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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT04305041
Registration number
NCT04305041
Ethics application status
Date submitted
9/03/2020
Date registered
12/03/2020
Titles & IDs
Public title
Substudy 02A: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents in Participants With Programmed Cell-death 1 (PD-1) Refractory Melanoma (MK-3475-02A/KEYMAKER-U02)
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Scientific title
A Phase 1/2 Open-label Rolling-arm Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Participants With Melanoma (KEYMAKER-U02): Substudy 02A
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Secondary ID [1]
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MK-3475-02A
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Secondary ID [2]
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3475-02A
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Melanoma
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Condition category
Condition code
Cancer
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Malignant melanoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Other - Pembrolizumab
Treatment: Other - Quavonlimab
Treatment: Other - Vibostolimab
Treatment: Drugs - Lenvatinib
Treatment: Drugs - ATRA
Experimental: Pembrolizumab + Quavonlimab + Vibostolimab - Participants will receive pembrolizumab intravenously (IV) plus quavonlimab IV plus vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.
Experimental: Pembrolizumab + Quavonlimab + Lenvatinib - Participants will receive pembrolizumab IV plus quavonlimab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
Experimental: Pembrolizumab + all-trans retinoic acid (ATRA) - Participants will receive pembrolizumab IV plus ATRA orally at specified doses on specified days for a total treatment duration of up to approximately 2 years
Treatment: Other: Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Treatment: Other: Quavonlimab
Administered via IV infusion at a specified dose on specified days
Treatment: Other: Vibostolimab
Administered via IV infusion at a specified dose on specified days
Treatment: Drugs: Lenvatinib
Administered via oral capsules at a specified dose on specified days
Treatment: Drugs: ATRA
Administered via oral capsules at a specified dose on specified days
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Intervention code [1]
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Treatment: Other
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Intervention code [2]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Percentage of participants who experience an adverse event (AE)
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Assessment method [1]
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An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience an AE will be reported.
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Timepoint [1]
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Up to ~28 months
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Primary outcome [2]
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Percentage of participants who discontinue study treatment due to an AE
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Assessment method [2]
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An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study treatment due to an AE will be reported.
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Timepoint [2]
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Up to ~24 months
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Primary outcome [3]
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Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
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Assessment method [3]
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ORR is defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by blinded independent central review (BICR). RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
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Timepoint [3]
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Up to ~30 months
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Secondary outcome [1]
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Duration of Response (DOR) per RECIST 1.1
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Assessment method [1]
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For participants in the analysis population who show a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters), DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 as assessed by BICR. RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
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Timepoint [1]
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Up to ~30 months
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Eligibility
Key inclusion criteria
* Has histologically or cytologically confirmed melanoma
* Has unresectable Stage III or Stage IV melanoma, not amenable to local therapy
* Has progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other therapies
* Has imaging documenting progression per RECIST 1.1 and iRECIST after initiation of an anti-PD-1/L1 agent, or by RECIST 1.1 if progression occurred on adjuvant therapy or in the setting of rapid progression.
* Has not received more than 3 lines of therapy for their advanced melanoma
* Has provided a tumor biopsy
* Male participants who receive lenvatinib or ATRA are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 7 days after the last dose of lenvatinib or ATRA; for male participants who only receive pembrolizumab, quavonlimab, vibostolimab, or a combination, no contraception measures are needed
* Female participant are not pregnant or breastfeeding and are either not a woman of child-bearing potential (WOCBP) OR use a contraceptive method that is highly effective or are abstinent from heterosexual intercourse during the intervention period and for at least 120 days after the last dose of pembrolizumab, quavonlimab, vibostolimab or 30 days after the last dose of lenvatinib or ATRA, whichever occurs last
* Has adequate organ function
* Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia)
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Minimum age
18
Years
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Maximum age
120
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7 days before the first dose of study intervention
* Has a known additional malignancy that is progressing or requires active treatment within the past 2 years
* Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has ocular or mucosal melanoma
* Has known hypersensitivity including previous clinically significant hypersensitivity reaction to treatment with another mAb
* Has an active autoimmune disease that has required systemic treatment in the past 2 years
* Has an active infection requiring systemic therapy
* Has known history of human immunodeficiency virus (HIV)
* Has known history of hepatitis B
* Has a history of (noninfectious) pneumonitis
* Has a history of active tuberculosis (TB)
* Has received prior systemic anticancer therapy within 4 weeks prior to randomization
* Has received prior radiotherapy within 2 weeks of first dose of study intervention
* Has had major surgery <3 weeks prior to first dose of study intervention
* Has received a live vaccine within 30 days before the first dose of study intervention
* Has participated in a study of an investigational agent within 4 weeks prior to the first dose of study intervention
* Has had an allogeneic tissue/solid organ transplant
* Has a pre-existing Grade =3 gastrointestinal fistula or nongastrointestinal fistula
* Has radiographic evidence of encasement of invasion of major blood vessel or of intratumoral cavitation
* Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study intervention
* Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Active, not recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
26/06/2020
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
3/04/2030
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Actual
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Sample size
Target
200
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
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Recruitment hospital [1]
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Calvary Mater Newcastle-Medical Oncology ( Site 1404) - Waratah
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Recruitment hospital [2]
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Melanoma Institute Australia ( Site 1402) - Wollstonecraft
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Recruitment hospital [3]
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Tasman Oncology Research Pty Ltd ( Site 1403) - Southport
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Recruitment hospital [4]
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Fiona Stanley Hospital ( Site 1401) - Murdoch
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Recruitment postcode(s) [1]
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2298 - Waratah
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Recruitment postcode(s) [2]
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2065 - Wollstonecraft
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Recruitment postcode(s) [3]
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4215 - Southport
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Recruitment postcode(s) [4]
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6150 - Murdoch
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Recruitment outside Australia
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United States of America
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State/province [1]
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California
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United States of America
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Colorado
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Maryland
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New York
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North Carolina
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Ohio
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Oregon
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Pennsylvania
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Tennessee
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Texas
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Virginia
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France
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Bouches-du-Rhone
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France
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Gironde
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France
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Haute-Garonne
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France
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Ile-de-France
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France
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Rhone
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France
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Paris
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Israel
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Afula
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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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Ramat Gan
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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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Padova
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Italy
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Siena
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Switzerland
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Geneve
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Switzerland
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Vaud
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Switzerland
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Zurich
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Merck Sharp & Dohme LLC
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Address
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Ethics approval
Ethics application status
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Summary
Brief summary
Substudy 02A is part of a larger research study that is testing experimental treatments for melanoma, a type of skin cancer. The larger study is the umbrella study. The goal of substudy 02A is to evaluate the safety and efficacy of investigational treatment arms in participants with PD-1 refractory melanoma to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available. As of Amendment 4 (effective date: 05JAN2022), a third arm has been opened to participant enrollment, treatment with pembrolizumab and all-trans retinoic acid (ATRA). Enrollment into the first two arms, treatment with pembrolizumab + quavonlimab+ vibostolimab and treatment with pembrolizumab + quavonlimab + lenvatinib has been completed per protocol as of September 2021.
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Trial website
https://clinicaltrials.gov/study/NCT04305041
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
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Medical Director
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Address
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Merck Sharp & Dohme LLC
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Fax
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Contact person for public queries
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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When will data be available (start and end dates)?
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Available to whom?
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Available for what types of analyses?
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How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT04305041