| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Advanced Renal Cell Carcinoma |
| Carcinoma renal avanzado |
|
| E.1.1.1 | Medical condition in easily understood language |
| Advanced Renal Cell Carcinoma |
| Carcinoma renal avanzado |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10067946 |
| E.1.2 | Term | Renal cell carcinoma |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 |
1. To compare MK-6482 to everolimus with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR)
2. To compare MK-6482 to everolimus with respect to overall survival (OS) |
1.Comparar MK-6482 con everolimus en cuanto a la supervivencia sin progresión (SSP) conforme a los criterios RECIST 1.1, evaluada mediante una revisión central independiente y enmascarada (RCIE)
2.Comparar MK-6482 con everolimus en cuanto a la supervicencia global (SG) |
|
| E.2.2 | Secondary objectives of the trial |
1. To compare MK-6482 to everolimus with respect to objective response rate (ORR) based on RECIST 1.1 as assessed by BICR
2. To evaluate the duration of response (DOR) as assessed by BICR according to RECIST 1.1
3. To evaluate the safety and tolerability of MK-6482 compared to everolimus
4. To evaluate time to deterioration (TTD) and change from baseline in health-related quality of life (HRQoL) using the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy – Kidney Symptom Index-Disease-related Symptoms (FKSI-DRS)
5. To characterize health utility as measured using the European Quality of Life-5 dimensions-5 levels (EuroQoL EQ-5D-5L) |
1.Comparar MK-6482 con everolimus en cuanto a la tasa de respuesta objetiva (TRO) conforme a los criterios RECIST 1.1, evaluada mediante una RCIE.
2. Evaluar la duración de respuesta (DR) conforme a los criterios RECIST 1.1, según una RCIE.
3. Evaluar la seguridad y la tolerabilidad de MK-6482 en comparación con everolimus.
4. Evaluar el THD y la variación de la CVRS con respecto al momento basal mediante los cuestionarios QLQ-C30 de la EORTC y FKSI-DRS.
5. Caracterizar la utilidad de salud medida mediante el cuestionario EQ-5D-5L de EuroQoL. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| Merck will conduct Future Biomedical Research on DNA (Blood, Tissue) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time. |
| Merck realizará investigaciones biomédicas futuras con las muestras obtenidas (sangre, tejido) para tal finalidad durante este ensayo clínico. Estas investigaciones tendrán por objeto el análisis de biomarcadores con el fin de abordar aspectos nuevos que no se describen en otras partes del protocolo (como parte del ensayo principal) y solo se llevarán a cabo en muestras de los pacientes que hayan otorgado el consentimiento correspondiente. El objetivo de la obtención de muestras para investigaciones biomédicas futuras es estudiar e identificar biomarcadores que proporcionen información a los científicos sobre las enfermedades y sus tratamientos. El objetivo último es utilizar tal información para desarrollar fármacos más seguros y eficaces o para garantizar que los sujetos reciban la dosis correcta del fármaco en el momento preciso. |
|
| E.3 | Principal inclusion criteria |
1. Has unresectable, locally advanced or metastatic clear cell RCC
2. Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
3. Has received systemic treatment for locally advanced or metastatic RCC with a PD-1/L1 checkpoint inhibitor (at least 2 doses of a PD-1/L1 checkpoint inhibitor) and a VEGF-targeted therapy (including tyrosine kinase inhibitors or monoclonal antibodies) as monotherapy, or in combination
4. Has received no more than 3 prior systemic regimens for locally advanced or metastatic RCC
5. For the most recently received regimen, has demonstrated disease progression as defined by RECIST 1.1
6. Is male or female, who is at least 18 years of age at the time of signing the informed consent
7. Has a KPS score of at least 70% assessed within 7 days prior to the first dose of study intervention
8. A male participant must agree to use contraception during the treatment period and for at least 95 days, corresponding to time needed to eliminate any study intervention(s) and refrain from donating sperm during this period
9. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
a. Not a WOCBP
OR
b. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 95 days after the last dose of study intervention, corresponding to time needed to eliminate any study intervention(s)
10. The participant (or legally acceptable representative if applicable) provides written informed consent for the study. The participant may also provide consent for FBR. However, the participant may participate in the main study without participating in FBR
11. Has adequate organ function; all screening laboratory tests should be performed within 10 days prior to the first dose of study intervention |
1. Presencia de CR de células claras irresecable, localmente avanzado o metastásico.
2. Presencia de enfermedad mensurable conforme a los criterios RECIST 1.1, según la evaluación del investigador o radiólogo del centro. Las lesiones ubicadas en una zona previamente irradiada se considerarán mensurables siempre que se haya constatado progresión en dichas lesiones.
