E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic hepatitis B |
Chronische hepatitis B |
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E.1.1.1 | Medical condition in easily understood language |
viral liver infection with hepatitis B virus
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virale leverontsteking door het hepatitis B virus |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
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 |
The main objective of this study is to assess incidence of, clinical determinants for, dose reduction in and reversibility of tenofovir associated KPTD in HBV-monoinfected patients.
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Het primaire doel van deze studie is de incidentie, klinische determinanten, effect van dosisreductie en reversibiliteit van KPTD vast te stellen bij chronisch HBV-geïnfecteerde TDF-gebruikers. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to assess kidney tubular function in patients with cHBV on entecavir and without treatment, to relate plasma and intracellular levels of tenofovir (diphosphate) to the occurrence of KPTD and to report on plasma and intracellular levels of tenofovir (diphosphate) in cHBV.
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Secundaire doelen zijn het evalueren van de renale proximale tubulusfunctie bij cHBV-patienten op entecavir; het relateren van plasma en intracellulaire spiegels van tenofovir (difosfaat) aan het optreden van KPTD en het rapporteren van plasma en intracellulaire spiegels van tenofovir (difosfaat) bij cHBV-patienten. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
all adult, cHBV-infected patients on tenofovir or entecavir or without treatment are eligable |
alle chronisch HBV-geinfecteerden van 18 jaar of ouder op tenofovir of entecavir therapie of zonder therapie kunnen deelnemen |
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E.4 | Principal exclusion criteria |
HIV-infection |
HIV-infectie |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. The prevalence and incidence of renal insufficiency and kidney proximal tubular dysfunction (KPTD) in chronic hepatitis B patients on tenofovir, entecavir or without treatment.
KPTD is defined as the presence of at least two of the following; a decreased renal threshold phosphate concentration (TmP/GFR < 0.80
mmol/L), any normoglycemic (<10 mmol/L) glycosuria, hyperaminoaciduria, hyper β2-microglobulinuria (normal < 400 µg/L), increased
retinol binding protein loss (normal < 0.017 mg RBP/mmol creatinine), hyperuricosuria (normal < 5 mmol/24h).
Renal insufficiency is defined as a confirmed renal clearance of < 80 mL/min, or a confirmed >25% decrease in renal clearance since initiation of TDF.
2. Reversibility of renal insufficiency and KPTD following dose reduction at 24 weeks.
Reversibility is defined as GFR within 10% of baseline GFR/no agreement with KPTD criteria |
1. De prevalentie en incidentie van nierinsufficientie en KPTD bij chronische hepatitis B patiënten op tenofovir, entecavir en zonder behandeling.
Nierinsufficiientie wordt gedefinieerd als een bevestigde GFR < 80 ml/min, of een bevestigde daling van de GFR van >25% tov baseline.
KPTD wordt gedefinieerd als de aanwezigheid van tenminste 2 van de volgenden: een verminderde renale fosfaatdrempel (TmP/GFR < 0.80 mmol/L), normoglycemische glucosurie, hyperaminoacidurie, hyper-beta2-microglobulinurie (normaal < 400 ug/L), verhoogde retinol bindend proteïne excretie in de urine (normaal < 0.017 mg RBP/mmol kreatinine), hyperuricosurie (normaal < 5 mmol/24u).
2. Reversibiliteit van KPTD na TDF dosis-reductie
Reversibiliteit nierinsufficientie wordt gedefinieerd als een geschatte GFR binnen 10% van de baseline GFR, reversibiliteit KPTD wordt gedefinieerd als het niet meer voldoen aan deze definitie. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. week 48
2. week 24 after dose reduction |
1. week 48
2. week 24 na dosisreductie |
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E.5.2 | Secondary end point(s) |
1. The values of plasma TFV, urine TFV and intracellular TFV-DP levels in studygroup 1 on normal TDF dose and in those on reduced TDF dose.
2. The relation between plasma TFV, urine TFV and intracellular TFV-DP levels and the occurrence of KPTD in studygroup 1.
3. The percentage of patients in studygroup 1, meeting the criteria for dose reduction, maintaining adequate viral suppression. |
1. De waarden van plasma TFV, urine TFV en intracellulair TFV-DP bij studiegroep 1 op de gebruikelijke TDF dosering en na dosisreductie.
2. De relatie tussen plasma TFV, urine TFV en de intracellulaire TFV-DP spiegels en het optreden van nierinsufficientie en/of KPTD bij studiegroep 1.
3. Het percentage patienten in studiegroep 1 dat virologisch gesupprimeerd blijft na dosisreductie |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 and 2: At week 4, 12, 24, 36, 48 and after tenofovir dose reduction at week 4, 12, 24, 36, 48.
3: At week 4, 8, 12, 24, 36 and 48 after dose reduction.
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1 en 2: Op week 4, 12, 24, 36, 48 en na tenofovir dosis reductie op week 4, 12, 24, 36, 48.
3: Op week 4, 8, 12, 24, 36 en 48 na dosis reductie.
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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 | No |
E.6.6 | Pharmacokinetic | No |
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 | No |
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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LVLS |
Laatste bezoek van de als laatste geincludeerde patient. |
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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 | 0 |