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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02181413




Registration number
NCT02181413
Ethics application status
Date submitted
27/06/2014
Date registered
4/07/2014

Titles & IDs
Public title
A Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Participants With Multiple Myeloma Following Autologous Stem Cell Transplant
Scientific title
A Phase 3, Randomized, Placebo-Controlled, Double-Blind Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Patients With Multiple Myeloma Following Autologous Stem Cell Transplant
Secondary ID [1] 0 0
U1111-1155-8695
Secondary ID [2] 0 0
C16019
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Autologous Stem Cell Transplant 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

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

Experimental: Ixazomib Citrate - Ixazomib citrate 3 mg, capsules, orally, once, on Days 1, 8 and 15 in a 28-day cycle for Cycles 1 through 4. Ixazomib citrate 4 mg, capsules, orally, once, on Days 1, 8 and 15 in a 28-day cycle for Cycles 5 through 26 until progressive disease (PD), unacceptable toxicity, or discontinuation for alternate reasons. Participants who have had any dose reductions due to adverse events (AEs) would not be dose escalated.

Placebo comparator: Placebo - Ixazomib citrate placebo-matching capsules, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 1 through 26 until PD, unacceptable toxicity, or discontinuation for alternate reasons.


Treatment: Drugs: Ixazomib Citrate
Ixazomib citrate capsules

Treatment: Drugs: Placebo
Ixazomib citrate placebo-matching capsules

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

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS)
Timepoint [1] 0 0
Randomization up to End of treatment (EOT) (24 months); thereafter followed up every 4 weeks until progression of disease or death (to data cutoff: approximately 4 years)
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Baseline up to Follow up period (107 months)
Secondary outcome [2] 0 0
Percentage of Participants With Any Best Response Category Before PD or Subsequent Therapy
Timepoint [2] 0 0
Baseline up to EOT (24 months) and thereafter every 4 weeks until initiation of the next line of therapy (up to 107 months)
Secondary outcome [3] 0 0
Time to Progression (TTP)
Timepoint [3] 0 0
Baseline until PD (Month 107)
Secondary outcome [4] 0 0
Second Progression Free Survival (PFS2)
Timepoint [4] 0 0
Baseline up to EOT (24 months); thereafter followed up every 4 weeks until initiation of next-line therapy and then every 12 weeks until second progressive disease (PD2) or death (up to Month 107)
Secondary outcome [5] 0 0
Time to Start of the Next Line of Therapy
Timepoint [5] 0 0
Baseline up to start of next line of therapy (after 24 months treatment period followed by every 4 weeks PFS and PD follow up period)
Secondary outcome [6] 0 0
Time to End of the Next Line of Therapy
Timepoint [6] 0 0
Baseline up to end of next line of therapy (Month 107)
Secondary outcome [7] 0 0
Duration of the Next Line of Therapy
Timepoint [7] 0 0
From the start of next line therapy after PD to the last dose of next line therapy (up to Month 107)
Secondary outcome [8] 0 0
Percentage of Participants Who Develop A New Primary Malignancy
Timepoint [8] 0 0
Baseline until death or termination of the study (up to Month 107)
Secondary outcome [9] 0 0
Number of Participants With Conversion From Minimal Residual Disease (MRD) Positive to MRD Negative, and Maintenance of MRD Negativity
Timepoint [9] 0 0
Baseline up to EOT (24 months)
Secondary outcome [10] 0 0
Correlation Between MRD Status and Progression Free Survival (PFS) and Overall Survival (OS)
Timepoint [10] 0 0
Baseline up to Month 107
Secondary outcome [11] 0 0
OS Benefits in a High-Risk Population
Timepoint [11] 0 0
Randomization up to Month 107
Secondary outcome [12] 0 0
PFS Benefits in a High-Risk Population
Timepoint [12] 0 0
Randomization up to Month 107
Secondary outcome [13] 0 0
Eastern Cooperative Oncology Group (ECOG) Performance Score
Timepoint [13] 0 0
Baseline up to EOT (24 months), thereafter every 4 weeks until initiation of next line therapy
Secondary outcome [14] 0 0
Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) or Serious Adverse Events (SAEs)
Timepoint [14] 0 0
First dose of study drug through 30 days after last dose of study drug (up to 24 months)
Secondary outcome [15] 0 0
Number of Participants With Markedly Abnormal Clinical Laboratory Values
Timepoint [15] 0 0
Baseline through 30 days after the last dose of study drug (up to 24 months)
Secondary outcome [16] 0 0
Health-related Quality of Life (HRQL) Score Based on The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Quality of Life Domain
Timepoint [16] 0 0
Baseline up to PD (up to Month 107)
Secondary outcome [17] 0 0
Plasma Concentration of Ixazomib
Timepoint [17] 0 0
Day 1 of Cycle 1 at multiple time points (up to 4 hours) post-dose; Days 8 and 15 of Cycle 1, Days 1 and 8 of Cycle 2, Day 1 of Cycles 3 through 10 (each cycle of 28 days) predose
Secondary outcome [18] 0 0
Time to Resolution of Peripheral Neuropathy (PN) Events
Timepoint [18] 0 0
From randomization date through 30 days after the last dose of drug (up to 24 months)
Secondary outcome [19] 0 0
Time to Improvement of PN Events
Timepoint [19] 0 0
From randomization date through 30 days after the last dose of drug (up to 24 months)