3. Recepción de tratamiento sistémico por el CR localmente avanzado o metastásico con un inhibidor del punto de control inmunológico PD-1/L1 (al menos 2 dosis de un inhibidor del punto de control inmunológico PD-1/L1) y un tratamiento dirigido contra VEGF (incluidos inhibidores de la tirosina cinasa o anticuerpos monoclonales) en monoterapia o en combinación.
4. Recepción de no más de tres pautas sistémicas previas por el CR localmente avanzado o metastásico.
5. En relación con la pauta recibida más recientemente, progresión de la enfermedad demostrada conforme a los criterios RECIST 1.1.
6. Varón o mujer de 18 años o más de edad en el momento de firmar el consentimiento informado.
7. Puntuación KPS ≥ 70 % en los 7 días previos a la primera dosis de la intervención del estudio.
8. Los varones deben comprometerse a utilizar métodos anticonceptivos durante el período de tratamiento y hasta, como mínimo, 95 días después de la última dosis de la intervención del estudio, lo que corresponde al tiempo necesario para eliminar la intervención del estudio, así como a abstenerse de donar semen durante este período.
9. Podrán participar en el estudio mujeres que no estén embarazadas, ni amamantando y que cumplan al menos una de las condiciones siguientes:
a. No es una mujer en edad fértil (MEF).
O
b. Es una MEF que se compromete a seguir las normas relativas a métodos anticonceptivos que se recogen durante el período de tratamiento y hasta, como mínimo, 95 días después de la última dosis de la intervención del estudio, lo que corresponde al tiempo necesario para eliminar la intervención del estudio.
10. El participante (o su representante legal cuando proceda) otorga su consentimiento informado por escrito para el estudio. El participante también podrá otorgar su consentimiento para investigaciones biomédicas futuras. No obstante, podrá participar en el estudio principal sin necesidad de hacerlo en las investigaciones biomédicas futuras.
11. Presencia de una función orgánica adecuada; todas las pruebas analíticas de selección deberán realizarse en los 10 días previos a la primera dosis de la intervención del estudio. |
|
| E.4 | Principal exclusion criteria |
1. A WOCBP who has a positive urine pregnancy test within 3 days prior to randomization or treatment allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
2. Has hypoxia as defined by a pulse oximeter reading <92% at rest or requires intermittent or chronic supplemental oxygen
3. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
4. Has known CNS metastases and/or carcinomatous meningitis
5. Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure. Medically controlled arrhythmia stable on medication is permitted
6. Has poorly controlled hypertension defined as SBP ≥150 mm Hg and/or DBP ≥90 mm Hg
7. Has moderate to severe hepatic impairment (Child-Pugh B or C)
8. Received colony-stimulating factors (eg, G-CSF, GM-CSF or recombinant EPO) within 28 days prior to the first dose of study intervention
9. Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study
10. Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel obstruction, malabsorption)
11. Has known hypersensitivity or allergy to the active pharmaceutical ingredient or any component of the study intervention (MK-6482 or everolimus) formulations
12. Has received prior treatment with MK-6482 or another HIF-2α inhibitor
13. Has received prior treatment with everolimus or any other specific or selective TORC1/PI3K/AKT inhibitor (eg, temsirolimus) in the advanced disease setting
14. Has received any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before randomization
15. Has received any type of systemic anticancer antibody (including investigational antibody) within 4 weeks before randomization
16. Has received prior radiotherapy within 2 weeks prior to first dose of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids. A 1-week washout is required for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease
17. Has had major surgery within 3 weeks prior to first dose of study intervention
18. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed
19. Is currently receiving either strong (eg, itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (eg, ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of CYP3A4 that cannot be discontinued for the duration of the study
20. Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John’s Wort) or moderate (eg, bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study
21. Is currently receiving a drug that is a substrate of P-gp (eg, cyclosporin, elacridar, ketoconazole, quinidine, reserpine, ritonavir, tacrolimus, valspodar, verapamil, zosuquidar) that cannot be discontinued for the duration of the study
22. Is currently receiving a drug that is an inhibitor of P-gp (eg, digoxin, fexofenadine, loperamide, quinidine, talinolol, vinblastine) that cannot be discontinued for the duration of the study
23. Is currently participating in a study of an investigational agent or is currently using an investigational device
24. Has an active infection requiring systemic therapy
25. Has active TB
26. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
27. Has a known history of HIV infection
28. Has a known history of HBV (defined as HBsAg reactive) or known active HCV (defined as HCV RNA [qualitative] is detected) infection
29. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 95 days after the last dose of study intervention |
1. Mujer en edad fértil que dé positivo en una prueba de embarazo en orina realizada en las 3h previas a la aleatorización o asignación del tratamiento. Cuando el resultado de la prueba en orina sea positivo o no pueda confirmarse que es negativo, será necesario hacer una prueba de embarazo en suero.
2. Presencia de hipoxia
3. Presencia de otra neoplasia maligna conocida que esté en progresión o que haya precisado tratamiento activo en los últimos tres años.
4. Presencia de metástasis en el SNC y/o de meningitis carcinomatosa.
5. Presencia de una cardiopatía clínicamente significativa, como angina inestable, infarto agudo de miocardio en los 6 meses previos al día 1 de administración del fármaco del estudio o insuficiencia cardíaca congestiva en clase III o IV de la New York Heart Association. Se permite la existencia de una arritmia médicamente controlada y estable con medicación.
6. Presencia de hipertensión arterial mal controlada..
7. Presencia de insuficiencia hepática moderada o grave
8. Recepción de factores estimuladores de colonias en los 28 días previos a la primera dosis de la intervención del estudio.
9. Trastorno psiquiátrico o por abuso de sustancias que pueda dificultar el cumplimiento de los requisitos del estudio.
10. Incapacidad de tragar medicación administrada por vía oral o presencia de un trastorno digestivo que afecta a la absorción.
11. Hipersensibilidad o alergia conocida al principio activo o a cualquiera de los componentes de las formulaciones de la intervención del estudio.
12. Recepción de tratamiento previo con MK-6482 u otro inhibidor de HIF-2α.
13. Recepción de tratamiento previo con everolimus o cualquier otro inhibidor específico o selectivo de TORC1/PI3K/AKT en el contexto de la enfermedad avanzada.
14. Recepción de cualquier tipo de inhibidor de cinasas de molécula pequeña (incluidos inhibidores de cinasas experimentales) en las dos semanas previas a la aleatorización.
15. Recepción de cualquier tipo de anticuerpo antineoplásico sistémico (incluidos anticuerpos experimentales) en las cuatro semanas previas a la aleatorización.
16. Recepción de radioterapia en las dos semanas previas a la primera dosis de la intervención del estudio. Los participantes deberán haberse recuperado de toda la toxicidad relacionada con la radioterapia y no precisar corticoides. Se permite un reposo farmacológico de una semana en caso de radioterapia paliativa (< 2 semanas de radioterapia) por enfermedad que no afecta al sistema nervioso central (SNC).
17. Intervención de cirugía mayor en las tres semanas previas a la primera dosis de las intervenciones del estudio.
18. Recepción de una vacuna de microorganismos vivos en los 30 días previos a la administración de la primera dosis del fármaco del estudio. Las vacunas inyectables contra la gripe estacional contienen, por lo general, virus muertos y están permitidas; en cambio, las vacunas antigripales intranasales son vacunas de virus vivos atenuados y no están permitidas.
19. Recepción activa de inhibidores potentes o moderados de la enzima CYP3A4 que no puedan suspenderse durante el estudio.
20. Recepción activa de inductores potentes o moderados de la enzima CYP3A4 que no puedan suspenderse durante el estudio.
21. Recepción activa de un fármaco que sea sustrato de la gp-P que no pueda suspenderse durante el estudio.
22. Recepción activa de un fármaco que sea inhibidor de la gp-P que no pueda suspenderse durante el estudio.
23. Participación activa en un estudio de un fármaco en investigación o uso activo de un dispositivo en investigación.
24. Infección activa con necesidad de tratamiento sistémico.
25. Tuberculosis activa.
26. Diagnóstico de inmunodeficiencia o recepción de tratamiento sistémico crónico con esteroides (en dosis superiores a 10 mg diarios de prednisona o equivalente) o cualquier otra forma de tratamiento inmunodepresor en los siete días previos a la primera dosis de la intervención del estudio.
27. Antecedentes de infección por VIH.
28. Antecedentes de infección por el virus de la hepatitis B (reactividad del antígeno de superficie del virus de la hepatitis B [HBsAg]) o de infección activa por el virus de la hepatitis C (definida como detección de ARN del virus de la hepatitis C [VHC] [cualitativo]).
