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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01598987
First received: March 1, 2012
Last updated: November 29, 2016
Last verified: November 2016
  Purpose
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.

Condition Intervention Phase
Renal Function
Liver Transplant
Drug: Introduction of everolimus with reduced cyclosporine or tacrolimus dose, the earliest 1 month and the latest 6 months after liver transplantation.
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change in Glomerular Filtration Rate [ Time Frame: At 12-month after start of study drug ] [ Designated as safety issue: No ]
    Renal function assessed by estimated Glomerular Filtration Rate 12-month after start of study drug.


Secondary Outcome Measures:
  • Rate of composite efficacy failure of treated biopsy proven acute rejection (tBPAR), graft loss (GL) or death (D). [ Time Frame: At 12-month after start of study drug ] [ Designated as safety issue: No ]
    Efficacy failure rate of tBPAR, GL, or D.at 12-month after start of study drug

  • Number of Adverse Events [ Time Frame: At 12-month and 24-month after start of study drug ] [ Designated as safety issue: Yes ]

    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.



Enrollment: 56
Study Start Date: October 2012
Study Completion Date: June 2016
Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus based regimen
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).
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.

Detailed 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).
  Eligibility

Ages Eligible for Study:   1 Month to 17 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01598987

  Show 32 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01598987     History of Changes
Other Study ID Numbers: CRAD001H2305  2011-003069-14 
Study First Received: March 1, 2012
Last Updated: November 29, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Paediatric liver transplantation
Everolimus
Reduced calcineurin inhibitor
Cyclosporine, tacrolimus
Renal function
composite efficacy endpoint (biopsy proven acute rejection death, graft loss)

Additional relevant MeSH terms:
Liver Extracts
Everolimus
Sirolimus
Tacrolimus
Cyclosporins
Cyclosporine
Hematinics
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on December 05, 2016