E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Lupus Nephritis |
Néphrite Lupique |
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E.1.1.1 | Medical condition in easily understood language |
Lupus Nephritis |
Néphrite Lupique |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025140 |
E.1.2 | Term | Lupus nephritis |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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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 |
OBJECTIVE: To study the effects of first-line Rituximab (RTX) therapy without interference with previous immunosuppressive treatments. This will require a ‘screening biopsy’ (standard of care) and a control biopsy performed 6 months after first RTX administration. The aim is not to demonstrate the clinical efficacy of this approach but to verify ex-vivo that RTX administered as a first-line therapy modulates favorably the renal lymphocyte B populations and could be effective in the absence of oral corticosteroid therapy. The renal and urinary lymphocyte B populations will be analysed in flow cytometry and also in single cell in order to study their transcriptome and to identify in the kidney and in the urines the presence of plasmablasts (present in large quantity in the untreated patients); and the presence of plasma cells and long-lived plasma cells (probably responsible for recurrences). |
Le but est d'étudier les effets du RTX administré en première intention, sans interférence avec des traitements immunosuppresseurs antérieurs. Ceci nécessitera une biopsie de départ (traitement standard) et une biopsie de contrôle réalisée 6 mois après l’administration du RTX. Le but n’est pas de démontrer l’efficacité clinique de cette approche mais de vérifier, ex vivo, que le Rituximab administré en première intention module favorablement les populations lymphocytaires B rénales, et pourrait être efficace en l’absence de corticothérapie orale. Les populations lymphocytaires B rénales et urinaires seront analyser en cytométrie de flux et aussi en single cell afin d’étudier leur transcriptome et d’identifier dans le rein et dans les urines la présence de plasmablastes (présents en grande quantité chez les malades non-traités), de plasma cells et de long-lived plasma cells (probablement responsables des récidives). |
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E.2.2 | Secondary objectives of the trial |
Not applicable |
Pas d'application |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age ≥ 15y (except if local ethics committee imposes ≥ 18y) and ≤ 65 y systemic lupus erythematosus, according to (ACR/SLICC criteria early untreated Lupus nephritis class III or IV (ISN/RPS 2003), associated or not to class V uP/C ratio ≥1 mg/mg measured in a 24-h urine collection No immunosuppressive therapy (never) No targeted biological therapy never) No renal failure (eGFR < 60 mL/min) No Biological and clinical nephrotic syndrome Contraception (any type) Signed informed consent (drafted according to local practice and approuved by the local ethics committee) |
Patients âgés de 15 à 65 ans Lupus erythémateux disséminé (critères ACR/SLICC) NL incidente de classe III ou IV (ISN/RPS 2003), associée ou non à une classe V Rapport uP/C ≥1 mg/mg mesuré dans une collecte urinaire de 24-heures Absence de traitement immunosuppresseur (jamais) Absence de traitement biologique ciblé (jamais) Absence d’insuffisance rénale (eGFR ≥60 ml/min) Absence de syndrome néphrotique biologique et clinique Contraception (hormonale ou stérilet) Signature du consentement éclairé |
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E.4 | Principal exclusion criteria |
Pregnancy Breast-feeding Renal failure (eGFR < 60 mL/min) Biological and clinical nephrotic syndrome HIV, HCV, HBV infections Active tuberculosis History of malignancy (except non-melanoma skin and cervical intraepithelial cervical cancer) Previous targeted biological therapy Intercurrent disease interfering with treatment and/or clinical evaluation |
Grossesse Allaitement Insuffisance rénale (eGFR <60 ml/min) Syndrome néphrotique biologique et clinique Infection par HIV, HCV, HBV Tuberculose active Antécédent néoplasique (à l’exception du cancer cervical intraépithélial et des cancers cutanés non-mélanome) Traitement immunosuppresseur préalable Traitement biologique ciblé préalable Maladie intercurrente interférant avec le traitement et/ou son évaluation
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E.5 End points |
E.5.1 | Primary end point(s) |
Disappearance of intra-renal and urinary plasmablasts (assessed by kidney biopsy and urine collection - Month 6 after initiation of RTX treatment) |
Disparition des plasmablastes intra-rénaux et urinaires à 6 mois |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Month 6 after initiation of RTX treatment |
biopsie
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E.5.2 | Secondary end point(s) |
50% reduction in proteinuria Lowering of histological activity index (Morel-Maroger and NIH) assessed by second renal biopsy at Month 6 after initiation of RTX treatment.
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Diminution de 50% de la protéinurie Diminution de l’indice d’activité histologique (Morel-Maroger et NIH) sur la biopsie de contrôle |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Month 6 after initiation of RTX 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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
The renal and urinary lymphocyte B populations will be analysed in flow cytometry and also in single cell in order to study their transcriptome and to identify in the kidney and in the urines the presence of plasmablasts (present in large quantity in the untreated patients); and the presence of plasma cells and long-lived plasma cells (probably responsible for recurrences). |
Les populations lymphocytaires B rénales et urinaires seront analyser en cytométrie de flux et aussi en single cell afin d’étudier leur transcriptome et d’identifier dans le rein et dans les urines la présence de plasmablastes (présents en grande quantité chez les malades non-traités), de plasma cells et de long-lived plasma cells (probablement responsables des récidives). |
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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) | 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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | 0 |