A Study of Zolbetuximab (IMAB362) in Adults With Pancreatic Cancer

NCT ID: NCT03816163

Last Updated: 2025-10-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

393 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-15

Study Completion Date

2026-08-31

Brief Summary

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Zolbetuximab is being studied as a treatment for people with pancreatic cancer. Most people with pancreatic cancer have a protein called Claudin 18.2 (CLDN18.2) in their tumor. Zolbetuximab is thought to work by attaching to CLDN 18.2 in their tumor. This switches on the body's immune system to attack the tumor. Zolbetuximab is a potential treatment for people with pancreatic cancer.

There is an unmet medical need to treat people with pancreatic cancer. This study will help find the dose of zolbetuximab to be used with chemotherapy and provide more information on this treatment in adults with metastatic pancreatic cancer. The study is currently ongoing globally. People in this study will be treated with either zolbetuximab and chemotherapy or chemotherapy by itself.

The study's main aims are to find a suitable dose of zolbetuximab to be used with chemotherapy in the second part of this study, to check if zolbetuximab and chemotherapy compared to chemotherapy by itself can improve the survival of people with pancreatic cancer, and to check the safety of zolbetuximab when given with chemotherapy and how well people cope with medical problems during the study.

Adults with metastatic pancreatic cancer can take part. Their cancer is metastatic, has the CLDN18.2 marker in a tumor sample and has not previously been treated with chemotherapy. Metastatic means the cancer has spread to other parts of the body. People cannot take part are if they have recently had radiotherapy and have not recovered, need to take medicines to suppress their immune system, have history of nervous system metastases from their pancreatic cancer, or they have other active cancers that need treatment. People who have a specific heart condition or infections also cannot take part.

This study will be in 2 parts. Part 1 is called the Safety Lead-in Phase. Groups of people will receive 1 of 2 different doses of zolbetuximab: a lower dose or a higher dose, both together with chemotherapy. A medical expert panel will check the results and decide the dose to use in Part 2.

Part 2 is called the Randomization Phase. People will be put in 1 of 2 groups by chance and will be given different treatments either zolbetuximab and chemotherapy or chemotherapy by itself. The chance of receiving zolbetuximab and chemotherapy is twice as high as receiving chemotherapy by itself. In both parts of the study, zolbetuximab and chemotherapy or chemotherapy by itself will be given through a vein. This is called an infusion. Each treatment cycle is 4 weeks (28 days) long and people will have either 2 infusions of zolbetuximab and 3 infusions of chemotherapy or 3 infusions of chemotherapy by itself during each treatment cycle. People will visit the clinic on certain days during their treatment. The study doctors will check for any medical problems from zolbetuximab. Also, people in the study will have a health check including blood tests. On some visits they will also have scans to check for any changes in their cancer. Tumor samples will be taken before treatment if a previous sample is not available. People will have the option of giving a tumor sample after treatment has finished. People will visit the clinic after they stop treatment. They will be asked about any medical problems and will have a health check including blood tests. The number of visits and checks done at each visit will depend on the health of each person and whether they completed their treatment or not.

Detailed Description

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This study will have a safety lead in phase and a randomization phase.

Conditions

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Pancreatic Cancer Metastatic Pancreatic Cancer Metastatic Pancreatic Adenocarcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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zolbetuximab +nab-paclitaxel + gemcitabine

Participants will be treated with zolbetuximab in combination with nab-paclitaxel and gemcitabine for the phase 1 portion of the study to establish the recommended dose of zolbetuximab for the phase 2 portion. In the phase 2 portion, the participants will be treated with zolbetuximab at dose determined by the phase 1 portion of the study in combination with nab-paclitaxel and gemcitabine. Participants will be treated on continuous cycles until they no longer derive clinical benefit in the judgment of the treating physician, have unacceptable toxicity, undergo hematopoietic stem cell transplantation (HSCT), or meet one of the discontinuation criteria; whichever occurs first.

Group Type EXPERIMENTAL

zolbetuximab

Intervention Type DRUG

Administered as an intravenous infusion.

nab-paclitaxel

Intervention Type DRUG

Administered as an intravenous infusion

gemcitabine

Intervention Type DRUG

Administered as an intravenous infusion

nab-paclitaxel + gemcitabine

Participants will be treated with nab-paclitaxel and gemcitabine. Participants will be treated on continuous cycles until they no longer derive clinical benefit in the judgment of the treating physician, have unacceptable toxicity, undergo hematopoietic stem cell transplantation (HSCT), or meet one of the discontinuation criteria; whichever occurs first.

Group Type ACTIVE_COMPARATOR

nab-paclitaxel

Intervention Type DRUG

Administered as an intravenous infusion

gemcitabine

Intervention Type DRUG

Administered as an intravenous infusion

Interventions

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zolbetuximab

Administered as an intravenous infusion.

Intervention Type DRUG

nab-paclitaxel

Administered as an intravenous infusion

Intervention Type DRUG

gemcitabine

Administered as an intravenous infusion

Intervention Type DRUG

Other Intervention Names

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IMAB362

Eligibility Criteria

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Inclusion Criteria

* A female subject is eligible to participate if she is not pregnant or lactating and at least 1 of the following conditions applies:

* Not a woman of childbearing potential (WOCBP) OR
* WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 6 months after the final study drug administration.
* Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study drug administration.
* Female subject must not donate ova starting at screening and throughout the study period, and for 6 months after the final study drug administration.
* A male subject with female partner(s) of child-bearing potential must agree to use contraception during the treatment period and for at least 6 months after the final study drug administration.
* A male subject must not donate sperm during the treatment period and for at least 6 months after the final study drug administration.
* Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 6 months after the final study drug administration.
* Subject agrees not to participate in other interventional studies while receiving study drug in present study.
* Subject has histologically or cytologically confirmed adenocarcinoma of pancreas.
* Subjects must have metastatic pancreatic adenocarcinoma that has not been previously treated with chemotherapy.

* Prior treatment with fluorouracil (5-FU) or GEM administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed
* If a subject received adjuvant therapy, tumor recurrence or disease progression must have occurred at least 6 months after completing the last dose of the adjuvant therapy.
* Subjects whose disease progressed on prior treatment with Nab-P and GEM are not eligible.
* Subject has a measurable lesion(s) on at least 1 metastatic site based on RECIST 1.1 within 28 days prior to randomization. For subjects with only 1 measurable lesion and prior radiotherapy, the lesion must be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
* Subject's tumor sample has CLDN18.2 expression in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central immunohistochemistry (IHC) testing
* Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Subject has predicted life expectancy ≥ 12 weeks.
* Subject must meet all of the following criteria based on the laboratory tests that will be collected within 14 days prior to randomization. In case of multiple laboratory data within this period, the most recent data should be used.

* Hemoglobin ≥ 9 g/dl (no transfusion within 14 days of start of study treatment)
* Absolute neutrophil count ≥ 1.5 x 10\^9/L
* Platelets ≥ 100 x 10\^9/L
* Albumin ≥ 2.5 g/dL
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN without liver metastases (≤ 5 x ULN if liver metastases are present)
* Estimated creatinine clearance ≥ 30 mL/min
* Prothrombin time/international normalized ratio (INR) and partial thromboplastin time ≤ 1.5 x ULN (except for subjects receiving anticoagulation therapy)

Exclusion Criteria

* Subject has received other investigational treatment within 28 days prior to randomization.
* Subject has received radiotherapy for metastatic pancreatic adenocarcinoma ≤ 14 days prior to randomization and has not recovered from any related toxicity.
* Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to randomization. Subject using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone or up to 10 mg per day of prednisone), receiving a single dose of systemic corticosteroids or receiving systemic corticosteroids as premedication for radiologic imaging contrast use are allowed.
* Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibody, including humanized or chimeric antibodies.
* Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment.
* Subject has a known history of a positive test for human immunodeficiency virus infection or known active hepatitis B (positive HBs antigen \[Ag\]) or hepatitis C infection. NOTE: Screening for these infections should be conducted per local requirements.

1. For subjects who are negative for HBs Ag, but hepatitis B core antibody positive, a hepatitis B virus DNA test will be performed and if positive, the subject will be excluded.
2. Subjects with positive hepatitis C serology but negative hepatitis C virus RNA test results are eligible.
3. Subjects treated for hepatitis C with undetectable viral load results are eligible.
* Subject has a history of interstitial pneumonia or pulmonary fibrosis.
* Subject has pleural effusion or ascites ≥ Grade 3.
* Subject has an active autoimmune disease that has required systemic treatment in the past 3 months prior to randomization.
* Subject has active infection requiring systemic therapy that has not completely resolved per investigator judgment within 7 days prior to randomization.
* Subject has significant cardiovascular disease, including:

* Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis within 6 months prior to randomization;
* History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
* QTc interval \> 450 msec for male subjects; QTc interval \> 470 msec for female subjects;
* Cardiac arrhythmias requiring anti-arrhythmic medications (Subjects with rate controlled atrial fibrillation for \> 1 month prior to randomization.)
* Subject has a history of central nervous system metastases and/or carcinomatous meningitis from pancreatic adenocarcinoma.
* Subject has known peripheral sensory neuropathy ≥ Grade 2 unless the absence of deep tendon reflexes is the sole neurological abnormality.
* Subject has had a major surgical procedure ≤ 28 days prior to randomization.
* Subject without complete recovery from a major surgical procedure ≤ 14 days prior to randomization.
* Psychiatric illness or social situations that would preclude study compliance.
* Subject has another malignancy for which treatment is required.
* Subject has any concurrent disease, infection or co-morbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Astellas Pharma Global Development, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Astellas Pharma Global Development

Locations

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Site ES34022

Córdoba, , Spain

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Site ES34005

Lleida, , Spain

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Site ES34015

Madrid, , Spain

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Site ES34006

Madrid, , Spain

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Site ES34009

Madrid, , Spain

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Site ES34026

Málaga, , Spain

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Site ES34017

Santiago de Compostela, , Spain

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Site TW88608

New Taipei City, , Taiwan

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Site TW88602

Taichung, , Taiwan

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Site TW88601

Taipei, , Taiwan

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Site TW88609

Taipei, , Taiwan

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Site TR90004

Ankara, , Turkey (Türkiye)

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Site TR90006

Ankara, , Turkey (Türkiye)

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Site TR90003

Diyarbakır, , Turkey (Türkiye)

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Site TR90002

Istanbul, , Turkey (Türkiye)

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Site TR90001

Konya, , Turkey (Türkiye)

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St. Joseph Heritage Medical Group

Fullerton, California, United States

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TOI Clinical research

Whittier, California, United States

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Midstate Medical Center

Meriden, Connecticut, United States

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Lynn Cancer Institute

Boca Raton, Florida, United States

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Baptist Health

Miami, Florida, United States

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Cancer Treatment Centers of Atlanta

Newnan, Georgia, United States

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University of Illinois at Chicago

Chicago, Illinois, United States

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Norton Cancer Institute (NCI)

Louisville, Kentucky, United States

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Ochsner Health System

New Orleans, Louisiana, United States

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David C Pratt Cancer Center

Creve Coeur, Missouri, United States

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Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

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Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States

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Roswell Park Cancer Institute

Buffalo, New York, United States

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Memorial Sloan Kettering Commack

Commack, New York, United States

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Memorial Sloan Kettering Westchester

Harrison, New York, United States

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Northwell Health Cancer Institute

Lake Success, New York, United States

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Memorial Sloan-Kettering Cancer Center

New York, New York, United States

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Memorial Sloan Kettering Nassau

Uniondale, New York, United States

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Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

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Novant Health

Winston-Salem, North Carolina, United States

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Houston Methodist Hospital

Houston, Texas, United States

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Utah Cancer Specialists

Salt Lake City, Utah, United States

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MultiCare Regional Cancer Center - Gig Harbor

Gig Harbor, Washington, United States

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Vista Oncology

Olympia, Washington, United States

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Virginia Mason

Seattle, Washington, United States

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Site AU61008

Gosford, New South Wales, Australia

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Site AU61007

Wollongong, New South Wales, Australia

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Site AU61005

Fitzroy, Victoria, Australia

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Site AU61006

Warrnambool, Victoria, Australia

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Site BR55012

Porto Alegre, Rio Grande do Sul, Brazil

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Site BR55009

Centro Passo Fundo, , Brazil

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Site BR55008

Rio Grande, , Brazil

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Site BR55004

Santa Catarina, , Brazil

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Site BR55010

São Paulo, , Brazil

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Site BR55011

São Paulo, , Brazil

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Site CN86001

Beijing, , China

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Site CN86008

Beijing, , China

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Site CN86014

Beijing, , China

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Site CN86026

Changchun, , China

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Site CN86009

Chongqing, , China

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Site CN86004

Guangdong, , China

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Site CN86020

Guangdong, , China

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Site CN86016

Guangzhou, , China

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Site CN86012

Harbin, , China

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Site CN86002

Hubei, , China

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Site CN86005

Jiangsu, , China

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Site CN86011

Jiangsu, , China

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Site CN86025

Jiangsu, , China

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Site CN86023

Shandong, , China

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Site CN86006

Shanghai, , China

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Site CN86013

Shanghai, , China

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Site CN86019

Shanghai, , China

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Site CN86007

Tianjin, , China

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Site CN86022

Xinjiang, , China

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Site CN86024

Yanxi, , China

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Site CN86003

Zhejiang, , China

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Site CN86018

Zhejiang, , China

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Site CN86010

Zhengzhou, , China

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Site FR33008

Besançon, Besancon Cedex, France

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Site FR33010

Brest, Brest Cedex, France

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Site FR33015

Caen, Cedex 5, France

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Site FR33006

Chambray, Cedex 9, France

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Site FR33012

Herblain, Herblain Cedex, France

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Site FR33016

La Chaussée-Saint-Victor, Loir-et-Cher, France

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Site FR33009

Nancy, Nancy Cedex, France

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Site FR33017

Rouen, Normandy, France

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Site FR33003

Aquitaine, Pessac, France

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Site FR33013

Villejuif, Villejuif Cedex, France

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Site FR33001

Bayonne, , France

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Site FR33018

Bordeaux, , France

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Site FR33002

Grenoble, , France

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Site FR33019

La Roche-sur-Yon, , France

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Site FR33021

Nice, , France

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Site FR33023

Pierre-Bénite, , France

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Site FR33014

Plérin, , France

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Site FR33005

Pringy, , France

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Site FR33007

Strasbourg, , France

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Site IR35301

Elm Park, Dublin, Ireland

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Site IT39006

Rozzano, Milan, Italy

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Site IT39004

Candiolo, Torino, Italy

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Site IT39002

Cremona, , Italy

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Site IT39010

Lombardia, , Italy

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Site IT39003

Milan, , Italy

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Site IT39014

Toscana, , Italy

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Site IT39008

Veneto, , Italy

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Site JP81007

Nagoya, Aichi-ken, Japan

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Site JP81001

Kashiwa, Chiba, Japan

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Site JP81005

Sapporo, Hokkaido, Japan

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Site JP81006

Yokohama, Kanagawa, Japan

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Site JP81003

Kashihara, Nara, Japan

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Site JP81011

Bunkyo-ku, Tokyo, Japan

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Site JP81012

Chuo-ku, Tokyo, Japan

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Site JP81014

Koto-ku, Tokyo, Japan

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Site JP81013

Mitaka, Tokyo, Japan

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Site JP81002

Shinjuku-ku, Tokyo, Japan

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Site JP81015

Ube, Yamaguchi, Japan

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Site JP81004

Fukuoka, , Japan

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Site JP81010

Osaka, , Japan

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Site JP81009

Wakayama, , Japan

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Site MX52004

Distrito Federal, , Mexico

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Site MX52003

San Luis Potosí City, , Mexico

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Site MX52005

Veracruz, , Mexico

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Site KR82005

Seongnam-si, Gyeonggi-do, South Korea

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Site KR82008

Suwon, Gyeonggi-do, South Korea

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Site KR82010

Daegu, , South Korea

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Site KR82009

Gyeonggi-do, , South Korea

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Site KR82001

Seoul, , South Korea

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Site KR82003

Seoul, , South Korea

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Site KR82004

Seoul, , South Korea

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Site KR82007

Seoul, , South Korea

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Site KR82002

Seoul, , South Korea

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Site KR82006

Seoul, , South Korea

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Site ES34004

Llobregat, Barcelona, Spain

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Site ES34003

Pamplona, Navarre, Spain

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Site ES34010

Barcelona, , Spain

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Site ES34013

Barcelona, , Spain

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Site ES34007

Barcelona, , Spain

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Site ES34018

Barcelona, , Spain

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Site ES34021

Barcelona, , Spain

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Site ES34014

Cáceres, , Spain

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Countries

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United States Australia Brazil China France Ireland Italy Japan Mexico South Korea Spain Taiwan Turkey (Türkiye)

Other Identifiers

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2018-002551-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CTR20220914

Identifier Type: REGISTRY

Identifier Source: secondary_id

2024-510985-17-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

8951-CL-5201

Identifier Type: -

Identifier Source: org_study_id

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