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

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)

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.

Study Overview

• Status: Completed
• Conditions: Liver Transplantation
• Intervention / Treatment: Drug: Advagraf; Drug: Mycophenolate Mofetil; Drug: Corticosteroids; Drug: Basiliximab

• Study Type: Interventional
• Enrollment (Actual): 893
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • 160
• Austria
  • Innsbruck, Austria, 6020
    • 001
• Belarus
  • Minsk, Belarus, 220116
    • 146
• Belgium
  • Brussels, Belgium, 1070
    • 008
  • Gent, Belgium, 9000
    • 006
  • Leuven, Belgium, 3000
    • 009
  • Liege, Belgium, 4000
    • 010
• Brazil
  • Sao Paulo, Brazil
    • 163
• Canada
  • Edmonton, Canada, T6G2XB
    • 153
  • Halifax, Canada, B3H2Y9
    • 150
  • London, Canada, N6A5A5
    • 151
  • Montreal, Canada, H2X3J4
    • 152
  • Vancouver, Canada, N5Z3X7
    • 154
• Colombia
  • Bogata, Colombia
    • 169
• Czechia
  • Prague, Czechia, 14021
    • 147
• Finland
  • Helsinki, Finland, 130
    • 026
• France
  • Besancon, France, 25030
    • 041
  • Bordeaux, France, 33076
    • 157
  • Caen, France, 14033
    • 043
  • Creteil, France, 94000
    • 031
  • Lyon, France, 69317
    • 039
  • Marseille, France, 13385
    • 045
  • Montpelier, France, 34295
    • 158
  • Nice, France, 06202
    • 037
  • Paris, France, 75571
    • 042
  • Paris, France, 75651
    • 044
  • Paris, France, 92118
    • 035
  • Strasbourg, France, 67098
    • 038
  • Toulouse, France, 31054
    • 033
  • Villejuif, France, 94804
    • 034
• Germany
  • Berlin, Germany, 13353
    • 056
  • Erlangen, Germany, 91054
    • 058
  • Frankfurt, Germany, 60559
    • 051
  • Gottingen, Germany, 37099
    • 055
  • Hannover, Germany, 30625
    • 057
  • Jena, Germany, 07747
    • 142
  • Kiel, Germany, 24105
    • 053
  • Leipzig, Germany, 4103
    • 054
  • Mainz, Germany
    • Site: 156
  • Munster, Germany, 48149
    • 052
  • Regensberg, Germany, 93042
    • 060
  • Tubingen, Germany, 72076
    • 059
• Hungary
  • Budapest, Hungary, 1082
    • 061
• Ireland
  • Dublin, Ireland, 4
    • 070
• Italy
  • Bergamo, Italy, 24122
    • 073
  • Bologna, Italy, 40138
    • 075
  • Genova, Italy, 16132
    • 076
  • Naples, Italy, 80131
    • 077
  • Naples, Italy, 80131
    • 079
  • Padova, Italy, 35127
    • 072
  • Rome, Italy, 144
    • 074
  • Udine, Italy, 33100
    • 071
• Mexico
  • Mexico City, Mexico
    • Site: 166
• Poland
  • Warsaw, Poland, 02-097
    • 086
  • Warsaw, Poland, 2006
    • 087
• Romania
  • Bucharest, Romania, 22328
    • 091
• Russian Federation
  • Moscow, Russian Federation, 123182
    • 096
  • Moscow, Russian Federation, 129090
    • 097
• South Africa
  • Johannesburg, South Africa
    • 148
• Spain
  • A Coruna, Spain, 15006
    • 114
  • Barcelona, Spain, 08036
    • 109
  • Barcelona, Spain, 08907
    • 106
  • Barcelona, Spain, 8035
    • 110
  • Madrid, Spain, 28034
    • 115
  • Madrid, Spain, 28041
    • 108
  • Madrid, Spain, 28222
    • 117
  • Zaragoza, Spain, 50009
    • 116
• Sweden
  • Gothenberg, Sweden, 41345
    • 126
• Switzerland
  • Zurich, Switzerland, 8091
    • 131
• United Kingdom
  • Birmingham, United Kingdom, Bi5 2TH
    • 136
  • Leeds, United Kingdom, LS9 7TF
    • 171
  • London, United Kingdom, SE5 9RS
    • 138

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dosing Regimen 1; Advagraf + MMF + Corticosteroids (Bolus)	Drug: Advagraf; Capsule; Other Names: FK506E; MR4; tacrolimus modified release; Drug: Mycophenolate Mofetil; Solution for infusion; Other Names: MMF; Drug: Corticosteroids; IV bolus; Other Names: Methylprednisolone or equivalent
Experimental: Dosing Regimen 2; Advagraf + MMF + Basiliximab + Corticosteroids (Bolus)	Drug: Advagraf; Capsule; Other Names: FK506E; MR4; tacrolimus modified release; Drug: Mycophenolate Mofetil; Solution for infusion; Other Names: MMF; Drug: Corticosteroids; IV bolus; Other Names: Methylprednisolone or equivalent; Drug: Basiliximab; IV infusion; Other Names: Simulect
Experimental: Dosing Regimen 3; Advagraf (5 days delay) + MMF + Basiliximab + Corticosteroids (Bolus)	Drug: Advagraf; Capsule; Other Names: FK506E; MR4; tacrolimus modified release; Drug: Mycophenolate Mofetil; Solution for infusion; Other Names: MMF; Drug: Corticosteroids; IV bolus; Other Names: Methylprednisolone or equivalent; Drug: Basiliximab; IV infusion; Other Names: Simulect

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Glomerular filtration rate (GFR) at 24 Weeks after transplantation estimated using the MDRD4 formula	24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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
GFR at 24 Weeks after transplantation measured by Iothalamate clearance	24 weeks
GFR at 24 Weeks after transplantation estimated using a Cystatin C based formula	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 acute rejection	24 weeks
Incidence of and time to first incidence of corticosteroid-resistant acute rejection	24 weeks
Overall frequency of acute rejection episodes	24 weeks
Incidence of and time to first incidence of biopsy confirmed acute rejection	24 weeks
Incidence of and time to first incidence of biopsy confirmed corticosteroid-resistant acute rejection	24 weeks
Overall frequency of biopsy confirmed acute rejection episodes	24 weeks
Severity of biopsy confirmed acute rejection episodes	24 weeks

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Chair: Use Central Contact, Astellas Pharma Global Development - EU

Publications and helpful links

Helpful Links

• Link to results on Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2009
• Primary Completion (Actual): January 4, 2013
• Study Completion (Actual): January 4, 2013

Study Registration Dates

• First Submitted: November 10, 2009
• First Submitted That Met QC Criteria: November 10, 2009
• First Posted (Estimated): November 11, 2009

Study Record Updates

• Last Update Posted (Actual): November 1, 2024
• Last Update Submitted That Met QC Criteria: October 30, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Immunosuppression; Transplant; Liver; Advagraf
• Additional Relevant MeSH Terms: Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Protective Agents; Antibiotics, Antitubercular; Antitubercular Agents; Neuroprotective Agents; Calcineurin Inhibitors; Basiliximab; Mycophenolic Acid; Methylprednisolone; Tacrolimus
• Other Study ID Numbers: PMR-EC-1106; 2008-002231-32 (EudraCT Number: EudraCT); 2010-021075-89 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR