A Paediatric, Open, Follow up Study With Modigraf Examining Safety and Efficacy in de Novo Allograft Recipients (PROGRESSION)

A Long-term, Open-label, Non-comparative Study to Evaluate the Safety and Efficacy of a Modigraf® Based Immunosuppression Regimen in Paediatric Solid Allograft Recipients

The purpose of this study, a follow up to study FG506-CL-0403, is to see how safe and effective Modigraf® is (Part A) and to see how safe and effective it is to change your child's medication from Modigraf® to Prograf® (Part B).

Study Overview

• Status: Terminated
• Conditions: Liver Transplantation; Kidney Transplantation; Heart Transplantation
• Intervention / Treatment: Drug: Tacrolimus granules; Drug: Tacrolimus capsules

Detailed Description

To monitor the safety and efficacy of Modigraf® (tacrolimus granules) in stable paediatric allograft recipients (Part A) and to monitor dose changes and tacrolimus whole blood trough levels after conversion from a Modigraf based Immunosuppression regimen to a Prograf® based Immunosuppression regimen (Part B).

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Site BE40 Clinique Univ. Saint Luc
• France
  • Bron, France, 69677
    • Site FR60 Groupement Hospitalier EST
  • Paris Cedex 19, France, 75945
    • Site FR61 Hopital Robert Debre
• Germany
  • Hannover, Germany, 30625
    • Site DE31 Kliniken der Medizinischen Hoc
  • Heidelberg, Germany, 69120
    • Site DE30 Universitätsklin Heidelberg
• Poland
  • Warsaw, Poland, 04-730
    • Site PL50 Centrum Zdrowia Dziecka
• Spain
  • Madrid, Spain, 28007
    • Site ES22 H.U. Gregorio Maranon
  • Madrid, Spain, 28046
    • Site ES20 Hospital Universitario La Paz
  • Madrid, Spain, 28046
    • Site ES21 Hospital Universitario La Paz
  • Madrid, Spain, 28046
    • Site ES23 Hospital Universitario La Paz
• United Kingdom
  • Liverpool, United Kingdom, L12 2AP
    • Site GB14 Alder Hey Children Hospital
  • Manchester, United Kingdom, M13 9WL
    • Site GB13 Cent. Manchester Uni. Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 8 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

F506-CL-0404 Part A

• Subject was ≤12 years of age at enrolment into study F506-CL-0403
• Subject received at least one dose of Modigraf in the F506-CL-0403 study

F506-CL-0404 Part B

• Subject received at least one dose of Modigraf in the F506-CL-0403 study
• Subject participated in F506-CL-0404 Part A
• Subject has continuously been dosed with Twice daily (BID) Modigraf since the End of Study Visit for Part A (ESVA) from F506-CL-0404 Part A
• Subject is stable and has had no dose changes in the preceding 2 weeks

Exclusion Criteria:

F506-CL-0404 Part A

• As all subjects included in this study conform to the exclusion criteria in study F506-CL-0403, hence no specific exclusion criteria are relevant for this study

F506-CL-0404 Part B

• There are no specific exclusion criteria for this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Heart Transplant (Tacrolimus granules); In Part A of the study, participants who are heart transplant recipients receive tacrolimus granules-based immunosuppressive regimen twice daily for a maximum of 1 year or until commercial availability of tacrolimus granules in the participant's country.	Drug: Tacrolimus granules; oral; Other Names: Modigraf
Experimental: Part A: Liver Transplant (Tacrolimus granules); In Part A of the study, participants who are liver transplant recipients receive tacrolimus granules-based immunosuppressive regimen twice daily for a maximum of 1 year or until commercial availability of tacrolimus granules in the participant's country.	Drug: Tacrolimus granules; oral; Other Names: Modigraf
Experimental: Part A: Kidney Transplant (Tacrolimus granules); In Part A of the study, participants who are kidney transplant recipients receive tacrolimus granules-based immunosuppressive regimen twice daily for a maximum of 1 year or until commercial availability of tacrolimus granules in the participant's country.	Drug: Tacrolimus granules; oral; Other Names: Modigraf
Experimental: Part B: All Participants (Tacrolimus capsules); In Part B of the study, participants who are heart, kidney or liver transplant recipients and who are converted from tacrolimus granules-based immunosuppression regimen, receive tacrolimus capsules twice daily for 1 month and thereafter receive commercially available tacrolimus capsules.	Drug: Tacrolimus capsules; oral; Other Names: Prograf

