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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03114657




Registration number
NCT03114657
Ethics application status
Date submitted
28/03/2017
Date registered
14/04/2017
Date last updated
16/07/2020

Titles & IDs
Public title
A Study of Crenezumab Versus Placebo to Evaluate the Efficacy and Safety 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
2016-003288-20
Secondary ID [2] 0 0
BN29553
Universal Trial Number (UTN)
Trial acronym
CREAD 2
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 77 in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Scale Score
Timepoint [1] 0 0
Baseline, Week 77
Secondary outcome [1] 0 0
Change From Baseline to Week 77 in Alzheimer's Disease Assessment Scale-Cognition 13 (ADAS-Cog-13) Subscale Score
Timepoint [1] 0 0
Baseline, Week 77
Secondary outcome [2] 0 0
Change From Baseline to Week 77 in Alzheimer's Disease Assessment Scale-Cognition 11 (ADAS-Cog-11) Subscale Score
Timepoint [2] 0 0
Baseline, Week 77
Secondary outcome [3] 0 0
Change From Baseline to Week 77 on Severity of Dementia, Assessed Using the CDR-Global Score (CDR-GS)
Timepoint [3] 0 0
Baseline, Week 77
Secondary outcome [4] 0 0
Change From Baseline to Week 77 on Severity of Dementia, Assessed Using the Mini Mental State Evaluation (MMSE)
Timepoint [4] 0 0
Baseline, Week 77
Secondary outcome [5] 0 0
Change From Baseline to Week 77 on Function as Assessed by (ADCS-ADL) Total Score
Timepoint [5] 0 0
Baseline, Week 77
Secondary outcome [6] 0 0
Change From Baseline to Week 77 on Function as Assessed by (ADCS-iADL) Instrumental Score
Timepoint [6] 0 0
Baseline, Week 77
Secondary outcome [7] 0 0
Change From Baseline to Week 77 on Function as Assessed by the Functional Activities Questionnaire (FAQ) Total Score
Timepoint [7] 0 0
Baseline, Week 77
Secondary outcome [8] 0 0
Change From Baseline to Week 77 on a Measure of Dependence Level Assessed From the ADCS-ADL Score
Timepoint [8] 0 0
Baseline, Week 77
Secondary outcome [9] 0 0
Change From Baseline to Week 53 on Behavior in Neuropsychiatric Inventory Questionnaire (NPI-Q) Total Score
Timepoint [9] 0 0
Baseline, Week 53
Secondary outcome [10] 0 0
Quality of Life-Alzheimer's Disease (QoL-AD) Scale Score
Timepoint [10] 0 0
Baseline, Week 77
Secondary outcome [11] 0 0
Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) Scale Score
Timepoint [11] 0 0
Baseline, Week 53
Secondary outcome [12] 0 0
European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Domain Scores for Participants
Timepoint [12] 0 0
Baseline, Week 77
Secondary outcome [13] 0 0
European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Domain Scores for Caregivers
Timepoint [13] 0 0
Baseline, Week 77
Secondary outcome [14] 0 0
Percentage of Participants With Adverse Event (AEs) and Serious Adverse Event (SAEs)
Timepoint [14] 0 0
Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
Secondary outcome [15] 0 0
Percentage of Participants With Anti-Crenezumab Antibodies
Timepoint [15] 0 0
Baseline up to Week 105
Secondary outcome [16] 0 0
Serum Concentration of Crenezumab
Timepoint [16] 0 0
Pre-infusion (0 hour), 60-90 minutes post-infusion on Day 1 Week 1 and on Week 25; Weeks 13 (Pre-dose), 37 (Pre-dose), 53 (Pre-dose) and 77 (Pre-dose) (infusion length = as per the Pharmacy Manual)
Secondary outcome [17] 0 0
