E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
De novo renal transplant recipients |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | M15 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023438 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This exploratory study will be conducted in two phases to compare in terms of safety and efficacy an initially intensified dosing regimen of Myfortic® versus a standard dosing regimen of Myfortic®.
Primary objective of Phase I: Comparison of MPA exposure (AUC [0-12]) of two different Myfortic® dosing regimens including time to achieve an MPA AUC of > 40 mg*h/L.
Primary objective of Phase II: To assess time to occurrence of treatment failures, defined as a composite endpoint of biopsy proven acute rejection, graft loss, and death, loss to follow up and discontinuations from study drug treatment due to lack of efficacy or toxicity (at least one condition must be present) during the first 6 months post transplantation or at month 6 post transplantation. |
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E.2.2 | Secondary objectives of the trial |
Phase I:
• To assess safety and tolerability
•To assess the incidence of BPAR and Graft Loss
•To assess the pharmacokinetic profile of Myfortic®
•To assess IMPDH activity
Phase II:
• To assess occurrence of treatment failures at additional timepoints day 28 and day 84
• To assess rates of events for the following endpoints on day 28, 84, and 180: - Treated biopsy-proven acute rejection (BPAR), death or graft loss - Treated BPAR, death, graft loss or loss to follow up - Death, graft loss or loss to follow-up - Treated acute rejection - Treated acute rejection, death, graft loss, or loss to follow up
• To assess all individual components of the composite endpoint “treatment failure”
• To assess time to “event” for the composite endpoint as well as all individual components of that endpoint “treatment failure”
• To assess renal function
• To assess safety and tolerability
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Inclusion Criteria 1. Males or females, aged between 18 and 70 years 2. Recipients of de novo cadaveric, living unrelated or living related kidney transplants 3. Females capable of becoming pregnant must have a negative serum pregnancy test within 7 days prior to or at Baseline, and are required to practice an approved method of birth control for the duration of the study and for a period of 6 weeks following discontinuation of study medication, even where there has been a history of infertility 4. Patients who are willing and able to participate in the study and from whom written informed consent has been obtained
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E.4 | Principal exclusion criteria |
Exclusion Criteria 1. More than one previous renal transplantation 2. Graft loss due to immunological reasons in the first year after transplantation (in case of secondary transplantation) 3. Multi-organ recipients (e.g., kidney and pancreas) or previous transplant with any other organ, different from kidney 4. Patients receiving a kidney from a non-heart beating donor 5. Patients who are recipients of A-B-O incompatible transplants 6. Patients with a current peak PRA of > 50% 7. Patients with already existing antibodies against the HLA-type of the receiving transplant 8. Patients with any known hypersensitivity to mycophenolic acid or cyclosporine A, or other components of the formulations (e.g. lactose, see also SmPCs) 9. Patients who have received an investigational immunosuppressive drug within four weeks prior to study entry (Baseline visit) 10. Patients with thrombocytopenia (platelets < 100,000/mm³), with an absolute neutrophil count of < 2,000/mm³ or leucopenia (leucocytes < 3,000/mm³), or hemoglobin < 6 g/dL 11. Patients with symptoms of significant mental illness. Inability to cooperate or communicate with the investigator, who are unlikely to comply with the study requirements, or who are unable to give informed consent 12. Patients with a history of malignancy during the last five years, except squamous or basal cell carcinoma of the skin 13. Patients who are HIV positive or Hepatitis B surface antigen positive. 14. Evidence of severe liver disease (incl. abnormal liver enzyme profile, i.e. AST, ALT or total bilirubin > 3 times UNL) 15. Females of childbearing potential who are planning to become pregnant, who are pregnant and/or lactating, who are unwilling to use effective means of contraception (see also section 8.2 in the protocol) 16. Presence of a clinically significant infection requiring continued therapy, severe diarrhea, active peptic ulcer disease, or uncontrolled diabetes mellitus that in the opinion of the investigator would interfere with the appropriate conduct of the study 17. Evidence of drug or alcohol abuse 18. Patients receiving drugs known as strong inhibitors or inducers of CsA and/or Myfortic® drug metabolism (for drug interactions see Appendix 3 to this protocol).
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint of Phase I is the MPA exposure of two different Myfortic® dosing regimens at different timepoints after transplantation. Primary endpoint of Phase II is the time to occurrence of treatment failures up to or at Month 6 with two different Myfortic® dosing regimens. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard dosing regimen of Myfortic® |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |