E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Malignancies Associated with EphA2 Expression |
Neoplasias malignas avanzadas asociadas con la expresión de EphA2 |
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E.1.1.1 | Medical condition in easily understood language |
Cancer tumors that have recurred after or did not respond to standard of care treatments |
Tumores cancerosos que han reaparecido después o no respondieron a los tratamientos de atención estándar. |
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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 | LLT |
E.1.2 | Classification code | 10065147 |
E.1.2 | Term | Malignant solid tumor |
E.1.2 | System Organ Class | 100000004864 |
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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 |
The primary objectives of the escalation (Parts A-1 and A-2) are: • To assess safety and tolerability of BT5528 in patients with advanced solid tumor malignancies associated with EphA2-expression and/or specified tumors identified as positive for EphA2 tumor expression as a monotherapy (Part A-1) and in combination with nivolumab (Part A-2) • To define the maximum tolerated dose of BT5528, if observed, and determine a recommended Phase II dose as a monotherapy (Part A-1) and in combination with nivolumab (Part A-2)
The primary objectives of the expansions (Parts B-1 and B-2) are: • To assess the clinical activity of BT5528 in patients with selected adenocarcinoma non small cell lung cancer (NSCLC), or other tumor subtype(s) identified as positive for EphA2 tumor expression as a monotherapy (Part B-1) and in combination with nivolumab (Part B-2) using RECIST 1.1 |
Los objetivos principales del aumento escalonado de la dosis (partes A-1 y A-2) son: • Evaluar la seguridad y la tolerabilidad de BT5528 en pacientes con tumores malignos sólidos avanzados asociados a la expresión de EphA2 o tumores identificados como positivos para expresión tumoral de EphA2 en monoterapia (parte A-1) y en combinación con nivolumab (parte A-2). • Definir la dosis máxima tolerada (DMT) de BT5528, en caso de observarse, y determinar una dosis recomendada para la fase II (DRF2) en monoterapia (parte A-1) y en combinación con nivolumab (parte A-2). Los objetivos principales de las ampliaciones (partes B-1 y B-2) son: • Evaluar la actividad clínica de BT5528 en pacientes con determinado cáncer de pulmón no microcítico (CPNM) de tipo adenocarcinoma, u otros subtipos tumorales identificados como positivos para la expresión tumoral de EphA2 en monoterapia (parte B-1) y en combinación con nivolumab (parte B-2) conforme a los criterios RECIST 1.1. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the escalation (Parts A-1 and A-2) : • To assess preliminary signals of anti-tumor activity achieved with BT5528 administration in patients with advanced solid tumor malignancies associated with EphA2-expression and/or specified tumors identified as positive for EphA2 tumor expression as a monotherapy (Parts A-1) and in combination with nivolumab (Parts A-2) • To determine pharmacokinetic parameters of BT5528 and MMAE (as appropriate) • To determine incidence of anti-drug antibody development The secondary objectives of the expansions (Parts B-1 and B-2) study are: • To assess safety and tolerability of BT5528 in patients with selected adenocarcinoma NSCLC, or other tumor subtype(s) identified as positive for EphA2 tumor expression indications as a monotherapy (Part B-1) and in combination with nivolumab (Part B-2) • To determine pharmacokinetic parameters of BT5528 and MMAE (as appropriate) • To determine incidence of anti-drug antibody development |
Los objetivos secundarios de la escalada(Partes A-1 y A-2):•Evaluar las señales preliminares de la actividad antitumoral lograda con la administración de BT5528 en pacientes con neoplasias malignas de tumores sólidos avanzados asociados con la expresión de EphA2 y o tumores especificados identificados como positivos para la expresión del tumor de EphA2 como monoterapia y en combinación con nivolumab•Para determinar los parámetros farmacocinéticos de BT5528 y MMAE•Para determinar la incidencia del desarrollo de anticuerpos antidrogas. Los objetivos secundarios del estudio de expansiones (PartesB-1 y B-2) son:•Evaluar la seguridad y tolerabilidad de BT5528 en pacientes con CPCNP de adenocarcinoma seleccionado u otro subtipo(s) de tumor identificado como positivo para indicaciones de expresión tumoral EphA2 como monoterapia y en combinación con nivolumab•Para determinar los parámetros farmacocinéticos de BT5528 y MMAE•Para determinar la incidencia del desarrollo de anticuerpos antidrogas |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent; at least 18 years of age 2. ECOG Performance Status score of 0 or 1; measurable disease per RECIST v1.1 3. Acceptable organ function: - Creatinine clearance ≥50 mL/min by Cockcroft-Gault equation or 24-hour urine collection - Total bilirubin ≤1.5 × ULN - Serum albumin ≥2.5 g/dL - AST ≤2.5 × ULN or ≤5 × ULN in presence of liver metastases - ALT ≤2.5 × ULN or ≤5 × ULN in presence of liver metastases - INR <1.3 or ≤ institutional ULN 4. Acceptable hematologic function (no red blood cell or platelet transfusions or growth factors allowed within 4 weeks of first dose of BT5528): - Hemoglobin ≥9 g/dL - ANC ≥1500 cells/mm3 - Platelet count ≥75,000 cells/mm3 5. Negative pregnancy test for women of childbearing potential. Male patients with female partners of childbearing potential and female patients of childbearing potential must follow highly effective contraception (oral and hormonal contraceptives allowed) at least as conservative as Clinical Trial Facilitation Group recommendations for less than 1% failure rate during participation in the study and for 6 months after last dose of study drug. Male patients must refrain from donating sperm during study participation and for 6 months after last dose of study drug and women must not breastfeed or donate eggs. 6. Availability of archived tumor samples within 12 months prior to the date of the first dose of BT5528 or willingness to provide fresh tumor biopsy during screening. 7. Life expectancy ≥12 weeks 10. Willing and able to comply with protocol and study procedures.
Additional Inclusion Criteria – Part A 1. Patients with metastatic recurrent histologically confirmed malignant solid tumor who must have exhausted all appropriate treatment options per local guidelines and must have failed at least one prior line of therapy with evidence of radiographic progression on the most recent line of therapy. If applicable, patients who received prior immunotherapy, the last dose must have been at least 28 days prior to the first dose of BT5528 study treatment. Patients with pancreatic cancer are allowable but are planned for less than 50% of total patients enrolled in each escalation cohort. The Sponsor or SRC may decide to require enrollment of specific tumor types or subtypes at any point during the escalation if it is felt necessary to enrich the evaluation of biomarkers, safety or PK in a specific tumor type. 2.Patients enrolling in Cohort 4 or later for the Part A-1 monotherapy, or enrolling in Cohort 3 or later for the Part A-2 combination therapy, must have tumor tissue (fresh or archived) submitted to central laboratory with confirmation of positive EphA2 tumor expression prior to initiating study treatment. Patients with Ovarian cancer enrolling in Cohort 4 or later for the Part A-1 monotherapy, or enrolling in Cohort 3 or later for the Part A-2 combination therapy must have tumor tissue (fresh or archived) submitted to central laboratory for retrospective analysis of EphA2 tumor expression but may be enrolled without prior confirmation of EphA2 expression.
Additional Inclusion Criteria – Part B 1.Patients with metastatic recurrent disease histologically confirmed to be an adenocarcinoma subtype of NSCLC (adeno-NSCLC), or other tumor subtype(s) are eligible and must have exhausted all appropriate treatment options per local guidelines including progression on or after platinum-based chemotherapy; or must not have been a candidate for or must have received any other approved therapies including appropriate treatment for driver mutation disease, if applicable; and must have failed at least one prior line of therapy with evidence of radiographic progression on the most recent line of therapy. If applicable, patients who received prior immunotherapy, the last dose must have been at least 28 days prior to the first dose of BT5528 study treatment. 2. Patients must have tumor tissue (fresh or archived), except where the SRC has waived this requirement, submitted for assessment by central laboratory with confirmation of positive EphA2 tumor expression prior to initiation of BT5528 study treatment. . At least 6 patients per expansion cohort must have at least 1 tumor lesion amenable to biopsy and must be willing to submit tumor tissue for research purposes including the screening tumor sample collected prior to first dose of BT5528 and undergo additional post dose biopsy of tumor tissue and normal tissue (e.g. skin) collected 4 hours – 7 days following any dose of BT5528 within Cycle 1 is preferred, or if not feasible then any later cycle is allowed. A normal tissue (e.g. skin) biopsy is required on the same day, preferably collected as close as possible to the same time as tumor tissue is collected. |
1. Consentimiento informado por escrito;al menos 18 años de edad 2. Puntaje de ECOG Performance Status de 0 o 1; enfermedad medible según RECIST v1.1 3. Función de órgano aceptable:- Aclaramiento de creatinina ≥50 ml / min según la ecuación de Cockcroft-Gault o recolección de orina de 24 horas- Bilirrubina total ≤1,5 × LSN- Albúmina sérica ≥2,5 g / dL- AST ≤2,5 × LSN o ≤5 × LSN en presencia de metástasis hepáticas- ALT ≤2,5 × LSN o ≤5 × LSN en presencia de metástasis hepáticas- INR <1,3 o ≤ ULN institucional 4. Función hematológica aceptable (no se permiten transfusiones de glóbulos rojos o plaquetas ni factores de crecimiento dentro de las 4 semanas posteriores a la primera dosis de BT5528):-Hemoglobina ≥9 g / dL- ANC ≥1500 células / mm3- Recuento de plaquetas ≥75.000 células / mm3 5. Prueba de embarazo negativa para mujeres en edad fértil. Los pacientes varones con parejas femeninas en edad fértil y las pacientes mujeres en edad fértil deben seguir métodos anticonceptivos altamente eficaces (se permiten anticonceptivos orales y hormonales) al menos tan conservadores como las recomendaciones del Grupo de facilitación de ensayos clínicos para una tasa de fracaso inferior al 1% durante la participación en el estudio y para 6 meses después de la última dosis del fármaco del estudio. Los pacientes masculinos deben abstenerse de donar esperma durante la participación en el estudio y durante los 6 meses posteriores a la última dosis del fármaco del estudio y las mujeres no deben amamantar ni donar óvulos. 6. Disponibilidad de muestras tumorales archivadas dentro de los 12 meses anteriores a la fecha de la primera dosis de BT5528 o disposición para proporcionar una biopsia tumoral reciente durante la detección. 7. Esperanza de vida≥12 semanas 10. Dispuesto y capaz de cumplir con el protocolo y los procedimientos del estudio. |
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E.4 | Principal exclusion criteria |
1. Chemotherapy treatments within 14 days prior to first dose of study treatment. For other anticancer treatments, treatment within 28 days or 5 half-lives, whichever shorter. If NSCLC with EGFRmt, osimertinib or other TKI treatments or cytotoxic chemotherapy within 14 days prior to first dose of study treatment. Prior toxicities must have resolved to grade 1 per CTCAE v 5.0 (except alopecia which must be no greater than Grade 2). For immunotherapy, including immune checkpoint inhibitors, within 28 days prior to the first dose of study treatment. 2. Experimental treatments within 4 weeks of first dose of BT5528 study treatment. 3. Current treatment with strong inhibitors or inducers of CYP3A4 or strong inhibitors of P-gp including herbal- or food-based. 4. Known sensitivity to any of the ingredients of investigational product or MMAE. 5. Significant medical condition, life-threatening illness, active uncontrolled infection or organ system dysfunction (such as ascites, coagulopathy, encephalopathy), or other reasons which could compromise patient’s safety, or interfere with or compromise study outcome integrity including consideration of gastrointestinal, skin and pulmonary co-morbidities and including review of screening chest CT to ensure no clinically significant co-morbidities. 6. Major surgery (excluding placement of vascular access) within 4 weeks of first dose of BT5528 study treatment and must have recovered adequately prior to starting study therapy 7. Receipt of live vaccine within 30 days of study treatment 8. Uncontrolled, symptomatic brain metastases (must have stable neurologic status following local therapy for at least 4 weeks without use of steroids or on stable or decreasing dose of less than or equal to 10 mg daily prednisone or equivalent and must be without neurologic dysfunction that would confound evaluation of neurologic and other AEs.) 9. Patients with uncontrolled hypertension (systolic BP ≥139 mmHg; diastolic BP ≥89 mmHg) prior to first dose of BT5528 study treatment (must have been in stable control for at least 3 months) 10. History or current evidence of any condition, therapy or laboratory abnormality that might confound study results , interfere with patient’s participation, or is not in the best interest of the patient to participate including but not limited to: - Patients with history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, congestive heart failure or symptoms of NYHA Class III-IV documented within 6 months prior to first dose of BT5528 or: i. Mean resting QTcF >470 msec ii. Any factors that increase risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age, or any concomitant medication known to prolong the QT interval iii. Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECGs, e.g., complete left bundle branch block, third degree heart block 11. Known HIV or AIDS 12. Patients with a positive hepatitis B surface antigen and/or anti-hepatitis B core antibody. Patients with a negative PCR assay are permitted with appropriate antiviral therapy 13. Active hepatitis C infection with positive viral load if hepatitis C virus antibody positive (if antibody is negative then viral load not applicable). Patients who have been treated for hepatitis C infection can be included if they have documented sustained virologic response of ≥12 weeks. 14. Thromboembolic events and/or bleeding disorders within 3 months (e.g., deep vein thrombosis or pulmonary embolism) prior to the first dose of BT5528 study treatment. 15. History of another malignancy within 3 years before the first dose of BT5528, or any evidence of residual disease from a previously diagnosed malignancy (excluding adequately treated with curative intent basal cell carcinoma, squamous cell of the skin, cervical intraepithelial neoplasia/cervical carcinoma in situ or melanoma in situ or ductal carcinoma in situ of the breast). 16. Systemic anti-infective treatment or fever within the last 14 days prior to first dose of BT5528 study treatment. 17. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures
Additional Exclusion Criteria Part A-2 and B-2 Nivolumab Combination Cohorts: 1. Prior intolerance to immune checkpoint inhibitor 2. Known hypersensitivity to checkpoint inhibitor therapy 3. Prior organ transplant (including allogeneic) 4. Diagnosis of clinically relevant immunodeficiency 5. Active systemic infection requiring therapy 6. More than 10 mg daily prednisone equivalent or other strong immunosuppressant 7. History of autoimmune disease except alopecia or vitiligo 8. History of interstitial lung disease |
1.Tratamientos de quimioterapia en los 14días anteriores a la primera dosis del tratamiento del estudio. En el caso de otros tratamientos antineoplásicos,tratamiento en el plazo de 28días o 5semividas,lo que suponga menos tiempo. En caso de CPNM con mutación del EGFR,osimertinib u otros inhibidores de las tirosina-cinasas o quimioterapia citotóxica en los 14días previos a la primera dosis del tratamiento del estudio.Los efectos tóxicos previos deberán haberse resuelto a un grado1 según los criterios terminológicos comunes para acontecimientos adversos, versión5.0.Inmunoterapia,incluidos inhibidores de puntos de control inmunológico,en los 28 días previos a la primera dosis del tratamiento del estudio.2.Tratamiento experimental en las 4semanas previas a la primera dosis del tratamiento del estudio con BT5528.3.Tratamiento presente con inhibidores o inductores potentes de la enzima CYP3A4 o inhibidores potentes de la gp-P,incluidos productos de herbolario o alimentos.4.Sensibilidad conocida a cualquiera de los componentes del producto en investigación o monometil auristatinaE.5Enfermedad importante,enfermedad potencialmente mortal,infección activa no controlada o disfunción orgánica u otros motivos que,en opinión del investigador,podrían comprometer la seguridad del paciente o interferir o comprometer la integridad de los criterios de valoración del estudio, incluida la consideración de enfermedades concomitantes digestivas,cutáneas y pulmonares, y la revisión de la TC de tórax de selección para garantizar la ausencia de enfermedades concomitantes clínicamente significativas.6.Cirugía mayor en las 4semanas previas a la primera dosis del tratamiento del estudio con BT5528, que deberá haberse recuperado debidamente antes de iniciar el tratamiento del estudio.7.Recepción de una vacuna de microorganismos vivos en los 30días previos al tratamiento del estudio.8. Metástasis cerebrales sintomáticas no controladas.9.Pacientes con hipertensión no controlada (presión arterial [PA] sistólica ≥ 139 mm Hg; PA diastólica ≥ 89 mmHg) antes de la primera dosis deltratamiento del estudio con BT5528 (debe haber estado en control estable durante al menos 3meses).10.Antecedentes o signos actuales de cualquier estado,tratamiento o anomalía analítica que,en opinión del investigador,podría confundir los resultados del estudio,dificultar la participación del paciente o motivar que la participación no sea lo más conveniente para el paciente,por ejemplo:Antecedentes de episodio vascular cerebral,angina inestable,infarto de miocardio,insuficiencia cardíaca congestiva o síntomas de claseIII-IV de la New York Heart Association documentados en los 6meses previos a la primera dosis de BT5528,o bien:i.Media del intervalo QT corregido en reposo >470ms.ii.Cualquier factor que aumente el riesgo de prolongación del intervalo QTc o el riesgo de episodios arrítmicos,por ejemplo,insuficiencia cardíaca,hipopotasemia, síndrome de QT largo congénito,antecedentes familiares de síndrome de QT largo o muerte súbita inexplicada con menos de 40años o cualquier medicación concomitante que se sepa que prolonga el intervalo QT.iii.Cualquier anomalía clínicamente importante del ritmo,la conducción o la morfología de los electrocardiogramas en reposo,como bloqueo completo de rama izquierda o bloqueo cardíaco de tercer grado.11.Infección conocida por el virus de la inmunodeficiencia humana o síndrome de inmunodeficiencia adquirida.12.Positividad del antígeno de superficie del virus de la hepatitisB o de anticuerpos contra el antígeno central del virus de la hepatitisB.Los pacientes con un resultado negativo en la reacción en cadena de la polimerasa podrán participar si reciben el tratamiento antiviral adecuado.13.Infección activa por el virus de la hepatitisC con carga viral positiva si hay anticuerpos contra el virus de la hepatitisC positivos(si los anticuerpos son negativos, la carga viral no procede).Podrán participar pacientes que hayan recibido tratamiento para la infección por el virus de la hepatitisC si presentan respuesta virológica sostenida documentada.14.Episodios tromboembólicos o trastornos hemorrágicos en los 3meses previos a la primera dosis del tratamiento del estudio con BT5528.15.Antecedentes de otra neoplasia maligna en los 3años previos a la primera dosis de BT5528 o cualquier signo de enfermedad residual de una neoplasia maligna diagnosticada previamente.16.Tratamiento antiinfeccioso sistémico o fiebre en los 14días previos a la primera dosis del tratamiento del estudio con BT5528.17.Enfermedades psicológicas o situaciones familiares,sociológicas o geográficas que no permitan cumplir el protocolo o los procedimientos de seguimiento descritos en el protocolo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Part A-1 and A-2 (escalations): Treatment-emergent adverse events (TEAEs), laboratory, ECG and vital sign abnormalities using CTCAE v5.0 criteria
2. Part A-1 and A-2 (escalations): Dose-limiting toxicities as defined in the protocol
3. Part B-1 and B-2 (expansions): Objective response rate (ORR), duration of response (DOR), clinical benefit rate (CR + PR + SD ≥4 months), time to tumor progression (TTP), progression-free survival time (PFS), rate of PFS at 6 mos., rate of OS at 12 mos. all assessed per RECIST v1.1 criteria |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. From Cycle 1 Day 1 (each cycle is 28 days) until 30 days post last dose, safety reported as incidence of treatment-emergent adverse events
2. At the end of Cycle 1
3. PFS time: From Cycle 1 Day 1 until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months)
PFS at 6 months: From Cycle 1 Day 1 until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months)
Rate of OS at 12 months: From Cycle 1 Day 1 until death or loss of follow-up or withdrawal of consent (assessed every 3 months for up to 1 year) |
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E.5.2 | Secondary end point(s) |
1. Part A-1 and A-2 (escalations): Objective response rate (ORR), duration of response (DOR), clinical benefit rate (CR + PR + SD ≥4 months), time to tumor progression (TTP), progression-free survival time (PFS), rate of PFS at 6 mos., rate of OS at 12 mos. all assessed per RECIST v1.1 criteria
2. Part B-1 and B-2 (expansions): Treatment-emergent adverse events (TEAEs), laboratory, ECG and vital sign abnormalities using CTCAE v5.0 criteria
3. All Parts: Plasma concentrations of BT5528 and MMAE with appropriate pharmacokinetic derivations such as Cmax, Cmin, AUC, and elimination t½
4. All Parts: Measurement of ADA. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months)
PFS at 6 months: From Cycle 1 Day 1 until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months)
Rate of OS at 12 months: From Cycle 1 Day 1 until death or loss of follow-up or withdrawal of consent (assessed every 3 months up to 12 months)
2. From Cycle 1 Day 1 until 30 days post last dose
3. From Cycle 1, and end of each cycle until disease progression or death or new anti-cancer therapy or withdrawal of consent (assessed up to 12 months ) |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | 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 | 4 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 |
Korea, Republic of |
United States |
Belgium |
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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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 | 8 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 4 |