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


Tracking Information

Start Date  ICMJEOctober 2009
Estimated Primary Completion DateDecember 2012   (final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE 
 (submitted: November 10, 2009)
Glomerular filtration rate (GFR) at 24 Weeks after transplantation estimated using the MDRD4 formula [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
Original Primary Outcome Measures  ICMJESame as current
Change HistoryComplete list of historical versions of study NCT01011205 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE 
 (submitted: November 10, 2009)
  • 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) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • GFR at 24 Weeks after transplantation measured by Iothalamate clearance [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • GFR at 24 Weeks after transplantation estimated using a Cystatin C based formula [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Creatinine clearance at 24 Weeks after transplantation estimated using the Cockcroft and Gault formula [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of and time to first incidence of acute rejection [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Incidence of and time to first incidence of corticosteroid-resistant acute rejection [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Overall frequency of acute rejection episodes [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Incidence of and time to first incidence of biopsy confirmed acute rejection [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Incidence of and time to first incidence of biopsy confirmed corticosteroid-resistant acute rejection [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Overall frequency of biopsy confirmed acute rejection episodes [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Severity of biopsy confirmed acute rejection episodes [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Original Secondary Outcome Measures  ICMJESame as current

Descriptive Information

Brief Title  ICMJEPhase 3b Study to Evaluate Advagraf in Combination With Mycophenolate Mofetil and Basiliximab in Liver Transplantation
Official Title  ICMJEA 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)
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 
Study PhasePhase III
Study Type  ICMJEInterventional
Study Design  ICMJETreatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Condition  ICMJELiver Transplantation
Intervention  ICMJE
  • Drug: Advagraf
    Capsule
    Other Names:
    • FK506E
    • MR4
    • tacrolimus modified release
  • Drug: Mycophenolate Mofetil
    Solution for infusion
    Other Name: MMF
  • Drug: Basiliximab
    IV infusion
    Other Name: Simulect
  • Drug: Corticosteroids
    IV bolus
    Other Name: Methylprednisolone or equivalent
Study Arms / Comparison Groups
  • Dosing Regimen 1: Experimental
    Advagraf + MMF + Corticosteroids (Bolus)
    Interventions:
    • Drug: Advagraf
    • Drug: Mycophenolate Mofetil
    • Drug: Corticosteroids
  • Dosing Regimen 2: Experimental
    Advagraf + MMF + Basiliximab + Corticosteroids (Bolus)
    Interventions:
    • Drug: Advagraf
    • Drug: Mycophenolate Mofetil
    • Drug: Basiliximab
    • Drug: Corticosteroids
  • Dosing Regimen 3: Experimental
    Advagraf (5 days delay) + MMF + Basiliximab + Corticosteroids (Bolus)
    Interventions:
    • Drug: Advagraf
    • Drug: Mycophenolate Mofetil
    • Drug: Basiliximab
    • Drug: Corticosteroids

Recruitment Information

Estimated Enrollment  ICMJE900
Estimated Completion DateDecember 2012
Estimated Primary Completion DateDecember 2012   (final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
GenderBoth
Ages18 Years and older
Accepts Healthy VolunteersNo
Contacts  ICMJE
Contact: Medical Affairs Europe+ 44 1784 419400contact@nl.astellas.com
Location Countries  ICMJEAustria,   Belarus,   Belgium,   Czech Republic,   Denmark,   Finland,   France,   Germany,   Hungary,   Ireland,   Italy,   Norway,   Poland,   Romania,   Russian Federation,   Spain,   Sweden,   Switzerland,   United Kingdom

Administrative Information

NCT ID  ICMJENCT01011205
Responsible PartyDisclosure Office Europe, Astellas Pharma Europe BV
Study ID Numbers  ICMJEPMR-EC-1106, EuraCT number 2008-002231-32
Study Sponsor  ICMJEAstellas Pharma Inc
Collaborators  ICMJE 
Investigators  ICMJE
Study Chair:Use Central ContactAstellas Pharma Global Development - EU
Information Provided ByAstellas Pharma Inc