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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04544436




Registration number
NCT04544436
Ethics application status
Date submitted
4/09/2020
Date registered
10/09/2020

Titles & IDs
Public title
A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of a Higher Dose of Ocrelizumab in Adults With Relapsing Multiple Sclerosis (RMS)
Scientific title
A Phase IIIb Multicenter, Randomized, Double-Blind, Controlled Study to Evaluate the Efficacy, Safety and Pharmacokinetics of a Higher Dose of Ocrelizumab in Adults With Relapsing Multiple Sclerosis
Secondary ID [1] 0 0
2020-000893-69
Secondary ID [2] 0 0
BN42082
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ocrelizumab
Treatment: Drugs - Ocrelizumab
Treatment: Drugs - Antihistamine
Treatment: Drugs - Methylprednisolone

Experimental: Ocrelizumab Higher Dose - Participants will be randomized to receive a minimum of 5 higher treatment doses (1200 mg or 1800 mg) of ocrelizumab administered by intravenous (IV) infusion every 24 weeks in the double blind treatment (DBT) phase. During the optional open-label extension (OLE) phase, participants will continue with their assigned dose of ocrelizumab (either 1200 or 1800 mg) for approximately 96 weeks (4 doses in total). Mandatory methylprednisolone (or equivalent) and antihistaminic drug (e.g., diphenhydramine or equivalent) will be administered approximately 30-60 minutes prior to the start of each ocrelizumab infusion.

Active comparator: Ocrelizumab Approved Dose - Participants will be randomized to receive a minimum of 5 treatment doses of 600 mg ocrelizumab administered by intravenous (IV) infusion every 24 weeks in the DBT phase. During the optional OLE phase, participants will be offered a higher dose of ocrelizumab (either 1200 or 1800 mg), based on their body weight at OLE baseline, for approximately 96 weeks (4 doses in total). Mandatory methylprednisolone (or equivalent) and antihistaminic drug (e.g., diphenhydramine or equivalent) will be administered approximately 30-60 minutes prior to the start of each ocrelizumab infusion.


Treatment: Drugs: Ocrelizumab
The actual higher dose of ocrelizumab will be assigned to participants based on their body weight at baseline: 1200 mg (participants's body weight \<75 kg) or 1800 mg (participant's body weight \>/=75 kg). The first dose of ocrelizumab will be administered as two 600 mg or 900 mg intravenous (IV) infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 1200 mg or 1800 mg IV infusion every 24 weeks.

During the optional open-label extension (OLE) phase, participants will continue with their assigned dose of ocrelizumab (either 1200 or 1800 mg) for approximately 96 weeks (4 doses in total).

Treatment: Drugs: Ocrelizumab
Ocrelizumab will be administered at a dose of 600 milligram (mg) every 24 weeks. The first dose of ocrelizumab will be administered as two 300 mg intravenous (IV) infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 600 mg IV infusion every 24 weeks.

Treatment: Drugs: Antihistamine
Premedication with oral or IV antihistaminic drug (i.e., diphenhydramine 50 mg or an equivalent dose of an alternative) will be administered prior to each ocrelizumab infusion.

Treatment: Drugs: Methylprednisolone
Premedication with 100 mg of methylprednisolone (or equivalent) will be administered by IV infusion prior to each ocrelizumab infusion.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to Onset of 12-week cCDP (cCDP12)
Timepoint [1] 0 0
Baseline up to approximately 4.3 years
Secondary outcome [1] 0 0
Time to Onset of 24-week cCDP (cCDP24)
Timepoint [1] 0 0
Baseline up to approximately 4.3 years
Secondary outcome [2] 0 0
Time to Onset of 48-week cCDP (cCDP48)
Timepoint [2] 0 0
Baseline up to approximately 4.3 years
Secondary outcome [3] 0 0
Time to onset of cCDP12 independent of protocol-defined relapses (PDR)
Timepoint [3] 0 0
Baseline up to approximately 4.3 years
Secondary outcome [4] 0 0
Time to onset of 12-week CDP (CDP12)
Timepoint [4] 0 0
Baseline up to approximately 4.3 years
Secondary outcome [5] 0 0
Time to >/= 20% Increase in 12-week Confirmed by Timed 25-Foot Walk Test (T25FWT)
Timepoint [5] 0 0
Baseline up to approximately 4.3 years
Secondary outcome [6] 0 0
Annual rate of percent change from baseline in total brain volume
Timepoint [6] 0 0
Baseline up to approximately 4.3 years
Secondary outcome [7] 0 0
Time to 12-week Confirmed 4-point Worsening in Symbol Digit Modality Test (SDMT)
Timepoint [7] 0 0
Baseline up to approximately 4.3 years
Secondary outcome [8] 0 0
Time to 12-week confirmed 8-point increase in 12-Item Multiple Sclerosis Walking Scale (MSWS-12)
Timepoint [8] 0 0
Baseline up to approximately 4.3 years
Secondary outcome [9] 0 0
Change in NfL at Week 48 for patients assigned to the higher dose ocrelizumab group
Timepoint [9] 0 0
Baseline up to approximately 4.3 years
Secondary outcome [10] 0 0
Change in NfL at Week 48 for patients assigned to the approved dose ocrelizumab group
Timepoint [10] 0 0
Baseline up to approximately 4.3 years
Secondary outcome [11] 0 0
Serum Concentration of Ocrelizumab at Specified Time points
Timepoint [11] 0 0
Week 0, 2, 12, 24, 36, 48, 60, 72, 84, 96, 120
Secondary outcome [12] 0 0
B-cell levels in blood
Timepoint [12] 0 0
Baseline up to approximately 4.3 years
Secondary outcome [13] 0 0
Proportion of Participants Achieving 5 or Less B-cells per Microliter of Blood
Timepoint [13] 0 0
Baseline up to approximately 4.3 years
Secondary outcome [14] 0 0
Proportion of Participants Achieving 5 or Less B-cells per Microliter of Blood in Participants with the High versus Low Affinity Fcgamma Receptor 3A (FcgR3A) Genotype per Arm
Timepoint [14] 0 0
Week 0, 2, 12, 24, 36, 48, 60, 72, 84, 96, 120
Secondary outcome [15] 0 0
Change from Baseline in the Anti-Drug Antibody (ADA) Levels
Timepoint [15] 0 0
Week 0, 24, 48, 72, 96, 120
Secondary outcome [16] 0 0
Levels of Neurofilament Light Chain (NfL) in Blood
Timepoint [16] 0 0
Baseline up to approximately 4.3 years
Secondary outcome [17] 0 0
Levels of Interleukin-6 (IL-6) in Blood
Timepoint [17] 0 0
Baseline up to approximately 4.3 years
Secondary outcome [18] 0 0
Levels of Blood B-cells
Timepoint [18] 0 0
Baseline up to approximately 4.3 years
Secondary outcome [19] 0 0
Levels of Lymphocytes in Blood
Timepoint [19] 0 0
Baseline up to approximately 4.3 years
Secondary outcome [20] 0 0
Proportion of Participants with Different DNA Genotypes
Timepoint [20] 0 0
Week 0

Eligibility
Key inclusion criteria
* Diagnosis of relapsing multiple sclerosis (RMS) (i.e., RRMS or aSPMS where participants still experience relapses) in accordance with the revised McDonald Criteria 2017
* At least two documented clinical relapses within the last 2 years prior to screening, or one clinical relapse in the year prior to screening. No relapse 30 days prior to screening and at baseline.
* Participants must be neurologically stable for at least 30 days prior to randomization and baseline.
* Expanded disability status scale (EDSS) score, at screening and baseline, from 0 to 5.5 inclusive.
* Average T25FWT score over two trials at screening and over two trials at baseline respectively, up to 150 (inclusive) seconds
* Average 9HPT score over four trials at screening and over four trials at baseline respectively, up to 250 (inclusive) seconds
* Documented MRI of brain with abnormalities consistent with MS at screening.
* Participants requiring symptomatic treatment for MS and/or physiotherapy must be treated at a stable dose. No initiation of symptomatic treatment for MS or physiotherapy within 4 weeks of randomization.
* Females of childbearing potential, agreement to remain abstinent or use adequate contraceptive methods.
* Female participants without reproductive potential may be enrolled e.g. if post-menopausal or if surgically sterile
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* History of primary progressive MS at screening.
* Any known or suspected active infection at screening or baseline (except nailbed infections), or any major episode of infection requiring hospitalization or treatment with IV antimicrobials within 8 weeks or treatment with oral antimicrobials within 2 weeks, prior to and during screening.
* History of confirmed or suspected progressive multifocal leukoencephalopathy.
* History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening.
* Immunocompromised state.
* Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization.
* Inability to complete an MRI or contraindication to gadolinium administration.
* Contraindications to mandatory pre-medications for IRRs.
* Known presence of other neurologic disorders that could interfere with the diagnosis of MS or assessments of efficacy and/or safety during the study
* Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study.
* Significant, uncontrolled disease that may preclude participant from participating in the study.
* History of or currently active primary or secondary, non-drug-related, immunodeficiency.
* Pregnant or breastfeeding or intending to become pregnant
* Lack of peripheral venous access.
* History of alcohol or other drug abuse within 12 months prior to screening.
* Treatment with any investigational agent within 24 weeks prior to screening or treatment with any experimental procedure for MS.
* Previous use of anti-CD20s (including ocrelizumab), unless the last infusion was more than 2 years before screening, B-cell count is normal, and the stop of the treatment was not motivated by safety reasons or lack of efficacy.
* Previous treatment with fingolimod, siponimod, or ozanimod within 6 weeks of baseline
* Previous treatment with natalizumab within 4.5 months of baseline
* Previous treatment with interferons beta (1a or 1b), or glatiramer acetate within 2 weeks of baseline
* Any previous treatment with mitoxantrone, cladribine, atacicept, alemtuzumab, and daclizumab
* Previous treatment with any other immunomodulatory or immunosuppressive medication not already listed above without appropriate washout as described in the applicable local label. If the washout requirements are not described in the applicable local label, then the wash out period must be five times the half-life of the medication.
* Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation.
* Any previous history of transplantation or anti-rejection therapy.
* Treatment with intravenous (IV) immunoglobulin (Ig) or plasmapheresis within 12 weeks prior to randomization.
* Systemic corticosteroid therapy within 4 weeks prior to screening.
* Positive screening tests for active, latent, or inadequately treated hepatitis B.
* Sensitivity or intolerance to any ingredient (including excipients) of ocrelizumab.
* Any additional exclusionary criterion as per ocrelizumab local label, if more stringent than the above.

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
26/11/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/08/2028
Actual
Sample size
Target
Accrual to date
Final
864
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Austin Hospital; Department of Neurology - Heidelberg
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
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Alabama
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Arizona
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California
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Colorado
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Florida
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United States of America
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Indiana
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Kansas
Country [8] 0 0
United States of America
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Louisiana
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United States of America
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Maine
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Massachusetts
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Michigan
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Missouri
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Nevada
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New York
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Ohio
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Oklahoma
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Pennsylvania
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Tennessee
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Texas
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Washington
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Argentina
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Buenos Aires
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Argentina
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San Miguel de Tucuman
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Belgium
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Bruxelles
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Belgium
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Overpelt
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Brazil
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PR
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Brazil
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RS
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Brazil
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SC
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Brazil
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Glostrup
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France
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Bordeaux
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France
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Clermont Ferrand
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Lille
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France
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Rouen
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Germany
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Berlin
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Germany
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Bochum
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Dresden
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Kiel
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Leipzig
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Germany
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Tübingen
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Germany
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Ulm
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Germany
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Wiesbaden
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Athens
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Thessaloniki
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Lublin
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Plewiska
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Pozna?
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Rzeszów
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Szczecin
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Warszawa
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Portugal
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Braga
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Portugal
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Lisboa
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Russian Federation
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Krasnojarsk
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Russian Federation
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Leningrad
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Russian Federation
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Moskovskaja Oblast
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Russian Federation
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Sankt Petersburg
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Russian Federation
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Sverdlovsk
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Russian Federation
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Tatarstan
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Russian Federation
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Uljanovsk
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Russian Federation
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Saratov
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Russian Federation
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Tomsk
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Spain
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LA Coruña
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Spain
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Madrid
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Spain
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Pontevedra
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Spain
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Barcelona
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Spain
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Cadiz
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Spain
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Malaga
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Switzerland
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Basel
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Switzerland
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Bern
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Switzerland
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Lugano
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Turkey
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Kocaeli
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Ukraine
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Chernihiv Governorate
Country [87] 0 0
Ukraine
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Katerynoslav Governorate
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Ukraine
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Kharkiv Governorate
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Ukraine
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KIEV Governorate
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Ukraine
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Chernihiv
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Ukraine
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Chernivtsi
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Ukraine
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Ivano-Frankivsk
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Ukraine
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Kharkov
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United Kingdom
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Plymouth

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
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?
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
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?


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/NCT04544436