Eligibility
Key inclusion criteria
1. Adult male or female participants 18 years or older with a confirmed diagnosis of symptomatic multiple myeloma according to standard criteria.
2. Documented results of cytogenetics/ fluorescence in situ hybridization (FISH) obtained at any time before transplant, and International Staging System (ISS) staging at the time of diagnosis available.
3. Underwent standard of care (SOC) induction therapy (induction therapy must include proteasome inhibitor (PI) and/or immunomodulating drugs (IMiD)-based regimens as primary therapy for multiple myeloma), followed by a single autologous stem cell transplant (ASCT) with a high-dose melphalan (200 mg/m^2) conditioning regimen, within 12 months of diagnosis. Vincristine, Adriamycin [doxorubicin], and dexamethasone (VAD) is not an acceptable induction therapy for this trial.
4. Started screening no earlier than 75 days after transplant, completed screening within 15 days, and randomized no later than 115 days after transplant.
5. Must have not received post-ASCT consolidation therapy.
6. Documented response to ASCT (PR, VGPR, CR/stringent complete response [sCR]) according to IMWG criteria.
7. ECOG performance status of 0 to 2.
8. Female participants who:

* If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 90 days after the last dose of study drug, AND
* Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.) Male participants, even if surgically sterilized (ie, status postvasectomy), who:
* Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, AND
* Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.)
9. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
10. Suitable venous access for the study-required blood sampling.
11. Is willing and able to adhere to the study visit schedule and other protocol requirements.
12. Must meet the following clinical laboratory criteria at study entry:

* Absolute neutrophil count (ANC) = 1,000 per cubic milliliter (/mm^3) and platelet count = 75,000/mm^3. Platelet transfusions to help participants meet eligibility criteria are not allowed within 3 days before randomization.
* Total bilirubin = 1.5 * the upper limit of the normal range (ULN).
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 * ULN.
* Calculated creatinine clearance = 30 milliliter per minute (mL/min).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Multiple myeloma that has relapsed following primary therapy or is not responsive to primary therapy. For this study, stable disease following ASCT will be considered nonresponsive to primary therapy.
2. Double (tandem) ASCT.
3. Radiotherapy within 14 days before the first dose of study drug.
4. Diagnosed or treated for another malignancy within 5 years before randomization or previously diagnosed with another malignancy with evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
5. Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.
6. Major surgery within 14 days before randomization.
7. Central nervous system involvement.
8. Infection requiring intravenous (IV) antibiotic therapy or other serious infection within 14 days before randomization.
9. Diagnosis of Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
10. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
11. Systemic treatment with strong cytochrome P450 3A (CYP3A) inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort within 14 days before randomization in the study.
12. Active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.
13. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens (eg, peripheral neuropathy that is Grade 1 with pain or Grade 2 or higher of any cause).
14. Psychiatric illness/social situation that would limit compliance with study requirements.
15. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
16. Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal (GI) procedure that could interfere with the oral absorption or tolerance of treatment.
17. Treatment with any investigational products within 60 days before the first dose of the study drug regimen.

