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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02927067




Registration number
NCT02927067
Ethics application status
Date submitted
29/09/2016
Date registered
6/10/2016

Titles & IDs
Public title
A Study of Maribavir Compared to Valganciclovir to Treat Cytomegalovirus Infections in People Who Have Received Stem Cell Transplants
Scientific title
A Phase 3, Multicenter, Randomized, Double-blind, Double-dummy, Active-controlled Study to Assess the Efficacy and Safety of Maribavir Compared to Valganciclovir for the Treatment of Cytomegalovirus (CMV) Infection in Hematopoietic Stem Cell Transplant Recipients
Secondary ID [1] 0 0
2015-004726-34
Secondary ID [2] 0 0
SHP620-302
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cytomegalovirus (CMV) 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Maribavir
Treatment: Drugs - Valganciclovir
Other interventions - Placebo

Active comparator: Valganciclovir 900 mg BID - Participants received 900 milligrams (mg) of valganciclovir along with a placebo matched to maribavir, twice daily (BID) orally for 8 weeks. Valganciclovir dose was allowed to be adjusted to 450 mg BID or 450 mg QD based on renal function impairment assessed at baseline or development of neutropenia during the study.

Experimental: Maribavir 400 mg BID - Participants received 400 mg of maribavir along with a placebo matched to valganciclovir, BID orally for 8 weeks.


Treatment: Drugs: Maribavir
Participants will receive 400 mg of maribavir BID orally.

Treatment: Drugs: Valganciclovir
Participants will receive valganciclovir tablets orally.

Other interventions: Placebo
Participants will receive placebo tablets matched to either maribavir or valganciclovir.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Who Achieved Confirmed Clearance of Plasma Cytomegalovirus (CMV) Deoxyribose Nucleic Acid (DNA) at the End of Study Week 8
Timepoint [1] 0 0
Week 8
Secondary outcome [1] 0 0
Number of Participants Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control at the End of Week 8, Followed by Maintenance of Treatment Effect at Week 16
Timepoint [1] 0 0
Week 8 up to Week 16
Secondary outcome [2] 0 0
Number of Participants Who Achieved Confirmed Clearance of Plasma CMV DNA (CMV Viremia Clearance) at Week 8 After Receiving 8 Weeks of Study Assigned Treatment
Timepoint [2] 0 0
Week 8
Secondary outcome [3] 0 0
Number of Participants Who Achieved Confirmed CMV Viremia Clearance After Receiving 8 Weeks of Study-assigned Treatment Through Weeks 12, 16 and 20
Timepoint [3] 0 0
Week 8 through Weeks 12, 16 and 20
Secondary outcome [4] 0 0
Number of Participants Who Maintained Confirmed CMV Viremia Clearance at Week 8 After Receiving Study-Assigned Treatment Through Study Weeks 12 and 20 Regardless of Whether Study Assigned Treatment Was Completed
Timepoint [4] 0 0
Week 8 through Weeks 12 and 20
Secondary outcome [5] 0 0
Number of Participants With Confirmed Recurrence of Viremia During First 8 Weeks of the Study
Timepoint [5] 0 0
Up to Week 8
Secondary outcome [6] 0 0
Number of Participants With Confirmed Recurrence of Viremia During the Follow-up Period
Timepoint [6] 0 0
From Week 9 up to Week 20
Secondary outcome [7] 0 0
Number of Participants With Confirmed Recurrence of Viremia at Any Time During the Study
Timepoint [7] 0 0
Up to Week 20
Secondary outcome [8] 0 0
Number of Participants With Confirmed Recurrence of Viremia While on Study Treatment and Off Treatment
Timepoint [8] 0 0
Baseline up to Week 20
Secondary outcome [9] 0 0
Number of Participants With Grade 3 or 4 (Shift From Baseline Grade <3) and Grade 4 Neutropenia (Shift From Baseline Grade <4) While on Study Treatment
Timepoint [9] 0 0
From start of study drug to end of study drug + 1 day (up to approximately Week 8)
Secondary outcome [10] 0 0
Number of Participants With Treatment-Emergent Adverse Events During the On-Treatment Period
Timepoint [10] 0 0
From the start of the study treatment to 7 days after the last dose of study treatment (up to approximately Week 9)
Secondary outcome [11] 0 0
Predose Concentration (Cmin) of Maribavir
Timepoint [11] 0 0
Weeks 1, 4, and 8: pre-morning dose
Secondary outcome [12] 0 0
Area Under the Concentration-Time Curve Over the 12-Hour Dosing Interval at Steady State AUC(0-tau) of Maribavir for Adolescent Participants Only
Timepoint [12] 0 0
Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
Secondary outcome [13] 0 0
Maximum Observed Plasma Concentration (Cmax) of Maribavir for Adolescent Participants Only
Timepoint [13] 0 0
Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
Secondary outcome [14] 0 0
Time When Maximum Concentration is Observed (Tmax) of Maribavir for Adolescent Participants Only
Timepoint [14] 0 0
Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
Secondary outcome [15] 0 0
Apparent Oral Clearance (CL/F) of Maribavir for Adolescent Participants Only
Timepoint [15] 0 0
Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
Secondary outcome [16] 0 0
Apparent Volume of Distribution (Vz/F) of Maribavir for Adolescent Participants Only
Timepoint [16] 0 0
Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1

Eligibility
Key inclusion criteria
* Be able to provide written, personally signed, and dated informed consent to participate in the study before completing any study-related procedures. As applicable, a parent/both parents or legally authorized representative (LAR) must provide signature of informed consent and there must be documentation of assent by the participants before completing any study-related procedures. During the COVID-19 public health emergency, informed consent from a potential or current trial participant may, if permitted by local laws and regulations, be obtained via electronic informed consent (eIC) capabilities or an electronic face-to-face consent interview when these individuals are unable to travel to the site (FDA COVID-19 Guidance, 27 January 2021, Q11).
* Be greater than or equal to (>=) 16 years of age at the time of consent.
* Be a recipient of hematopoietic stem cell transplant.
* Have a documented asymptomatic CMV infection, with a screening value of CMV DNA >=1365 International Units per millilitre (IU/mL) to less than or equal to (<=) 273000 IU/mL in whole blood or >=455 IU/mL to <=91000 IU/mL in plasma in 2 consecutive assessments, separated by at least 1 day, as determined by local or central specialty laboratory quantitative polymerase chain reaction (qPCR) or comparable quantitative CMV DNA results. Both samples should be taken within 14 days prior to randomization with second sample obtained within 5 days prior to randomization. Same laboratory and same sample type (whole blood or plasma) should be used for these assessments. Asymptomatic CMV infection is defined as an infection that does not present with tissue invasive CMV disease, as assessed by the investigator. Participants with CMV DNA less than (<) 910 and >=455 IU/mL in plasma or <2730 and >=1365 IU/mL in whole blood will also need to meet at least 1 of the following criteria for high-risk CMV infection to be eligible:

1. Human leukocyte antigen (HLA)-related (sibling) donor with at least 1 mismatch at 1 of the following 3 HLA-gene loci: HLA-A, -B or -DR,
2. Haploidentical donor
3. Unrelated donor with at least 1 mismatch at 1 of the following 4 HLA -gene loci: HLA-A, -B, -C and -DRB1,
4. Use of umbilical cord blood as stem cell source,
5. Use of ex vivo T-cell-depleted grafts,
6. Grade 2 or greater graft-versus-host-disease (GVHD), requiring the use of systemic corticosteroids (defined as the use of >=1 milligram per kilogram per day (mg/kg/day) of prednisone or equivalent dose of another corticosteroid).
* Have the current CMV infection as the first episode of CMV viremia after HSCT, either primary or reactivation, which in the investigator's opinion requires treatment.
* Per investigator's judgment, be eligible for treatment with valganciclovir.
* Have all of the following results as part of screening laboratory assessments (results from either the central laboratory or a local laboratory can be used for qualification):

