| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Locally advanced or metastatic urothelial cancer |
| Cáncer urotelial localmente avanzado o metastásico |
|
| E.1.1.1 | Medical condition in easily understood language |
| Cancerous tumour of the bladder |
| Tumor canceroso de la vejiga |
|
| 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 | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10046714 |
| E.1.2 | Term | Urothelial carcinoma bladder |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 |
| To compare the overall survival (OS) of subjects with locally advanced or metastatic urothelial cancer treated with enfortumab vedotin (EV) to the OS of subjects treated with chemotherapy |
| Comparar la supervivencia global (OS, overall survival) de los sujetos con cáncer urotelial localmente avanzado o metastásico tratados con enfortumab vedotina (EV) y la supervivencia global de los sujetos tratados con quimioterapia |
|
| E.2.2 | Secondary objectives of the trial |
To compare progression-free survival on study therapy (PFS1) per Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 of subjects treated with EV to subjects treated with chemotherapy
To compare the overall response rate (ORR) per RECIST V1.1 of EV to chemotherapy
To evaluate the duration of response (DOR) per RECIST V1.1 of EV and chemotherapy
To compare the disease control rate (DCR) per RECIST V1.1 of EV to chemotherapy
To assess the safety and tolerability of EV
To assess quality of life (QOL) and Patient Reported Outcomes (PRO) parameters |
Comparar la supervivencia sin progresión con el tratamiento del estudio (PFS1, progression-free survival on study therapy) de los sujetos tratados con EV y los sujetos tratados con quimioterapia, según los Response Evaluation Criteria in Solid Tumors (RECIST) V1.1
Comparar la tasa global de respuesta (ORR, overall response rate) de EV y quimioterapia, según los RECIST V1.1
Evaluar la duración de la respuesta (DOR, duration of response) de EV y quimioterapia, según los RECIST V1.1
Comparar la tasa de control de la enfermedad (DCR, disease control rate) de EV y quimioterapia, según los RECIST V1.1
Evaluar la seguridad y la tolerabilidad de EV
Evaluar la calidad de vida (QOL, quality of life) y los resultados comunicados por los pacientes (PRO, patient reported outcomes) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations must be obtained from the subject prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
2. Subject is legally an adult according to local regulation at the time of signing informed consent.
3. Subject has histologically or cytologically confirmed urothelial carcinoma. Subjects with urothelial carcinoma (transitional cell) with squamous differentiation or mixed cell types are eligible.
4. Subject must have experienced radiographic progression or relapse during or after a CPI (anti-PD1 or anti-PD-L1) for locally advanced or metastatic disease. Subjects who discontinued CPI treatment due to toxicity are eligible provided that they have evidence of disease progression following discontinuation. The CPI need not be the most recent therapy. Subjects for whom the most recent therapy has been a non-CPI based regimen are eligible if they have progressed/relapsed during or after their most recent therapy.
Locally advanced disease must not be amenable to resection with curative intent per the treating physician.
5. Subject must have received a platinum containing regimen (cisplatin or carboplatin) in the metastatic/locally advanced, neoadjuvant or adjuvant setting. If platinum was administered in the adjuvant/neoadjuvant setting subject must have progressed within 12 months of completion.
6. Subject has radiologically documented metastatic or locally advanced disease at baseline.
7. An archival tumor tissue sample should be available for submission to central laboratory prior to study treatment. If an archival tumor tissue sample is not available, a fresh tissue sample should be provided. If a fresh tissue sample cannot be provided due to safety concerns, enrollment into the study must be discussed with the medical monitor.
8. Subject has ECOG PS of 0 or 1
9. The subject has the following baseline laboratory data:
● absolute neutrophil count (ANC) ≥ 1500/mm3
● platelet count ≥ 100 × 10^9/L
● hemoglobin ≥ 9 g/dL
● serum bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects with Gilbert’s disease
● creatinine clearance (CrCl) ≥ 30 mL/min as estimated per institutional standards or as measured by 24 hour urine collection (glomerular filtration rate [GFR] can also be used instead of CrCl)
● alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 3 x ULN for subjects with liver metastases
10. Female subject must either:
● Be of nonchildbearing potential:
● Postmenopausal (defined as at least 1 year without any menses for which there is no other obvious pathological or physiological cause) prior to screening, or
● Documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy).
