A Study to Investigate Efficacy, Safety, and Tolerability of Remibrutinib Compared With Placebo in Adults With CINDU Inadequately Controlled by H1-antihistamines

NCT ID: NCT05976243

Last Updated: 2025-12-22

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

PHASE3

Total Enrollment

364 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-07

Study Completion Date

2028-08-01

Brief Summary

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This is a Phase 3, parallel group, placebo-controlled, double-blind, confirmatory study in patients with CINDU, with an optional Open-label Extension (OLE).

The purpose of the core period (52 weeks of treatment) of this study is to evaluate the efficacy, safety, and tolerability of remibrutinib (LOU064) vs. placebo in adults suffering from CINDU inadequately controlled by H1-antihistamines (H1-AHs).

The purpose of the OLE period is to collect long-term efficacy, safety, and tolerability data on remibrutinib in participants after having completed the Core period

Detailed Description

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This study consists of a core and extension periods.

The Core period (6 arms) has a total duration of up to 60 weeks including a double-blind placebo-controlled treatment period until Week 24 followed by open-label treatment with remibrutinib up to Week 52. The primary endpoint for all CINDU subtypes is assessed at Week 12.

The Core period consists of:

* Screening period (up to 4 weeks): During the screening period, participants who have provided informed consent will be assessed for study eligibility.
* Double-blind, placebo-controlled treatment period (24 weeks): 24 weeks of double-blind treatment with remibrutinib or placebo.
* Open-label treatment period (28 weeks): 28 weeks of open-label treatment with remibrutinib.
* Follow-up period: 4 weeks of treatment free follow-up. The open-label extension period consists of observation and treatment period. At the end of the core period of the study, if participants continue to experience symptoms, they will transition to the treatment period in OLE. If they do not experience symtpoms they will transition to the observation period in the OLE.

The duration of the Open-label Extension period will be approximately 3 years where participants can switch from observation to treatment depending on if they start developing symptoms. Only those participants participating in the Open-label Extension Treatment period will receive remibrutinib. The participants in the Open-label Extension Observation period will not receive remibrutinib

Conditions

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Chronic Inducible Urticaria

Keywords

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CINDU Chronic inducible urticaria BTK remibrutinib symptomatic dermographsim cold urticaria cholinergic urticaria

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
This masking applies to the core period. There is no masking in the open-label extension (OLE).

Study Groups

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Remibrutinib, symptomatic dermographism group

Remibrutinib oral twice daily in participants with symptomatic dermographism

Group Type EXPERIMENTAL

Remibrutinib

Intervention Type DRUG

Remibrutinib treated groups and arms

Placebo, symptomatic dermographism group

Placebo oral twice daily, symptomatic dermographism

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Placebo treated groups and arms

Remibrutinib, cold urticaria group

Remibrutinib oral twice daily, cold urticaria

Group Type EXPERIMENTAL

Remibrutinib

Intervention Type DRUG

Remibrutinib treated groups and arms

Placebo, cold urticaria group

Placebo oral twice daily, cold urticaria

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Placebo treated groups and arms

Remibrutinib, cholinergic urticaria group

Remibrutinib oral twice daily, cholinergic urticaria

Group Type EXPERIMENTAL

Remibrutinib

Intervention Type DRUG

Remibrutinib treated groups and arms

Placebo, cholinergic urticaria

Placebo oral twice daily, cholinergic urticaria

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Placebo treated groups and arms

Interventions

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Placebo

Placebo treated groups and arms

Intervention Type OTHER

Remibrutinib

Remibrutinib treated groups and arms

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Male and female participants ≥18 years of age at the time of signing of the ICFs
2. Confirmed CINDU diagnosis (as per guidelines) for symptomatic dermographism, cold urticaria or cholinergic urticaria for ≥ 4 months (defined as onset of CINDU with supporting documentation (e.g medical record, clinical history, photographs)) and inadequate control with H1-AH at local label approved doses at the time of randomization
3. The following response to the provocation test for each subtype is required at the randomization visit :

* Symptomatic Dermographism: A Total Fric Score of ≥3 using the FricTest® 4.0 and a numerical rating scale score of ≥5 for itch after the provocation test.
* Cold Urticaria: A Critical Threshold Temperature of ≥15°C using the TempTest® 4.0 and a numerical rating scale score of ≥5 for itch after the provocation test.
* Cholinergic Urticaria: A physician global assessment of severity of hives ≥ 2 using the Pulse-controlled ergometry test and a numerical rating scale score of ≥5 for itch after the provocation test.
4. Cold Urticaria: Positive ice-cube test resulting in hives at the provocation site for participants at Screening.
5. Cholinergic urticaria: Participants must show sweating in performing the pulse-controlled ergometry test on day of randomization. Participants with anhidrosis must not be included.


1. Participants who have completed the Core period up to Week 52 and are willing to enter the OLE period

Exclusion Criteria

* 1\. Previous use of remibrutinib or other BTK inhibitors.
2. Participants who have concomitant CSU at screening. Participants with resolved CSU at the time of screening can be included in the study.
3. Participants who have a familial form (e.g familial cold autoinflammatory syndrome, familial cold urticaria) of the target CINDU that is being considered for the participant's inclusion in this study.
4. Participants having a more defined other form of inducible urticaria than the target CINDU that is being considered for the participant's inclusion in this study.
5. Diseases, other than chronic inducible urticaria, with urticaria or angioedema symptoms including but not limited to urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema
6. Any other skin disease associated with chronic itching that might influence, in the investigator's opinion, the study evaluations and results (e.g., atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.) or skin diseases associated with only wheals and no itch e.g asymptomatic dermographism
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Istanbul, Basaksehir, Turkey (Türkiye)

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Istanbul, Fatih, Turkey (Türkiye)

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Kayseri, Melikgazi, Turkey (Türkiye)

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Istanbul, Uskudar, Turkey (Türkiye)

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Oxford, , United Kingdom

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Hanoi, , Vietnam

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Novartis Investigative Site

Ho Chi Minh City, , Vietnam

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Allervie Clinical Research

Birmingham, Alabama, United States

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Acuro Research Inc

Little Rock, Arkansas, United States

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Kern Research

Bakersfield, California, United States

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Allergy and Asthma Specialists Group

Huntington Beach, California, United States

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Antelope Valley Clinical Trials

Lancaster, California, United States

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Asthma and Allergy Associates P C

Colorado Springs, Colorado, United States

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Florida Ctr Allergy Asthma Research

Aventura, Florida, United States

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Sarasota Clinical Research

Sarasota, Florida, United States

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Univ of South Florida Asthma Allergy and Immunology CRU

Tampa, Florida, United States

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Aeroallergy Research Laboratories

Savannah, Georgia, United States

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Treasure Valley Medical Research

Boise, Idaho, United States

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Endeavor Health

Glenview, Illinois, United States

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Asthma and Allergy Center of Chicago S C

River Forest, Illinois, United States

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The Indiana Clinical Trials Center

Plainfield, Indiana, United States

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Allergy and Asthma Specialist P S C

Owensboro, Kentucky, United States

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John Hopkins University

Baltimore, Maryland, United States

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Allergy Asthma and Clinical Research

Oklahoma City, Oklahoma, United States

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Allergy and Clinical Immunology Associates

Pittsburgh, Pennsylvania, United States

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National Allergy and Asthma Research LLS

North Charleston, South Carolina, United States

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PanAmerican Clinical Research

Brownsville, Texas, United States

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Western Sky Medical Research

El Paso, Texas, United States

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RFSA Dermatology

San Antonio, Texas, United States

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STAAMP Research LLC

San Antonio, Texas, United States

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Complete Dermatology

Sugar Land, Texas, United States

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Allergy Associates of Utah

Sandy City, Utah, United States

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Novartis Investigative Site

Caba, Buenos Aires, Argentina

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CABA, Buenos Aires, Argentina

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Rosario, Santa Fe Province, Argentina

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CABA, , Argentina

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Woolloongabba, Queensland, Australia

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Carlton, Victoria, Australia

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Melbourne, Victoria, Australia

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Alphaville Barueri, São Paulo, Brazil

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Santo André, São Paulo, Brazil

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Sorocaba, São Paulo, Brazil

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Winnipeg, Manitoba, Canada

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Hamilton, Ontario, Canada

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Trois-Rivières, Quebec, Canada

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Fuzhou, Fujian, China

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Guangzhou, Guangdong, China

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Guangzhou, Guangdong, China

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Changsha, Hunan, China

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Wuxi, Jiangsu, China

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Changchun, Jilin, China

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Jinan, Shandong, China

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Chengdu, Sichuan, China

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Chengdu, Sichuan, China

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Ürümqi, Xinjiang, China

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Hangzhou, Zhejiang, China

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Yiwu, Zhejiang, China

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Beijing, , China

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Beijing, , China

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Jinan, , China

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Shanghai, , China

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Tianjin, , China

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Barranquilla, Atlántico, Colombia

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Barranquilla, Atlántico, Colombia

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Clermont-Ferrand, , France

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Grenoble, , France

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Montpellier, , France

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Nantes, , France

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Paris, , France

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Pierre-Bénite, , France

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Rouen, , France

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Toulouse, , France

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Göttingen, Lower Saxony, Germany

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Dresden, Saxony, Germany

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Berlin, , Germany

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Mainz, , Germany

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Münster, , Germany

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Stade, , Germany

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Tübingen, , Germany

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Hong Kong, , Hong Kong

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Debrecen, Hajdu Bihar Megye, Hungary

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Debrecen, Hajdú-Bihar, Hungary

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Szolnok, Jász-Nagykun-Szolnok, Hungary

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Bangalore, Karnataka, India

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Mysore, Karnataka, India

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New Delhi, National Capital Territory of Delhi, India

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Haifa, , Israel

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Jerusalem, , Israel

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Ramat Gan, , Israel

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Tel Aviv, , Israel

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Ancona, AN, Italy

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Milan, MI, Italy

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Rozzano, MI, Italy

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Kitakyushu, Fukuoka, Japan

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Sapporo, Hokkaido, Japan

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Kamimashi-gun, Kumamoto, Japan

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Habikino, Osaka, Japan

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Takatsuki, Osaka, Japan

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Ohtsu, Shiga, Japan

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Izumo, Shimane, Japan

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Shimotsuga Gun, Tochigi, Japan

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Bunkyo-ku, Tokyo, Japan

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Itabashi-ku, Tokyo, Japan

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Shinjuku Ku, Tokyo, Japan

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Tachikawa, Tokyo, Japan

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Hiroshima, , Japan

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Muar town, Johor, Malaysia

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Ipoh, Perak, Malaysia

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George Town, Pulau Pinang, Malaysia

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Utrecht, , Netherlands

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Bydgoszcz, , Poland

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Warsaw, , Poland

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Coimbra, , Portugal

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Lisbon, , Portugal

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Vila Nova de Gaia, , Portugal

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Bucharest, District 2, Romania

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Singapore, , Singapore

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Kežmarok, , Slovakia

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Trnava, , Slovakia

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Žilina, , Slovakia

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Suwon, Gyeonggi-do, South Korea

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Seoul, , South Korea

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Santiago, A Coruna, Spain

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Granada, Andalusia, Spain

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Barcelona, Catalonia, Spain

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Alicante, , Spain

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Barcelona, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Valencia, , Spain

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Bangkok, , Thailand

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Bangkok, , Thailand

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Chiang Mai, , Thailand

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Sakarya, Adapazari, Turkey (Türkiye)

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Countries

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United States Argentina Australia Brazil Canada China Colombia France Germany Hong Kong Hungary India Israel Italy Japan Malaysia Netherlands Poland Portugal Romania Singapore Slovakia South Korea Spain Thailand Turkey (Türkiye) United Kingdom Vietnam

Other Identifiers

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2023-505739-12-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CLOU064M12301

Identifier Type: -

Identifier Source: org_study_id