E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Therapy for chronic HCV-infected
renal transplant patients |
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E.1.1.1 | Medical condition in easily understood language |
Therapy for chronic HCV-infected
renal transplant patients |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054990 |
E.1.2 | Term | Immunodeficiency secondary to organ transplantation |
E.1.2 | System Organ Class | 100000004870 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002724 |
E.1.2 | Term | Anti-HCV positive |
E.1.2 | System Organ Class | 100000004848 |
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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 |
To assess the rate of sustained virologic resonse (SVR) in all treated renal transplant patients at week 12 after the end of treatment.
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E.2.2 | Secondary objectives of the trial |
The proportion of renal transplant patients with a sustained virologic response (HCV-RNA levels <15IU/ml) at week 4 and 24 after the end of treatment. Patient/graft survival at week 12 and 24 after the end of treatment Acute Rejection including incidence, severity, type, treatment including time to event analyses Renal Function as determined by serum creatinine, calculated glomerular filtration rate (cGFR; CKD-EPI formula), the cGFR slope and CKD stages at week 12 and 24 after the end of treatment Change of C0 levels and daily dosing of Calcineurin-Inhibitors Qualitiy TOF urin analysis of drug metabolism Safety including adverse events (AEs) and serious AEs (SAEs), events of special interest: infections, opportunistic infections, malignancies, PTLDs, clinically significant changes in vital signs, clinically significant laboratory test abnormalities including proteinuria Tolerability of treatment regimen including treatment failures and reason for treatment failures
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. >18 year old renal transplant recipients 2. Renal transplant patients with chronic HCV-infection, Genotyp Ia and Ib with HCV RNA 3. Renal transplant patients with untreated or previously failed treatment of HCV-infection 4. Renal transplant patients with calculated glomerular filtration rate (cGFR) according to the CKD-EPI formula >30ml/min 5. Patients who are willing and able to participate in the study and from whom written informed consent has been obtained 6. Women of childbearing potential (WOCBP) should have a negative pregnancy test (serum or urine) within 1 week prior to beginning therapy. WOCBP must be willing to agree to contraceptive practices |
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E.4 | Principal exclusion criteria |
1. WOCBP who is either pregnant, lactating, planning to become pregnant or with a positive serum or urine pregnancy test 2. Subjects with active peptic ulcer disease, chronic diarrhea, or gastrointestinal malabsorption 3. Treatment with any investigational drug within 3 months preceding the study 4. Patient with a history of malignancies in the last 5 years with the exception of local, noninvasive, fully excised: cutaneous basal cell carcinoma or cutaneous squamous cell carcinoma 5. Patients with Co-infection with HIV or HBV 6. Patients with evidence of a medical condition associated with chronic decompensated liver disease (Child-Pugh class B or C) 7. Patients who suffered from severe rejection (≥ Banff II acute rejection), recurrent acute rejection, or steroid resistant rejection within 6 months of enrolment in this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of renal transplant patients with a sustained virologic response (HCV-RNA levels <15IU/ml) at week 12 after the end of treatment.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks after end of therapy |
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E.5.2 | Secondary end point(s) |
1. The proportion of renal transplant patients with a sustained virologic response (HCV-RNA levels <15IU/ml) at week 4 and 24 after the end of treatment. 2. Patient and graft survival at week 12 and 24 after the end of treatment 3. Acute Rejection (BPAR and treated), including incidence, severity (according to Banff grades), type (T-cell mediated, and antibody mediated), treatment (steroid resistant rejection, antibody treated rejection, rejection requiring conversion of baseline immunosuppressant) including time to event analyses 4. Renal Function as determined by serum creatinine, calculated glomerular filtration rate (cGFR) according to the CKD-EPI formula, the cGFR slope and different CKD stages at week 12 and 24 after the end of treatment 5. Change of C0 levels and daily dosing of Calcineurin-Inhibitors 6. Qualitiy TOF urin analysis of drug metabolism 7. Proportion of Safety events of the treatment regimen including adverse events (AEs) and serious AEs (SAEs), events of special interest: infections, opportunistic infections, malignancies, PTLDs, clinically significant changes in vital signs, clinically significant laboratory test abnormalities including proteinuria 8. Proportion of patients with treatment failures (virus breakthrough and relapse)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
week 4, 12, 24 after treatment |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
E.8.7 | Trial has a data monitoring committee | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |