E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Genetic disease resulting in high concentrations of the amino acid cystine in the urine, leading to the formation of cystine stones in the kidney. |
Maladie génétique provoquant des concentrations élevées d'un amino-acide, la cystine, dans les urines, entrainant la formation de cristaux puis de calculs dans le rein.
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011778 |
E.1.2 | Term | Cystinuria |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and the tolerability of ADV7103 and standard of care (SoC) after a long-term treatment.
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Évaluer la sécurité d’emploi et la tolérabilité d’ADV7103 et de la norme de soin (NdS) après un traitement à long terme. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of ADV7103 and SoC on urine pH during a long-term treatment (proportion/number of responders with urine pH values in the first morning urines and in pre-dose urines ≥ 7.0 and ≥ 7.5) • To evaluate the efficacy of ADV7103 and SoC on cystine crystalluria (including the volume of crystals of cystine - Vcys) and other other cystinuric parameters during a long-term treatment • To evaluate the efficacy of ADV7103 and SoC on other urine parameters during a longterm treatment • To evaluate the efficacy of ADV7103 and SoC on cystine calculi during a long-term treatment • To evaluate the time for any potential adding of a second line therapy with cystine chelators. • To evaluate the paraclinical and biological safety of ADV7103 and SoC during a long-term treatment. |
• Évaluer l'effet d’ADV7103 et de la NdS sur le pH urinaire pendant un traitement à long terme (proportion/nombre de répondeurs présentant des valeurs de pH urinaire des premières urines du matin et des urines en pré-dose ≥ 7.0 et ≥ 7.5) • Évaluer l'effet d'ADV7103 et de la NdS sur la cristallurie de la cystine (incluant le volume des cristaux de cystine - Vcys) et d'autres paramètres cystinuriques pendant un traitement à long terme. • Evaluer l'effet d'ADV7103 et de la NdS sur d'autres paramètres urinaires pendant un traitement à long terme. • Évaluer l'effet d’ADV7103 et de la NdS sur les calculs de cystine pendant un traitement à long terme. • Evaluer le temps d’ajout potentiel d’un traitement de seconde intention avec des produits chélateurs de cystine. • Evaluer la sécurité d’emploi paraclinique et biologique d'ADV7103 et de la NdS pendant un traitement à long terme. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
ADV7103 Cohort : • Patient who has participated to and completed the previous B12CS Study or B13CS Study.
SoC Cohort : • Patient who has a diagnosis of cystinuria based on medical diagnosis (at least one previous or current episode of calculus of cystine, and/or one previous or current episode of cystine crystalluria) or on genetic diagnosis (only for patients of Subset 4). • Patient treated with an alkalising treatment at a well-adapted dose (defined as a daily dose deemed by the investigator aiming to maintain overtime urinary pH value ≥ 7.0 and/or compatible with an acceptable safety profile and/or patient’s constraints or compliance). • Patient who, when treated with a second line therapy (chelator agent), presents a disease status enabling interruption of the chelator agent during the course of the B10CS research. • Patient male or female, including child aged between 6 months and 17 years old and adult aged ≥ 18 years old up to 70 years old. |
Cohorte ADV7103 : • Patient qui a achevé l'étude précédente B12CS ou B13CS.
Cohorte Norme de Soin (NdS) : • Patient qui a un diagnostic de cystinurie basé sur un diagnostic médical (au moins un précédent ou actuel épisode de calcul de cystine, et/ou un précédent ou actuel épisode de cristallurie de cystine) ou un diagnostic génétique (seulement pour les patients de la Sous-classe d’âge 4)) • Patient traité avec un traitement alcalinisant à une dose bien adaptée (définie comme étant la dose quotidienne considérée par l’investigateur comme permettant de maintenir dans le temps une valeur de pH urinaire ≥ 7.0 et/ou compatible avec un profil de sécurité d’emploi acceptable et/ou avec les contraintes et l’observance du patient) • Patient qui, quand il est traité avec un traitement de seconde intention (agent chélateur), présente un statut de la maladie permettant l’interruption de l’agent chélateur tout au long du programme de recherche B10CS. • Patient homme ou femme, incluant les enfants âgés entre 6 mois et 17 ans et les adultes de 18 jusqu’à 70 ans. |
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E.4 | Principal exclusion criteria |
ADV7103 Cohort : • Patient who has not participated to B12CS Study or B13CS Study • Patient for whom any safety issue could contraindicate her/his participation to the extension study.
Soc Cohort : • Patient treated with the second line therapy and who cannot stop cystine chelating agents (sulfhydryl compounds) during the B14CS study. • Patient who presents kalaemia > 5.0 mmol/L. • Patient who presents a moderate or severe renal impairment (estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 according to Schwartz formula for the children and both MDRDs and CKD-EPI for adults). |
Cohorte ADV7103 : • Patient who has not participated to B12CS Study or B13CS Study • Patient for whom any safety issue could contraindicate her/his participation to the extension study.
Cohorte NdS : • Patient traité avec un traitement de seconde intention et qui ne peut pas arrêter les agents chélateurs de cystine (composés sulfhydryles). • Patient qui présente une kaliémie > 5.0 mmol/L. • Patient qui présente une insuffisance rénale modérée ou sévère (Débit de filtration glomérulaire estimé (DFGe) < 45 mL/min/1.73 m2 selon la formule de Schwartz pour les enfants et les formules MDRDs et CKD-EPI pour les adultes).
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E.5 End points |
E.5.1 | Primary end point(s) |
Number and proportion of patients who have experienced treatment-emergent adverse events during the course of the study. |
Nombre et proportion de patients qui ont ressenti des événements indésirables relatif au traitement au cours de l'étude. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
all along the study |
tout au long de l'étude |
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E.5.2 | Secondary end point(s) |
Main secondary efficacy endpoint: Values of the urine pH with a glass electrode pH-meter |
Critère d'évaluation secondaire principal d'efficacité: Valeurs du pH urinaire à mesurer avec un pH-mètre à électrode de verre |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- at each site visit from Visit 1 to Visit 7, in the fresh first and second morning urines - between site visits, at home, at least twice a week (total 4 time-points per week), including 2 time-points per day, in the morning and in the evening at approximately 12h-interval and before the treatment administration, in the first fresh morning urines and in the fresh evening urines, respectively |
- À chaque visite sur site, de la Visite 1 (M1, Jour 1) à la Visite 7 (M24), dans les premières et secondes urines fraîches du matin avant l'administration de traitement - Entre les visites sur site, au domicile, au moins 2 jours par semaine (au total 4 fois par semaine), 2 fois par jour, le matin et en soirée à approximativement 12h d’intervalle et avant l'administration du traitement, dans les premières urines fraîches du matin (t0) et dans les urines fraîches du soir (t12h), respectivement. |
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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 |
Acceptability, compliance and quality of life |
Acceptabilité, observance et qualité de vie |
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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 | 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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Contextuel avec un "bras comparateur" |
Contextual with a "comparator arm" |
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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 |
préparations officinales et hospitalières |
officinal and hospital preparations |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
France |
Spain |
United Kingdom |
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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 |
Dernière visite du dernier 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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |