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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05079230




Registration number
NCT05079230
Ethics application status
Date submitted
4/10/2021
Date registered
15/10/2021

Titles & IDs
Public title
Study of Magrolimab Versus Placebo in Combination With Venetoclax and Azacitidine in Participants With Acute Myeloid Leukemia
Scientific title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Magrolimab Versus Placebo in Combination With Venetoclax and Azacitidine in Newly Diagnosed, Previously Untreated Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy
Secondary ID [1] 0 0
2021-003434-36
Secondary ID [2] 0 0
GS-US-590-6154
Universal Trial Number (UTN)
Trial acronym
ENHANCE-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 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

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Magrolimab
Treatment: Drugs - Venetoclax
Treatment: Drugs - Azacitidine
Treatment: Drugs - Magrolimab Placebo

Experimental: Magrolimab + Venetoclax + Azacitidine - Participants will receive

* magrolimab: 1 mg/kg priming dose on Days 1 and 4; 15 mg/kg on Day 8; and 30 mg/kg on Days 11, 15, and then every week for 5 doses and every 2 weeks thereafter
* venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter
* azacitidine: 75 mg/m\^2 on Days 1-7 or Days 1-5 and 8-9 of each cycle

Each cycle is 28 days.

Placebo comparator: Magrolimab Placebo + Venetoclax + Azacitidine - Participants will receive

* magrolimab placebo: Days 1, 4, 8, 11, and 15, then every week for 5 doses and every 2 weeks thereafter
* venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter
* azacitidine: 75 mg/m\^2 on Days 1-7 or Days 1-5 and 8-9 of each cycle

Each cycle is 28 days.


Treatment: Drugs: Magrolimab
Administered intravenously (IV)

Treatment: Drugs: Venetoclax
Tablets administered orally

Treatment: Drugs: Azacitidine
Administered according to region-specific drug labeling, either subcutaneously (SC) or intravenously (IV)

Treatment: Drugs: Magrolimab Placebo
Administered intravenously (IV)

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

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Randomization up to death or end of study (up to 5 years) whichever occurs first
Secondary outcome [1] 0 0
Rate of Complete Remission (CR) + Complete Remission With Partial Hematologic Recovery (CRh)
Timepoint [1] 0 0
Up to 7 months
Secondary outcome [2] 0 0
Rate of Complete Remission (CR)
Timepoint [2] 0 0
Up to 7 months
Secondary outcome [3] 0 0
Event-Free Survival (EFS)
Timepoint [3] 0 0
Randomization up to end of study (up to 5 years)
Secondary outcome [4] 0 0
Duration of CR + CRh in Participants who achieved Complete Remission (CR) or Complete Remission With Partial Hematologic Recovery (CRh)
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [5] 0 0
Duration of Complete Remission (DCR) in Participants who achieved Complete Remission (CR)
Timepoint [5] 0 0
Up to 5 years
Secondary outcome [6] 0 0
Rate of CR/Complete Remission With Partial Hematologic Recovery Without Minimal Residual Disease (CRhMRD-)
Timepoint [6] 0 0
Up to 5 years
Secondary outcome [7] 0 0
Rate of Complete Remission Without Minimal Residual Disease (CRMRD-)
Timepoint [7] 0 0
Up to 5 years
Secondary outcome [8] 0 0
Transfusion Independence Conversion Rate
Timepoint [8] 0 0
First dose date up to End of Treatment (EOT) (up to 5 years)
Secondary outcome [9] 0 0
Time to First Deterioration (TTD) on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) Scale
Timepoint [9] 0 0
Randomization up to end of study (up to 5 years)
Secondary outcome [10] 0 0
TTD on the EORTC QLQ-C30 Physical Functioning Scale
Timepoint [10] 0 0
Randomization up to end of study (up to 5 years)
Secondary outcome [11] 0 0
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
Timepoint [11] 0 0
First dose date up to last dose date (up to 5 years) plus 70 days
Secondary outcome [12] 0 0
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
Timepoint [12] 0 0
First dose date up to last dose date (up to 5 years) plus 70 days
Secondary outcome [13] 0 0
Serum Concentration of Magrolimab over time
Timepoint [13] 0 0
First dose date up to EOT (up to 5 years)
Secondary outcome [14] 0 0
Rate of Anti-Magrolimab Antibody Incidence
Timepoint [14] 0 0
First dose date up to EOT (up to 5 years)
Secondary outcome [15] 0 0
Magnitude of Anti-Magrolimab Antibody Incidence
Timepoint [15] 0 0
First dose date up to EOT (up to 5 years)

Eligibility
Key inclusion criteria
Key

* Previously untreated individuals with histological confirmation of acute myeloid leukemia (AML) by World Health Organization (WHO) criteria who are ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to age, or comorbidity. Individuals must be considered ineligible for intensive chemotherapy, defined by the following:

* = 75 years of age; Or
* = 18 to 74 years of age with at least 1 of the following comorbidities:

* Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3
* Diffusing capacity of the lung of carbon monoxide = 65% or forced expiratory volume in 1 second = 65%
* Left ventricular ejection fraction = 50%
* Baseline creatinine clearance = 30 mL/min to < 45 mL/min calculated by the Cockcroft Gault formula or measured by 24-hour urine collection
* Hepatic disorder with total bilirubin > 1.5 x upper limit of normal (ULN)
* Any other comorbidity that the investigator judges to be incompatible with intensive chemotherapy
* ECOG performance status:

* Of 0 to 2 for individuals = 75 years of age Or
* Of 0 to 3 for individuals = 18 to 74 years of age
* Individuals with white blood cell (WBC) count = 20 x 10^3/µL prior to randomization. If the individual's WBC is > 20 x10^3/µL prior to randomization, the individual can be enrolled, assuming all other eligibility criteria are met. However, the WBC should be = 20 x 10^3/µL prior to the first dose of study treatment and prior to each magrolimab/placebo dose during Cycle 1.

* Note: Individuals can be treated with hydroxyurea and/or leukapheresis prior to randomization and throughout the study to reduce the WBC to = 20 x 10^3/µL to enable eligibility for study drug dosing
* Hemoglobin must be = 9 g/dL prior to initial dose of study treatment

* Note: Transfusions are allowed to meet hemoglobin eligibility
* Pretreatment blood cross-match completed

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior treatment with any of the following:

* cluster of differentiation 47 (CD47) or signal regulatory protein alpha (SIRPa)-targeting agents
* Antileukemic therapy for the treatment of AML (eg, hypomethylating agents (HMAs), low-dose cytarabine, and/or venetoclax), excluding hydroxyurea

* Note: Individuals with prior MDS who have not received prior HMAs or venetoclax or chemotherapeutic agents for MDS may be enrolled in the study. Prior treatment with myelodysplastic syndrome (MDS) therapies including, but not limited to lenalidomide, erythroid-stimulating agents, or similar red blood cell negative (RBC-), white blood cell negative (WBC-), or platelet-direct therapies or growth factors is allowed for these individuals.
* Clinical suspicion of or documented active central nervous system (CNS) involvement with AML
* Individuals who have acute promyelocytic leukemia
* Second malignancy, except MDS, treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which individuals are not on active anticancer therapies and have had no evidence of active malignancy for at least 1 year

Note: 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 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)
ACT,NSW,QLD,VIC
Recruitment hospital [1] 0 0
Canberra Hospital - Woden
Recruitment hospital [2] 0 0
Border Medical Oncology Research Unit - Albury
Recruitment hospital [3] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [4] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [5] 0 0
St George Hospital, Clinical Research Unit Haemotology, Division of Cancer Services - Sydney
Recruitment hospital [6] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [7] 0 0
Monash University, Eastern Health-Box Hill Hospital - Box Hill
Recruitment hospital [8] 0 0
Northern Health - Epping
Recruitment hospital [9] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2606 - Woden
Recruitment postcode(s) [2] 0 0
2640 - Albury
Recruitment postcode(s) [3] 0 0
2139 - Concord
Recruitment postcode(s) [4] 0 0
2170 - Liverpool
Recruitment postcode(s) [5] 0 0
2217 - Sydney
Recruitment postcode(s) [6] 0 0
4215 - Southport
Recruitment postcode(s) [7] 0 0
3128 - Box Hill
Recruitment postcode(s) [8] 0 0
3076 - Epping
Recruitment postcode(s) [9] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
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
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Iowa
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
New Jersey
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Oklahoma
Country [15] 0 0
United States of America
State/province [15] 0 0
Oregon
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
Rhode Island
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Utah
Country [20] 0 0
United States of America
State/province [20] 0 0
Washington
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
Austria
State/province [23] 0 0
Vienna
Country [24] 0 0
Austria
State/province [24] 0 0
Wien
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Belgium
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Antwerp
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Belgium
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Brussels
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Belgium
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Gent
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Belgium
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Haine-Saint-Paul
Country [29] 0 0
Belgium
State/province [29] 0 0
Leuven
Country [30] 0 0
Belgium
State/province [30] 0 0
Liege
Country [31] 0 0
Canada
State/province [31] 0 0
Halifax
Country [32] 0 0
Canada
State/province [32] 0 0
Montreal
Country [33] 0 0
Canada
State/province [33] 0 0
Toronto
Country [34] 0 0
Canada
State/province [34] 0 0
Winnipeg
Country [35] 0 0
Czechia
State/province [35] 0 0
Jihormoravsky KRAJ
Country [36] 0 0
Czechia
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Olomouc
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Czechia
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Ostrava
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Czechia
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Prague
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Czechia
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Praha 2
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France
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Amiens Cedex 1
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France
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Angers
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Bobigny
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Creteil
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La Tronche
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France
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Le Chesnay Cedex
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France
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Lille Cedex
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France
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Lyon Cedex 08
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France
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Nantes
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France
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Paris
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France
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Pierre-Bénite
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France
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Strasbourg
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France
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Toulouse
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France
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Vandoeuvre-les-Nancy
Country [54] 0 0
Germany
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Berlin
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Germany
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Bonn
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Germany
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Braunschweig
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Germany
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Dusseldorf
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Germany
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Düsseldorf
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Germany
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Flensburg
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Germany
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Frankfurt
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Germany
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Hamburg
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Germany
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Hannover
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Germany
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Magdeburg
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Germany
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Minden
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Germany
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Muenchen
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Germany
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Oldenburg
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Germany
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Regensburg
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Germany
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Ulm
Country [69] 0 0
Hong Kong
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Hong Kong
Country [70] 0 0
Hungary
State/province [70] 0 0
Budapest
Country [71] 0 0
Hungary
State/province [71] 0 0
Gyor
Country [72] 0 0
Hungary
State/province [72] 0 0
Hajdu-bihar
Country [73] 0 0
Hungary
State/province [73] 0 0
Szeged
Country [74] 0 0
Israel
State/province [74] 0 0
Haifa
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Israel
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Jerusalem
Country [76] 0 0
Israel
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Petah Tikva
Country [77] 0 0
Israel
State/province [77] 0 0
Ramat Gan
Country [78] 0 0
Italy
State/province [78] 0 0
Ancona
Country [79] 0 0
Italy
State/province [79] 0 0
Bergamo
Country [80] 0 0
Italy
State/province [80] 0 0
Bologna
Country [81] 0 0
Italy
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Milano
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Italy
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Monza
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Italy
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Perugia
Country [84] 0 0
Italy
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Pesaro
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Korea, Republic of
State/province [85] 0 0
Seoul
Country [86] 0 0
Netherlands
State/province [86] 0 0
's-Hertogenbosch
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Netherlands
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Amersfoort
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Netherlands
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Amsterdam
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Netherlands
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Breda
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Netherlands
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Den Haag
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Netherlands
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Enschede
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Groningen
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Leeuwarden
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Maastricht
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Nieuwegein
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Netherlands
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Nijmegen
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Netherlands
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Rotterdam
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Norway
State/province [98] 0 0
Oslo
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Poland
State/province [99] 0 0
Lublin
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Poland
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Opole
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Poland
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Lódz
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Spain
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Alava
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Spain
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Barcelona
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Spain
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Cordoba
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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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Salamanca
Country [108] 0 0
Spain
State/province [108] 0 0
Santiago de Compostela
Country [109] 0 0
Spain
State/province [109] 0 0
Valencia
Country [110] 0 0
Switzerland
State/province [110] 0 0
Berne
Country [111] 0 0
Taiwan
State/province [111] 0 0
Kaohsiung
Country [112] 0 0
Taiwan
State/province [112] 0 0
Taichung
Country [113] 0 0
Taiwan
State/province [113] 0 0
Taipei
Country [114] 0 0
United Kingdom
State/province [114] 0 0
Blackpool
Country [115] 0 0
United Kingdom
State/province [115] 0 0
Bristol
Country [116] 0 0
United Kingdom
State/province [116] 0 0
Leeds
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Liverpool
Country [118] 0 0
United Kingdom
State/province [118] 0 0
London
Country [119] 0 0
United Kingdom
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Manchester
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United Kingdom
State/province [120] 0 0
Newcastle upon Tyne
Country [121] 0 0
United Kingdom
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Oxford
Country [122] 0 0
United Kingdom
State/province [122] 0 0
Warwick
Country [123] 0 0
United Kingdom
State/province [123] 0 0
Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
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)?
No
No/undecided IPD sharing reason/comment


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.