| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsed or Refractory Multiple Myeloma (RRMM) |
| Mieloma múltiple recidivante o resistente (MMRR) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Multiple Myeloma |
| Mieloma múltiple |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10028228 |
| E.1.2 | Term | Multiple myeloma |
| 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 progression-free survival (PFS) based on the International Myeloma Working Group (IMWG) response criteria (Kumar 2016). |
| Comparar la SSP de los pacientes conforme a los criterios de respuesta del Grupo Internacional de Trabajo del Mieloma (International Myeloma Working Group, IMWG) (Kumar 2016). |
|
| E.2.2 | Secondary objectives of the trial |
Secondary (to compare in the SPd Arm versus the EloPd Arm):
- To compare clinical efficacy
- To assess the safety and tolerability of SPd versus EloPd in patients with RRMM
- To compare the impact of treatment on HR-QoL
- To characterize PK of selinexor and pomalidomide.
Exploratory objective:
To identify predictive biomarkers of response to treatment and explore treatment mechanism of action in patients with RRMM. |
Secundarios (para comparar el grupo de SPd con el grupo de EloPd):
- Comparar la eficacia clínica
- Evaluar la seguridad y tolerabilidad de SPd frente a EloPd en pacientes con MMRR
- Comparar el efecto del tratamiento sobre la CdVRS
- Caracterizar la FC de selinexor y pomalidomida
Objetivo exploratorio:
Identificar biomarcadores predictivos de la respuesta al tratamiento y explorar el mecanismo de acción del tratamiento en pacientes con
MMRR |
|
| 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 |
Correlative Study #1: Immuno-characterization and preclinical development of multi-specific nanobodies (optional)
Immune cells of patients with MM undergoing selinexor treatment will be profiled at different timepoints (after inclusion and 6 months of treatment or time point of progression). For identification of the most relevant targets via multiparametric flow cytometry analysis of the TIGIT axis and purinergic signaling, two bone marrow and peripheral blood aspirates per patient (20 patients on selinexor, 20 patients without selinexor) will be assessed.
The monitoring of immune cell-proliferation and their conversion of ATP to ADO with and without blockade of CD38, CD39 and CD73 by using nanobodies will be assessed for bone marrow and peripheral blood aspirates (5 patients on selinexor, 5 patients without selinexor) by analyses of the cell-titer glo, AMP glo and HPLC.
The evaluation of the functional relevance of the multi-enzymatic inhibition with a combinatorial blockade of the TIGIT pathway will be conducted by using half-life extended Nbs and hcAbs lacking Fc effector function (LALAPG mutants) to block CD38, CD39 and CD73 alone or in combination to reduce conversion of proinflammatory ATP to anti-inflammatory ADO.
Established cancer cell killing assays will be performed for evaluation of the multi-specific Nbs using allogeneic T cells sorted from primary MM samples (bone marrow and peripheral blood aspirate of 10 patients on selinexor, 10 patients without selinexor), healthy donors and MM cell cell lines.
Direct targeting of CD38, CD39 and CD73 alone and in combination with inhibition of TIGIT, PVR, PVRL2 expressing cells like MM cells and regulatory T cells by ADCC and CDC will be evaluated in vitro using new engineered hcAbs carrying wildtype or enhanced Fc effector functions (ADES mutants). ADCC assays with NK-92-CD16 effector cell and CDC assays using human serum as source of complement (bone marrow and peripheral blood aspirate per patient (12 patients on selinexor, 12 patients without selinexor) will be performed.
Correlative Study #2: Monitoring Multiple myeloma bone marrow inflammation at the single cell level (optional)
The effects of selinexor treatment on the pro-tumor stromal inflammation and on the myeloma immune environment will be analyzed. Specifically: identification of changes in the stromal and immune microenvironment, as well as in the tumor cells in response to selinexor treatment; identification of changes in bone marow inflammation in patients responding to selinexor therapy.
Single cell RNA sequencing will be used to map the response of inflammatory stromal cells, together with the bone marrow immune environment and the myeloma cells to selinexor at the single cell level. Multiplex immunoassays will be performed to track bone marrow inflammation.
Experiments will be performed on set of patients to identify alterations associated with selinexor response. Patients reaching MRD-negativity will be compared to patients who do not reach MRD-negativity.
Correlative Study #3: Lambda translocations in RRMM patients treated with SPd vs EPd (optional)
Using an additional FISH probe (XL 22q11 Ig lambda Break Apart, Metasystems) the percentage of lambda translocated patients in the RRMM setting will be defined and it will be investigated whether Selinexor or Elotuzumab added to IMiDs backbone can revert the high-risk behavior of lambda translocated patients.
Correlative Study #4: Bone marrow aspirates (mandatory)
A portion of the bone marrow aspirates collected at Screening will be shipped to a central laboratory for exploratory studies. This portion of bone marrow aspirate will have CD138 + and CD138- cells isolated. They are to be frozen in DMSO until sequencing of RNA and DNA is performed. Studies may include transcriptomic, genomic, and/or proteomic analyses to identify predictive biomarkers of selinexor response and to characterize the mechanism of action of selinexor. |
|
| E.3 | Principal inclusion criteria |
Patients are eligible to be included in the trial only if they meet all of the following criteria:
1. Relapsed or refractory MM per IMWG criteria with measurable disease defined by at least 1 of the following:
a. Serum M-protein > or =0.5 g/dL (> or =5 g/L) by serum electrophoresis (SPEP) or, for immunoglobulin (Ig) A or D myeloma, by quantitative serum IgA or IgD levels
b. Urinary M-protein excretion > or =200 mg/24 hours
c. Serum free light chain (FLC) > or =100 mg/L, provided that the FLC ratio is abnormal (normal FLC ratio: 0.26 to 1.65).
2. Received at least 1 and no more than 4 lines of prior anti-MM regimens. Induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 regimen.
3. Patients must have prior therapy which must include an anti-CD38 mAb and > or =2 consecutive cycles of the following agents given alone or in combinations: lenalidomide, proteasome inhibitor.
4. Patients must have prior therapy with anti-CD38 mAb in one of the following ways:
a. Received anti-CD38 mAb as their immediate last treatment prior to study entry (50% of patients)
b. Received prior anti-CD38 mAb other than in immediate last treatment prior to study entry (50% of patients)
5. Eastern Cooperative Oncology Group (ECOG) performance status of < or =2.
6. Resolution of any clinically significant non-hematological toxicities (if any) from previous treatments to Grade < or =1 by Cycle 1 Day 1 (C1D1). Patients with clinically significant Grade 2 neuropathy from previous treatments may be included.
7. Adequate hepatic function within 28 days prior to C1D1:
a. Total bilirubin <2 × upper limit of normal (ULN) (except patients with Gilbert’s syndrome who must have a total bilirubin of <3 × ULN)
b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 × ULN.
8. Adequate renal function within 28 days prior to C1D1 (estimated creatinine clearance [CrCl] of ≥15 mL/min (not requiring dialysis), calculated using the formula of Cockcroft and Gault (provided in Section 12.5.8) or measured by 24-hour urine collection).
9. Adequate hematopoietic function within 7 days prior to C1D1 defined as absolute neutrophil count > or =1.5x 10^9/L, hemoglobin > or =8.5 g/dL and platelet count > or =100 x 10^9/L (patients for whom <50% of bone marrow nucleated cells are plasma cells) or > or =75 x 10^9/L (patients for whom > or =50% of bone marrow nucleated cells are plasma cells).
a. Patients receiving hematopoietic growth factor support, including erythropoietin, darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and platelet stimulators (e.g., eltrombopag, romiplostim, or interleukin-11) must have a 2-week interval between growth factor support and the Screening assessments, but they may receive
growth factor support during the study.
b. Patients must have:
• At least a 2-week interval from the last red blood cell (RBC) transfusion prior to the Screening hemoglobin assessment, and
• At least a 1-week interval from the last platelet transfusion prior to the Screening platelet assessment.
However, patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study.
10. Female patients of childbearing potential must have a negative serum pregnancy test within 10 to 14 days and a second test within 24 hours prior to the first dose of study treatment. Female patients of childbearing potential and fertile male patients who are sexually active must use highly effective methods of contraception throughout the study and for 3 months following the last dose of study treatment.
11. Age > or =18 years at the time of signing informed consent.
12. Written informed consent signed in accordance with federal, local, and institutional guidelines.
13. Patients must be able and willing to take enteric-coated aspirin according to clinical practice, or if history of prior thrombotic disease, must be fully anticoagulated with warfarin (INR 2-3) or be treated with full-dose, low molecular weight heparin, as if to treat deep venous thrombosis (DVT)/pulmonary embolism (PE) at the Investigator's discretion. For patients on warfarin, INR should be repeated as clinically indicated. |
1. MM recidivante o resistente y enfermedad medible de acuerdo con los criterios del IMWG, definida por al menos 1 de los siguientes valores:
a. Proteína M en suero > o =0,5 g/dl (> o =5 g/l) determinada mediante electroforesis de proteínas séricas (EFPS) o, en caso de mieloma de inmunoglobulinas (Ig) A o D, mediante análisis cuantitativo de los niveles séricos de IgA o IgD
b. Excreción urinaria de proteína M > o =200 mg/24 horas c. Cadenas ligeras libres (CLL) en suero > o =100 mg/l, siempre que el cociente de CLL sea
anómalo (cociente de CLL normal: 0,26 a 1,65)
2. Al menos 1 y no más de 4 pautas terapéuticas previas para el MM. El tratamiento de inducción seguido de un trasplante de células madre y el tratamiento de consolidación/mantenimiento se considerarán 1 pauta.
3. Tratamiento previo con un AcM anti-CD38 y un número de ciclos consecutivos > o =2 de los siguientes fármacos administrados en monoterapia o en combinación: lenalidomida, inhibidor del proteasoma.
4. Tratamiento previo con un AcM anti-CD38 de una de las siguientes formas:
a. AcM anti-CD38 como último tratamiento inmediatamente anterior a la incorporación al estudio (50 % de los pacientes)
b. AcM anti-CD38 previo, pero no como último tratamiento inmediatamente anterior a la incorporación al estudio (50 % de los pacientes)
5. ECOG < o = 2
6. Resolución de cualquier toxicidad no hematológica clínicamente significativa debida a los tratamientos previos hasta un grado < o = 1 para el día 1 del ciclo 1 (D1C1). Los pacientes con neuropatía de grado 2 clínicamente significativa de tratamientos anteriores pueden ser incluidos.
7. Función hepática adecuada en los 28 días anteriores al D1C1:
a. Bilirrubina total <2 × LSN (excepto en pacientes con síndrome de Gilbert, que deben tener un valor de bilirrubina total <3 × LSN)
b. Aspartato aminotransferasa (AST) y alanina aminotransferasa (ALT) <2,5 × LSN
8. Función renal adecuada en los 28 días anteriores al D1C1 (aclaramiento de creatinina [ACr] estimado > o =15 ml/min [sin necesidad de diálisis], calculado mediante la fórmula de Cockcroft y Gault o determinado mediante recogida de orina de 24 horas).
9. Función hematopoyética adecuada en los 7 días previos al D1C1, definida por un recuento absoluto de neutrófilos > o =1,5 × 10 9 /l, hemoglobina > o =8,5 g/dl y recuento de plaquetas > o =100 × 10 9 /l (pacientes en que una proporción <50 % de las células nucleadas de la médula ósea son células plasmáticas) o > o =75 × 10 9 /l (pacientes en que una proporción > o =50 % de las células nucleadas de la médula ósea son células plasmáticas).
a. Los pacientes que reciban factores de crecimiento hematopoyético, como eritropoyetina, darbepoetina, factor estimulante de colonias de granulocitos (G-CSF), factor estimulante de colonias de granulocitos y macrófagos (GM-CSF) y estimulantes de plaquetas (p. ej., eltrombopag, romiplostim o interleucina-11), deben dejar transcurrir un intervalo de 2 semanas entre la administración del factor de crecimiento y las evaluaciones de la selección, sin embargo, pueden recibir el factor de crecimiento durante el estudio.
b. Los pacientes deben dejar transcurrir:
− un intervalo de al menos 2 semanas entre la última transfusión de eritrocitos y la evaluación de hemoglobina de la selección, y
− un intervalo de al menos 1 semana entre la última transfusión de plaquetas y la evaluación de plaquetas de la selección.
Sin embargo, los pacientes pueden recibir transfusiones de eritrocitos y/o plaquetas, según esté clínicamente indicado conforme a las normas del centro durante el estudio.
10. Las pacientes con capacidad de concebir deben dar negativo en una prueba de embarazo en suero realizada en los 10 a 14 días anteriores a la primera dosis del tratamiento del estudio y dar negativo en una segunda prueba realizada en las 24 horas anteriores a la primera dosis del tratamiento del estudio. Las pacientes con capacidad de concebir y los pacientes fértiles sexualmente activos deben utilizar métodos anticonceptivos muy eficaces durante todo el estudio y durante 3 meses después de la última dosis del tratamiento del estudio.
11. Edad > o =18 años
12. Consentimiento informado por escrito
13. Capacidad y disposición para tomar ácido acetilsalicílico en comprimidos gastrorresistentes de acuerdo con la práctica clínica o, en caso de antecedentes de enfermedad trombótica, estar en anticoagulación total con warfarina (índice internacional normalizado [INR] 2-3) o recibir tratamiento con dosis completas de heparina de bajo peso molecular, como para tratar la trombosis venosa profunda (TVP)/embolia pulmonar (EP), a criterio del investigador. Para pacientes en tratamiento con Warfarina, el INR debe repetirse según indicación clínica. |
|
| E.4 | Principal exclusion criteria |
1. Smoldering MM.
2. Plasma cell leukemia.
3. Documented active systemic amyloid light chain amyloidosis.
4. Active central nervous system MM.
5. Prior treatment with a selective inhibitor of nuclear export (SINE) compound, including selinexor.
6. Prior treatment with pomalidomide and/or elotuzumab.
7. Any concurrent medical condition or disease that is likely to interfere with study procedures.
8. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to C1D1. Patients on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable.
9. Known intolerance, hypersensitivity, or contraindication to any of the study treatments.
10. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy (including investigational therapies and high dose dexamethasone [i.e., 40 mg daily for 4 days per week]) < or = 2 weeks prior to C1D1. Patients on long-term glucocorticoids during Screening
do not require a washout period but must be able to tolerate the specified dexamethasone dose in this study.
11. Prior autologous stem cell transplantation <60 days or allogeneic stem cell transplantation <4 months prior to C1D1.
12. Major surgery within 4 weeks prior to C1D1.
13. Active graft versus host disease after allogeneic stem cell transplantation.
14. Pregnant or breastfeeding females.
15. In the opinion of the Investigator, patients who are below their ideal body weight and would be unduly impacted by changes in their weight.
16. Clinically significant cardiac disease, including:
a. Myocardial infarction within 6 months before C1D1, or unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV).
b. Uncontrolled cardiac arrhythmia (CTCAE v. 5.0 Grade 2 or higher) or clinically significant ECG abnormalities.
c. Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF [Protocol APPENDIX 4]) >470 msec.
17. Any active gastrointestinal dysfunction interfering with the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment.
18. Any active, serious psychiatric, medical, or other conditions/situations that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give
informed consent.
19. Contraindication to any of the required concomitant drugs or supportive treatments.
20. Patients unwilling or unable to comply with the protocol. |
1. MM asintomático.
2. Leucemia de células plasmáticas.
3. Amiloidosis de cadenas ligeras sistémica activa documentada.
4. MM activo del sistema nervioso central.
5. Tratamiento previo con un inhibidor selectivo de la exportación nuclear (SINE), como selinexor.
6. Tratamiento previo con pomalidomida y/o elotuzumab.
7. Cualquier trastorno o enfermedad concurrente que sea probable que interfiera en los procedimientos del estudio.
8. Infección activa no controlada que requiera antibióticos, antivíricos o antifúngicos por vía parenteral en la semana anterior al D1C1. Se aceptará a los pacientes que reciban profilaxis antibiótica o que presentan una infección controlada en el plazo de 1 semana antes del D1C1.
9. Intolerancia, hipersensibilidad o contraindicación conocidas a cualquiera de los tratamientos del estudio.
10. Radioterapia, quimioterapia, inmunoterapia o cualquier otro tratamiento antineoplásico, incluidos los tratamientos en investigación y dexametasona a dosis alta [es decir, 40 mg/día durante 4 días por semana]), en un plazo < o = 2 semanas antes del D1C1 Los pacientes que, en la selección, estén recibiendo tratamiento a largo plazo con glucocorticoides no requieren un periodo de reposo farmacológico, pero deben ser capaces de tolerar la dosis especificada de dexametasona en este estudio.
11. Autotrasplante de células madre en un plazo <60 días o alotrasplante de células madre en un plazo <4 meses antes del D1C1.
12. Intervención de cirugía mayor en las 4 semanas anteriores al D1C1.
13. Enfermedad de injerto contra huésped activa tras alotrasplante de células madre.
14. Mujeres embarazadas o en periodo de lactancia.
15. Pacientes que, en opinión del investigador, están por debajo de su peso corporal ideal y que se verían indebidamente afectados por los cambios en su peso.
16. Cardiopatía clínicamente significativa, a saber:
a. Infarto de miocardio en los 6 meses anteriores al D1C1 o enfermedad/afección inestable o no controlada que está asociada a la función cardíaca o que la afecta (p. ej., angina inestable, insuficiencia cardíaca congestiva de clase III-IV de la Asociación de Cardiología de Nueva
York [New York Heart Association, NYHA]).
b. Arritmia cardíaca no controlada (de grado 2 o superior según los CTCAE v5.0) o anomalías clínicamente significativas en el ECG.
c. ECG de 12 derivaciones en la selección que muestra un intervalo QT inicial corregido mediante la fórmula de Fridericia (QTcF) >470 ms (APÉNDICE 4).
17. Cualquier disfunción gastrointestinal activa que interfiera en la capacidad del paciente para tragar comprimidos o en la absorción del tratamiento del estudio.
18. Cualquier situación o trastorno psiquiátrico, físico o de otro tipo, activo y grave que, en opinión del investigador, pudiera interferir en el tratamiento, el cumplimiento terapéutico o la capacidad de dar el consentimiento informado.
19. Contraindicación de cualquiera de los fármacos concomitantes o tratamientos complementarios requeridos.
20. Falta de disposición o de capacidad para cumplir con el protocolo. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression-free survival (PFS), defined as time from date of randomization until the date of first confirmed progressive disease (PD), per IMWG response criteria, or death due to any cause, whichever occurs first. |
| SSP, definida como el tiempo transcurrido desde la fecha de la aleatorización hasta la fecha de la primera confirmación de progresión de la enfermedad (PE) conforme a los criterios de respuesta del IMWG o la muerte por cualquier causa, lo que suceda antes. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Throughout the course of the study. |
| A lo largo del curso del ensayo |
|
| E.5.2 | Secondary end point(s) |
Key Secondary Efficacy Endpoints:
• Overall Response Rate (ORR), defined as any response > or = PR (i.e., PR [partial response], VGPR [very good partial response], CR ([complete response], or sCR [stringent complete response])
• Overall survival (OS)
Additional Secondary Endpoints:
• Clinical benefit rate (CBR), defined as response > or = MR
• Duration of response (DOR)
• Time to next treatment (TNT)
• Time to initial response (TTR)
• Time to best response (TTBR)
• Time to progression (TTP)
• Time to second disease progression (PFS2)
Safety and tolerability of study treatment will be evaluated based on AE reports, vital signs, clinical laboratory results, electrocardiogram (ECG) and physical examination findings, by means of the occurrence, nature, and severity of AEs as categorized by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Patient-reported quality of life (QoL), as measured by the European Organization for Research and Treatment of Cancer- quality of life (EORTC-QLQ-C30), EORTC-QLQ-MY20, and EQ-5D-5L instruments.