1. Absolute neutrophil count to >=1000 per cubic millimeter (/mm^3) [1.0*10^9/L].
2. Platelet count >=25,000/mm^3 [25*10^9/L].
3. Hemoglobin >=8 grams per deciliter (g/dL).
4. Estimated creatinine clearance >=30 milliliters per minute (mL/min).
* Have a negative serum beta human chorionic gonadotropin (beta-HCG) pregnancy test at screening, if a female of child bearing potential. Urine pregnancy tests may be done per institutional requirements; however they are not sufficient for eligibility determination. Sexually active females of child bearing potential must agree to comply with any applicable contraceptive requirements of the protocol. If male, must agree to use an acceptable method of birth control, as defined in the protocol, during the study treatment administration period and for 90 days afterward the last dose of study treatment.
* Be able to swallow tablets.
* Have life expectancy of >=8 weeks.
* Weigh >=40 kilograms (kg).
* Be willing and have an understanding and ability to fully comply with study procedures and restrictions defined in the protocol.
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Have CMV tissue invasive disease as assessed by the investigator at the time of screening and randomization at Visit 2/Day 0.
* Have a CMV infection that is known to be genotypically resistant to ganciclovir, valganciclovir, foscarnet, or cidofovir based on documented evidence.
* Be presenting with recurrent CMV infection (defined as a new detection of CMV infection in a participants who had at least one previously documented episode of CMV infection post-transplant, and who has had at least 2 weeks of undetectable CMV DNA between the episodes during active surveillance, based on same local laboratory and same sample type). The Participants must also have been off any anti-CMV treatment between the current and prior infection. Otherwise, the current infection may be considered continuation of the prior infection.
* Require ganciclovir, valganciclovir, foscarnet, or cidofovir administration for conditions other than CMV when study treatment is initiated (example: herpes simplex virus [HSV] co-infection requiring use of any of these agents after the randomization) or would need a co-administration with maribavir for CMV infection.
* Be receiving leflunomide, letermovir, or artesunate when study treatment is initiated.

Note: Participants who may be receiving leflunomide must discontinue the use at least 14 days prior to randomization at Visit 2/Day 0 and the first dose of study treatment. Participants receiving letermovir must discontinue use 3 days prior to first dose of study treatment. Participants receiving artesunate must discontinue the use prior to the first dose of study treatment.

* Be on treatment with anti-CMV agents (ganciclovir, valganciclovir, foscarnet or letermovir) for the current CMV infection for longer than 72 hours.
* Have known hypersensitivity to the active substance or to an excipient of the study treatments.
* Have severe vomiting, diarrhea, or other severe gastrointestinal illness within 24 hours prior to the first dose of study treatment that would preclude administration of oral medication.
* Require mechanical ventilation or vasopressors for hemodynamic support at the time of randomization.
* Be female and pregnant or nursing.
* Have previously completed, discontinued, or have been withdrawn from this study.
* Have received any investigational agent with known anti-CMV activity within 30 days before initiation of study treatment or CMV vaccine at any time.
* Have received any unapproved agent or device within 30 days before initiation of study treatment.
* Have any clinically significant medical or surgical condition that, in the investigator's opinion, could interfere with interpretation of study results, contraindicate the administration of the assigned study treatment, or compromise the safety or well-being of the participant.
* Have previously received maribavir.
* Have serum aspartate aminotransferase (AST) greater than (>) 5 times upper limit of normal (ULN) at screening, or serum alanine aminotransferase (ALT) >5 times ULN at screening, or total bilirubin >= 3.0*ULN at screening (except for documented Gilbert's syndrome), as analyzed by local or central laboratory.
* Have known (previously documented) positive results for human immunodeficiency virus (HIV). Participants must have a confirmed negative HIV test result within 3 months of study entry or, if unavailable, be tested by a local laboratory during the screening period.
* Have active malignancy with the exception of nonmelanoma skin cancer, as determined by the investigator. Participants who experience relapse or progression of their underlying malignancy (for which HSCT was performed), as determined by the investigator, are not to be enrolled.
* Be undergoing treatment for acute or chronic hepatitis C

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/04/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2022
Sample size
Target
Accrual to date
Final
553
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Westmead Hospital - Westmead
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
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
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
Michigan
Country [10] 0 0
United States of America
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Minnesota
Country [11] 0 0
United States of America
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New Jersey
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United States of America
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New York
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United States of America
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Pennsylvania
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United States of America
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Tennessee
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United States of America
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Texas
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United States of America
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Washington
Country [17] 0 0
United States of America
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Wisconsin
Country [18] 0 0
Austria
State/province [18] 0 0
Wien
Country [19] 0 0
Austria
State/province [19] 0 0
Linz
Country [20] 0 0
Belgium
State/province [20] 0 0
Antwerpen
Country [21] 0 0
Belgium
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Brussels
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Belgium
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Oost-Vlaanderen
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Belgium
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Vlaams Brabant
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Belgium
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West-Vlaanderen
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Belgium
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Liège
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Canada
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British Columbia
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Canada
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Nova Scotia
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Canada
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Ontario
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China
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Beijing
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China
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Guangdong
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China
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Jiangsu
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China
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Changsha
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China
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Guangzhou
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China
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Hangzhou Zhejiang
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China
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Zhengzhou
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Croatia
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Zagreb
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Czechia
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Praha, Hlavní Mesto
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Czechia
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Praha
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France
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Bas-Rhin
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France
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Gironde
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France
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Haute-Vienne
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France
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Isère
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France
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Loire-Atlantique
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France
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Maine-et-Loire
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France
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Val-de-Marne
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France
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Besnçon
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France
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Nice
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France
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Paris
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France
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Toulouse cedex 9
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Germany
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Nordrhein-Westfalen
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Germany
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Rheinland-Pfalz
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Germany
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Saarland
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Germany
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Sachsen
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Germany
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Augsburg
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Germany
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Berlin
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Germany
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Halle
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Germany
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Hamburg
Country [58] 0 0
Germany
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Rostock
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Germany
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Stuttgart
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Germany
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Tübingen
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Greece
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Attiki
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Greece
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Thessaloniki
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Hungary
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Budapest
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Israel
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HaMerkaz
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Israel
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Yerushalayim
Country [66] 0 0
Israel
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Haifa
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Israel
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Tel-Aviv
Country [68] 0 0
Italy
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Lombardia
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Italy
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Piemonte
Country [70] 0 0
Italy
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Veneto
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Italy
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Firenze
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Italy
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Milano
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Italy
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Roma
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Italy
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Torino
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Korea, Republic of
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Busan
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Korea, Republic of
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Daegu
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New Zealand
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Auckland
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New Zealand
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South Island
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Poland
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Dolnoslaskie
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Poland
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Mazowieckie
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Poland
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Gdansk
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Russian Federation
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Sankt-Peterburg
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Russian Federation
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Irkutsk
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Russian Federation
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Kirov
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Singapore
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Singapore
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Spain
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Barcelona
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Spain
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Cantabria
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Spain
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Castilla Y León
Country [89] 0 0
Spain
State/province [89] 0 0
Cordoba
Country [90] 0 0
Spain
State/province [90] 0 0
Granada
Country [91] 0 0
Spain
State/province [91] 0 0
Madrid
Country [92] 0 0
Spain
State/province [92] 0 0
Málaga
Country [93] 0 0
Spain
State/province [93] 0 0
San Sebastian Gipuzkoa
Country [94] 0 0
Spain
State/province [94] 0 0
Valencia
Country [95] 0 0
Switzerland
State/province [95] 0 0
Zurich
Country [96] 0 0
Turkey
State/province [96] 0 0
Adana
Country [97] 0 0
Turkey
State/province [97] 0 0
Ankara
Country [98] 0 0
United Kingdom
State/province [98] 0 0
Birmingham
Country [99] 0 0
United Kingdom
State/province [99] 0 0
London, City Of
Country [100] 0 0
United Kingdom
State/province [100] 0 0
London
Country [101] 0 0
United Kingdom
State/province [101] 0 0
Merseyside
Country [102] 0 0
United Kingdom
State/province [102] 0 0
Manchester
Country [103] 0 0
United Kingdom
State/province [103] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Shire
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Takeda Development Center Americas, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Shire
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Available to whom?
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/takeda/


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02927067