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

Phase 3

Completed

• Conditions: Liver Transplantation
• Interventions: Drug: Advagraf; Drug: Mycophenolate Mofetil; Drug: Basiliximab; Drug: Corticosteroids

• Registration Number: NCT01011205
• Lead Sponsor: Astellas Pharma Inc

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-09-30
• Study First Submitted: 2009-11-10
• Study First Submitted QC: 2009-11-10
• Study First Posted: 2009-11-11
• Primary Completion: 2013-01-04
• Study Completion: 2013-01-04
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-30
• Last Update Posted: 2024-11-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 893

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dosing Regimen 3	Advagraf	Advagraf (5 days delay) + MMF + Basiliximab + Corticosteroids (Bolus)
Dosing Regimen 2	Corticosteroids	Advagraf + MMF + Basiliximab + Corticosteroids (Bolus)
Dosing Regimen 2	Advagraf	Advagraf + MMF + Basiliximab + Corticosteroids (Bolus)
Dosing Regimen 3	Corticosteroids	Advagraf (5 days delay) + MMF + Basiliximab + Corticosteroids (Bolus)
Dosing Regimen 1	Corticosteroids	Advagraf + MMF + Corticosteroids (Bolus)
Dosing Regimen 1	Advagraf	Advagraf + MMF + Corticosteroids (Bolus)
Dosing Regimen 1	Mycophenolate Mofetil	Advagraf + MMF + Corticosteroids (Bolus)
Dosing Regimen 2	Mycophenolate Mofetil	Advagraf + MMF + Basiliximab + Corticosteroids (Bolus)
Dosing Regimen 2	Basiliximab	Advagraf + MMF + Basiliximab + Corticosteroids (Bolus)
Dosing Regimen 3	Mycophenolate Mofetil	Advagraf (5 days delay) + MMF + Basiliximab + Corticosteroids (Bolus)
Dosing Regimen 3	Basiliximab	Advagraf (5 days delay) + MMF + Basiliximab + Corticosteroids (Bolus)

Primary Outcome Measures

Name	Time	Method
Glomerular filtration rate (GFR) at 24 Weeks after transplantation estimated using the MDRD4 formula	24 weeks

Secondary Outcome Measures

Name	Time	Method
Overall frequency of biopsy confirmed acute rejection episodes	24 weeks
GFR at 24 Weeks after transplantation measured by Iothalamate clearance	24 weeks
Severity of biopsy confirmed acute rejection episodes	24 weeks
Overall frequency of acute rejection episodes	24 weeks
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)	24 weeks
Incidence of and time to first incidence of acute rejection	24 weeks
GFR at 24 Weeks after transplantation estimated using a Cystatin C based formula	24 weeks
Incidence of and time to first incidence of biopsy confirmed corticosteroid-resistant acute rejection	24 weeks
Creatinine clearance at 24 Weeks after transplantation estimated using the Cockcroft and Gault formula	24 weeks
Incidence of and time to first incidence of corticosteroid-resistant acute rejection	24 weeks
Incidence of and time to first incidence of biopsy confirmed acute rejection	24 weeks

Trial Locations

Locations (72)

026; 🇫🇮 Helsinki, Finland

146; 🇧🇾 Minsk, Belarus

006; 🇧🇪 Gent, Belgium

053; 🇩🇪 Kiel, Germany

126; 🇸🇪 Gothenberg, Sweden

057; 🇩🇪 Hannover, Germany

039; 🇫🇷 Lyon, France

056; 🇩🇪 Berlin, Germany

147; 🇨🇿 Prague, Czechia

037; 🇫🇷 Nice, France

153; 🇨🇦 Edmonton, Canada

058; 🇩🇪 Erlangen, Germany

142; 🇩🇪 Jena, Germany

042; 🇫🇷 Paris, France

044; 🇫🇷 Paris, France

043; 🇫🇷 Caen, France

031; 🇫🇷 Creteil, France

045; 🇫🇷 Marseille, France

158; 🇫🇷 Montpelier, France

150; 🇨🇦 Halifax, Canada

009; 🇧🇪 Leuven, Belgium

010; 🇧🇪 Liege, Belgium

034; 🇫🇷 Villejuif, France

152; 🇨🇦 Montreal, Canada

008; 🇧🇪 Brussels, Belgium

169; 🇨🇴 Bogata, Colombia

041; 🇫🇷 Besancon, France

157; 🇫🇷 Bordeaux, France

038; 🇫🇷 Strasbourg, France

136; 🇬🇧 Birmingham, United Kingdom

108; 🇪🇸 Madrid, Spain

171; 🇬🇧 Leeds, United Kingdom

117; 🇪🇸 Madrid, Spain

061; 🇭🇺 Budapest, Hungary

163; 🇧🇷 Sao Paulo, Brazil

051; 🇩🇪 Frankfurt, Germany

055; 🇩🇪 Gottingen, Germany

151; 🇨🇦 London, Canada

052; 🇩🇪 Munster, Germany

077; 🇮🇹 Naples, Italy

072; 🇮🇹 Padova, Italy

071; 🇮🇹 Udine, Italy

054; 🇩🇪 Leipzig, Germany

035; 🇫🇷 Paris, France

Site: 156; 🇩🇪 Mainz, Germany

033; 🇫🇷 Toulouse, France

138; 🇬🇧 London, United Kingdom

070; 🇮🇪 Dublin, Ireland

131; 🇨🇭 Zurich, Switzerland

060; 🇩🇪 Regensberg, Germany

059; 🇩🇪 Tubingen, Germany

115; 🇪🇸 Madrid, Spain

109; 🇪🇸 Barcelona, Spain

106; 🇪🇸 Barcelona, Spain

110; 🇪🇸 Barcelona, Spain

116; 🇪🇸 Zaragoza, Spain

160; 🇦🇷 Buenos Aires, Argentina

001; 🇦🇹 Innsbruck, Austria

154; 🇨🇦 Vancouver, Canada

073; 🇮🇹 Bergamo, Italy

075; 🇮🇹 Bologna, Italy

076; 🇮🇹 Genova, Italy

079; 🇮🇹 Naples, Italy

074; 🇮🇹 Rome, Italy

Site: 166; 🇲🇽 Mexico City, Mexico

086; 🇵🇱 Warsaw, Poland

087; 🇵🇱 Warsaw, Poland

091; 🇷🇴 Bucharest, Romania

096; 🇷🇺 Moscow, Russian Federation

097; 🇷🇺 Moscow, Russian Federation

148; 🇿🇦 Johannesburg, South Africa

114; 🇪🇸 A Coruna, Spain