A Study in Kidney Transplant Subjects to Investigate the Optimal Suppression of Immunity to Help Prevent Kidney Rejection (OSAKA)

A Multicenter, Four Arm, Randomized, Open Label Clinical Study Investigating Optimized Dosing in a Prograf®-/Advagraf®-Based Immunosuppressive Regimen in Kidney Transplant Subjects (OSAKA Study)

To compare how well the new formulation of Tacrolimus® used once daily, in combination with other drugs helps prevent the rejection of a new kidney after transplantation compared to the twice daily dose of Tacrolimus

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: Mycophenolate Mofetil; Drug: Advagraf®; Drug: Prograf®; Drug: methylprednisolone / prednisone; Drug: Simulect

• Study Type: Interventional
• Enrollment (Actual): 1252
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1425FAB
  • Cordoba, Argentina, X5016KEH
• Austria
  • Innsbruck, Austria, A-6020
  • Linz, Austria, A-4010
  • Wien, Austria, A-1090
• Belgium
  • Brussels, Belgium, 1200
  • Brussels, Belgium, 1070
  • Ghent, Belgium, 9000
  • Leuven, Belgium, 3000
• Czechia
  • Brno, Czechia, 65691
  • Hradec Kravlove, Czechia, 50005
  • Ostrava, Czechia, 70852
  • Prague, Czechia, 14021
• France
  • Angers Cedex 01, France, 49033
  • Bordeaux, France, 33076
  • Brest Cedex 2, France, 29609
  • Creteil Cedex, France, 94010
  • La Tronche, France, 38700
  • Le Kremlin Bicetre Cedex, France, 94275
  • Limoges Cedex 1, France, 87042
  • Lyon Cedex 3, France, 69437
  • Nantes, France, 44035
  • Nice Cedex, France, 06002
  • Paris Cedex, France, 75908
  • Paris Cedex 15, France, 75743
  • Paris Cedex 20, France, 75970
  • Rennes Cedex 9, France, 35033
  • St. Etienne, France, 42055
  • Strasbourg Cedex, France, 67091
  • Suresnes Cedex, France, 92151
  • Toulouse Cedex, France, 31054
  • Tours Cedex 9, France, 37044
  • Vandoeuvre, France, 54511
• Germany
  • Aachen, Germany, 52074
  • Berlin, Germany, 13353
  • Essen, Germany, 45147
  • Frankfurt, Germany, 60590
  • Freiburg I. Br, Germany, 79106
  • Halle, Germany, 06120
  • Hamburg, Germany, 20251
  • Hannover, Germany, 30625
  • Jena, Germany, 07747
  • Kaiserslautern, Germany, 67655
  • Kiel, Germany, 24105
  • Leipzig, Germany, 04103
  • Munchen, Germany, 81675
  • Munster, Germany, 48149
  • Regensburg, Germany, 93042
  • Rostock, Germany, 18057
  • Tubingen, Germany, 72076
• Greece
  • Athens, Greece, 11527
  • Thessaloniki, Greece, 54642
• Hungary
  • Budapest, Hungary, 1082
  • Szeged, Hungary, 6720
• Ireland
  • Dublin, Ireland
• Italy
  • Ancona, Italy, 60020
  • Bologna, Italy, 40138
  • Milano, Italy, 20162
  • Padova, Italy, 35128
  • Roma, Italy, 00144
  • Siena, Italy, 53100
  • Treviso, Italy, 31100
• Netherlands
  • Maastricht, Netherlands, 6202 AZ
• Norway
  • Oslo, Norway, NO-0027
• Poland
  • Bialystok, Poland, 15-540
  • Gdansk, Poland, 80-211
  • Lublin, Poland, 20-090
  • Poznan, Poland, 60-479
  • Warsaw, Poland, 022-006
  • Wroclaw, Poland, 50-419
• Portugal
  • Lisboa, Portugal, 1069-639
  • Porto, Portugal, 4099-001
• Romania
  • Bucharest, Romania, 022328
  • Cluj Napoca, Romania, 400006
• Russian Federation
  • Moscow, Russian Federation, 123182
  • Moscow, Russian Federation, 129090
  • Omsk, Russian Federation, 644112
  • St. Petersburg, Russian Federation, 197110
  • Volgograd, Russian Federation, 404120
• Slovakia
  • Banska Bysterica, Slovakia, 975 17
  • Kosice, Slovakia, 040 11
• South Africa
  • Cape Town, South Africa, 7925
  • Johannesburg, South Africa, 2193
• Spain
  • A Coruna, Spain, 15006
  • Albacete, Spain, 02006
  • Alicante, Spain, 03010
  • Barakaldo-Vizcaya, Spain, 48903
  • Barcelona, Spain, 08035
  • Barcelona, Spain, 08907
  • Cadiz, Spain, 11009
  • Granada, Spain, 18012
  • Madrid, Spain, 28046
  • Madrid, Spain, 28034
  • Madrid, Spain, 28007
  • Murcia, Spain, 30120
  • Oviedo, Spain, 33006
  • Palma de Mallorca, Spain, 07014
  • Pamplona, Spain, 31080
  • Salamanca, Spain, 37007
  • Sevilla, Spain, 41013
  • Valencia, Spain, 46017
  • Valencia, Spain, 46009
  • Zaragoza, Spain, 50009
• Sweden
  • Stockholm, Sweden, S-14186
  • Uppsala, Sweden, S-75185
• Switzerland
  • Zurich, Switzerland, 8091
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
  • Glasgow, United Kingdom, G11 6NT
  • Leicester, United Kingdom, LE54PW
  • Manchester, United Kingdom, M13 9WL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• End stage kidney disease and a suitable candidate for primary renal transplantation or re-transplantation (unless the graft was lost from rejection within 12 months)
• Receiving a kidney transplant from a cadaveric or living (non HLA identical) donor with compatible ABO blood type
• Female subject of childbearing potential must have a negative serum pregnancy test at enrollment and must agree to maintain effective birth control during the study

