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

Liver Transplant Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01598987
• Other study ID #: CRAD001H2305
• Secondary ID: 2011-003069-14
• Status: Completed
• Phase: Phase 3
• First received: March 1, 2012
• Last updated: November 29, 2016
• Start date: October 2012
• Est. completion date: June 2016

Study information

• Verified date: November 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study is 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.

Description:

Study is active and ongoing but no longer recruiting since December 2014. The study Data Monitoring Committee meeting communicated to Novartis safety findings in the group of children younger than 7 years of age: 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Month to 17 Years

Eligibility

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 ßHCG 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Transplant
• Renal Function

Intervention

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

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Parkville	Victoria
Belgium	Novartis Investigative Site	Bruxelles
Canada	Novartis Investigative Site	Edmonton	Alberta
Denmark	Novartis Investigative Site	København Ø
France	Novartis Investigative Site	Bron
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Regensburg
Germany	Novartis Investigative Site	Tübingen
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Italy	Novartis Investigative Site	Bergamo	BG
Italy	Novartis Investigative Site	Padova	PD
Italy	Novartis Investigative Site	Roma	ITA
Italy	Novartis Investigative Site	Torino	TO
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Madrid
Sweden	Novartis Investigative Site	Stockholm
United Kingdom	Novartis Investigative Site	Leeds
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	West Midlands	Birmingham
United States	Novartis Investigative Site	Charleston	South Carolina
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Madison	Wisconsin
United States	Novartis Investigative Site	New Haven	Connecticut
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	Salt Lake City	Utah
United States	Novartis Investigative Site	St Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Denmark,  France,  Germany,  Hungary,  Italy,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Glomerular Filtration Rate	Renal function assessed by estimated Glomerular Filtration Rate 12-month after start of study drug.	At 12-month after start of study drug	No
Secondary	Rate of composite efficacy failure of treated biopsy proven acute rejection (tBPAR), graft loss (GL) or death (D).	Efficacy failure rate of tBPAR, GL, or D.at 12-month after start of study drug	At 12-month after start of study drug	No
Secondary	Number of Adverse Events	AE/SAEs as per preferred term and system organ class Incidence of treatment-related side effects Incidence and reason (e.g. AE) for premature discontinuation of study medication, and premature withdrawal from the study.; Incidence and reason (e.g. AE) for dose interruption and dose adjustment of study medication.	At 12-month and 24-month after start of study drug	Yes