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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02598297




Registration number
NCT02598297
Ethics application status
Date submitted
27/10/2015
Date registered
5/11/2015

Titles & IDs
Public title
Phase III Study Investigating the Efficacy and Safety of Ruxolitinib in Early Myelofibrosis Patients With High Molecular Risk Mutations.
Scientific title
A Randomized, Double Blind, Placebo-controlled, Multicenter, Phase III Study Investigating the Efficacy and Safety of Ruxolitinib in Early Myelofibrosis Patients With High Molecular Risk Mutations
Secondary ID [1] 0 0
2014-004928-21
Secondary ID [2] 0 0
CINC424A2353
Universal Trial Number (UTN)
Trial acronym
ReTHINK
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelofibrosis With High Molecular Risk Mutations 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

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

Active comparator: Ruxolitinib - Two tablets of ruxolitinib 5 mg were administered orally twice per day.

Placebo comparator: Ruxolitinib Placebo - Two tablets of 5mg placebo were administered orally twice per day.


Treatment: Drugs: Ruxolitinib
5 mg tablet for oral use

Treatment: Drugs: Ruxolitinib Placebo
5 mg placebo tablet for oral use
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS-1)
Timepoint [1] 0 0
From randomization till disease progression (estimated to be assessed up 48 months)
Secondary outcome [1] 0 0
Time to Primary Progression (TTP)
Timepoint [1] 0 0
From randomization till progression (estimated to be assessed up to 48 months)
Secondary outcome [2] 0 0
Percentage Change in Spleen Volume From Baseline
Timepoint [2] 0 0
From baseline and assessed on 12 week intervals until end of treatment (EOT)
Secondary outcome [3] 0 0
Percentage Change in Symptoms From Baseline Using MF-7
Timepoint [3] 0 0
From Baseline and assessed every 4 weeks until end of treatment
Secondary outcome [4] 0 0
Number of Participants With Specific Subscale Scores (From Baseline) Using EQ-5D
Timepoint [4] 0 0
From Baseline and assessed every 4 weeks until end of treatment
Secondary outcome [5] 0 0
Overall Survival
Timepoint [5] 0 0
Time from randomization to date of death due to any cause (estimated to be assessed up to 48 months).
Secondary outcome [6] 0 0
Plasma Ruxolitinib Concentrations
Timepoint [6] 0 0
Week 12, Wk 48
Secondary outcome [7] 0 0
Progression Free Survival (PFS-2)
Timepoint [7] 0 0
From date of randomization until second disease progression or death, whichever comes first (estimated to be assessed up to 72 months)
Secondary outcome [8] 0 0
Quality-adjusted Life Years From Baseline
Timepoint [8] 0 0
Change from Baseline compared with scheduled study visits at the following intervals every 4 weeks up to week 24, every 8 weeks up to Week 48, every 12 weeks past Wk 48 until End of treatment and 30 day follow up visit
Secondary outcome [9] 0 0
Time to First Progressive Splenomegaly (TTPS)
Timepoint [9] 0 0
From randomization until earliest time to progressive splenomegaly (estimated to be assessed up to 48 months)
Secondary outcome [10] 0 0
Time to First Symptomatic Progression (TTSP)
Timepoint [10] 0 0
From randomization until symptomatic progression (MF-7)(estimated to be assessed up to 48 months)

Eligibility
Key inclusion criteria
* Confirmed diagnosis of MF with bone marrow fibrosis of at least Grade 1; irrespective of JAK2 mutational status
* Patients with at least one mutation in one of the five HMR genes (ASXL1, EZH2, SRSF2 and IDH1/2)
* Patients with non-palpable spleen or spleen palpable = 5 cm from the left costal margin to the point of greatest splenic protrusion
* Patients with MF-7 score of = 15, with each individual symptom score of = 3
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients with prior treatment with ruxolitinib or other JAK inhibitors.

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
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/02/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/10/2017
Sample size
Target
Accrual to date
Final
49
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Concord NSW
Recruitment hospital [2] 0 0
Novartis Investigative Site - Liverpool
Recruitment hospital [3] 0 0
Novartis Investigative Site - Wooloongabba
Recruitment hospital [4] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
2139 - Concord NSW
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
4102 - Wooloongabba
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Salzburg
Country [2] 0 0
Austria
State/province [2] 0 0
Vienna
Country [3] 0 0
Belgium
State/province [3] 0 0
Antwerpen
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Belgium
State/province [4] 0 0
Leuven
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Belgium
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Liege
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Brazil
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SP
Country [7] 0 0
Brazil
State/province [7] 0 0
Sao Paulo
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Denmark
State/province [9] 0 0
Aalborg
Country [10] 0 0
Denmark
State/province [10] 0 0
Herlev
Country [11] 0 0
France
State/province [11] 0 0
Bayonne Cedex
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France
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Angers Cedex 1
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France
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Brest
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France
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Chambéry Cedex
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France
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Grenoble
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France
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Lille Cedex
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France
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Nice Cedex
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France
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Rouen Cedex 1
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France
State/province [19] 0 0
Vandoeuvre Les Nancy
Country [20] 0 0
Germany
State/province [20] 0 0
Schleswig-holstein
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Germany
State/province [21] 0 0
Aachen
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Germany
State/province [22] 0 0
Bochum
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Germany
State/province [23] 0 0
Bonn
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Germany
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Chemnitz
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Germany
State/province [25] 0 0
Dresden
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Germany
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Essen
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Germany
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Halle S
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Germany
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Heilbronn
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Germany
State/province [29] 0 0
Koeln
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Germany
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Leipzig
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Germany
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Muenchen
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Germany
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Nordhorn
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Germany
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Rostock
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Germany
State/province [34] 0 0
Ulm
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Greece
State/province [35] 0 0
GR
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Greece
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Athens
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Greece
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Patras
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Hong Kong
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Hong Kong
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Hungary
State/province [39] 0 0
Budapest
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Hungary
State/province [40] 0 0
Debrecen
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Hungary
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Kaposvar
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Israel
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Afula
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Tel Aviv
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Israel
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Zrifin
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Italy
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BA
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Italy
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BO
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Italy
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BS
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CT
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Italy
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FI
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Italy
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Lazio
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Italy
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MI
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Italy
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PV
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Italy
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RE
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Italy
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TO
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Italy
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TR
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Italy
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VA
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Japan
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Aichi
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Japan
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Fukuoka
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Gunma
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Japan
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Hyogo
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Japan
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Kanagawa
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Japan
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Osaka
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Japan
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Tokyo
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Japan
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Yamanashi
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Norway
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Bergen
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Norway
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Loerenskog
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Poland
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Lodz
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Torun
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Poland
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Wroclaw
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Portugal
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Faro
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Portugal
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Porto
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Russian Federation
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Moscow
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Russian Federation
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Saint Petersburg
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Russian Federation
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St Petersburg
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Singapore
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Singapore
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Spain
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Andalucia
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Madrid
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Sweden
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Göteborg
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Sweden
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Huddinge
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Sweden
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Lund
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Sweden
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Uddevalla
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Switzerland
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Basel
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Switzerland
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St Gallen
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Switzerland
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Zuerich
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Taiwan
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Chiayi Hsien
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Taiwan
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Kaohsiung City
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Taiwan
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Taipei
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Taiwan
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Taoyuan
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Turkey
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Ankara
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Turkey
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Istanbul
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Turkey
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Samsun
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Turkey
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Talas / Kayseri
Country [95] 0 0
United Kingdom
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Birmingham
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United Kingdom
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Bristol
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United Kingdom
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Leeds
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United Kingdom
State/province [98] 0 0
London
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United Kingdom
State/province [99] 0 0
Manchester

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 is 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?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02598297