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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03711162




Registration number
NCT03711162
Ethics application status
Date submitted
15/10/2018
Date registered
18/10/2018

Titles & IDs
Public title
A Clinical Study to Test How Effective and Safe GLPG1690 is for Subjects With Idiopathic Pulmonary Fibrosis (IPF) When Used Together With Standard of Care
Scientific title
A Phase 3, Randomized, Double-blind, Parallel-group, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Two Doses of GLPG1690 in Addition to Local Standard of Care for Minimum 52 Weeks in Subjects With Idiopathic Pulmonary Fibrosis
Secondary ID [1] 0 0
2018-001405-87
Secondary ID [2] 0 0
GLPG1690-CL-303
Universal Trial Number (UTN)
Trial acronym
ISABELA1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Idiopathic Pulmonary Fibrosis 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GLPG1690
Treatment: Drugs - Placebo

Experimental: GLPG1690 600 mg - Participants received GLPG1690 (ziritaxestat) 600 mg, film-coated tablets orally once daily (mean GLPG1690 exposure was up to 325.3 days) in addition to local standard of care. Standard of care included either pirfenidone or nintedanib at a stable dose for at least 2 months before screening, and during screening; or neither pirfenidone or nintedanib (for any reason).

Experimental: GLPG1690 200 mg - Participants received GLPG1690 (ziritaxestat) 200 mg as film-coated tablet for oral use once daily (mean GLPG1690 exposure was up to 356.0 days) in addition to local standard of care. Standard of care included either pirfenidone or nintedanib at a stable dose for at least 2 months before screening, and during screening; or neither pirfenidone or nintedanib (for any reason).

Placebo comparator: Placebo - Participants received GLPG1690 (ziritaxestat) matching placebo tablets for oral use once daily (mean GLPG1690 exposure was up to 353.4 days) in addition to local standard of care. Standard of care included either pirfenidone or nintedanib at a stable dose for at least 2 months before screening, and during screening; or neither pirfenidone or nintedanib (for any reason).


Treatment: Drugs: GLPG1690
GLPG1690, film-coated tablets for oral use.

Treatment: Drugs: Placebo
Matching placebo, film-coated tablets for oral use.

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

Outcomes
Primary outcome [1] 0 0
Annual Rate of Decline in FVC up to Week 52
Timepoint [1] 0 0
Baseline up to week 52
Secondary outcome [1] 0 0
Percentage of Participants With Disease Progression up to Week 52
Timepoint [1] 0 0
Up to week 52
Secondary outcome [2] 0 0
Percentage of Participants With Respiratory-Related Hospitalization Until End of Study (EoS)
Timepoint [2] 0 0
Up to EoS (week 121)
Secondary outcome [3] 0 0
Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 52
Timepoint [3] 0 0
Baseline, week 52
Secondary outcome [4] 0 0
Annual Rate of Decline in FVC Until EoS
Timepoint [4] 0 0
Baseline up to EoS (week 121)
Secondary outcome [5] 0 0
Percentage of Participants With Disease Progression Until EoS
Timepoint [5] 0 0
Up to EoS (week 121)
Secondary outcome [6] 0 0
Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 100
Timepoint [6] 0 0
Baseline, week 100
Secondary outcome [7] 0 0
Percentage of Participants With All Cause Hospitalization Until EoS
Timepoint [7] 0 0
Up to EoS (week 121)
Secondary outcome [8] 0 0
Percentage of Participants With Respiratory Related Mortality Until EoS
Timepoint [8] 0 0
Up to EoS (week 121)
Secondary outcome [9] 0 0
Percentage of Participants Hospitalized for Non-elective Lung Transplant Until EoS
Timepoint [9] 0 0
Up to EoS (week 121)
Secondary outcome [10] 0 0
Percentage of Participants With Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation Until EoS
Timepoint [10] 0 0
Up to EoS (week 121)
Secondary outcome [11] 0 0
Percentage of Participants With All Cause Mortality or Hospitalization for Non-elective Lung Transplant Until EoS
Timepoint [11] 0 0
Up to EoS (week 121)
Secondary outcome [12] 0 0
Percentage of Participants With All Cause Mortality, Hospitalization for Non-elective Lung Transplant or Hospitalization for Qualifying for Lung Transplant Until EoS
Timepoint [12] 0 0
Up to EoS (week 121)
Secondary outcome [13] 0 0
Percentage of Participants With All-Cause Mortality or Hospitalization That Meets >=10% Absolute Decline in %FVC or Respiratory-Related Hospitalization Until EoS
Timepoint [13] 0 0
Up to EoS (week 121)
Secondary outcome [14] 0 0
Percentage of Participants With All-Cause Mortality or Respiratory-Related Hospitalizations Until EoS
Timepoint [14] 0 0
Up to EoS (week 121)
Secondary outcome [15] 0 0
FVC at Week 52
Timepoint [15] 0 0
Week 52
Secondary outcome [16] 0 0
Change From Baseline in FVC at Week 52
Timepoint [16] 0 0
Baseline, week 52
Secondary outcome [17] 0 0
Percent Change From Baseline in FVC at Week 52
Timepoint [17] 0 0
Baseline, week 52
Secondary outcome [18] 0 0
FVC at Week 112
Timepoint [18] 0 0
Week 112
Secondary outcome [19] 0 0
Change From Baseline in FVC at Week 112
Timepoint [19] 0 0
Baseline, week 112
Secondary outcome [20] 0 0
Percent Change From Baseline in FVC at Week 112
Timepoint [20] 0 0
Baseline, week 112
Secondary outcome [21] 0 0
Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 52: FVC Change Within =5
Timepoint [21] 0 0
Baseline, week 52
Secondary outcome [22] 0 0
Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 112: FVC Change Within =5
Timepoint [22] 0 0
Baseline, week 112
Secondary outcome [23] 0 0
Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 52: FVC Change Within =10
Timepoint [23] 0 0
Baseline, week 52
Secondary outcome [24] 0 0
Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 112: FVC Change Within =10
Timepoint [24] 0 0
Baseline, week 112
Secondary outcome [25] 0 0
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Timepoint [25] 0 0
Baseline up to 30 days after the last dose (up to week 121)
Secondary outcome [26] 0 0
Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100
Timepoint [26] 0 0
Baseline, week 52, week 100
Secondary outcome [27] 0 0
Change From Baseline in Visual Analogue Score (VAS): Cough at Week 52 and Week 100
Timepoint [27] 0 0
Baseline, week 52, week 100
Secondary outcome [28] 0 0
Change From Baseline in Visual Analogue Score (VAS): Urge to Cough at Week 52 and Week 100
Timepoint [28] 0 0
Baseline, week 52, week 100
Secondary outcome [29] 0 0
Change From Baseline in European Quality Of Life (EQ) VAS at Week 52 and Week 100
Timepoint [29] 0 0
Baseline, week 52, week 100
Secondary outcome [30] 0 0
Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100
Timepoint [30] 0 0
Baseline, week 52, week 100
Secondary outcome [31] 0 0
Area Under The Concentration Time Curve (AUC) of Ziritaxtestat
Timepoint [31] 0 0
Sparse samples collected on day 1 pre-dose, day 85 post-dose, day 237 post-dose, day 183 pre-dose, day 365 pre-dose
Secondary outcome [32] 0 0
Maximum Observed Plasma Concentration (Cmax) of Ziritaxtestat
Timepoint [32] 0 0
Sparse samples collected on day 1 pre-dose, day 85 post-dose, day 237 post-dose, day 183 pre-dose, day 365 pre-dose
Secondary outcome [33] 0 0
Change From Baseline in Total Distance Walked in Six-minute Walk Test (6MWT) at Week 52 and Week 100
Timepoint [33] 0 0
Baseline, week 52, week 100
Secondary outcome [34] 0 0
Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO) (Corrected for Hemoglobin [Hb]) at Week 52 and Week 100
Timepoint [34] 0 0
Baseline, week 52, week 100

Eligibility
Key inclusion criteria
* Male or female subject aged =40 years on the day of signing the Informed Consent Form (ICF).
* A diagnosis of IPF within 5 years prior to the screening visit, as per applicable American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) guidelines at the time of diagnosis.
* Chest high-resolution computed tomography (HRCT) historically performed within 12 months prior to the screening visit and according to the minimum requirements for IPF diagnosis by central review based on subject's HRCT only (if no lung biopsy (LB) available), or based on both HRCT and LB (with application of the different criteria in either situation). If an evaluable HRCT <12 months prior to screening is not available, an HRCT can be performed at screening to determine eligibility, according to the same requirements as the historical HRCT.
* Subjects receiving local standard of care for the treatment of IPF, defined as either pirfenidone or nintedanib at a stable dose for at least two months before screening, and during screening; or neither pirfenidone or nintedanib (for any reason). A stable dose is defined as the highest dose tolerated by the subject during those two months.
* The extent of fibrotic changes is greater than the extent of emphysema on the most recent HRCT scan (investigator-determined).
* Meeting all of the following criteria during the screening period: FVC =45% predicted of normal, Forced expiratory volume in 1 second (FEV1)/FVC =0.7, diffusing capacity of the lung for carbon monoxide (DLCO) corrected for Hb =30% predicted of normal.
* Estimated minimum life expectancy of at least 30 months for non IPF related disease in the opinion of the investigator.
* Male subjects and female subjects of childbearing potential agree to use highly effective contraception/preventive exposure measures from the time of first dose of investigational medicinal product (IMP) (for the male subject) or the signing of the ICF (for the female subject), during the study, and until 90 days (male) or 30 days (female) after the last dose of IMP.
* Able to walk at least 150 meters during the 6-Minute Walk Test (6MWT) at screening Visit 1; without having a contraindication to perform the 6MWT or without a condition putting the subject at risk of falling during the test (investigator's discretion). The use of a cane is allowed, the use of a stroller is not allowed at all for any condition. At Visit 2, for the oxygen titration test, resting oxygen saturation (SpO2) should be =88% with maximum 6 L O2/minute; during the walk, SpO2 should be =83% with 6 L O2/minute or =88% with 0, 2 or 4 L O2/minute.
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* History of malignancy within the past 5 years (except for carcinoma in situ of the uterine cervix, basal cell carcinoma of the skin that has been treated with no evidence of recurrence, prostate cancer that has been medically managed through active surveillance or watchful waiting, squamous cell carcinoma of the skin if fully resected, and Ductal Carcinoma In Situ).
* Clinically significant abnormalities detected on ECG of either rhythm or conduction, a QT interval corrected for heart rate using Fridericia's formula (QTcF) >450 ms, or a known long QT syndrome. Patients with implantable cardiovascular devices (e.g. pacemaker) affecting the QT interval time may be enrolled in the study based upon investigator judgment following cardiologist consultation if deemed necessary, and only after discussion with the medical monitor.
* Acute IPF exacerbation within 6 months prior to screening and/or during the screening period. The definition of an acute IPF exacerbation is as follows: Previous or concurrent diagnosis of IPF; Acute worsening or development of dyspnea typically < 1 month duration; Computed tomography with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with usual interstitial pneumonia pattern and deterioration not fully explained by cardiac failure or fluid overload.
* Lower respiratory tract infection requiring treatment within 4 weeks prior to screening and/or during the screening period.
* Interstitial lung disease associated with known primary diseases (e.g. sarcoidosis and amyloidosis), exposures (e.g. radiation, silica, asbestos, and coal dust), or drugs (e.g. amiodarone).
* Diagnosis of severe pulmonary hypertension (investigator- determined).
* Unstable cardiovascular, pulmonary (other than IPF), or other disease within 6 months prior to screening or during the screening period (e.g. acute coronary disease, heart failure, and stroke).
* Had gastric perforation within 3 months prior to screening or during screening, and/or underwent major surgery within 3 months prior to screening, during screening or have major surgery planned during the study period.
* History of nintedanib-related increase in ALT and/or AST of >5 x upper limit of the normal range (ULN) and increased susceptibility to elevated LFT; moderate to severe hepatic impairment (Child-Pugh B or C) and/or abnormal liver function test (LFT) at screening, defined as aspartate aminotransferase (AST), and/or alanine aminotransferase (ALT), and/or total bilirubin =1.5 x upper limit of the normal range (ULN), and/or gamma glutamyl transferase (GGT) =3 x ULN. Retesting is allowed once for abnormal LFT.
* Abnormal renal function defined as estimated creatinine clearance, calculated according to Cockcroft-Gault calculation (CCr) <30 mL/min. Retesting is allowed once.
* Use of any of the following therapies within 4 weeks prior to screening and during the screening period, or planned during the study: warfarin, imatinib, ambrisentan, azathioprine, cyclophosphamide, cyclosporine A, bosentan, methotrexate, sildenafil (except for occasional use), prednisone at steady dose >10 mg/day or equivalent.

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 assessing the outcomes
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)
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [3] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [4] 0 0
Corte Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [5] 0 0
Lung Research Queensland - Chermside
Recruitment hospital [6] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [7] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [8] 0 0
Austin Health - Heidelberg
Recruitment hospital [9] 0 0
Respiratory Clinical Trials Pty Ltd - Kent Town
Recruitment hospital [10] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
5042 - Bedford Park
Recruitment postcode(s) [3] 0 0
VIC 3128 - Box Hill
Recruitment postcode(s) [4] 0 0
NSW 2050 - Camperdown
Recruitment postcode(s) [5] 0 0
QLD 4060 - Chermside
Recruitment postcode(s) [6] 0 0
NSW 2139 - Concord
Recruitment postcode(s) [7] 0 0
NSW 2010 - Darlinghurst
Recruitment postcode(s) [8] 0 0
3084 - Heidelberg
Recruitment postcode(s) [9] 0 0
SA 5067 - Kent Town
Recruitment postcode(s) [10] 0 0
VIC 3004 - Melbourne
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
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
Country [10] 0 0
United States of America
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Kentucky
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United States of America
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Louisiana
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United States of America
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Maryland
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United States of America
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Massachusetts
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Michigan
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United States of America
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Minnesota
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Missouri
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Nebraska
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New York
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North Carolina
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Ohio
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United States of America
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Oregon
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Pennsylvania
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Rhode Island
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Tennessee
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Texas
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Utah
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Virginia
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Washington
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United States of America
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Wisconsin
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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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Leuven
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Belgium
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Yvoir
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Brazil
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Porto Alegre
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Brazil
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Santo André
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Chile
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Concepción
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Chile
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Curicó
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Chile
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Quillota
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Chile
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Santiago
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Talca
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Chile
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Valparaíso
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Chile
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Viña Del Mar
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Czechia
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Brno
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Czechia
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Ostrava
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Czechia
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Praha
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Denmark
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Aarhus
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Denmark
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Hellerup
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Denmark
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Odense
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Germany
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Bad Berka
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Germany
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Berlin
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Germany
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Coswig
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Germany
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Hannover
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Germany
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Heidelberg
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Germany
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Leipzig
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Germany
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Rosenheim
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Greece
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Athens
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Greece
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Iraklio
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Greece
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Larissa
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Greece
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Thessaloníki
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Japan
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Hamamatsu
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Japan
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Kumamoto
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Sakai
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Seto
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Tokyo
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Japan
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Yokohama
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Peru
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Chancay
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Peru
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Lima Cercado
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Peru
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Lima
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Peru
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San Isidro
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Peru
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San Miguel
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Peru
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Santiago De Surco
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Spain
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Pontevedra
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Pamplona
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Spain
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Santander
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Spain
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Valencia
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Taiwan
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Kaohsiung City
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Taiwan
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New Taipei City
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Taiwan
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Taipei
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Turkey
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Istanbul
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Turkey
State/province [82] 0 0
Izmir
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Turkey
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Mersin
Country [84] 0 0
United Kingdom
State/province [84] 0 0
Birmingham
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United Kingdom
State/province [85] 0 0
Bristol
Country [86] 0 0
United Kingdom
State/province [86] 0 0
Cambridge
Country [87] 0 0
United Kingdom
State/province [87] 0 0
Cottingham
Country [88] 0 0
United Kingdom
State/province [88] 0 0
Exeter
Country [89] 0 0
United Kingdom
State/province [89] 0 0
Liverpool
Country [90] 0 0
United Kingdom
State/province [90] 0 0
London
Country [91] 0 0
United Kingdom
State/province [91] 0 0
Manchester
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United Kingdom
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Newcastle
Country [93] 0 0
United Kingdom
State/province [93] 0 0
Nottingham
Country [94] 0 0
United Kingdom
State/province [94] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Galapagos NV
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Galapagos Study Director, MD
Address 0 0
Galapagos NV
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?

Results publications and other study-related documents

No documents have been uploaded by study researchers.