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
Completed
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,QLD,SA,VIC
Recruitment hospital [1] 0 0
St George Hospital - Kogarah
Recruitment hospital [2] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [3] 0 0
Westmead Hospital - Westmead
Recruitment hospital [4] 0 0
Icon Cancer Care South Brisbane - South Brisbane
Recruitment hospital [5] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [6] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [7] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [8] 0 0
Austin Health - Heidelberg
Recruitment hospital [9] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
2298 - Waratah
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
4215 - Southport
Recruitment postcode(s) [6] 0 0
5000 - Adelaide
Recruitment postcode(s) [7] 0 0
5011 - Woodville South
Recruitment postcode(s) [8] 0 0
3084 - Heidelberg
Recruitment postcode(s) [9] 0 0
3004 - 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
Minnesota
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
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West Virginia
Country [7] 0 0
Argentina
State/province [7] 0 0
Buenos Aires
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Argentina
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Santa Fe
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Argentina
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Ciudad Autonoma de Buenos Aires
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Austria
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Linz
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Austria
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Salzburg
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Austria
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Wien
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Hainaut
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Antwerpen
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Parana
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Rio Grande Do Sul
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Santa Catarina
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Brazil
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Sao Paulo
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Brazil
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Rio De Janeiro
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Brazil
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Rio de Janeiro
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Ontario
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Quebec
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Medellin
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Olomouc
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Aarhus N
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Roskilde
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Vejle
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Limoges
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Paris
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Baden-Wurttemberg
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Germany
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Bayern
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Germany
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Hessen
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Germany
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Niedersachsen
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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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Sachsen
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Germany
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Berlin
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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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Ludwigshafen
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Germany
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Tubingen
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Greece
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Attiki
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Greece
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Athens
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Greece
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Thessaloniki
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Hungary
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Budapest
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Hungary
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Debrecen
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Hungary
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Kaposvar
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Hungary
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Szeged
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Ashkelon
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Israel
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Nahariya
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Israel
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Petach Tikva
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Israel
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Ramat-Gan
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Israel
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Rehovot
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Israel
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Safed
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Israel
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Tel Aviv
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Israel
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Tzrifin
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Italy
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Abruzzo
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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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Marche
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Italy
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Piemonte
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Italy
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Potenza
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Italy
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Umbria
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Italy
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Bologna
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Italy
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Brescia
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Italy
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Firenze
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Italy
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Genova
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Italy
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Meldola
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Italy
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Milano
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Italy
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Rimini
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Hyogo
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Iwate
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Niigata
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Saitama
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Tokyo
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Fukuoka-City
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Nagoya-City
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Nagoya
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Shibukawa
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Tachikawa
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Toyohashi-City
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Korea, Republic of
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Gyeonggido
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Daejeon
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Korea, Republic of
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Incheon
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Seoul
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Mexico
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Jalisco
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Nuevo Leon
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Netherlands
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Zuid-Holland
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Groningen
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Rotterdam
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Utrecht
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Norway
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Oppland
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Norway
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Sor-Trondelag
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Norway
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Oslo
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Norway
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Stavanger
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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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Pomorskie
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Poland
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Slaskie
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Poland
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Brzozow
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Poland
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Lodz
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Portugal
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Braga
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Portugal
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Coimbra
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Portugal
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Porto
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Singapore
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Singapore
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South Africa
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Gauteng
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Spain
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Barcelona
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Spain
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Madrid, Communidad Delaware
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Spain
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Navarra
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Spain
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Cordoba
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Girona
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Spain
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Madrid
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Spain
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Murcia
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Spain
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Salamanca
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Spain
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Sevilla
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Sweden
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Skane Lan
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Sweden
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Vastra Gotalands Lan
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Sweden
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Stockholm
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Sweden
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Uppsala
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Switzerland
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Basel-Stadt (de)
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Switzerland
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Zurich (de)
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Taiwan
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Kaohsiung
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Taiwan
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Taipei
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Taiwan
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Taoyuan City
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Thailand
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Krung Thep Maha Nakhon-Bangkok
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Turkey
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Ankara
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Turkey
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Denizli
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Istanbul
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Kayseri
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Trabzon
Country [154] 0 0
Ukraine
State/province [154] 0 0
Kyiv
Country [155] 0 0
United Kingdom
State/province [155] 0 0
Hampshire
Country [156] 0 0
United Kingdom
State/province [156] 0 0
London, City Of
Country [157] 0 0
United Kingdom
State/province [157] 0 0
Oxfordshire
Country [158] 0 0
United Kingdom
State/province [158] 0 0
Surrey
Country [159] 0 0
United Kingdom
State/province [159] 0 0
Yorkshire
Country [160] 0 0
United Kingdom
State/province [160] 0 0
Leicester
Country [161] 0 0
United Kingdom
State/province [161] 0 0
London
Country [162] 0 0
United Kingdom
State/province [162] 0 0
Swansea

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

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
Takeda
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.