● Or, if of childbearing potential:
● Agree not to try to become pregnant during the study and for at least 6 months after the final study drug administration,
● And have a negative urine or serum pregnancy test within 7 days prior to Day 1 (Females with false positive results and documented verification of negative pregnancy status are eligible for participation),
● And if heterosexually active, agree to consistently use 1 form of highly effective birth control * starting at screening and throughout the study period and for at least 6 months after the final study drug administration.
11. Female subject must agree not to breastfeed or donate ova starting at screening and throughout the study period, and for at least 6 months after the final study drug administration.
12. A sexually active male subject with female partner(s) who is of childbearing potential is eligible if:
● Agrees to use a male condom starting at screening and continue throughout the study treatment and for 6 months after final study drug administration. If the male subject has not had a vasectomy or is not sterile as defined below his female partner(s) is utilizing 1 form of highly effective birth control starting at screening and continue throughout study treatment and for 6 months after the male subject receives his final study drug administration.
13. Male subject must not donate sperm starting at screening and throughout the study period, and for at least 6 months after the final study drug administration.
14. Male subject with a pregnant or breastfeeding partner(s) must agree to abstinence or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for at least 6 months after the final study drug administration.
15. Subject agrees not to participate in another interventional study while on treatment in present study.
Waivers to the inclusion criteria will NOT be allowed. |
1.El sujeto habrá firmado el consentimiento informado por escrito aprobado por el Comité de Ética de la Investigación y otorgado su aceptación de las cláusulas de confidencialidad de acuerdo con las regulaciones nacionales antes de cualquier procedimiento relacionado con el estudio (incluida la retirada de medicamentos prohibidos, si procede).2.El sujeto es adulto, según la legislación nacional, en el momento de firmar el consentimiento informado.
3.El sujeto presenta carcinoma urotelial confirmado histológicamente o citológicamente. Son elegibles los sujetos con carcinoma urotelial (células de transición) con los tipos de diferenciación escamosa o células mixtas.4.El sujeto debe haber experimentado progresión radiológica o recidiva durante o después de un inhibidor de los puntos de control inmunitario (CPI) (anti-PD1 o anti-PD-L1)para el tumor localmente avanzado o metastásico.Son elegibles los sujetos que hayan suspendido el tratamiento con CPI por toxicidad, siempre que hayan presentado signos de progresión del tumor después de la suspensión.No es preciso que el CPI sea el tratamiento más reciente. on elegibles los sujetos cuyo tratamiento más reciente haya sido un régimen basado en un fármaco distinto de un CPI si han experimentado progresión/recidiva durante o después del tratamiento más reciente. Según el médico responsable, no es factible la resección del tumor localmente avanzado con intención curativa. 5.El sujeto debe haber recibido un régimen que contuviera platino (cisplatino o carboplatino) en el contexto de tumor metastásico/localmente avanzado y tratamiento neoadyuvante o adyuvante.Si el platino se administró como adyuvante/neoadyuvante, el tumor debe haber progresado en el plazo de 12 meses desde la finalización del tratamiento. 6.El tumor debe ser metastásico o localmente avanzado, con documentación radiológica, en el punto basal. 7.Antes del tratamiento del estudio, se deberá disponer de una muestra de tejido tumoral de archivo para envío al laboratorio central.Si no se dispone de una muestra de tejido tumoral de archivo, se obtendrá una muestra reciente.Si no se puede obtener una muestra reciente por cuestiones de seguridad, la inclusión en el estudio se comentará con el monitor médico. 8.El estado funcional ECOG del sujeto es de 0 o 1. 9.Los datos de laboratorio basales del sujeto son:•número absoluto de neutrófilos (ANC, absolute neutrophil count) ≥1.500/mm3 •número de plaquetas ≥100 × 109/l •hemoglobina ≥9 g/dl •bilirrubina en suero ≤ 1,5 × límite superior de la normalidad (ULN, upper limit of normal) o ≤ 3 × ULN en sujetos con enfermedad de Gilbert •aclaramiento de creatinina (CrCl, creatinine clearance) ≥ 30 ml/min según estimación con los estándares del centro o medición en orina de 24 horas (en lugar del CrCl, también se puede utilizar la tasa de filtración glomerular [GFR, glomerular filtration rate]) •alanina aminotransferasa (ALT, alanine aminotransferase) y aspartato aminotransferasa (AST, aspartate aminotransferase) ≤ 2,5 × ULN o ≤ 3 x ULN en sujetos con metástasis hepáticas 10.Las mujeres deberán:•No ser potencialmente fértiles •Posmenopausia(ausencia de menstruación desde al menos 1 año antes, no debida a otra causa patológica o fisiológica) antes de la selección o •Esterilidad quirúrgica documentada(p.ej.,histerectomía, salpingectomía bilateral, ooforectomía bilateral). •O,si son potencialmente fértiles: •Estar de acuerdo en no intentar quedarse embarazadas durante el estudio y por lo menos hasta 6 meses después del final de la administración del fármaco del estudio,•Y disponer de una prueba de embarazo negativa en orina o suero en los 7 días previos al Día 1(serán elegibles las mujeres con resultado falso positivo y verificación documentada de la inexistencia de embarazo),•Y,si ejercen actividad heterosexual, estar de acuerdo en utilizar regularmente un método anticonceptivo altamente eficaz a partir de la selección, durante todo el período de estudio y hasta por lo menos 6 meses después del final de la administración del fármaco del estudio.11.La mujer deberá estar de acuerdo en no amamantar ni ser donante de óvulos a partir de la selección,durante todo el período de estudio y hasta por lo menos 6 meses después del final de la administración del fármaco del estudio.12.Un varón sexualmente activo con pareja(s) femenina(s) que sea(n) potencialmente fértil(es) es elegible si:•Está de acuerdo en utilizar preservativo a partir de la selección, durante todo el tratamiento del estudio y hasta 6 meses después del final de la administración del fármaco del estudio. Si al varón no se le ha practicado vasectomía o no es estéril, tal como se define más adelante, su(s) pareja(s) femenina(s) utilizará(n) un método anticonceptivo altamente eficaz a partir de la selección, durante todo el tratamiento del estudio y hasta 6 meses después de que el varón haya recibido la última administración del fármaco del estudio. Po favor, refieranse al protocolo para consultar el resto de criterios. |
|
| E.4 | Principal exclusion criteria |
1. Subject has preexisting sensory or motor neuropathy Grade ≥ 2.
2. Subject has active central nervous system (CNS) metastases. Subjects with treated CNS metastases are permitted on study if all the following are true:
● CNS metastases have been clinically stable for at least 6 weeks prior to screening
● If requiring steroid treatment for CNS metastases, the subject is on a stable dose ≤ 20 mg/day of prednisone or equivalent for at least 2 weeks
● Baseline scans show no evidence of new or enlarged brain metastasis
● Subject does not have leptomeningeal disease
3. Subject has ongoing clinically significant toxicity (Grade 2 or higher with the exception of alopecia) associated with prior treatment (including systemic therapy, radiotherapy or surgery). Subject with hypothyroidism or panhypopituitarism related to treatment with PD-1 and PD-L1 inhibitors may be enrolled. Subject on hormone replacement therapy may be enrolled if on a stable dose. Subjects with ongoing immunotherapy related colitis, uveitis, or pneumonitis or subjects with other immunotherapy related AEs requiring high doses of steroids (> 20 mg/day of prednisone or equivalent) are excluded.
4. Subject has prior treatment with EV or other monomethyl auristatin E (MMAE)-based ADCs.
5. Subject has received prior chemotherapy for urothelial cancer with all available study therapies in the control arm (i.e., both prior paclitaxel and docetaxel in regions where vinflunine is not an approved therapy, or prior paclitaxel, docetaxel and vinflunine in regions where vinflunine is an approved therapy).
Note: after vinflunine cap is reached, subjects who have received both docetaxel and paclitaxel will be excluded.
6. Subject has received more than 1 prior chemotherapy regimen for locally advanced or metastatic urothelial cancer, including chemotherapy for adjuvant or neo-adjuvant disease if recurrence occurred within 12 months of completing therapy. The substitution of carboplatin for cisplatin does not constitute a new regimen provided no new chemotherapeutic agents were added to the regimen.
7. Subject has history of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Subjects with nonmelanoma skin cancer, localized prostate cancer treated with curative intent with no evidence of progression, low-risk or very low-risk (per standard guidelines) localized prostate cancer under active surveillance/watchful waiting without intent to treat, or carcinoma in situ of any type (if complete resection was performed) are allowed.
8. Subject is currently receiving systemic antimicrobial treatment for viral, bacterial, or fungal infection at the time of first dose of EV. Routine antimicrobial prophylaxis is permitted.
9. Subject has known active Hepatitis B (e.g., HBsAg reactive) or active hepatitis C (e.g., HCV RNA [qualitative] is detected).
10. Subject has known history of human immunodeficiency virus (HIV) infection (HIV 1 or 2).
11. Subject has documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms (including congestive heart failure) consistent with New York Heart Association Class III-IV within 6 months prior to the first dose of study drug.
12. Subject has radiotherapy or major surgery within 4 weeks prior to first dose of study drug.
13. Subject has had chemotherapy, biologics, investigational agents, and/or antitumor treatment with immunotherapy that is not completed 2 weeks prior to first dose of study drug.
14. Subject has known hypersensitivity to EV or to any excipient contained in the drug formulation of EV.
15. Subject has known severe hypersensitivity to docetaxel, paclitaxel, polysorbate 80, and vinflunine or other vinca alkaloids (vinblastine,vincristine, vindesine, vinorelbine).
16. Subject requires ongoing therapy with a medication that is a strong inhibitor or inducer of the cytochrome P450 3A4 (CYP3A4) enzymes.
17. Subject has known active keratitis or corneal ulcerations.
18. Subject has other underlying medical condition that, in the opinion of the investigator, would impair the ability of the subject to receive or tolerate the planned treatment and follow-up.
19. History of uncontrolled diabetes mellitus within 3 months of the first dose of study drug. Uncontrolled diabetes is defined as hemoglobin A1C (HbA1c) ≥ 8% or HbA1c between 7 and < 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
Waivers to the exclusion criteria will NOT be allowed. |
1.Neuropatía sensitiva o motora preexistente de Grado ≥2.2.Metástasis del sistema nervioso central (CNS, central nervous system) activas.Se aceptará la inclusión de sujetos con metástasis del sistema nervioso central tratadas si se cumple todo lo siguiente:•Las metástasis del sistema nervioso central han permanecido clínicamente estables desde al menos 6 semanas antes de la selección •Si se requiere tratamiento de las metástasis del sistema nervioso central con corticoesteroides, el sujeto recibe una dosis estable ≤ 20 mg/día de prednisona o equivalente desde hace al menos 2 semanas•Las pruebas de imagen en el punto basal no revelan metástasis cerebrales nuevas o aumento de volumen de las existentes•El sujeto no presenta enfermedad leptomeníngea
3.Toxicidad en curso clínicamente importante(Grado ≥ 2 excepto la alopecia)asociada con el tratamiento previo(ya sea tratamiento sistémico, radioterapia o cirugía).Se podrán reclutar sujetos con hipotiroidismo o panhipopituitarismo relacionado con el tratamiento a base de inhibidores de PD-1 y PD-L1;así como sujetos en tratamiento hormonal sustitutivo, si la dosis es estable. Se excluirán los sujetos con colitis, uveítis o neumonitis en curso por inmunoterapia y también los sujetos con otros acontecimientos adversos debidos a la inmunoterapia que requieran dosis elevadas de corticoesteroides(>20mg/día de prednisona o equivalente).4.Tratamiento previo con EV u otros conjugados anticuerpo-fármaco basados en la monometil auristatina E(MMAE,monometil auristatine E).
5.Quimioterapia previa para el cáncer urotelial con todos los tratamientos del estudio disponibles en el grupo de control(es decir,paclitaxel y docetaxel previos en las regiones geográficas en las que no está aprobado el tratamiento con vinflunina, o paclitaxel, docetaxel y vinflunina en las regiones en las que está aprobado el tratamiento con vinflunina).Nota:una vez que se haya llegado al límite de sujetos establecido para la vinflunina, se excluirá a los sujetos que hayan recibido docetaxel y paclitaxel.6.Más de 1 régimen de quimioterapia previo para el cáncer urotelial localmente avanzado o metastásico, incluida quimioterapia adyuvante o neoadyuvante, si se produjo recurrencia de la enfermedad en el plazo de 12 meses una vez terminado el tratamiento.La sustitución de cisplatino por carboplatino no constituye un nuevo régimen siempre que no se añadan nuevos quimioterápicos al régimen.7.Antecedentes de otra neoplasia maligna en los 3 años anteriores a la primera dosis del fármaco del estudio, o cualquier signo de enfermedad residual de una neoplasia maligna diagnosticada con anterioridad.Se permite el reclutamiento de sujetos con cáncer de piel no melanómico o cáncer de próstata localizado tratados con intención curativa sin signos de progresión, cáncer de próstata localizado de bajo riesgo o de muy bajo riesgo (según las normas estándar) en vigilancia/actitud expectante activa sin intención de tratar o carcinoma in situ de cualquier tipo (si se practicó resección completa).8.Tratamiento antimicrobiano sistémico por infección vírica, bacteriana o fúngica en el momento de la primera dosis de EV. Se permitirá la profilaxis antimicrobiana habitual.9.Hepatitis B activa(p.ej.,reactivo a HBsAg) o hepatitis C activa (p.ej.,se detecta HCV RNA [cualitativo]).10.Antecedentes de infección por el virus de la inmunodeficiencia humana(HIV, human immunodeficiency virus)(HIV 1 o 2).11.Antecedentes documentados de un episodio vascular cerebral(ictus o accidente isquémico transitorio), angina de pecho inestable, infarto de miocardio o síntomas cardíacos (incluida insuficiencia cardíaca congestiva) compatible con Clase III-IV de la New York Heart Association, en los 6 meses anteriores a la primera dosis del fármaco del estudio.12.Radioterapia o cirugía mayor en las 4 semanas previas a la primera dosis del fármaco del estudio.13.Quimioterapia,productos biológicos,productos de investigación y/o tratamiento antineoplásico con inmunoterapia que no se ha completado 2 semanas antes de la primera dosis del fármaco del estudio.14.Hipersensibilidad conocida a EV o a cualquiera de los excipientes de la formulación(como histidina,dihidrato de trehalosa y polisorbato 20).15.Hipersensibilidad severa conocida a docetaxel,paclitaxel,polisorbato 80,vinflunina o a otros alcaloides de la vinca(vinblastina,vincristina,vindesina, vinorelbina).16.Necesidad de tratamiento continuo con un medicamento que es un inhibidor o inductor potente de las enzimas del citocromo P450 3A4(CYP3A4).
17.Presencia de queratitis o úlcera corneal activa.18.Presencia de otra afección médica subyacente que,en opinión del investigador,reduciría la capacidad del sujeto para recibir o tolerar el tratamiento o el seguimiento previstos. Por favor, refieranse al protocolo para consultar el resto de criterios. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Overall survival |
| Supervivencia global |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
o Up to 36 months (Primary)
o Up to 24 months (Secondary) |
o Hasta 36 meses (Primario)
o Hasta 24 meses (Secundario) |
|
| E.5.2 | Secondary end point(s) |
● PFS1 by RECIST V1.1
● ORR (CR + PR) by RECIST V1.1
● DCR (CR + PR + SD) by RECIST V1.1
● DOR by RECIST V1.1
● Safety variables (e.g., AEs, laboratory tests, vital sign measurements, 12-lead ECG and ECOG PS)
● QOL and PRO parameters (QLQ-C30 and EQ-5D-5L) |
● Supervivencia sin progresión con el tratamiento del estudio (PFS1) según los Response Evaluation Criteria in Solid Tumors (RECIST) V1.1
● Tasa global de respuesta (ORR, overall response rate) de EV y quimioterapia, según los RECIST V1.1
● Duración de la respuesta (DOR, duration of response) de EV y quimioterapia, según los RECIST V1.1
● Tasa de control de la enfermedad (DCR, disease control rate) de EV y quimioterapia, según los RECIST V1.1
● Evaluar la seguridad y la tolerabilidad de EV
● Evaluar la calidad de vida (QOL, quality of life) y los resultados comunicados por los pacientes (PRO, patient reported outcomes) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Please refer to section E.5.2 and also to the protocol |
| Por favor, refieranse a la sección E.5.2 y también al protocolo |
|
| 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 | Yes |
| 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) | 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 | 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) | 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 | 19 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 90 |
| 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 |
| Argentina |
| Australia |
| Austria |
| Belgium |
| Brazil |
| Canada |
| Denmark |
| France |
| Germany |
| Italy |
| Japan |
| Korea, Republic of |
| Netherlands |
| Portugal |
| Russian Federation |
| Spain |
| Switzerland |
| Taiwan |
| 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
|
| LSLV |
| Ultimo sujeto última visita |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 34 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 36 |
Print
