Clinical trial NCT01598987: Efficacy, Safety and Tolerability of Everolimus in Combination With Reduced Exposure Cyclosporine or Tacrolimus in Paediatric Liver Transplant Recipients.
Official title: A 24-month, Multi-center, Single Arm, Prospective Study to Evaluate Renal Function, Efficacy, Safety and Tolerability of Everolimus in Combination With Reduced Exposure Cyclosporine or Tacrolimus in Paediatric Liver Transplant Recipients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-05-15
Enrollment: 56
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: Study is completed (was active and ongoing but no longer recruiting since December 2014). The study Data Monitoring Committee meeting communicated to Novartis the following safety findings in the study population: high rate of premature discontinuation of study medication, high rate of post-transplant lymphoproliferative disease and high rate of related serious infections leading to hospitalization. In light of the safety findings, Novartis followed the DMC recommendation to discontinue the study medication in this age group and to stop enrolling new patients in this study (regardless of age).

Eligibility criteria: Key Inclusion Criteria:

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.

Key Exclusion Criteria:

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.

Primary outcomes:
measure: Change From Baseline in Estimated Glomerular Filtration Rate - Month 12
timeFrame: Baseline, Month 12
Secondary outcomes:
measure: Kaplan-Meier Estimates for Failure Rates of Efficacy Endpoints
timeFrame: At 12-month and 24-month after start of study drug
measure: Change From Baseline in Estimated Glomerular Filtration Rate - Month 24
timeFrame: Baseline, Month 24
measure: Growth Development - Height at Baseline and Month 12
timeFrame: Baseline, Month 12
measure: Growth Development - Weight at Baseline and Month 12
timeFrame: Baseline, Month 12
measure: Growth Development - Weight at Baseline and Month 24
timeFrame: Baseline, Month 24
measure: Growth Development - Height at Baseline and Month 24
timeFrame: Baseline, Month 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: New Haven
country: United States
facility: Novartis Investigative Site
state: Connecticut
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: St Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: Charleston
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Salt Lake City
country: United States
facility: Novartis Investigative Site
state: Utah
city: Madison
country: United States
facility: Novartis Investigative Site
state: Wisconsin
city: Parkville
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: København Ø
country: Denmark
facility: Novartis Investigative Site
city: Bron
country: France
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Regensburg
country: Germany
facility: Novartis Investigative Site
city: Tübingen
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Bergamo
country: Italy
facility: Novartis Investigative Site
state: BG
city: Roma
country: Italy
facility: Novartis Investigative Site
state: ITA
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: West Midlands
country: United Kingdom
facility: Novartis Investigative Site
state: Birmingham
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: