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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04191096




Registration number
NCT04191096
Ethics application status
Date submitted
5/12/2019
Date registered
9/12/2019

Titles & IDs
Public title
Efficacy and Safety of Pembrolizumab (MK-3475) Plus Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (MK-3475-991/KEYNOTE-991)
Scientific title
A Phase 3, Randomized, Double-blind Trial of Pembrolizumab (MK-3475) Plus Enzalutamide Plus ADT Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (KEYNOTE-991)
Secondary ID [1] 0 0
MK-3475-991
Secondary ID [2] 0 0
3475-991
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Hormone-Sensitive Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate
Inflammatory and Immune System 0 0 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Pembrolizumab
Treatment: Drugs - Enzalutamide
Treatment: Drugs - Androgen Deprivation Therapy (ADT)
Other interventions - Placebo

Experimental: Pembrolizumab + Enzalutamide + ADT - Starting on Day 1 of each 21-day cycle, participants receive 200 mg pembrolizumab IV every 3 weeks (Q3W) for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met.

Placebo comparator: Placebo + Enzalutamide + ADT - Starting on Day 1 of each 21-day cycle, participants receive placebo IV Q3W for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met.


Treatment: Other: Pembrolizumab
Pembrolizumab is administered as an IV infusion at 200 mg on Day 1 of each 21-day cycle for up to 35 cycles.

Treatment: Drugs: Enzalutamide
Enzalutamide is administered orally as capsules/tablets at a dosage of 160 mg daily. Enzalutamide is administered continuously until criteria for discontinuation are met.

Treatment: Drugs: Androgen Deprivation Therapy (ADT)
Stable regimen of ADT (LHRH agonist or antagonist) at a dose and frequency of administration that is consistent with the local product label.

Other interventions: Placebo
Placebo infusion solution is administered as an IV infusion on Day 1 of each 21-day cycle for up to 35 cycles.

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Timepoint [1] 0 0
Up to approximately 32 months
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 32 months
Secondary outcome [1] 0 0
Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST)
Timepoint [1] 0 0
Up to Approximately 32 months
Secondary outcome [2] 0 0
Time to First Symptomatic Skeletal-related Event (TTSSRE)
Timepoint [2] 0 0
Up to Approximately 32 months
Secondary outcome [3] 0 0
Time to Prostate-specific Antigen (PSA) Progression
Timepoint [3] 0 0
Up to Approximately 32 months
Secondary outcome [4] 0 0
Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of PCWG-Modified RECIST 1.1 as Assessed by BICR
Timepoint [4] 0 0
Up to Approximately 32 months
Secondary outcome [5] 0 0
Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item #3 ("Worst Pain in 24 Hours") and Opiate Use
Timepoint [5] 0 0
Up to Approximately 32 months
Secondary outcome [6] 0 0
Time From Randomization to Disease Progression as Determined by Investigator Assessment After Next-line of Therapy or Death From Any Cause, Whichever Occurs First (PFS2)
Timepoint [6] 0 0
Up to Approximately 32 months
Secondary outcome [7] 0 0
Prostate-specific Antigen (PSA) Response Rate
Timepoint [7] 0 0
Up to Approximately 32 Months
Secondary outcome [8] 0 0
Prostate-specific Antigen (PSA) Undetectable
Timepoint [8] 0 0
Up to Approximately 32 Months
Secondary outcome [9] 0 0
Objective Response Rate (ORR) Per PCWG-Modified RECIST 1.1 as Assessed by BICR
Timepoint [9] 0 0
Up to Approximately 32 Months
Secondary outcome [10] 0 0
Duration of Response (DOR) Per PCWG- Modified RECIST 1.1 as Assessed by BICR
Timepoint [10] 0 0
Up to Approximately 32 Months
Secondary outcome [11] 0 0
Number of Participants Who Experience an Adverse Event (AE)
Timepoint [11] 0 0
Up to Approximately 59 Months
Secondary outcome [12] 0 0
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
Timepoint [12] 0 0
Up to Approximately 59 Months

Eligibility
Key inclusion criteria
* Male participants with histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
* Has metastatic disease assessed by investigator and verified by BICR by either =2 bone lesions on bone scan and/or visceral disease by computed tomography/magnetic resonance imaging (CT/MRI)
* Willing to maintain continuous Androgen Deprivation Therapy (ADT) with a luteinizing-hormone releasing hormone (LHRH) agonists or antagonists during study treatment or have a history of bilateral orchiectomy
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 10 days of randomization
* Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses prior to randomization
* Has adequate organ function
* Has provided newly obtained core or excisional biopsy (obtained within 12 months of screening) from soft tissue not previously irradiated (samples from tumors progressing in a prior site of radiation are allowed). Participants with bone only or bone predominant disease may provide a bone biopsy sample
* Male participants must agree to the following during the intervention period and for at least 120 days after the last dose of study intervention: Refrain from donating sperm PLUS either be abstinent from heterosexual intercourse and agree to remain abstinent OR agree to use contraception, unless confirmed to be azoospermic
* Male participants must agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person of any sex
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* Has a known additional malignancy that is progressing or has required active treatment in the last 3 years
* Has an active autoimmune disease that has required systemic treatment in past 2 years
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
* Has undergone major surgery including local prostate intervention (excluding prostate biopsy) within 28 days prior to randomization and not recovered adequately from the toxicities and/or complications
* Has a gastrointestinal disorder affecting absorption or is unable to swallow tablets/capsules
* Has an active infection (including tuberculosis) requiring systemic therapy
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
* Has known active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
* Has known or suspected central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has a history of seizure or any condition that may predispose to seizure
* Has a history of loss of consciousness within 12 months of screening
* Has had myocardial infarction or uncontrolled angina within 6 months prior to randomization, or has New York Heart Association class III or IV congestive heart failure or a history of New York Heart Association class III or IV congestive heart failure
* Has hypotension (systolic blood pressure <86 millimeters of mercury [mmHg]) or uncontrolled hypertension (systolic blood pressure >170 mmHg or diastolic blood pressure >105 mmHg) at the screening visit
* Has a history of clinically significant ventricular arrhythmias
* Has hypersensitivity to pembrolizumab and/or enzalutamide and/or any of their excipients
* Has received prior ADT as neoadjuvant/adjuvant therapy for non-metastatic prostate cancer for >39 months in duration or within 9 months prior to randomization or with evidence of disease progression while receiving ADT
* Has had prior treatment with a next generation hormonal agent (eg, abiraterone, enzalutamide, apalutamide, darolutamide)
* Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand 2 (anti PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
* Has received a live vaccine within 30 days prior to randomization
* Has a "superscan" bone scan
* Has had an allogenic tissue/solid organ transplant
* Is expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
* Has received any prior pharmacotherapy, radiation therapy or surgery for metastatic prostate cancer with the following exceptions:

1. Up to 3 months of ADT or orchiectomy with or without concurrent first-generation antiandrogens, if patient was not treated with docetaxel
2. May have 1 course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 4 weeks prior to randomization
3. For participants with low volume metastatic disease, may have 1 course of definitive radiotherapy if it was administered at least 4 weeks prior to randomization
4. Up to 6 cycles of docetaxel therapy with final treatment administration completed within 2 months of randomization and no evidence of disease progression. In these participants up to 6 months of ADT permitted

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
Active, not recruiting
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,VIC,WA
Recruitment hospital [1] 0 0
Chris OBrien Lifehouse ( Site 0300) - Camperdown
Recruitment hospital [2] 0 0
Port Macquarie Base Hospital ( Site 0301) - Port Macquarie
Recruitment hospital [3] 0 0
Riverina Cancer Care Center ( Site 0302) - Wagga Wagga
Recruitment hospital [4] 0 0
Gallipoli Medical Research Foundation ( Site 0309) - Greenslopes
Recruitment hospital [5] 0 0
John Flynn Hospital & Medical Centre ( Site 0308) - Tugun
Recruitment hospital [6] 0 0
Box Hill Hospital ( Site 0304) - Box Hill
Recruitment hospital [7] 0 0
Monash Health ( Site 0305) - Clayton
Recruitment hospital [8] 0 0
Peter MacCallum Cancer Centre ( Site 0306) - Melbourne
Recruitment hospital [9] 0 0
Fiona Stanley Hospital ( Site 0311) - Murdoch
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [3] 0 0
2650 - Wagga Wagga
Recruitment postcode(s) [4] 0 0
4120 - Greenslopes
Recruitment postcode(s) [5] 0 0
4224 - Tugun
Recruitment postcode(s) [6] 0 0
3128 - Box Hill
Recruitment postcode(s) [7] 0 0
3168 - Clayton
Recruitment postcode(s) [8] 0 0
3000 - Melbourne
Recruitment postcode(s) [9] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alaska
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United States of America
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California
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Colorado
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United States of America
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Connecticut
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United States of America
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District of Columbia
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United States of America
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Georgia
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Illinois
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Kansas
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Maryland
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Nevada
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New York
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North Carolina
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Ohio
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Pennsylvania
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South Carolina
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Tennessee
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Virginia
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Washington
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Austria
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Oberosterreich
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Salzburg
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Wien
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Maule
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Rhone
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Baden-Wurttemberg
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Bayern
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Germany
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Niedersachsen
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Sachsen-Anhalt
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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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Cork
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Dublin
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Ireland
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Limerick
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Waterford
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Haifa
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Israel
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Jerusalem
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Israel
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Kfar Saba
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Israel
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Petach Tikva
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Israel
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Tel Aviv
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Israel
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Zerifin
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Italy
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Italy
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Pordenone
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Italy
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Bari
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Italy
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Catania
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Italy
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Milano
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Italy
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Napoli
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Italy
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Roma
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Italy
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Terni
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Verona
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Chiba
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Ehime
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Hokkaido
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Kanagawa
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Nara
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Osaka
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Saitama
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Shizuoka
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Yamaguchi
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Fukuoka
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Nagano
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Tokyo
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Jeonranamdo
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Kyonggi-do
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Korea, Republic of
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Taegu-Kwangyokshi
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Korea, Republic of
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Seoul
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Mexico
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Jalisco
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Noord-Holland
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Utrecht
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New Zealand
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Auckland
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Peru
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Ariqipa
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Peru
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La Libertad
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Peru
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Lima
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Poland
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Kujawsko-pomorskie
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Malopolskie
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Mazowieckie
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Podkarpackie
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Slaskie
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Wielkopolskie
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Poland
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Zachodniopomorskie
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Russian Federation
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Krasnoyarskiy Kray
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Russian Federation
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Moskva
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Russian Federation
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Nizhegorodskaya Oblast
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Russian Federation
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Omskaya Oblast
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Spain
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Barcelona
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Spain
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Gerona
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Spain
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Lugo
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Spain
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Madrid
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Spain
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Sevilla
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Switzerland
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Grisons
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Switzerland
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Sankt Gallen
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Switzerland
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Vaud
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Switzerland
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Zurich
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Taiwan
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Kaohsiung
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Taiwan
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Tainan
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Taiwan
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Taipei
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Taiwan
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Taoyuan
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Thailand
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Krung Thep Maha Nakhon
Country [142] 0 0
Thailand
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Khon Kaen
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Turkey
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Adana
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Turkey
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Ankara
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Turkey
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Istanbul
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Turkey
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Izmir
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Turkey
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Konya
Country [148] 0 0
United Kingdom
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Aberdeen City
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United Kingdom
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Cornwall
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United Kingdom
State/province [150] 0 0
London, City Of
Country [151] 0 0
United Kingdom
State/province [151] 0 0
Cardiff

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
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?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.