29. Embarazo, período de lactancia o intención de concebir o engendrar un hijo durante el período previsto del estudio, desde la visita de selección hasta 95 días después de la última dosis de la intervención del estudio |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
2. Overall Survival (OS) |
1. Supervivencia sin progresión (SSP) según RECIST 1.1
2. Supervivencia global (SG) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to approximately 47 months
2. Up to approximately 47 months |
1. Hasta aproximadamente a los 47 meses
2. Hasta aproximadamente a los 47 meses |
|
| E.5.2 | Secondary end point(s) |
1. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
2. Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
3. Number of Participants Who Experience One or More Adverse Events (AEs)
4. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
5. Time to Deterioration in Health-Related Quality-of-Life (HRQoL) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 29 and 30 Score
6. Time to Deterioration in Physical Functioning Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 1- 5 Score
7. Time to Deterioration in Disease Symptoms Using the Functional Assessment of Cancer Therapy – Kidney Symptom Index-Disease-related Symptoms (FKSI-DRS) Items 1-9 Score
8. Change From Baseline in Health-Related Quality-of-Life (HRQoL) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 29 and 30 Score
9. Change From Baseline in Physical Functioning Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 1- 5 Score
10. Change From Baseline in Disease Symptoms Using the Functional Assessment of Cancer Therapy – Kidney Symptom Index-Disease-related Symptoms (FKSI-DRS) Items 1-9 Score
11. Change from Baseline in European Quality of Life 5 Dimensions, 5-level Questionnaire (EuroQoL EQ-5D-5L) Health Utility Score |
1. Tasa de respuesta objetiva (TRO) según RECIST 1.1
2.Duración de la respuesta (DR) según RECIST 1.1
3. Número de participantes que experimentan uno o más acontecimientos adversos (AA)
4. Número de participantes que suspenden la intervención del estudio debido a acontecimientos adversos
5. Tiempo hasta el deterioro (THD) en la calidad de vida relacionada con la salud (CVRS) mediante el cuestionario QLQ-C30 de la EORTC (apartados 29 y 30)
6. THD en el funcionamiento físico según el cuestionario QLQ-C30 de la EORTC (apartados 1-5)
7. THD en los síntomas de la enfermedad según la subescala FKSI-DRS (apartados 1-9).
8. Cambios desde el momento basal en la calidad de vida relacionada con la salud (CVRS) mediante el cuestionario QLQ-C30 de la EORTC (apartados 29 y 30)
9. Cambios desde el momento basal en el funcionamiento físico según el cuestionario QLQ-C30 de la EORTC (apartados 1-5)
10. Cambios desde el momento basal en los síntomas de la enfermedad según la subescala FKSI-DRS (apartados 1-9).
11. Cambios desde el momento basal en la utilidad de salud según el cuestionario EQ-5D-5L. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to approximately 47 months
2. Up to approximately 47 months
3. Up to approximately 47 months
4. Up to approximately 47 months
5. Up to approximately 47 months
6. Up to approximately 47 months
7. Up to approximately 47 months
8. Baseline (Day 1) and up to approximately 47 months
9. Baseline (Day 1) and up to approximately 47 months
10. Baseline (Day 1) and up to approximately 47 months
11. Baseline (Day 1) and up to approximately 47 months |
1. Hasta aproximadamente a los 47 meses
2. Hasta aproximadamente a los 47 meses
3. Hasta aproximadamente a los 47 meses
4. Hasta aproximadamente a los 47 meses
5. Hasta aproximadamente a los 47 meses
6. Hasta aproximadamente a los 47 meses
7. Hasta aproximadamente a los 47 meses
8. En el momento basal (día 1) y hasta aproximadamente a los 47 meses.
9. En el momento basal (día 1) y hasta aproximadamente a los 47 meses.
10. En el momento basal (día 1) y hasta aproximadamente a los 47 meses.
11. En el momento basal (día 1) y hasta aproximadamente a los 47 meses. |
|
| 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 | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| 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) | 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 | Yes |
| 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 | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 100 |
| 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 |
| Canada |
| Chile |
| Czech Republic |
| Denmark |
| Finland |
| France |
| Germany |
| Hong Kong |
| Hungary |
| Ireland |
| Italy |
| Japan |
| Korea, Republic of |
| Norway |
| Russian Federation |
| Spain |
| Taiwan |
| Turkey |
| Ukraine |
| United Kingdom |
| United States |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
