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

NCT01371344 | Terminated Phase 4

• 2 other identifiers: F506-CL-04042009-012259-21
• Study Type: interventional
• Target: 47
• Locations: 6 countries
• Sites: 12

Brief Summary

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).

Conditions

Heart Transplantation; Kidney Transplantation; Liver Transplantation

Keywords

Liver Transplantation; Kidney Transplantation; Heart Transplantation; Pharmacokinetics

Outcome Measures

Primary Outcomes (11)

• 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

Study Arms (4)

Part A: Heart Transplant (Tacrolimus granules)

EXPERIMENTAL

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

Part A: Liver Transplant (Tacrolimus granules)

EXPERIMENTAL

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

Part A: Kidney Transplant (Tacrolimus granules)

EXPERIMENTAL

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

Part B: All Participants (Tacrolimus capsules)

EXPERIMENTAL

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

Interventions

Tacrolimus granules DRUG

oral

Also known as: Modigraf

Part A: Heart Transplant (Tacrolimus granules); Part A: Kidney Transplant (Tacrolimus granules); Part A: Liver Transplant (Tacrolimus granules)

Tacrolimus capsules DRUG

oral

Also known as: Prograf

Part B: All Participants (Tacrolimus capsules)

Eligibility Criteria

• Age: 0 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• F506-CL-0404 Part A
• F506-CL-0404 Part B

Sponsors & Collaborators

• Astellas Pharma Europe Ltd.: lead

Study Sites (12)

Site BE40 Clinique Univ. Saint Luc

Brussels, 1200, Belgium

Location

Site FR60 Groupement Hospitalier EST

Bron, 69677, France

Location

Site FR61 Hopital Robert Debre

Paris, 75945, France

Location

Site DE31 Kliniken der Medizinischen Hoc

Hanover, 30625, Germany

Location

Site DE30 Universitätsklin Heidelberg

Heidelberg, 69120, Germany

Location

Site PL50 Centrum Zdrowia Dziecka

Warsaw, 04-730, Poland

Location

Site ES22 H.U. Gregorio Maranon

Madrid, 28007, Spain

Location

Site ES20 Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Site ES21 Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Site ES23 Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Site GB14 Alder Hey Children Hospital

Liverpool, L12 2AP, United Kingdom

Location

Site GB13 Cent. Manchester Uni. Hospital

Manchester, M13 9WL, United Kingdom

Location

Related Links

• Link to results on the Astellas Clinical Study Results website

MeSH Terms

Interventions

Tacrolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Senior Study Manager

  Astellas Pharma Europe Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2011
• First Posted: June 10, 2011
• Study Start: June 24, 2011
• Primary Completion: April 2, 2017
• Study Completion: April 2, 2017
• Last Updated: November 1, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2); GB (2); DE (2); BE (1); PL (1); ES (4)