Plasma Amyloid Beta (Abeta) 40 Concentrations
Timepoint [17] 0 0
Week 1 Day 1; Weeks 53
Secondary outcome [18] 0 0
Plasma Amyloid Beta (Abeta) 42 Concentrations
Timepoint [18] 0 0
Week 1 Day 1; Weeks 53
Secondary outcome [19] 0 0
Percentage Change From Baseline to Week 105 in Whole Brain 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 Ventricle Volume as Determined by Magnetic Resonance Imaging (MRI)
Timepoint [20] 0 0
Baseline, Week 105
Secondary outcome [21] 0 0
Percentage Change From Baseline to Week 105 in Hippocampal Volume as Determined by Magnetic Resonance Imaging (MRI)
Timepoint [21] 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)
NSW,SA
Recruitment hospital [1] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [2] 0 0
Central Coast Neurosciences Research - Erina
Recruitment hospital [3] 0 0
Hornsby Ku-ring-gai Hospital; Division of Rehabilitation & Aged Care - Hornsby
Recruitment hospital [4] 0 0
The Queen Elizabeth Hospital; Neurology - Woodville
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2250 - Erina
Recruitment postcode(s) [3] 0 0
2077 - Hornsby
Recruitment postcode(s) [4] 0 0
5011 - Woodville
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
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
District of Columbia
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Georgia
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
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
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
Mississippi
Country [13] 0 0
United States of America
State/province [13] 0 0
Nebraska
Country [14] 0 0
United States of America
State/province [14] 0 0
Nevada
Country [15] 0 0
United States of America
State/province [15] 0 0
New Jersey
Country [16] 0 0
United States of America
State/province [16] 0 0
New York
Country [17] 0 0
United States of America
State/province [17] 0 0
North Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Ohio
Country [19] 0 0
United States of America
State/province [19] 0 0
Oregon
Country [20] 0 0
United States of America
State/province [20] 0 0
Pennsylvania
Country [21] 0 0
United States of America
State/province [21] 0 0
Tennessee
Country [22] 0 0
United States of America
State/province [22] 0 0
Texas
Country [23] 0 0
United States of America
State/province [23] 0 0
Virginia
Country [24] 0 0
Argentina
State/province [24] 0 0
Buenos Aires
Country [25] 0 0
Argentina
State/province [25] 0 0
Caba
Country [26] 0 0
Argentina
State/province [26] 0 0
Cordoba
Country [27] 0 0
Belgium
State/province [27] 0 0
Brugge
Country [28] 0 0
Belgium
State/province [28] 0 0
Kortrijk
Country [29] 0 0
Belgium
State/province [29] 0 0
Leuven
Country [30] 0 0
Brazil
State/province [30] 0 0
DF
Country [31] 0 0
Brazil
State/province [31] 0 0
MG
Country [32] 0 0
Brazil
State/province [32] 0 0
PR
Country [33] 0 0
Brazil
State/province [33] 0 0
RJ
Country [34] 0 0
Brazil
State/province [34] 0 0
RS
Country [35] 0 0
Brazil
State/province [35] 0 0
SP
Country [36] 0 0
Canada
State/province [36] 0 0
British Columbia
Country [37] 0 0
Canada
State/province [37] 0 0
Nova Scotia
Country [38] 0 0
Canada
State/province [38] 0 0
Ontario
Country [39] 0 0
Canada
State/province [39] 0 0
Quebec
Country [40] 0 0
China
State/province [40] 0 0
Beijing
Country [41] 0 0
China
State/province [41] 0 0
Tianjin (??)
