AZD0901 en participantes con tumores sólidos avanzados que expresan Claudin18.2
Un estudio multicéntrico, abierto y de fase II para evaluar la seguridad, la tolerabilidad, la eficacia, la farmacocinética y la inmunogenicidad de AZD0901 como monoterapia y en combinación con agentes anticancerígenos en participantes con tumores sólidos avanzados que expresan claudina 18.2.
The purpose of this study is to assess the safety, tolerability, efficacy, pharmacokinetics (PK), and immunogenicity of AZD0901 as monotherapy and in combination with anti-cancer agents in participants with locally advanced unresectable or metastatic solid tumours expressing CLDN18.2 .
Descripción general del estudio
Estado
Condiciones
Descripción detallada
This open-label, multi-centre study consists of individual sub studies, each evaluating the safety and tolerability of AZD0901.
Sub study 1 will investigate the safety, tolerability, and anti-tumour activity of AZD0901 monotherapy in participants with advanced or metastatic gastric esophageal cancer expressing CLDN18.2. Participants will receive AZD0901 monotherapy via intravenous (IV) infusion and will be randomised in to one of 2 arms.
Sub study 2 will consist of two parts, a safety run-in and a dose expansion part to investigate the safety and efficacy of AZD0901 in combination with different chemotherapy agents in participants with pancreatic cancer. Substudy 3 will investigate the safety, tolerability, and anti-tumour activity of AZD0901 monotherapy in participants with advanced or metastatic Biliary tract cancer.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
Contactos y Ubicaciones
Estudio Contacto
- Nombre: AstraZeneca Clinical Study Information Center
- Número de teléfono: 1-877-240-9479
- Correo electrónico: information.center@astrazeneca.com
Ubicaciones de estudio
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Melbourne, Australia, 3000
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Murdoch, Australia, WA6150
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Randwick, Australia, 2031
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Ontario
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Kingston, Ontario, Canadá, K7L 2V7
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Toronto, Ontario, Canadá, M5G 2M9
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Quebec
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Montreal, Quebec, Canadá, H3G 1A4
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Sherbrooke, Quebec, Canadá, J1G 2E8
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Gyeonggi-do, Corea del Sur, 13620
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Seoul, Corea del Sur, 03080
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Seoul, Corea del Sur, 06351
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Seoul, Corea del Sur, 05505
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Seoul, Corea del Sur, 03722
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Barcelona, España, 08035
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Madrid, España, 28007
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Madrid, España, 28040
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California
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Orange, California, Estados Unidos, 92868
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Palo Alto, California, Estados Unidos, 94304
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Santa Rosa, California, Estados Unidos, 95403
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Kentucky
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Louisville, Kentucky, Estados Unidos, 40202
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New York
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Commack, New York, Estados Unidos, 11725
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Rhode Island
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Providence, Rhode Island, Estados Unidos, 02903
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Texas
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Houston, Texas, Estados Unidos, 77030
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Tbilisi, Georgia, 0112
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Chūōku, Japón, 104-0045
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Kashiwa, Japón, 227-8577
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Kitaadachi-gun, Japón, 362-0806
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Kōtoku, Japón, 135-8550
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Nagoya, Japón, 464-8681
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Osakasayama-shi, Japón, 589-8511
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George Town, Malasia, 10450
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Johor Bahru, Malasia, 81100
- Terminado
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Kuala Lumpur, Malasia, 59100
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Kuala Selangor, Malasia, 62250
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Kuching, Malasia, 93586
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Chisinau, Moldava, MD-2025
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Krakow, Polonia, 31-501
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Warsaw, Polonia, 02-034
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Changsha, Porcelana, 410013
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Chengdu, Porcelana, 610041
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Glasgow, Reino Unido, G12 0YN
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Leeds, Reino Unido, LS9 7TF
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London, Reino Unido, NW3 2QG
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Oxford, Reino Unido, OX3 7LE
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Bukit Merah, Singapur, 169610
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Singapore, Singapur, 308433
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Singapore, Singapur, 119074
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Singapore, Singapur, 329563
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Kaohsiung City, Taiwán, 80756
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Taichung, Taiwán, 404
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Tainan, Taiwán, 70403
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Taipei, Taiwán, 11217
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Taoyuan, Taiwán, 00333
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
The list below is a summarised eligibility criteria for the study - refer to the study protocol for full criteria.
Master Inclusion Criteria applicable to all sub studies:
- Participant must be ≥ 18 years or the legal age of consent at the time of signing the ICF.
- Participants who are CLDN18.2 positive.
- Must have at least one measurable lesion according to RECIST v1.1.
- ECOG performance status of 0 to 1 with no deterioration over the previous 2 weeks prior first day of dosing.
- Predicted life expectancy of ≥ 12 weeks.
- Adequate organ and bone marrow function as defined by protocol.
- Body weight > 35 kg.
- Participants are willing to comply with contraception requirements.
Sub study 1 Specific Inclusion criteria:
- Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction.
- Advanced or metastatic GC/GEJC.
- Maximum 2 prior lines of systemic treatment for unresectable or metastatic disease.
Sub study 2 Specific Inclusion criteria:
- Participants diagnosed with histologically confirmed metastatic or advanced PDAC.
- Availability of an archival sample or a fresh tumour biopsy taken at screening.
- No prior treatments for unresectable or metastatic disease. Prior neoadjuvant/adjuvant chemotherapy is permitted as long as participants progressed ≥ 6 months (183 days) from the last dose.
Sub study 3 Specific Inclusion criteria
- Histologically confirmed, unresectable advanced, or metastatic adenocarcinoma of biliary tract, including cholangiocarcinoma (intrahepatic or extrahepatic) and gallbladder carcinoma (NOTE: Ampullary cancers are not eligible).
- Documented radiographic or clinical disease progression on or after at least one prior regimen and maximum 2 prior lines of systemic treatment for unresectable or metastatic disease.
Master Exclusion Criteria applicable to all sub studies:
- Unstable or active peptic ulcer disease or digestive tract bleeding including but not limited to clinically significant bleeding in the setting of prior CLDN18.2 directed therapy.
- Participants with clinically significant ascites that require drainage.
- A history of drug-induced non-infectious ILD/pneumonitis.
- Central nervous system metastases or CNS pathology.
- Peripheral neuropathy, sensory, or motor ≥ Grade 2 at screening.
- History of another primary malignancy.
- Prior exposure to any MMAE-based ADC.
- Prior exposure to any CLDN18.2 targeted agents except anti-CLDN18.2 monoclonal antibody.
Sub study 1 Specific Exclusion criteria:
- Participants with HER2-positive (3+ by IHC, or 2+ by IHC, and positive by ISH) or indeterminate GC/GEJC unless they have failed/not tolerated/or are not eligible for standard anti-HER2 therapy, where available.
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events.
- The use of concomitant medications known to prolong the QT/QTc interval.
Sub study 2 Specific Exclusion criteria:
- Known DPD enzyme deficiency based on local testing where testing is SoC.
- Use of strong inhibitor or inducer of UGT1A1.
- Use of strong inhibitors or inducers of CYP3A4.
- Known homozygous for the UGT1A1*28 allele based on local testing where testing is SoC.
Sub study 3 Specific Exclusion criteria
• Clinically significant biliary obstruction that has not resolved before enrollment.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Sub Study 1 - AZD0901 MONOTHERAPY
Sub Study 1 will investigate AZD0901 monotherapy in order to evaluate the safety, tolerability, and efficacy of AZD0901. |
Antibody-drug conjugate/Biologic
Otros nombres:
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Experimental: Sub Study 2 - AZD0901 IN COMBINATION WITH ANTI-CANCER AGENTS IN PANCREATIC DUCTAL ADENOCARCINOMA
Substudy 2 will investigate the safety and efficacy of AZD0901 as first line systemic treatment used in combination with different chemotherapy agents |
Antibody-drug conjugate/Biologic
Otros nombres:
Chemotherapy agents
Otros nombres:
Chemotherapy agents
Otros nombres:
Chemotherapy agents
Otros nombres:
Chemotherapy agents
Otros nombres:
Chemotherapy agents
Otros nombres:
Chemotherapy agents
Otros nombres:
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Experimental: Sub Study 3: AZD0901 MONOTHERAPY IN BILIARY TRACT CANCER
Substudy 3 Further evaluate the preliminary anti-tumour activity of AZD0901 monotherapy by assessment of DRR. |
Antibody-drug conjugate/Biologic
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Incidence of adverse events (AEs), serious AEs (SAEs). Changes from baseline in clinical laboratory parameters, vital signs, ECGs and physical examination. Rate of AEs leading to discontinuation of AZD0901, Occurrence of DLTs.
Periodo de tiempo: 30 days post treatment completion. AE Follow Up for 90 days post AZD0901 discontinuation.
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To investigate the safety and tolerability, of AZD0901 monotherapy or in combination with anti-cancer agents in particpants with advanced or metastatic solid tumours expressing CLDN18.2. |
30 days post treatment completion. AE Follow Up for 90 days post AZD0901 discontinuation.
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Objective Response Rate (ORR).
Periodo de tiempo: From date of first dose of AZD0901 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years).
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Proportion of participants with a confirmed Complete Response (CR) or Partial Response (PR) as determined by the Investigator at local site as per RECIST v1.1. |
From date of first dose of AZD0901 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years).
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Overall Survival (OS)
Periodo de tiempo: From date of first dose/randomisation until the date of death due to any cause (approximately 2 years).
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The analysis will include all dosed/randomised participants as assigned/randomised. All deaths will be included, regardless of whether the participant withdraws from therapy or receives another anticancer therapy. |
From date of first dose/randomisation until the date of death due to any cause (approximately 2 years).
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Progression Free Survival (PFS)
Periodo de tiempo: From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 2 years).
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Progression-free survival is defined as the time date of randomisation or enrollment until progression per RECIST v1.1 as assessed by the Investigator at local site, or death due to any cause, regardless of whether the participant withdraws from randomized therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST v1.1 progression. |
From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 2 years).
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Duration of Response (DoR)
Periodo de tiempo: From the date of first documented confirmed response until date of documented progression (approximately 2 years).
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The time from the date of first documented confirmed response until date of first documented progression per RECIST v1.1 or death due to any cause. |
From the date of first documented confirmed response until date of documented progression (approximately 2 years).
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Disease control rate (DCR)
Periodo de tiempo: Up to 11 weeks post date of first dose/randomisation
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The percentage of participants who have a confirmed CR or PR or who have SD per RECIST v1.1 as assessed by the Investigator at local site and derived from the raw tumour data up to 11 weeks after date of first dose/randomisation. |
Up to 11 weeks post date of first dose/randomisation
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Percentage change in tumor size
Periodo de tiempo: From start through to study completion.
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The best percentage change from baseline in tumor size is the largest decrease (or smallest increase) from baseline for a participant, using RECIST v1.1 assessments. |
From start through to study completion.
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Serum concentration of AZD0901 (total ADC), total antibody (conjugated and unconjugated) and total unconjugated MMAE
Periodo de tiempo: From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.
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To characterise the PK of AZD0901 monotherapy or in combination with anti cancer agents in participants with advanced or metastatic solid tumours expressing CLDN18.2. |
From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.
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Serum PK parameters of AZD0901, total antibody (conjugated and unconjugated) and MMAE including but not limited to AUC, Cmax, tmax, clearance and half-life, as data allow.
Periodo de tiempo: From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.
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To characterise the PK of AZD0901 monotherapy or in combination with anti cancer agents in participants with advanced or metastatic solid tumours expressing CLDN18.2. |
From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.
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Clinical activity by baseline and/or on-treatment tissue-based biomarkers including, but not limited to, gene expression, mutation profiles, DNA damage, protein expression, immune response and/or mechanisms of resistance.
Periodo de tiempo: From date of first dose of AZD0901 up to 7 weeks.
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To investigate baseline and/or on-treatment tissue-based RNA, DNA, and/or proteins, and association with clinical activity of AZD0901 (substudy 1). |
From date of first dose of AZD0901 up to 7 weeks.
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ADA status will be determined along with prevalence and incidence of anti-drug antibodies to AZD0901, and titer established.
Periodo de tiempo: From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.
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To determine the immunogenicity of AZD0901 monotherapy or in combination with anti-cancer agents in participants with advanced or metastatic solid tumours expressing CLDN18.2. |
From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.
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Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Neoplasias por sitio
- Neoplasias
- Neoplasias Gastrointestinales
- Neoplasias del Sistema Digestivo
- Enfermedades del Sistema Digestivo
- Enfermedades Gastrointestinales
- Enfermedades del Estómago
- Enfermedades del Tracto Biliar
- Neoplasias de Estómago
- Neoplasias del Tracto Biliar
- Compuestos heterocíclicos, 1 anillo
- Compuestos heterocíclicos
- Compuestos heterocíclicos, 2 anillos
- Compuestos heterocíclicos, anillo fusionado
- Campeptecina
- Alcaloides
- Enzimas y coenzimas
- Desoxicitidina
- Citidina
- Nucleósidos de pirimidina
- Pirimidinas
- Formiltetrahidrofolatos
- Tetrahidrofolatos
- Ácido fólico
- Pterins
- Pteridinas
- Uracílico
- Pirimidinonas
- Coenzimas
- Irinotecán
- Gemcitabina
- Fluorouracilo
- Leucovorina
- Sucrosofado de Irinotecan
Otros números de identificación del estudio
- D9800C00001
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
Marco de tiempo para compartir IPD
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Criterios de acceso compartido de IPD
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .