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Minimisation of TAC

Phase 3

Liver Transplant | Small molecule | Gastrointestinal |Novartis AG|Last Updated: Jun 13, 2019

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedACTIVE_CONTROLLEDBiomarker
Total Trials1
Total Enrollment217
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT02040584A Multicentre, Randomised, Open-label, Controlled, 12-month Follow-up Study to Assess Impact on Renal Function of an Immunosuppression Regimen Based on Tacrolimus Minimisation in Association With Everolimus in de Novo Liver Transplant Recipients.PHASE3 COMPLETED 217Dec 20, 2013Feb 10, 2016Jun 13, 201920 Spain
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Study Endpoints
Primary Endpoints
Percentages of Participants Showing Clinical Benefit by Renal Function Stratification
week 4, week 52.

Clinical benefit is defined as: • an improvement in 1 or 2 ranges of the eGFR, according to MDRD-4 at Week 52 post-transplant in patients with values of 30-\<45 or 45-\<60 mL/min/1.73 m2 in Week 4. or • stabilisation of eGFR in patients with values ≥60 mL/min/1.73 m2 at Week 4 and maintained at Week 52 post-transplant.

Secondary Endpoints
Changes in Creatinine Clearance - Cockcroft-Gault Formula
Screening visit (transplant), weeks 1,4,12,24,36 and 52 post-transplant
Changes in eGFR Based on the MDRD-4 Formula
Screening visit (transplant), weeks 1,4,12,24,36 and 52 post-transplant
eGFR Values(MDRD-4 Formula) According to the MELD Score
Screening visit (transplant), weeks 1,4,12,24,36 and 52 post-transplant
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Study Design & Arms
AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Minimisation of TACEXPERIMENTALTreatment with rTAC+EVR+corticosteroids
TAC + MMF + corticosteroidsACTIVE_COMPARATORTreatment with TAC + MMF + corticosteroids
Interventions
NameTypeDescription
Minimisation of TACDRUG•EVR: Treatment started at a total daily dose of 2 mg within 24 hours after randomisation. The dose of EVR was adjusted upon reaching trough levels (C-0h) in whole blood of 3-8 ng/mL. The daily dose (in two administrations) of EVR may have been modified to maintain trough levels (C-0h) in whole blood of 3-8 ng/mL until Week 52 post-transplant. •TAC: Once confirmation was obtained, beginning in Week 5, that trough levels (C-0h) in whole blood of EVR were between 3-8 ng/mL, minimisation of TAC began, in order to reach trough levels (C-0h) of TAC in whole blood of ≤5 ng/mL no later than four weeks after randomisation (Week 8), which were levels that should have been maintained until Week 52 post-transplant. •MMF was withdrawn at the same time that EVR was introduced. •oral corticosteroids was administered in accordance with local clinical practice, although a therapeutic strategy free of corticosteroids was permitted
TAC + MMF + corticosteroidsDRUG•Dose of TAC: Trough levels (C-0h) of TAC in whole blood should have been maintained between 6-10 ng/mL until Week 52 post-transplant. •Dose of MMF: Doses of 500-1000 mg/12 hrs was maintained until Week 52. •Corticosteroids: During the study, oral corticosteroids was administered in accordance with local clinical practice, although a therapeutic strategy free of corticosteroids was permitted (e.g. in patients with a history of HCV). It was recommended in any case that corticosteroids not be administered beyond Week 24 post-transplant except in cases of hepatopathy of autoimmune origin. At each centre all patients should have followed the same administration protocol for corticosteroids based on history of HCV.
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Eligibility Criteria
Age Range18 Years — 70 Years
SexALL
Healthy VolunteersNo
Study Sites20

Screening Visit - Inclusion Criteria 1. Recipients age 18 or over receiving a first liver transplant from a cadaver donor. 2. Patients diagnosed with HCC must meet the Milan radiological criteria at the time of transplant (1 nodule ≤5 cm in diameter, or 2-3 nodules, all \<3 cm in diameter) - at tim...

Countries:Spain
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