E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Autosomal dominant polycystic kidney disease |
Poliquistosis renal autosómica dominante |
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E.1.1.1 | Medical condition in easily understood language |
Autosomal dominant polycystic kidney disease |
Poliquistosis renal autosómica dominante |
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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 | LLT |
E.1.2 | Classification code | 10036046 |
E.1.2 | Term | Polycystic kidney, autosomal dominant |
E.1.2 | System Organ Class | 100000004850 |
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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 characterize the effect of GLPG2737 on growth in total kidney volume (TKV) compared to placebo. - To evaluate the safety and tolerability of oral doses of GLPG2737 compared to placebo. |
- Caracterizar el efecto de GLPG2737 en el aumento del volumen renal total (VRT) en comparación con el placebo. - Evaluar la seguridad y la tolerabilidad de dosis orales de GLPG2737 en comparación con el placebo. |
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E.2.2 | Secondary objectives of the trial |
- To characterize the effect of GLPG2737 on renal function (estimated glomerular filtration rate; eGFR) compared to placebo. - To characterize the pharmacokinetics (PK) of oral doses of GLPG2737 and its major metabolite G1125498 (M4) using population PK analyses. |
- Caracterizar el efecto de GLPG2737 en la función renal (tasa de filtración glomerular estimada; TFGe) en comparación con el placebo. - Caracterizar la farmacocinética (FC) de dosis orales de GLPG2737 y su principal metabolito G1125498 (M4) mediante análisis FC de la población. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female subject aged 18 to 50 years, inclusive. 2. Documented diagnosis of typical ADPKD, using the Ravine criteria. 3. Rapidly progressive disease, defined as presence of all of the following: -TKV >750 mL, as determined on imaging not older than 5 years before screening. If historical imaging is not available or older than 5 years, imaging can be performed during the screening period according to local clinical practice (i.e. echography, magnetic resonance imaging [MRI]). -Mayo ADPKD Classification Classes 1C to 1E. 4. eGFR at screening between 30-90 mL/min/1.73 m2 for subjects aged 18 to 40 years (inclusive), and between 30-60 mL/min/1.73 m2 for subjects aged 40 to 50 years. 5. Blood pressure ≤ 150/90 mmHg. In case the subject is treated for hypertension, he/she should be on a stable treatment regimen of antihypertensive therapy for at least 8 weeks prior to the screening visit, and during the screening period.
Reference is made to the protocol for a complete overview of the inclusion criteria. |
1. Sujetos de sexo masculino o femenino con una edad comprendida entre los 18 y los 50 años, ambos inclusive. 2. Diagnóstico documentado de PQRAD típica, mediante los criterios de Ravine. 3. Enfermedad de progresión rápida, definida como la presencia de todas las características siguientes: − VRT >750 ml, según se determine en las exploraciones por imagen realizadas no más de 5 años antes de la selección. Si no se dispone de exploraciones por imagen previas o estas se realizaron hace más de 5 años, se pueden realizar durante el periodo de selección de conformidad con la práctica clínica local (es decir, ecografía, resonancia magnética [RM]). − Clases 1C a 1E según la clasificación Mayo de la PQRAD. 4. TFGe en la selección entre 30-90 ml/min/1,73 m2 para los sujetos con edades comprendidas entre los 18 y los 40 años (ambos inclusive) y entre 30-60 ml/min/1,73 m2 para los sujetos con edades comprendidas entre los 40 y los 50 años. 5. Tensión arterial ≤150/90 mmHg. En caso de que el sujeto esté recibiendo tratamiento para la hipertensión, debe recibir una pauta posológica estable de antihipertensivos durante al menos 8 semanas anteriores a la visita de selección y durante el periodo de selección.
Referirse al protocolo para una revisión completa de los criterios de inclusión. |
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E.4 | Principal exclusion criteria |
1. Congenital absence of 1 kidney, or subject had a previous nephrectomy or has a transplanted kidney or a transplantation is planned in the foreseeable future. 2. Administration of polycystic kidney disease-modifying agents (e.g. tolvaptan) or interventions (such as cyst aspiration or cyst fenestration) within 12 weeks prior to the screening visit and during the screening period. In case tolvaptan is not being administered, this should be because of e.g. non-availability, intolerance, or physician’s clinical judgment. 3. Any condition or circumstances that, in the opinion of the investigator, may make a subject unlikely or unable to complete the study or comply with study procedures and requirements (e.g. unable to undergo MRI. For example subject's weight exceeds weight capacity of the MRI, ferromagnetic metal prostheses, aneurysm clips, severe claustrophobia, etc.).
Reference is made to the protocol for a complete overview of the exclusion criteria. |
1. Ausencia congénita de 1 riñón, o el sujeto se ha sometido previamente a una nefrectomía, o tiene un riñón trasplantado o tiene previsto someterse a un trasplante en un futuro próximo. 2. Administración de fármacos modificadores de la poliquistosis renal (p. ej., tolvaptán) o intervenciones (como la aspiración o fenestración de quistes) en las 12 semanas anteriores a la visita de selección y durante el periodo de selección. En caso de que no se esté administrando tolvaptán, esto se deberá, por ejemplo, a la no disponibilidad, la intolerancia o al criterio clínico del médico. 3. Cualquier enfermedad o circunstancia que, en opinión del investigador, pueda hacer que un sujeto tenga una probabilidad baja de completar el estudio o no pueda completarlo ni cumplir con los procedimientos y los requisitos del estudio (p. ej., no puede a someterse a una RM. Por ejemplo, el peso del sujeto supera la capacidad de peso de la RM, tiene prótesis de metal ferromagnético, grapas de aneurisma, claustrofobia grave, etc.).
Referirse al protocolo para una revisión completa de los criterios de exclusión. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Mean percent change from baseline of height-adjusted TKV (htTKV). - Frequency and severity of treatment-emergent adverse events (TEAEs), treatment-emergent serious AEs (SAEs), and TEAEs leading to treatment discontinuation. |
- Media del cambio porcentual con respecto al inicio en el VRT ajustado a la estatura (VRTae). - Frecuencia e intensidad de los acontecimientos adversos surgidos durante el tratamiento (AAST), los AA graves (AAG) surgidos durante el tratamiento y los AAST que provoquen la interrupción del tratamiento. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Various timepoints throughout the trial as specified in the protocol. |
Distintos tiempos a lo largo del ensayo clínico tal y como se especifica en el protocolo. |
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E.5.2 | Secondary end point(s) |
- Mean change from baseline estimated GFR (eGFR). - Estimated exposure (area under the curve [AUC], maximum plasma concentration [Cmax]), based on population PK analyses of GLPG2737 and its major metabolite M4. |
- Media del cambio con respecto al inicio en la TFG estimada (TFGe). - Exposición prevista (área bajo la curva [ABC], concentración plasmática máxima [Cmáx.]), según los análisis FC de la población de GLPG2737 y su principal metabolito M4. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Various timepoints throughout the trial as specified in the protocol. |
Distintos tiempos a lo largo del ensayo clínico tal y como se especifica en el protocolo. |
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability |
Tolerabilidad |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 | Yes |
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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The end of the study (EoS) is reached when the last follow-up visit, as planned according to the Schedule of Activities of the last subject is performed. |
El final del estudio (FE) se alcanza cuando se realiza la útima visita de seguimiento del último paciente, de acuerdo al esquema de actividades. |
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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 | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |