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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02670083




Registration number
NCT02670083
Ethics application status
Date submitted
28/01/2016
Date registered
1/02/2016
Date last updated
16/07/2020

Titles & IDs
Public title
A Study Evaluating the Efficacy and Safety of Crenezumab Versus Placebo in Participants With Prodromal to Mild Alzheimer's Disease (AD).
Scientific title
A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy And Safety Study of Crenezumab in Patients With Prodromal to Mild Alzheimer's Disease.
Secondary ID [1] 0 0
2015-003034-27
Secondary ID [2] 0 0
BN29552
Universal Trial Number (UTN)
Trial acronym
CREAD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

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

Placebo comparator: Placebo - Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.

Experimental: Crenezumab - Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.


Treatment: Drugs: Crenezumab
Crenezumab was administered by intravenous (IV) infusion at 60mg/kg as per the dosing schedule described above.

Treatment: Drugs: Placebo
Placebo was administered by intravenous (IV) infusion at 60mg/kg as per the dosing schedule described above.

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

Outcomes
Primary outcome [1] 0 0
Change From Baseline to Week 105 in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score
Timepoint [1] 0 0
Baseline, Week 105
Secondary outcome [1] 0 0
Change From Baseline to Week 105 on Cognition, as Assessed by Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) (Subscale) 13 (ADAS-Cog-13)
Timepoint [1] 0 0
Baseline, Week 105
Secondary outcome [2] 0 0
Change From Baseline to Week 105 on Cognition, as Assessed by Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) (Subscale) 11 (ADAS-Cog-11)
Timepoint [2] 0 0
Baseline, Week 105
Secondary outcome [3] 0 0
Change From Baseline to Week 105 on Severity of Dementia, Assessed Using the CDR-Global Score (CDR-GS)
Timepoint [3] 0 0
Baseline, Week 105
Secondary outcome [4] 0 0
Change From Baseline to Week 105 on Severity of Dementia, Assessed Using the Mini Mental State Evaluation (MMSE)
Timepoint [4] 0 0
Baseline, Week 105
Secondary outcome [5] 0 0
Change From Baseline to Week 105 on Function as Assessed by the ADCS-ADL Total Score
Timepoint [5] 0 0
Baseline, Week 105
Secondary outcome [6] 0 0
Change From Baseline to Week 105 on Function as Assessed by the ADCS-instrumental (ADCS-iADL) Subscore
Timepoint [6] 0 0
Baseline, Week 105
Secondary outcome [7] 0 0
Change From Baseline to Week 105 on a Measure of Dependence Derived From the ADCS-ADL Score
Timepoint [7] 0 0
Baseline, Week 105
Secondary outcome [8] 0 0
Change From Baseline to Week 105 Assessed Using the Neuropsychiatric Inventory Questionnaire (NPI-Q)
Timepoint [8] 0 0
Baseline, Week 105
Secondary outcome [9] 0 0
Quality of Life-Alzheimer's Disease (QoL-AD) Scale Score
Timepoint [9] 0 0
Baseline up to Week 105
Secondary outcome [10] 0 0
Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) Scale Score
Timepoint [10] 0 0
Baseline up to Week 105
Secondary outcome [11] 0 0
EQ-5D Questionnaire Domain Score for Participants
Timepoint [11] 0 0
Baseline up to Week 105
Secondary outcome [12] 0 0
EQ-5D Questionnaire Domain Score for Caregivers
Timepoint [12] 0 0
Baseline up to Week 105
Secondary outcome [13] 0 0
Percentage of Participants With Adverse Event (AEs) and Serious Adverse Event (SAEs)
Timepoint [13] 0 0
Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
Secondary outcome [14] 0 0
Percentage of Participants With Anti-Crenezumab Antibodies
Timepoint [14] 0 0
Baseline up to Week 105
Secondary outcome [15] 0 0
Serum Concentration of Crenezumab
Timepoint [15] 0 0
Pre-infusion (0 hour), 60-90 minutes post-infusion on Day 1 Week 1 and on Week 25; Weeks 13, 37 (Pre-dose), 53, 77 and 105 (infusion length = as per the Pharmacy Manual)
Secondary outcome [16] 0 0
Plasma Amyloid Beta (Abeta) 40 Concentrations
Timepoint [16] 0 0
Week 1 Day 1; Weeks 13, 25, 53, 77 and 105
Secondary outcome [17] 0 0
Plasma Amyloid Beta (Abeta) 42 Concentrations
Timepoint [17] 0 0
Week 1 Day 1; Weeks 13, 25, 53, 77 and 105
Secondary outcome [18] 0 0
Percentage Change From Baseline to Week 105 in Whole Brain Volume as Determined by Magnetic Resonance Imaging (MRI)
Timepoint [18] 0 0
Baseline, Week 105
Secondary outcome [19] 0 0
Percentage Change From Baseline to Week 105 in Ventricle Volume as Determined by Magnetic Resonance Imaging (MRI)
Timepoint [19] 0 0
Baseline, Week 105
Secondary outcome [20] 0 0
Percentage Change From Baseline to Week 105 in Hippocampal Volume as Determined by Magnetic Resonance Imaging (MRI)
Timepoint [20] 0 0
Baseline, Week 105

Eligibility
Key inclusion criteria
* Weight between 40 and 120 kilograms (Kg) inclusive
* Availability of a person (referred to as the "caregiver") who in the investigator's judgment:
* Has frequent and sufficient contact with the participant to be able to provide accurate information regarding the participant's cognitive and functional abilities, agrees to provide information at clinic visits (which require partner input for scale completion), signs the necessary consent form, and has sufficient cognitive capacity to accurately report upon the participant's behavior and cognitive and functional abilities
* Fluency in the language of the tests used at the study site
* Adequate visual and auditory acuity, in the investigator's judgment, sufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted)
* Evidence of the AD pathological process, by a positive amyloid assessment either on cerebrospinal fluid (CSF) amyloid beta 1-42 levels as measured on the Elecsys beta-amyloid(1-42) test system or amyloid PET scan by qualitative read by the core/central PET laboratory
* Demonstrated abnormal memory function at screening (up to 4 weeks before screening begins) or screening (FCSRT cueing index =<0.67 AND free recall =<27)
* Screening mini mental state examination (MMSE) score of greater than or equal to (>=) 22 points and Clinical Dementia Rating-Global Score (CDR-GS) of 0.5 or 1.0
* Meets National Institute on Aging/Alzheimer's Association (NIAAA) core clinical criteria for probable AD dementia or prodromal AD (consistent with the NIAAA diagnostic criteria and guidelines for mild cognitive impairment (MCI)
* If receiving symptomatic AD medications, the dosing regimen must have been stable for 3 months prior to screening
* Participant must have completed at least 6 years of formal education after the age of 5 years
Minimum age
50 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Any evidence of a condition other than AD that may affect cognition such as other dementias, stroke, brain damage, autoimmune disorders (e.g. multiple sclerosis) or infections with neurological sequelae.
* History of major psychiatric illness such as schizophrenia or major depression (if not considered in remission)
* At risk of suicide in the opinion of the investigator
* Any abnormal MRI findings, such as presence of cerebral vascular pathology, cortical stroke, etc or inability to tolerate MRI procedures or contraindication to MRI
* Unstable or clinically significant cardiovascular (e.g., myocardial infarction), kidney or liver disease
* Uncontrolled hypertension
* Screening hemoglobin A1c (HbA1C) >8%
* Poor peripheral venous access
* History of cancer except:

If considered to be cured or If not being actively treated with anti-cancer therapy or radiotherapy

- Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins

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 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
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)
SA,VIC,WA
Recruitment hospital [1] 0 0
The Queen Elizabeth Hospital; Neurology - Woodville
Recruitment hospital [2] 0 0
Caulfield Hospital; Aged Psychiatry Research Unit - Caulfield
Recruitment hospital [3] 0 0
Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre - Heidelberg West
Recruitment hospital [4] 0 0
Neurodegenerative Disorders Research; Neurology - West Perth
Recruitment postcode(s) [1] 0 0
5011 - Woodville
Recruitment postcode(s) [2] 0 0
3162 - Caulfield
Recruitment postcode(s) [3] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [4] 0 0
6005 - West 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
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Maine
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Mississippi
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Oklahoma
Country [17] 0 0
United States of America
State/province [17] 0 0
Oregon
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
Texas
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
United States of America
State/province [21] 0 0
Wisconsin
Country [22] 0 0
Austria
State/province [22] 0 0
Linz
Country [23] 0 0
Belgium
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Gent
Country [24] 0 0
Bulgaria
State/province [24] 0 0
Sofia
Country [25] 0 0
Canada
State/province [25] 0 0
British Columbia
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario
Country [27] 0 0
Canada
State/province [27] 0 0
Quebec
Country [28] 0 0
Costa Rica
State/province [28] 0 0
San Jose
Country [29] 0 0
Costa Rica
State/province [29] 0 0
San José
Country [30] 0 0
Croatia
State/province [30] 0 0
Zagreb
Country [31] 0 0
Czechia
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Hradec Králové
Country [32] 0 0
Czechia
State/province [32] 0 0
Praha
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Denmark
State/province [33] 0 0
Aarhus N
Country [34] 0 0
Denmark
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København Ø
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Finland
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Tampere
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Finland
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Turku
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France
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Bobigny
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France
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Bron
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France
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Montpellier
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France
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Paris
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France
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Poitiers
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France
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Strasbourg
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France
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Toulouse
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Germany
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München
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Germany
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Münster
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Germany
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Nürnberg
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Germany
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Rostock
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Germany
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Ulm
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Germany
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Westerstede
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Germany
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Witten
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Hong Kong
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Hong Kong
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Hungary
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Budapest
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Hungary
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Nyíregyháza
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Hungary
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Szeged
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Hungary
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Tatabánya
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Hungary
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VAC
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Italy
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Lazio
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Italy
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Liguria
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Italy
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Lombardia
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Italy
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Umbria
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Hiroshima
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Kyoto
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Mie
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Nagano
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Niigata
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Seoul
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Vilnius
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Culiacan
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Mexico
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Monterrey
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Mexico
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Saltillo
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Bialystok
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Poznan
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Siemianowice Slaskie
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Warszawa
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Portugal
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Amadora
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Portugal
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Loures
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Russian Federation
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Kazan
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Russian Federation
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Moscow
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Russian Federation
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Saratov
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Russian Federation
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St Petersburg
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Russian Federation
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St. Petersburg
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Slovenia
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Maribor
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Spain
State/province [87] 0 0
Barcelona
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Spain
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Caceres
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Spain
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Cantabria
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Spain
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Navarra
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Spain
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Salamanca
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Spain
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Albacete
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Spain
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Burgos
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Spain
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Madrid
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Spain
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Malaga
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Spain
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Murcia
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Spain
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Valencia
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Spain
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Zaragoza
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Sweden
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Malmö
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Sweden
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Mölndal
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Sweden
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Stockholm
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Switzerland
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Basel
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Turkey
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Ankara
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Turkey
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Eskisehir
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Turkey
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Istanbul
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Turkey
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Samsun
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Ukraine
State/province [107] 0 0
KIEV Governorate
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Ukraine
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Kiev
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United Kingdom
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Blackburn
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United Kingdom
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Chertsey
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United Kingdom
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Coventry
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United Kingdom
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London
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United Kingdom
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Manchester
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United Kingdom
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Newcastle Upon Tyne
Country [115] 0 0
United Kingdom
State/province [115] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.