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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04266301




Registration number
NCT04266301
Ethics application status
Date submitted
21/01/2020
Date registered
12/02/2020

Titles & IDs
Public title
Study of Efficacy and Safety of MBG453 in Combination With Azacitidine in Subjects With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2)
Scientific title
A Randomized, Double-blind, Placebo-controlled Phase III Multi-center Study of Azacitidine With or Without MBG453 for the Treatment of Patients With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2)
Secondary ID [1] 0 0
2019-002089-11
Secondary ID [2] 0 0
CMBG453B12301
Universal Trial Number (UTN)
Trial acronym
STIMULUS-MDS2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndromes 0 0
Leukemia, Myelomonocytic, Chronic 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Sabatolimab
Treatment: Drugs - Azacitidine
Treatment: Drugs - Placebo

Experimental: MBG453 (Sabatolimab) + Azacitidine - Participants will receive MBG453 plus Azacitidine

Placebo comparator: Placebo + Azacitidine - Participants will receive Placebo plus Azacitidine


Treatment: Drugs: Sabatolimab
A dose of MBG453 800 mg will be administered intravenously (IV) every 4 weeks (Q4W).

Treatment: Drugs: Azacitidine
A dose of Azacitidine 75 mg/m2 will be administered IV or subcutaneously (SC) on Day 1-7, or Day 1-5, 8 and 9.

Treatment: Drugs: Placebo
A dose of Placebo 800 mg will be administered intravenously every 4 weeks (Q4W).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
Up to 5 years after last patient randomized
Secondary outcome [1] 0 0
Key secondary endpoint 1: Time to definitive deterioration of fatigue using Functional Assessment of Cancer Therapy (FACIT)-Fatigue score
Timepoint [1] 0 0
Up to 5 years after last patient randomized
Secondary outcome [2] 0 0
Key secondary endpoint 2: Red Blood Cell transfusion-free intervals
Timepoint [2] 0 0
Up to 5 years after last patient randomized
Secondary outcome [3] 0 0
Key secondary endpoint: Percent of subjects with at least 3 point confirmed improvement from baseline in FACIT-fatigue scoresscore
Timepoint [3] 0 0
Up to 5 years after last patient randomized
Secondary outcome [4] 0 0
Key secondary endpoint 4: Percent of subjects with at least 10 point confirmed improvement from baseline in physical functioning using European Or ganization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30)
Timepoint [4] 0 0
Up to 5 years after last patient randomized
Secondary outcome [5] 0 0
Key secondary endpoint 5: Percent of subjects with at least 10 point confirmed improvement from baseline in emotional functioning using EORTC-QLQ-C30
Timepoint [5] 0 0
Up to 5 years after last patient randomized
Secondary outcome [6] 0 0
Percentage of subjects with either CR, or mCR, or PR, or HI in each treatment arm according to International Working Group for MDS (IWG-MDS) as per investigator assessment
Timepoint [6] 0 0
Up to 5 years after last patient randomized
Secondary outcome [7] 0 0
Percentage of subjects with SD in each treatment arm according to International Working Group for MDS (IWG-MDS) as per investigator assessment
Timepoint [7] 0 0
Up to 5 years after last patient randomized
Secondary outcome [8] 0 0
Progression Free Survival (PFS)
Timepoint [8] 0 0
Up to 5 years after last patient randomized
Secondary outcome [9] 0 0
Leukemia-free survival
Timepoint [9] 0 0
Up to 5 years after last patient randomized
Secondary outcome [10] 0 0
Number of transfusion dependent subjects at baseline who become Red Blood Cells/platelets transfusion independent after randomization
Timepoint [10] 0 0
Up to 5 years after last patient randomized as per IWG-MDS criteria
Secondary outcome [11] 0 0
Percentage of transfusion dependent subjects at baseline who become Red Blood Cells/platelets transfusion independent after randomization
Timepoint [11] 0 0
Up to 5 years after last patient randomized
Secondary outcome [12] 0 0
Pharmacokinetics of MBG453 (parameter Cmax)
Timepoint [12] 0 0
At Day 8 of each cycle (1 cycle = 28 days) until cycle 9, at day 8 of cycle 12 and every 6 cycles thereafter up to 150 day after end of study drug
Secondary outcome [13] 0 0
Pharmacokinetics of MBG453 (parameter AUC)
Timepoint [13] 0 0
At Day 8 of each cycle (1 cycle = 28 days) until cycle 9, at day 8 of cycle 12 and every 6 cycles thereafter up to 150 day after end of study drug
Secondary outcome [14] 0 0
Anti-drug Antibody (ADA) prevalence at baseline and ADA incidence on-treatment
Timepoint [14] 0 0
At Day 8 of each cycle (1 cycle = 28 days) until cycle 9, at day 8 of cycle 12 and every 6 cycles thereafter up to 150 day after end of study drug
Secondary outcome [15] 0 0
Change from baseline in the European Quality of Life (EuroQol) - 5 Dimensions, 5 Level Questionnaire (EQ-5D-5L) score over time
Timepoint [15] 0 0
Up to 5 years after last patient randomized
Secondary outcome [16] 0 0
Change from baseline in the European Quality of Life (EuroQoL) - 5 Dimensions, 5 Level Questionnaire (EQ-5D-5L) Visual Analogue Scale over time
Timepoint [16] 0 0
Up to 5 years after last patient randomized
Secondary outcome [17] 0 0
Change from baseline to C12D1 of Global Health Status/Quality of Life scores using European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC-QLQ-C30)
Timepoint [17] 0 0
Up to cycle 12 day 1 (C12D1)(1 cycle = 28 days)

Eligibility
Key inclusion criteria
* Signed informed consent must be obtained prior to participation in the study
* Age = 18 years at the date of signing the informed consent form
* Morphologically confirmed diagnosis of myelodysplastic syndrome (MDS) based on WHO 2016 classification (Arber et al 2016) by local investigator assessment with one of the following Prognostic Risk Categories, based on the revised International Prognostic Scoring System (IPSS-R):

* Very high (> 6 points)
* High (> 4.5 - = 6 points)
* Intermediate (> 3 - = 4.5 points) Or Morphologically confirmed diagnosis of Chronic Myelomonocytic Leukemia -2 based on WHO 2016 classification (Arber et al 2016, including persistent monocytosis) by local investigator assessment with WBC < 13 x 109/L at time of initial diagnosis
* Indication for azacitidine treatment according to the investigator, based on local standard medical practice and institutional guidelines for treatment decisions
* Not eligible at time of screening for intensive chemotherapy according to the investigator, based on local standard medical practice and institutional guidelines for treatment decisions, including assessment of individual clinical factors such as age, comorbidities and performance status
* Not eligible at time of screening for hematopoietic stem cell transplantation (HSCT) according to the investigator, based on local standard medical practice and institutional guidelines for treatment decisions, including assessment of individual clinical factors such as age, comorbidities, performance status, and donor availability
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Minimum age
18 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior exposure to TIM-3 directed therapy at any time. Prior therapy with immune checkpoint inhibitors (e.g, anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2), cancer vaccines is allowed except if the drug was administered within 4 months prior to randomization
* Previous first-line treatment for intermediate, high, very high risk myelodysplastic syndromes (based on IPSS-R) or CMML with any antineoplastic agents including for example chemotherapy, lenalidomide and hypomethylating agents (HMAs) such as decitibine and azacitidine. However, previous treatment with hydroxyurea or leukopheresis to reduce WBC count is allowed prior to randomization.
* Investigational treatment received within 4 weeks or 5 half-lives of this investigational treatment, whatever is longer, prior to randomization. In case of a checkpoint inhibitor: a minimal interval of 4 months prior to randomization is necessary to allow randomization.
* Subjects with Myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al 2016) with revised International Prognostic Scoring System (IPSS-R) = 3
* Diagnosis of acute myeloid leukemia (AML) including acute promyelocytic leukemia and extra-medullary acute myeloid leukemia, primary or secondary myelofibrosis based on WHO 2016 classification (Arber et al 2016)
* Diagnosis of therapy related myeloid neoplasms based on WHO 2016 classification (Arber et al 2016)
* History of organ or allogeneic hematopoietic stem cell transplant

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/06/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/10/2024
Sample size
Target
Accrual to date
Final
530
Recruitment in Australia
Recruitment state(s)
QLD,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Wooloongabba
Recruitment hospital [2] 0 0
Novartis Investigative Site - Clayton
Recruitment hospital [3] 0 0
Novartis Investigative Site - Perth
Recruitment postcode(s) [1] 0 0
4102 - Wooloongabba
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
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Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Virginia
Country [10] 0 0
Argentina
State/province [10] 0 0
Buenos Aires
Country [11] 0 0
Austria
State/province [11] 0 0
Tyrol
Country [12] 0 0
Austria
State/province [12] 0 0
Graz
Country [13] 0 0
Austria
State/province [13] 0 0
Linz
Country [14] 0 0
Belgium
State/province [14] 0 0
Brasschaat
Country [15] 0 0
Belgium
State/province [15] 0 0
Roeselare
Country [16] 0 0
Brazil
State/province [16] 0 0
SC
Country [17] 0 0
Brazil
State/province [17] 0 0
SP
Country [18] 0 0
Canada
State/province [18] 0 0
Alberta
Country [19] 0 0
Canada
State/province [19] 0 0
Ontario
Country [20] 0 0
Chile
State/province [20] 0 0
Valparaiso
Country [21] 0 0
China
State/province [21] 0 0
Guangdong
Country [22] 0 0
China
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Hubei
Country [23] 0 0
China
State/province [23] 0 0
Jiangsu
Country [24] 0 0
China
State/province [24] 0 0
Jilin
Country [25] 0 0
China
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Sichuan
Country [26] 0 0
China
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Zhejiang
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China
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Beijing
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China
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Jinan
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China
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Shanghai
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China
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Tianjin
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Colombia
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Antioquia
Country [32] 0 0
Colombia
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Bogota
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Czechia
State/province [33] 0 0
Czech Republic
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Czechia
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CZE
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Czechia
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Brno Bohunice
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Czechia
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Praha
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Finland
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Helsinki
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Finland
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Kuopio
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France
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Grenoble
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France
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Lille
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France
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Paris 10
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France
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Toulouse
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France
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Tours
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France
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Vandoeuvre Les Nancy
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Germany
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North Rhine-Westphalia
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Germany
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Sachsen
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Germany
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Augsburg
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Germany
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Duesseldorf
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Germany
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Frankfurt
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Germany
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Greifswald
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Germany
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Jena
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Germany
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Kiel
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Germany
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Ulm
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Greece
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Evros
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Greece
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Patras
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India
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Gujrat
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India
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Haryana
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India
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TamilNadu
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West Bengal
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Delhi
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Afula
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Israel
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Tel Aviv
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Italy
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BO
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Italy
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CT
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Italy
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FI
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Italy
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GE
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Italy
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MI
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Italy
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RC
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Italy
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RM
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Japan
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Aichi
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Japan
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Chiba
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Fukuoka
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Hokkaido
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Kanagawa
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Japan
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Miyagi
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Japan
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Nagasaki
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Osaka
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Tokyo
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Yamagata
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Korea, Republic of
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Seocho Gu
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Korea, Republic of
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Seoul
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Lebanon
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Beirut
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Lithuania
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Vilnius
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Malaysia
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Sarawak
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Malaysia
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Kuala Lumpur
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Malaysia
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Pulau Pinang
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Malaysia
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Selangor
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Mexico
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Distrito Federal
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Edo Mexico
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Mexico
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Michoacan
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Mexico
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Estado de Mexico
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Netherlands
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Groningen
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Oman
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Muscat
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Portugal
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Lisboa
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Portugal
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Porto
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Russian Federation
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Saint Petersburg
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Saudi Arabia
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Riyadh
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Singapore
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Singapore
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Spain
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Andalucia
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Spain
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Asturias
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Spain
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Castilla Y Leon
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Spain
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Catalunya
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Spain
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Comunidad Valenciana
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Spain
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Madrid
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Spain
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Valencia
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Switzerland
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Bern
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Switzerland
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Zuerich
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Taiwan
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Hualien
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Taiwan
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Kaohsiung
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Taiwan
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Liouying Township
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Taiwan
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Taichung
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Taiwan
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Taipei
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Taiwan
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Taoyuan
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Thailand
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Hat Yai
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Thailand
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THA
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Thailand
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Bangkok
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Thailand
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Chiang Mai
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Turkey
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Ankara
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Turkey
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Edirne
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Turkey
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Izmir
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Turkey
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Pendik Istanbul
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Turkey
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Samsun
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United Kingdom
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Hants
Country [124] 0 0
United Kingdom
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Scotland
Country [125] 0 0
United Kingdom
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Manchester
Country [126] 0 0
United Kingdom
State/province [126] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04266301