Clinical trial NCT01011205: Phase 3b Study to Evaluate Advagraf in Combination With Mycophenolate Mofetil and Basiliximab in Liver Transplantation
Official title: A Multicenter, Three Arm, Randomized, Open Label Clinical Study to Compare Renal Function in Liver Transplant Recipients Receiving an Immunosuppressive Regimen of Advagraf (Immediately or Delayed Post-transplant) and MMF With or Without a Monoclonal Anti-IL2R Antibody (Basiliximab)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Liver Transplantation
Keywords: Immunosuppression
Liver
Transplant
Advagraf
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2009-11-11
Enrollment: 893
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Comparison of 3 dosing regimens of Advagraf to determine if there is a dosing regimen which may have the potential to cause fewer kidney problems.


Eligibility criteria: Inclusion Criteria:

* Undergoing orthotopic liver or split liver allograft transplantation
* Female subject of childbearing potential must have a negative serum or urine pregnancy test at enrollment and must agree to maintain effective birth control during the study

Exclusion Criteria:

* Receiving a multi-organ transplant or having previous received an organ transplant (including liver re-transplantation)
* Receiving an auxiliary graft or in whom a bio-artificial liver (cell system) has been used
* Receiving ABO incompatible graft or a graft from a non heart beating donor
* Ongoing dosing with systemic corticosteroids
* Subjects with systemic infection requiring treatment except viral hepatitis
* Diagnosis of new-onset malignancy prior to transplantation, with the exception of basocellular or squamous cell carcinoma of the skin which had been treated successfully. However, subjects with primary liver carcinoma can be included if they meet the following criteria:

  * \< 3 nodes
  * no node larger than 5 cm
  * no metastases
  * no vascular tumoral invasion
* Significant, uncontrolled concomitant infections and/or severe diarrhea, vomiting, active upper gastro-intestinal tract malabsorption or active peptic ulcer
* Subject or donor known to be HIV positive
* Known allergy or intolerance to tacrolimus, macrolide antibiotics, corticosteroids, basiliximab or mycophenolate mofetil or any of the product excipients
* Pregnant woman or breast-feeding mother
* Currently participating in another clinical trial, and/or has taken an investigational drug within 28 days prior to enrollment
* Unlikely to comply with the Visits scheduled in the protocol
* Any unstable medical condition that could interfere with the study objectives in the opinion of the Investigator
* Receiving prohibited concomitant therapy, or received prohibited concomitant therapy within 28 days prior to enrollment
* Any form of substance abuse, psychiatric disorder or condition which, in the opinion of the Investigator, may complicate communication with the Investigator

Primary outcomes:
measure: Glomerular filtration rate (GFR) at 24 Weeks after transplantation estimated using the MDRD4 formula
timeFrame: 24 weeks
Secondary outcomes:
measure: Incidence of and time to first incidence of the composite event: graft loss (defined as re-transplantation or death) or biopsy confirmed acute rejection (BCAR)
timeFrame: 24 weeks
measure: GFR at 24 Weeks after transplantation measured by Iothalamate clearance
timeFrame: 24 weeks
measure: GFR at 24 Weeks after transplantation estimated using a Cystatin C based formula
timeFrame: 24 weeks
measure: Creatinine clearance at 24 Weeks after transplantation estimated using the Cockcroft and Gault formula
timeFrame: 24 weeks
measure: Incidence of and time to first incidence of acute rejection
timeFrame: 24 weeks
measure: Incidence of and time to first incidence of corticosteroid-resistant acute rejection
timeFrame: 24 weeks
measure: Overall frequency of acute rejection episodes
timeFrame: 24 weeks
measure: Incidence of and time to first incidence of biopsy confirmed acute rejection
timeFrame: 24 weeks
measure: Incidence of and time to first incidence of biopsy confirmed corticosteroid-resistant acute rejection
timeFrame: 24 weeks
measure: Overall frequency of biopsy confirmed acute rejection episodes
timeFrame: 24 weeks
measure: Severity of biopsy confirmed acute rejection episodes
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: 160
city: Innsbruck
country: Austria
facility: 001
city: Minsk
country: Belarus
facility: 146
city: Brussels
country: Belgium
facility: 008
city: Gent
country: Belgium
facility: 006
city: Leuven
country: Belgium
facility: 009
city: Liege
country: Belgium
facility: 010
city: Sao Paulo
country: Brazil
facility: 163
city: Edmonton
country: Canada
facility: 153
city: Halifax
country: Canada
facility: 150
city: London
country: Canada
facility: 151
city: Montreal
country: Canada
facility: 152
city: Vancouver
country: Canada
facility: 154
city: Bogata
country: Colombia
facility: 169
city: Prague
country: Czechia
facility: 147
city: Helsinki
country: Finland
facility: 026
city: Besancon
country: France
facility: 041
city: Bordeaux
country: France
facility: 157
city: Caen
country: France
facility: 043
city: Creteil
country: France
facility: 031
city: Lyon
country: France
facility: 039
city: Marseille
country: France
facility: 045
city: Montpelier
country: France
facility: 158
city: Nice
country: France
facility: 037
city: Paris
country: France
facility: 042
city: Paris
country: France
facility: 044
city: Paris
country: France
facility: 035
city: Strasbourg
country: France
facility: 038
city: Toulouse
country: France
facility: 033
city: Villejuif
country: France
facility: 034
city: Berlin
country: Germany
facility: 056
city: Erlangen
country: Germany
facility: 058
city: Frankfurt
country: Germany
facility: 051
city: Gottingen
country: Germany
facility: 055
city: Hannover
country: Germany
facility: 057
city: Jena
country: Germany
facility: 142
city: Kiel
country: Germany
facility: 053
city: Leipzig
country: Germany
facility: 054
city: Mainz
country: Germany
facility: Site: 156
city: Munster
country: Germany
facility: 052
city: Regensberg
country: Germany
facility: 060
city: Tubingen
country: Germany
facility: 059
city: Budapest
country: Hungary
facility: 061
city: Dublin
country: Ireland
facility: 070
city: Bergamo
country: Italy
facility: 073
city: Bologna
country: Italy
facility: 075
city: Genova
country: Italy
facility: 076
city: Naples
country: Italy
facility: 077
city: Naples
country: Italy
facility: 079
city: Padova
country: Italy
facility: 072
city: Rome
country: Italy
facility: 074
city: Udine
country: Italy
facility: 071
city: Mexico City
country: Mexico
facility: Site: 166
city: Warsaw
country: Poland
facility: 086
city: Warsaw
country: Poland
facility: 087
city: Bucharest
country: Romania
facility: 091
city: Moscow
country: Russian Federation
facility: 096
city: Moscow
country: Russian Federation
facility: 097
city: Johannesburg
country: South Africa
facility: 148
city: A Coruna
country: Spain
facility: 114
city: Barcelona
country: Spain
facility: 109
city: Barcelona
country: Spain
facility: 106
city: Barcelona
country: Spain
facility: 110
city: Madrid
country: Spain
facility: 115
city: Madrid
country: Spain
facility: 108
city: Madrid
country: Spain
facility: 117
city: Zaragoza
country: Spain
facility: 116
city: Gothenberg
country: Sweden
facility: 126
city: Zurich
country: Switzerland
facility: 131
city: Birmingham
country: United Kingdom
facility: 136
city: Leeds
country: United Kingdom
facility: 171
city: London
country: United Kingdom
facility: 138
Study officials:
affiliation: Astellas Pharma Global Development - EU
name: Use Central Contact
role: STUDY_CHAIR
References: