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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04971226




Registration number
NCT04971226
Ethics application status
Date submitted
8/06/2021
Date registered
21/07/2021

Titles & IDs
Public title
A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP
Scientific title
A Phase III, Multi-center, Open-label, Randomized Study of Oral Asciminib Versus Investigator Selected TKI in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase
Secondary ID [1] 0 0
2021-000678-27
Secondary ID [2] 0 0
CABL001J12301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Myeloid Leukemia (CML) Philadelphia Chromosome Positive 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
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Imatinib
Treatment: Drugs - Nilotinib
Treatment: Drugs - Bosutinib
Treatment: Drugs - Dasatinib
Treatment: Drugs - Asciminib

Experimental: Asciminib - Patients will take asciminib 80 mg QD under fasting conditions on ongoing basis; Patients will be randomized 1:1 asciminib versus Investigator selected TKIs

Active comparator: Investigator selected TKIs - Patients will take on ongoing basis the Investigator selected TKIs that will include one of the below treatments:

Imatinib 400 mg QD administered with food Nilotinib 300 mg BID administered under fasting conditions Dasatinib 100 mg QD administered with or without a meal Bosotunib 400 mg QD administered with food


Treatment: Drugs: Imatinib
Comes in 100 mg and 400 mg tablets and taken orally

Treatment: Drugs: Nilotinib
Comes in 150 mg capsules and taken orally

Treatment: Drugs: Bosutinib
Comes in 100 mg and 400 mg tablets and taken orally

Treatment: Drugs: Dasatinib
Comes in 70 mg and 100 mg tablets and taken orally

Treatment: Drugs: Asciminib
Comes in 40 mg tablets and taken orally

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Major Molecular Response (MMR) at week 48
Timepoint [1] 0 0
at 48 weeks (48 weeks after last patient first dose)
Secondary outcome [1] 0 0
Major Molecular response at week 96
Timepoint [1] 0 0
at 96 weeks (96 weeks after last patient first dose)
Secondary outcome [2] 0 0
Time to discontinuation of study treatment due to Adverse Events (TTDAE)
Timepoint [2] 0 0
96 weeks after last patient first dose
Secondary outcome [3] 0 0
Major Molecular response at scheduled data collection time points
Timepoint [3] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [4] 0 0
Major Molecular response by scheduled data collection time points
Timepoint [4] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [5] 0 0
MR4.0 at scheduled data collection time points
Timepoint [5] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [6] 0 0
MR4.5 at all scheduled data collection time points
Timepoint [6] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [7] 0 0
MR4.0 by scheduled data collection time points
Timepoint [7] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [8] 0 0
MR4.5 by all scheduled data collection time points
Timepoint [8] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [9] 0 0
Complete Hematological response (CHR) at all scheduled data collection time points
Timepoint [9] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [10] 0 0
Complete Hematological response (CHR) by all scheduled data collection time points
Timepoint [10] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [11] 0 0
Complete Cytogenic response (CCyR) at Week 48 & Week 96
Timepoint [11] 0 0
at 48 weeks and at 96 weeks (48 weeks and 96 weeks after last patient first dose)
Secondary outcome [12] 0 0
Complete Cytogenic response (CCyR) by Week 48 & Week 96
Timepoint [12] 0 0
at 48 weeks and at 96 weeks (48 weeks and 96 weeks after last patient first dose)
Secondary outcome [13] 0 0
Duration of MMR
Timepoint [13] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [14] 0 0
Duration of MR4.0
Timepoint [14] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [15] 0 0
Duration of MR4.5
Timepoint [15] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [16] 0 0
Time to first MMR
Timepoint [16] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [17] 0 0
Time to first MR4.0
Timepoint [17] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [18] 0 0
Time to first MR4.5
Timepoint [18] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [19] 0 0
BCR-ABL1=1% at scheduled data collection time points
Timepoint [19] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [20] 0 0
BCR-ABL1=1% by scheduled data collection time points
Timepoint [20] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [21] 0 0
Time to treatment failure (TTF)
Timepoint [21] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [22] 0 0
Failure Free Survival (FFS)
Timepoint [22] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [23] 0 0
Event Free Survival (EFS)
Timepoint [23] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [24] 0 0
Progression Free Survival (PFS)
Timepoint [24] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [25] 0 0
Overall Survival (OS)
Timepoint [25] 0 0
Planned total follow-up duration of 5 years
Secondary outcome [26] 0 0
Trough plasma concentrations.
Timepoint [26] 0 0
48 weeks after last patient first dose
Secondary outcome [27] 0 0
Pharmacokinetics (PK) of Asciminib: Cmax
Timepoint [27] 0 0
48 weeks after last patient first dose
Secondary outcome [28] 0 0
PK of Asciminib: Tmax
Timepoint [28] 0 0
48 weeks after last patient first dose
Secondary outcome [29] 0 0
PK of Asciminib: AUCtau and AUClast
Timepoint [29] 0 0
48 weeks after last patient first dose
Secondary outcome [30] 0 0
PK of Asciminib: CL/F
Timepoint [30] 0 0
48 weeks after last patient first dose
Secondary outcome [31] 0 0
Change from baseline in overall scores and individual scales of the EORTC QLQ-C30
Timepoint [31] 0 0
baseline, 48 weeks after last patient first dose, 96 weeks after last patient first dose
Secondary outcome [32] 0 0
Change from baseline in overall scores and individual scales of the EORTC QLQ-CML24
Timepoint [32] 0 0
baseline, 48 weeks after last patient first dose, 96 weeks after last patient first dose

Eligibility
Key inclusion criteria
* Participants eligible for inclusion in this study must meet all of the following criteria:

1. Male or female patients = 18 years of age.
2. Participants with CML-CP within 3 months of diagnosis.
3. Diagnosis of CML-CP (ELN 2020 criteria) with cytogenetic confirmation of Philadelphia chromosome
* Documented chronic phase CML will meet all the below criteria (Hochhaus et al 2020):

* < 15% blasts in peripheral blood and bone marrow,
* < 30% blasts plus promyelocytes in peripheral blood and bone marrow,
* < 20% basophils in the peripheral blood,
* Platelet count = 100 x 109/L (= 100,000/mm3),
* No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0,or 1. 5. Adequate end organ function as defined by:
* Total bilirubin < 3 x ULN; patients with Gilbert's syndrome may only be included if total bilirubin = 3.0 x ULN or direct bilirubin = 1.5 x ULN
* Creatinine clearance (CrCl) = 30 mL/min as calculated using Cockcroft-Gault formula,
* Serum lipase = 1.5 x ULN. For serum lipase > ULN - = 1.5 x ULN, value must be considered not clinically significant and not associated with risk factors for acute pancreatitis 6. Participants must have the following laboratory values within normal limits or corrected to within normal limits with supplements prior to randomization:
* Potassium (potassium increase of up to 6.0 mmol/L is acceptable if associated with CrCl* = 90 mL/min)
* Total calcium (corrected for serum albumin); (calcium increase of up to 12.5 mg/dl or 3.1 mmol/L is acceptable if associated with CrCl* = 90 mL/min)
* Magnesium (magnesium increase of up to 3.0 mg/dL or 1.23 mmol/L if associated with CrCl* = 90 mL/min)
* For patients with mild to moderate renal impairment (CrCl* = 30 mL/min and <90 mL/min) - potassium, total calcium (corrected for serum albumin) and magnesium should be = LLN or corrected to within normal limits with supplements prior to randomization.
* *CrCl as calculated using Cockcroft-Gault formula 7. Ability to provide written informed consent prior to any study related screening procedures being performed.

8. Evidence of typical BCR-ABL1 transcript [e14a2 and/or e13a2] at the time of screening which is amenable to standardized Real time quantitative polymerase chain reaction (RQ-PCR) quantification.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previous treatment of CML with any other anticancer agents including chemotherapy and/or biologic agents or prior stem cell transplant, with the exception of hydroxyurea and/or anagrelide. Treatment with either imatinib, or nilotinib, or dasatinib or bosutinib for =2 weeks is allowed, but no other treatment with other tyrosine kinase inhibitors prior to randomization is permitted.
2. Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required).
3. Impaired cardiac function or cardiac repolarization abnormality including but not limited to any one of the following:

* History within 6 months prior to starting study treatment of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG)
* Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block)
* QTc = 450 ms (male patients), =460 ms (female patients) on the average of three serial baseline ECG (using the QTcF formula) as determined by central reading. If QTcF = 450 ms and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc.
* Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
* Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia
* Concomitant medication(s) with a "Known risk of Torsades de Pointes" per www.crediblemeds.org/ that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication.•Inability to determine the QTcF interval
4. Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes, active or uncontrolled infection; uncontrolled arterial or pulmonary hypertension, uncontrolled clinically significant hyperlipidemia). Please refer to Section 6.3.1
5. History of significant congenital or acquired bleeding disorder unrelated to cancer.
6. Major surgery within 4 weeks prior to study entry or who have not recovered from prior surgery.
7. History of other active malignancy within 3 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively
8. History of acute pancreatitis within 1 year prior to randomization or medical history of chronic pancreatitis.
9. History of chronic liver disease leading to severe hepatic impairment, or ongoing acute liver disease.

Other protocol-defined Inclusion/exclusion criteria will 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Kingswood
Recruitment hospital [2] 0 0
Novartis Investigative Site - Port Macquarie
Recruitment hospital [3] 0 0
Novartis Investigative Site - Adelaide
Recruitment hospital [4] 0 0
Novartis Investigative Site - SouthPort
Recruitment postcode(s) [1] 0 0
2747 - Kingswood
Recruitment postcode(s) [2] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
4215 - SouthPort
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
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Massachusetts
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United States of America
State/province [5] 0 0
North Carolina
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United States of America
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Oregon
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United States of America
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South Dakota
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United States of America
State/province [8] 0 0
Tennessee
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United States of America
State/province [9] 0 0
Texas
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Austria
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Upper Austria
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Belgium
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Bruxelles
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Belgium
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Leuven
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Bulgaria
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Varna
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Canada
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Alberta
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Canada
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Ontario
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China
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Guangdong
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China
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Henan
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China
State/province [18] 0 0
Hubei
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China
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Jiangsu
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China
State/province [20] 0 0
Shanxi
Country [21] 0 0
China
State/province [21] 0 0
Sichuan
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China
State/province [22] 0 0
Zhejiang
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China
State/province [23] 0 0
Beijing
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China
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Lanzhou
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China
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Tianjin
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Czechia
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Czech Republic
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Czechia
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CZE
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Czechia
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Poruba
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Denmark
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Aarhus
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Denmark
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Copenhagen
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Finland
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Helsinki
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France
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Bordeaux
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France
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Lyon
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France
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Nantes Cedex 1
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France
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Paris 10
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Germany
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Baden Wuerttemberg
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Germany
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Aachen
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Germany
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Berlin
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Germany
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Frankfurt
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Jena
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Luebeck
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Hungary
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Debrecen
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Hungary
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Kaposvar
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Hungary
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Kecskemet
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India
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Delhi
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Israel
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Petah Tikva
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Israel
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Ramat Gan
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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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MI
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Italy
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RE
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Italy
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RM
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Italy
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VR
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Japan
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Aichi
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Japan
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Fukuoka
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Japan
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Fukushima
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Japan
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Hokkaido
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Japan
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Hyogo
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Japan
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Okayama
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Japan
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Osaka
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Japan
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Tochigi
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Japan
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Yamanashi
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Japan
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Akita
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Japan
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Yamagata
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Korea, Republic of
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Gyeonggi Do
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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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Malaysia
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Pahang
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Malaysia
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Selangor
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Malaysia
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Pulau Pinang
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Netherlands
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Amsterdam
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Norway
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Bergen
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Norway
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Oslo
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Portugal
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Porto
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Portugal
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Vila Nova De Gaia
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Singapore
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Singapore
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Slovakia
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Slovak Republic
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Spain
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Andalucia
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Spain
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Catalunya
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Spain
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Murcia
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Spain
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Navarra
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Spain
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Madrid
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Sweden
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Goteborg
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Sweden
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Lund
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Sweden
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Stockholm
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Switzerland
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Bellinzona
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Taiwan
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Taichung
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United Kingdom
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London
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United Kingdom
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Nottingham
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United Kingdom
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Oxford

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 review panel on the basis of scientific merit. All data provided are anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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?
IPD available at link: https://www.clinicalstudydatarequest.com


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.