrolimus (C0 6-10 ng/ml) from D3-D5 post-transplantation to month 6 post-transplantation. Arm 2 : tacolimus (C0 6-10 ng/ml) from D3-D5 post-transplantation to 16 weeks post-transplantation at the latest.

Also known as: Prograf®

Everolimus (RAD001); Tacrolimus

everolimus DRUG

Arm 1: no everolimus Arm 2: everolimus (C0 6-10 ng/ml) from randomization to month 6 post-transplantation

Also known as: Certican® / RAD001

Everolimus (RAD001)

Basiliximab DRUG

Basiliximab was supplied to the participating centers as marketed, i.e. in packs containing one vial of 20-mg powder, and water for injection (WFI). 20 mg at D0 and D4

Also known as: Simulect®

Everolimus (RAD001); Tacrolimus

Mycophenolic Acid DRUG

Dose of 1440 mg/day from transplantation to month 6 post- transplantation

Also known as: Myfortic®

Everolimus (RAD001); Tacrolimus

Corticosteroids DRUG

Administration of oral corticosteroid therapy was at the discretion of the centers according to their usual practice

Everolimus (RAD001); Tacrolimus

Eligibility Criteria

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

You may qualify if:

• Man or woman aged 18 years or greater, recipient of a primary liver transplant from a deceased donor with whole or split liver

You may not qualify if:

• Patient recipient of multiple solid organ or islet cell tissue transplants, or have previously received an organ or tissue transplant
• Recipient of a liver from a living donor or cadaveric non heart beating donor
• ABO incompatible transplant graft
• Transplantation following autoimmune liver hepatitis, primitive sclerosing cholangitis or primitive biliary cirrhosis
• Estimated glomerular filtration rate ≤ 30ml/min at selection
• History of malignancy within the 5 past years, other than non-metastatic basal or squamous cell carcinoma and hepatocellular carcinoma
• Alpha-foeto-protein \> 1000 ng/ml (only in case of hepatocellular carcinoma)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (14)

Novartis Investigative Site

Besançon, 25030, France

Location

Novartis Investigative Site

Bordeaux, 33076, France

Location

Novartis Investigative Site

Chambray-lès-Tours, 37044, France

Location

Novartis Investigative Site

Clichy, 92110, France

Location

Novartis Investigative Site

Créteil, 94010, France

Location

Novartis Investigative Site

Grenoble, 38043, France

Location

Novartis Investigative Site

Lille, 59037, France

Location

Novartis Investigative Site

Marseille, 13385, France

Location

Novartis Investigative Site

Montpellier, 34295, France

Location

Novartis Investigative Site

Nice, 06202, France

Location

Novartis Investigative Site

Paris, 75651, France

Location

Novartis Investigative Site

Rennes, 35033, France

Location

Novartis Investigative Site

Toulouse, 31054, France

Location

Novartis Investigative Site

Villejuif, 94800, France

Location

MeSH Terms

Interventions

Tacrolimus; Everolimus; Basiliximab; Mycophenolic Acid; Adrenal Cortex Hormones

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Sirolimus; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2012
• First Posted: June 21, 2012
• Study Start: December 1, 2012
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: April 27, 2016
• Results First Posted: April 27, 2016

Record last verified: 2016-03

Locations

FR (14)