Exclusion Criteria:

• Receiving or having previously received an organ transplant other than a kidney
• Cold ischemia time of the donor kidney > 30 hours
• Receiving a graft from a non-heart-beating donor other than of Maastricht category 3 (withdrawn of support awaiting cardiac arrest)
• Significant liver disease, defined as having continuously elevated SGPT/ALT and/or SGOT/AST and/or total bilirubin levels ≥ 2 times the upper value of the normal range of the investigational site or is receiving a graft from a hepatitis C or B positive donor
• Requiring initial sequential or parallel therapy with immunosuppressive antibody preparation(s)
• Requiring ongoing dosing with a systemic immunosuppressive drug prior to transplantation.
• Significant, uncontrolled concomitant infections and/or severe diarrhea, vomiting, active upper gastro-intestinal tract malabsorption or active peptic ulcer
• Pregnant woman or breast-feeding mother
• 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
• 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
• Currently participating in another clinical trial, and/or has taken an investigational drug 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: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Prograf + MMF + Steroids; oral	Drug: Mycophenolate Mofetil; oral; Other Names: MMF; Drug: Prograf®; oral; Other Names: FK506; Tacrolimus; Drug: methylprednisolone / prednisone; oral; Other Names: corticosteroids
Active Comparator: Advagraf (dose 1) + MMF + steroids; oral	Drug: Mycophenolate Mofetil; oral; Other Names: MMF; Drug: Advagraf®; oral; Other Names: MR4; FK506XL; Tacrolimus extended release; Drug: methylprednisolone / prednisone; oral; Other Names: corticosteroids
Active Comparator: Advagraf (dose 2) + MMF + steroids; oral	Drug: Mycophenolate Mofetil; oral; Other Names: MMF; Drug: Advagraf®; oral; Other Names: MR4; FK506XL; Tacrolimus extended release; Drug: methylprednisolone / prednisone; oral; Other Names: corticosteroids
Active Comparator: Advagraf + MMF + Basilixmab + steroids; oral	Drug: Mycophenolate Mofetil; oral; Other Names: MMF; Drug: Advagraf®; oral; Other Names: MR4; FK506XL; Tacrolimus extended release; Drug: methylprednisolone / prednisone; oral; Other Names: corticosteroids; Drug: Simulect; oral; Other Names: basiliximab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Efficacy failure rate	24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Renal Function, acute rejection, Biopsy confirmed acute rejection	24 weeks

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Chair: Central Contact, Astellas Pharma Europe B.V.

Publications and helpful links

General Publications

• Kramer BK, Albano L, Banas B, Charpentier B, Backman L, Tedesco-Silva H Jr, Lehner F, Mondragon-Ramirez GA, Glyda M, Cassuto-Viguier E, Viklicky O, Mourad G, Rigotti P, Schleibner S, Kamar N. Efficacy of Prolonged- and Immediate-release Tacrolimus in Kidney Transplantation: A Pooled Analysis of Two Large, Randomized, Controlled Trials. Transplant Proc. 2017 Nov;49(9):2040-2049. doi: 10.1016/j.transproceed.2017.07.011.
• Albano L, Banas B, Klempnauer JL, Glyda M, Viklicky O, Kamar N; Optimising immunoSuppression After Kidney transplantation with ADVAGRAF Study Group. OSAKA trial: a randomized, controlled trial comparing tacrolimus QD and BD in kidney transplantation. Transplantation. 2013 Nov 27;96(10):897-903. doi: 10.1097/TP.0b013e3182a203bd. Erratum In: Transplantation. 2014 Mar 27;97(6):38.

Helpful Links

• Link to results on Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2008
• Primary Completion (Actual): March 2, 2010
• Study Completion (Actual): March 2, 2010

Study Registration Dates

• First Submitted: July 16, 2008
• First Submitted That Met QC Criteria: July 16, 2008
• First Posted (Estimated): July 17, 2008

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; Prograf; FK506; Transplant; Kidney; 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; Antineoplastic Agents, Hormonal; Enzyme Inhibitors; Protective Agents; Antibiotics, Antitubercular; Antitubercular Agents; Neuroprotective Agents; Calcineurin Inhibitors; Basiliximab; Prednisone; Mycophenolic Acid; Methylprednisolone; Tacrolimus
• Other Study ID Numbers: PMR-EC-1210; 2007-005376-13 (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