Selinexor and pomalidomide PK parameters, estimations of maximum plasma concentration (Cmax), area under the concentration versus time curve (AUC), and apparent clearance (CL/F), if feasible.
Exploratory end points:
Correlative studies (see Protocol Appendix 5) to evaluate response to treatment with selinexor as related but not limited to the following:
• Cytogenetic and fluorescence in situ hybridization (FISH) of prognostic biomarkers, including (p53 abnormalities (i.e., del 17p13) and other chromosomal aberrations (e.g., t[4;14], t[14;16], amp[1q21], del1p32 and MM cytogenetic classifications.
• Genetic analysis including but not limited to DNA and RNA sequencing of bone marrow samples. |
Criterios de valoración secundarios de la eficacia clave:
• TRG, definida como cualquier respuesta > o = RP (es decir, RP [respuesta parcial], RPMB [respuesta parcial muy buena], RC ([respuesta completa] o RCe [respuesta completa estricta])
• Supervivencia global (SG)
Criterios de valoración secundarios adicionales:
• Tasa de beneficio clínico (TBC), definida como respuesta > o =RM
• Duración de la respuesta (DR)
• Tiempo transcurrido hasta el siguiente tratamiento (TST)
• Tiempo transcurrido hasta la respuesta inicial (TRI)
• Tiempo transcurrido hasta la mejor respuesta (TMR)
• Tiempo transcurrido hasta la progresión (TTP)
• Tiempo transcurrido hasta la segunda progresión de la enfermedad (SSP2)
La seguridad y la tolerabilidad del tratamiento del estudio se evaluarán en función de los informes de AA, las constantes vitales, los resultados de los análisis clínicos, el electrocardiograma (ECG) y los hallazgos en la exploración física, por medio de la aparición, la naturaleza y la
intensidad de los AA, clasificados conforme a los Criterios Terminológicos Comunes para Acontecimientos Adversos (Common Terminology Criteria for Adverse Events, CTCAE) v5.0
Calidad de vida (CdV) notificada por el paciente, determinada mediante los instrumentos de calidad de vida de los pacientes con cáncer de la Organización Europea para la Investigación y el Tratamiento del Cáncer (European Organization for Research and Treatment of
Cancer, EORTC), EORTC-QLQ-C30 y EORTC-QLQ-MY20, y el cuestionario EQ-5D-5L
Parámetros FC de selinexor y pomalidomida, estimaciones de la concentración máxima en plasma ( Cmáx ), el área bajo la curva de concentración frente al tiempo (AUC) y el aclaramiento aparente (CL/F), si es viable
Criterios de valoración exploratorios:
Estudios de correlaciones (véase el APÉNCIDE 5) para evaluar la respuesta al tratamiento con selinexor según lo relacionado, pero no limitado a lo siguiente:
• Marcadores pronósticos detectados mediante citogenética e hibridación in situ con fluorescencia (FISH), entre otros, anomalías de p53 (es decir, del[17p13]) y otras aberraciones cromosómicas (p. ej., t[4;14], t[14;16], ganancia/amplificación[1q21], del[1p32] y clasificaciones citogenéticas del MM)
• Análisis genético que incluye, entre otros, secuenciación de ADN y ARN de muestras de médula
ósea |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Throughout the course of the study. |
| A lo largo del curso del ensayo |
|
| 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 | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| impact on health-related quality of life |
|
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
|
| 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 52 |
| 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 |
| United States |
| France |
| Germany |
| Italy |
| Netherlands |
| Spain |
| Greece |
|
| 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
|
| The End of Study (EoS) will be upon completion of the follow-up period for the last patient. This will occur when all patients in the trial have been followed for 36 months after enrollment, has died, has been lost to follow-up, has withdrawn consent, or Sponsor decision to terminate the trial, whichever occurs first. |
| El final del estudio (FdE) será cuando se complete el período de seguimiento del último paciente. Esto ocurrirá cuando todos los pacientes del ensayo hayan sido seguidos durante 36 meses después de la inclusión, hayan fallecido, se hayan perdido para el seguimiento, hayan retirado el consentimiento o el promotor haya decidido terminar el ensayo, lo que ocurra primero. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| 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 | 5 |
| 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 |
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