Efficacy, Safety and Tolerability of Everolimus in Combination With Reduced Exposure Cyclosporine or Tacrolimus in Paediatric Liver Transplant Recipients.

NCT01598987 | Completed Phase 3 Results DMC

• 2 other identifiers: CRAD001H23052011-003069-14
• Study Type: interventional
• Target: 56
• Locations: 12 countries
• Sites: 32

Brief Summary

This study was designed to assess the evolution of renal function and to collect efficacy, safety, and tolerability data of everolimus in co-exposure with reduced CNI in paediatric liver transplant recipients.

Conditions

Renal Function; Liver Transplant

Keywords

Paediatric liver transplantation; Everolimus; Reduced calcineurin inhibitor; Cyclosporine, tacrolimus; Renal function; Composite efficacy endpoint (treated biopsy proven acute rejection death, graft loss); Liver transplant

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Estimated Glomerular Filtration Rate - Month 12

  Evolution of renal function assessed by estimated Glomerular Filtration Rate (eGFR) calculated by the Chronic Kidney Disease in Children (CKiD) Schwartz formula (Schwartz 2009), expressed in mean change in eGFR of CKiD between start of study (baseline assessment) and Month 12.

  Baseline, Month 12

Secondary Outcomes (6)

• Kaplan-Meier Estimates for Failure Rates of Efficacy Endpoints

  At 12-month and 24-month after start of study drug

• Change From Baseline in Estimated Glomerular Filtration Rate - Month 24

  Baseline, Month 24

• Growth Development - Height at Baseline and Month 12

  Baseline, Month 12

• Growth Development - Weight at Baseline and Month 12

  Baseline, Month 12

• Growth Development - Weight at Baseline and Month 24

  Baseline, Month 24

Study Arms (1)

Everolimus based regimen

EXPERIMENTAL

Conversion at Baseline from an immunosuppressive regimen which contains either cyclosporine (CsA) or tacrolimus (TAC) with or without mycophenolic acid (MPA), with or without corticosteroids in a regimen which contains everolimus combined reduced dose of either cyclosporine (CsA) or tacrolimus (TAC). The dosing schedule was twice daily, 12 hours apart.

Drug: Introduction of everolimus with reduced cyclosporine or tacrolimus dose, the earliest 1 month and the latest 6 months after liver transplantation.

Interventions

Introduction of everolimus with reduced cyclosporine or tacrolimus dose, the earliest 1 month and the latest 6 months after liver transplantation. DRUG

Immunosuppression after liver transplantation. Pediatric transplant recipients received a starting dose of 0.8 mg/m\^2/dose in combination wit Cyclosporine A or 2.0 mg/m\^2/dose in combination with tacrolimus, twice-daily. Thereafter, doses were adjusted to achieve everolimus C-0h blood trough level between 3 to 8 ng/ml.

Everolimus based regimen

Eligibility Criteria

• Age: 1 Month - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Signed informed consent from both parents or legal guardian(s) prior to patient participation in the study.
• Paediatric liver transplant recipients aged greater than or equal to 1 month and younger than 18 years of age.
• Paediatric recipients at the earliest 1 month and latest 6 month after liver transplantation.

You may not qualify if:

• Patients with hepato-biliary malignancies and/or patients transplanted due to fulminant hepatitis /acute liver failure.
• Presence of thrombosis of any major hepatic arteries, major/reconstructed hepatic veins, portal vein or inferior vena cava at any time prior to the start of study drug.
• Patients with serum creatinine value \>2 times age-related ULN at Baseline or who received renal replacement therapy within one week prior to the start of study drug and patients with a confirmed spot urine protein/creatinine ratio indicating a urinary protein excretion \>500 mg/m2/24 hrs, at Baseline.
• Patients with clinically significant systemic infection and/or in a critical care setting requiring life support measures such as mechanical ventilation, dialysis, or vasopressor agents.
• Patients with a known hypersensitivity to the drugs used on study or their class, or to any of the excipients.
• Pregnant or nursing (lactating) female patients, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive βHCG laboratory test (\>9 mIU/mL) at Baseline.
• Female patients of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they agree for abstinence from sexual activity.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (32)

Novartis Investigative Site

Los Angeles, California, 90027, United States

Location

Novartis Investigative Site

New Haven, Connecticut, 06520, United States

Location

Novartis Investigative Site

Chicago, Illinois, 60637, United States

Location

Novartis Investigative Site

St Louis, Missouri, 63110, United States

Location

Novartis Investigative Site

New York, New York, 110032, United States

Location

Novartis Investigative Site

Charleston, South Carolina, 29425, United States

Location

Novartis Investigative Site

Houston, Texas, 77030-2400, United States

Location

Novartis Investigative Site

Salt Lake City, Utah, 84132, United States

Location

Novartis Investigative Site

Madison, Wisconsin, 53792, United States

Location

Novartis Investigative Site

Parkville, Victoria, 3052, Australia

Location

Novartis Investigative Site

Brussels, 1200, Belgium

Location

Novartis Investigative Site

Edmonton, Alberta, T6G 2B7, Canada

Location

Novartis Investigative Site

København Ø, DK-2100, Denmark

Location

Novartis Investigative Site

Bron, 69677, France

Location

Novartis Investigative Site

Hanover, Germany, 30625, Germany

Location

Novartis Investigative Site

Bonn, 53105, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Hamburg, 20246, Germany

Location

Novartis Investigative Site

Regensburg, 93053, Germany

Location

Novartis Investigative Site

Tübingen, 72076, Germany

Location

Novartis Investigative Site

Budapest, 1082, Hungary

Location

Novartis Investigative Site

Budapest, 1083, Hungary

Location

Novartis Investigative Site

Bergamo, BG, 24128, Italy

Location

Novartis Investigative Site

Roma, ITA, 00165, Italy

Location

Novartis Investigative Site

Padua, PD, 35128, Italy

Location

Novartis Investigative Site

Torino, TO, 10126, Italy

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Madrid, Madrid, 28046, Spain

Location

Novartis Investigative Site

Stockholm, SE-141 86, Sweden

Location

Novartis Investigative Site

West Midlands, Birmingham, B4 6NH, United Kingdom

Location

Novartis Investigative Site

Leeds, LS1 3EX, United Kingdom

Location

Novartis Investigative Site

London, SE5 9RS, United Kingdom

Location

Limitations and Caveats

Based on DMC recommendation, enrolment was terminated and patients below 7 years were converted form study medication to local standard of care but patients were followed up until Month 24.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2012
• First Posted: May 15, 2012
• Study Start: October 1, 2012
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: May 16, 2017
• Results First Posted: January 24, 2017

Record last verified: 2017-04

Locations

AU (1); BE (1); CA (1); DE (6); HU (2); SE (1); DK (1); ES (2); FR (1); US (9); IT (4); GB (3)