Country [42] 0 0
Denmark
State/province [42] 0 0
Aarhus N
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Denmark
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København Ø
Country [44] 0 0
Estonia
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Tallinn
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France
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Bordeaux
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France
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Colmar
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France
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Lille
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France
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Limoges
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France
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Paris
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France
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Reims
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France
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Rennes
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France
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Rouen
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France
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St Herblain
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France
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Villeurbanne
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Germany
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Berlin
Country [56] 0 0
Germany
State/province [56] 0 0
Frankfurt
Country [57] 0 0
Germany
State/province [57] 0 0
Freiburg
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Germany
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Homburg/Saar
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Germany
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Leipzig
Country [60] 0 0
Germany
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Mittweida
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Germany
State/province [61] 0 0
München
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Israel
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Haifa
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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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Lazio
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Italy
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Lombardia
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Italy
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Molise
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Italy
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Piemonte
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Italy
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Toscana
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Japan
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Aichi
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Japan
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Chiba
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Japan
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Fukuoka
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Hiroshima
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Japan
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Hyogo
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Japan
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Iwate
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Japan
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Kagawa
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Japan
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Kanagawa
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Japan
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Kyoto
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Japan
State/province [79] 0 0
Nagano
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Japan
State/province [80] 0 0
Okayama
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Japan
State/province [81] 0 0
Osaka
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Japan
State/province [82] 0 0
Shizuoka
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Japan
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Tokyo
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Korea, Republic of
State/province [84] 0 0
Busan
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Korea, Republic of
State/province [85] 0 0
Incheon
Country [86] 0 0
Korea, Republic of
State/province [86] 0 0
Seongnam-si
Country [87] 0 0
Korea, Republic of
State/province [87] 0 0
Seoul
Country [88] 0 0
Norway
State/province [88] 0 0
Lørenskog
Country [89] 0 0
Norway
State/province [89] 0 0
Oslo
Country [90] 0 0
Peru
State/province [90] 0 0
Lima
Country [91] 0 0
Poland
State/province [91] 0 0
Bydgoszcz
Country [92] 0 0
Poland
State/province [92] 0 0
Szczecin
Country [93] 0 0
Poland
State/province [93] 0 0
Warszawa
Country [94] 0 0
Poland
State/province [94] 0 0
Wroclaw
Country [95] 0 0
Portugal
State/province [95] 0 0
Braga
Country [96] 0 0
Portugal
State/province [96] 0 0
Coimbra
Country [97] 0 0
Portugal
State/province [97] 0 0
Matosinhos
Country [98] 0 0
Portugal
State/province [98] 0 0
Porto
Country [99] 0 0
Russian Federation
State/province [99] 0 0
Sankt Petersburg
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Russian Federation
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Sverdlovsk
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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
State/province [103] 0 0
Nizhny Novgorod
Country [104] 0 0
Russian Federation
State/province [104] 0 0
St Petersburg
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Russian Federation
State/province [105] 0 0
Tomsk
Country [106] 0 0
Serbia
State/province [106] 0 0
Belgrade
Country [107] 0 0
Serbia
State/province [107] 0 0
Kragujevac
Country [108] 0 0
South Africa
State/province [108] 0 0
Johannesburg
Country [109] 0 0
Spain
State/province [109] 0 0
Alicante
Country [110] 0 0
Spain
State/province [110] 0 0
Barcelona
Country [111] 0 0
Spain
State/province [111] 0 0
Caceres
Country [112] 0 0
Spain
State/province [112] 0 0
Cantabria
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Spain
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Girona
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Spain
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Guipuzcoa
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Spain
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LA Coruña
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Spain
State/province [116] 0 0
LA Rioja
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Spain
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Madrid
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Spain
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Navarra
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Spain
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Vizcaya
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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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Castellon
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Spain
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Cordoba
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Spain
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Salamanca
Country [125] 0 0
Spain
State/province [125] 0 0
Sevilla
Country [126] 0 0
Sweden
State/province [126] 0 0
Malmö
Country [127] 0 0
Sweden
State/province [127] 0 0
Mölndal
Country [128] 0 0
Taiwan
State/province [128] 0 0
Changhua County
Country [129] 0 0
Taiwan
State/province [129] 0 0
Kaohsiung
Country [130] 0 0
Taiwan
State/province [130] 0 0
New Taipei City
Country [131] 0 0
Taiwan
State/province [131] 0 0
Taipei
Country [132] 0 0
Taiwan
State/province [132] 0 0
Taoyuan
Country [133] 0 0
Turkey
State/province [133] 0 0
Ankara
Country [134] 0 0
Turkey
State/province [134] 0 0
Istanbul
Country [135] 0 0
Turkey
State/province [135] 0 0
Samsun
Country [136] 0 0
United Kingdom
State/province [136] 0 0
Cheltenham
Country [137] 0 0
United Kingdom
State/province [137] 0 0
Chertsey
Country [138] 0 0
United Kingdom
State/province [138] 0 0
Crowborough
Country [139] 0 0
United Kingdom
State/province [139] 0 0
Dundee
Country [140] 0 0
United Kingdom
State/province [140] 0 0
Edinburgh
Country [141] 0 0
United Kingdom
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Glasgow
Country [142] 0 0
United Kingdom
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London
Country [143] 0 0
United Kingdom
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Manchester
Country [144] 0 0
United Kingdom
State/province [144] 0 0
Oxford
Country [145] 0 0
United Kingdom
State/province [145] 0 0
Southampton

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.