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Number of Participants with Acute Rejection Episodes	Rejection episodes/acute rejections are indicated by clinical and/or laboratory signs, and are classified according to their rejection specific treatment: •Spontaneously Resolving Acute Rejection: not treated with new or increased corticosteroid medication, antibodies or any other medication and resolved, irrespective of any tacrolimus dose changes; •Corticosteroid Sensitive Acute Rejection: treated with new or increased corticosteroid medication only and which has resolved, irrespective of any tacrolimus dose changes; •Corticosteroid Resistant Acute Rejection: did not resolve following treatment with corticosteroids; - Resolved with further treatment: any acute rejection with an end date AND a treatment other than corticosteroid used; - Unresolved with further treatment: any acute rejection with no end date AND a treatment other than corticosteroid used; - Unresolved with no further treatment: any acute rejection with no end date AND ONLY corticosteroid treatment used.	Up to 12 months
Part A; Number of Participants with Biopsy-proven Acute Rejection Episodes (BPARs)	BPAR episodes are defined as acute rejection episodes confirmed by biopsy, and are classified according to their rejection specific treatment: •Spontaneously Resolving Acute Rejection: not treated with new or increased corticosteroid medication, antibodies or any other medication and resolved, irrespective of any tacrolimus dose changes; •Corticosteroid Sensitive Acute Rejection: treated with new or increased corticosteroid medication only and which has resolved, irrespective of any tacrolimus dose changes; •Corticosteroid Resistant Acute Rejection: did not resolve following treatment with corticosteroids; - Resolved with further treatment: any acute rejection with an end date AND a treatment other than corticosteroid used; - Unresolved with further treatment: any acute rejection with no end date AND a treatment other than corticosteroid used; - Unresolved with no further treatment: any acute rejection with no end date AND ONLY corticosteroid treatment used.	Up to 12 months
Part A: Severity of BPARs	The severity of BPARs is categorized with specific criteria by organ: For kidney transplant participants, according to Banff '97 Diagnostic categories for renal allograft biopsies - Banff '07 update (C4d deposition, Acute antibody-mediated rejection I, II, and III, Acute T cell mediated rejection IA, IB, IIA, IIB and III); for liver transplant participants, according to 1997 Banff Schema for Grading of Liver Allograft Rejection - Rejection Activity Index score (sum of grades: 1-mild, 2-moderate, 3-severe; range from 0-9); for heart, according to Standardized Nomenclature of the International Society of Heart and Lung Transplantation - Standardised Cardiac Biopsy Grading: Acute Cellular Rejection 2004 (mild, moderate, severe).	Up to 12 months
Part A: Patient Survival	Patient survival is reported as the number of deaths that occurred during Part A of the study.	Up to 12 months
Part A: Graft Survival	Graft survival is reported as the number of participants who experienced graft loss. Graft loss is defined as retransplantation or death or return to pretransplantation treatment modality for 6 weeks or longer. Additionally, kidney transplanted participants with ongoing dialysis at the end of study is counted as participants with graft loss.	Up to 12 months
Part A: Number of Participants with Adverse Events (AEs)	Safety is assessed by AEs, which includes abnormalities identified during a medical test (e.g. clinical laboratory tests, vital signs, etc.) if the abnormality induces clinical signs or symptoms, needs active intervention, interruption or discontinuation of study medication or is clinically significant. A serious AE (SAE) is an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, is life-threatening, requires or prolongs hospitalization or is considered medically important. A treatment emergent adverse event (TEAE) is defined as an AE observed after investigational drug administration.	From first dose of study drug up to 30 days after last dose of study drug (up to 13 months)
Part A: Tacrolimus Mean Trough Levels		Day 1, months 1, 2, 3, 6, 9, 12 (prior to each study drug dosing)
Part A: Number of Dose Adjustments	Study drug doses are adjusted based on clinical evidence of efficacy and occurrence of adverse events, and taking into consideration the recommended whole blood trough level range of 5-20 ng/ml.	Months 1, 2, 3, 6, 9, 12
Part B: Number of Participants with AEs	Safety is assessed by AEs, which included abnormalities identified during a medical test (e.g. clinical laboratory tests, vital signs, etc.) if the abnormality induces clinical signs or symptoms, needs active intervention, interruption or discontinuation of study medication or is clinically significant. A SAE is an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, is life-threatening, requires or prolongs hospitalization or is considered medically important. A TEAE is defined as an AE observed after investigational drug administration.	From first dose of study drug (tacrolimus capsules) up to 7 days after last dose (up to 38 days)
Part B: Tacrolimus Trough Levels Prior to and After Conversion	Values prior to conversion are the last trough level prior to first dose of study drug (tacrolimus capsules). Values after conversion are the first trough level after first dose of study drug (tacrolimus capsules).	Day -1 up to 1 month
Part B: Number of Dose Adjustments		From first dose of study drug up to 1 month

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe Ltd.
• Investigators: Study Director: Senior Study Manager, Astellas Pharma Europe Ltd.

Publications and helpful links

Helpful Links

• Link to results on the Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2011
• Primary Completion (Actual): April 2, 2017
• Study Completion (Actual): April 2, 2017

Study Registration Dates

• First Submitted: June 9, 2011
• First Submitted That Met QC Criteria: June 9, 2011
• First Posted (Estimated): June 10, 2011

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: Pharmacokinetics; Heart Transplantation; Kidney Transplantation; Liver Transplantation
• Additional Relevant MeSH Terms: Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: F506-CL-0404; 2009-012259-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.