Phase 3b Study to Evaluate Advagraf in Combination With Mycophenolate Mofetil and Basiliximab in Liver Transplantation

Condition(s) targeted: Liver Transplantation

Intervention: Advagraf (Drug); Mycophenolate Mofetil (Drug); Basiliximab (Drug); Corticosteroids (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Astellas Pharma Inc

Official(s) and/or principal investigator(s):
Use Central Contact, Study Chair, Affiliation: Astellas Pharma Global Development - EU

Overall contact:
Medical Affairs Europe, Phone: + 44 1784 419400, Email: contact@nl.astellas.com

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.

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

Primary outcome: Glomerular filtration rate (GFR) at 24 Weeks after transplantation estimated using the MDRD4 formula

Secondary outcome:

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)

GFR at 24 Weeks after transplantation measured by Iothalamate clearance

GFR at 24 Weeks after transplantation estimated using a Cystatin C based formula

Creatinine clearance at 24 Weeks after transplantation estimated using the Cockcroft and Gault formula

Incidence of and time to first incidence of acute rejection

Incidence of and time to first incidence of corticosteroid-resistant acute rejection

Overall frequency of acute rejection episodes

Incidence of and time to first incidence of biopsy confirmed acute rejection

Incidence of and time to first incidence of biopsy confirmed corticosteroid-resistant acute rejection

Overall frequency of biopsy confirmed acute rejection episodes

Severity of biopsy confirmed acute rejection episodes

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Medical Affairs Europe, Phone: + 44 1784 419400, Email: contact@nl.astellas.com

001, Innsbruck 6020, Austria; Recruiting

146, Minsk 220116, Belarus; Recruiting

007, Antwerp 2650, Belgium; Not yet recruiting

008, Brussels 1070, Belgium; Recruiting

006, Gent 9000, Belgium; Recruiting

009, Leuven 3000, Belgium; Recruiting

010, Liege 4000, Belgium; Recruiting

153, Edmonton T6G2XB, Canada; Recruiting

150, Halifax B3H2Y9, Canada; Recruiting

151, London N6A5A5, Canada; Recruiting

152, Montreal H2X3J4, Canada; Recruiting

154, Vancouver N5Z3X7, Canada; Recruiting

147, Prague 14021, Czech Republic; Recruiting

021, Copenhagen 2100, Denmark; Not yet recruiting

026, Helsinki 130, Finland; Recruiting

041, Besancon 25030, France; Not yet recruiting

157, Bordeaux 33076, France; Not yet recruiting

043, Caen 14033, France; Not yet recruiting

031, Creteil 94000, France; Not yet recruiting

032, Lyon 69437, France; Not yet recruiting

039, Lyon 69317, France; Not yet recruiting

045, Marseille 13385, France; Not yet recruiting

158, Montpelier 34295, France; Not yet recruiting

037, Nice 06202, France; Recruiting

035, Paris 92118, France; Recruiting

040, Paris 75679, France; Not yet recruiting

042, Paris 75571, France; Recruiting

044, Paris 75651, France; Not yet recruiting

036, Rennes 35033, France; Not yet recruiting

038, Strasbourg 67098, France; Not yet recruiting

033, Toulouse 31054, France; Recruiting

034, Villejuif 94804, France; Recruiting

056, Berlin 13353, Germany; Recruiting

058, Erlangen 91054, Germany; Recruiting

051, Frankfurt 60559, Germany; Recruiting

055, Gottingen 37099, Germany; Recruiting

057, Hannover 30625, Germany; Recruiting

142, Jena 07747, Germany; Recruiting

053, Kiel 24105, Germany; Recruiting

054, Leipzig 4103, Germany; Recruiting

143, Manz 156, Germany; Recruiting

141, Munich 81377, Germany; Not yet recruiting

052, Munster 48149, Germany; Recruiting

060, Regensberg 93042, Germany; Recruiting

059, Tubingen 72076, Germany; Recruiting

061, Budapest 1082, Hungary; Recruiting

070, Dublin 4, Ireland; Recruiting

073, Bergamo 24122, Italy; Recruiting

075, Bologna 40138, Italy; Not yet recruiting

076, Genova 16132, Italy; Recruiting

079, Naples 80131, Italy; Recruiting

077, Naples 80131, Italy; Recruiting

072, Padova 35127, Italy; Recruiting

078, Palermo 90134, Italy; Withdrawn

074, Rome 144, Italy; Recruiting

071, Udine 33100, Italy; Recruiting

081, Oslo 27, Norway; Withdrawn

086, Warsaw 02-097, Poland; Recruiting

087, Warsaw 2006, Poland; Recruiting

091, Bucharest 22328, Romania; Recruiting

096, Moscow 123182, Russian Federation; Recruiting

097, Moscow 129090, Russian Federation; Recruiting

098, St. Petersburg 197758, Russian Federation; Withdrawn

148, Johannesburg, South Africa; Recruiting

114, A Coruna 15006, Spain; Recruiting

110, Barcelona 8035, Spain; Recruiting

109, Barcelona 08036, Spain; Recruiting

106, Barcelona 08907, Spain; Recruiting

107, El Palmar 30120, Spain; Withdrawn

115, Madrid 28034, Spain; Recruiting

108, Madrid 28041, Spain; Recruiting

117, Madrid 28222, Spain; Recruiting

112, Malaga 29010, Spain; Withdrawn

111, Santiago de Compostela 15706, Spain; Withdrawn

113, Sevilla 41013, Spain; Withdrawn

116, Zaragoza 50009, Spain; Recruiting

126, Gothenberg 41345, Sweden; Recruiting

127, Uppsala 75185, Sweden; Withdrawn

131, Zurich 8091, Switzerland; Recruiting

136, Birmingham Bi5 2TH, United Kingdom; Recruiting

137, London NW3 2QG, United Kingdom; Not yet recruiting

138, London SE5 9RS, United Kingdom; Recruiting

Starting date: October 2009
Last updated: April 25, 2011