MedPath

A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Ocrelizumab in Adult Participants With Primary Progressive Multiple Sclerosis

Phase 3
Active, not recruiting
Conditions
Multiple Sclerosis, Primary Progressive
Interventions
Drug: Placebo matched to ocrelizumab
Drug: Placebo matched to fenebrutinib
Registration Number
NCT04544449
Lead Sponsor
Hoffmann-La Roche
Brief Summary

A study to evaluate the efficacy and safety of fenebrutinib on disability progression in adult participants with Primary Progressive Multiple Sclerosis (PPMS). All eligible participants will be randomized 1:1 to either daily oral fenebrutinib (and placebo) or intravenous (IV) ocrelizumab (and placebo) in a blinded fashion through an interactive voice or web-based response system (IxRS). 985 participants were enrolled and recruited globally. Participants who discontinue study medication early or discontinue from the study will not be replaced. The Open-Label Extension (OLE) phase is contingent on a positive benefit-risk result in the Primary Analysis of the study.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
985
Inclusion Criteria
  • For sites in Germany and Italy only, enrollment is restricted to participants aged 46-65 years
  • A diagnosis of PPMS in accordance to the revised 2017 McDonald Criteria (Thompson et al. 2018).
  • Disability progression in the 12 months prior to screening.
  • Expanded Disability Status Scale (EDSS) score from 3.0 to 6.5 inclusive at screening.
  • Pyramidal functional subscore >=2 at screening.
  • For participants currently receiving proton pump inhibitors (PPIs), H2-receptor antagonists (H2RAs), symptomatic treatment for MS (e.g. fampridine, cannabis) and/or physiotherapy: treatment at a stable dose during the screening period prior to the initiation of study treatment and plans to remain at a stable dose for the duration of study treatment.
  • Neurologically stable for at least 30 days prior to randomization and baseline assessments.
  • Ability to complete the 9-Hole Peg Test (9-HPT) for each hand in <240 seconds.
  • Ability to perform Timed 25-Foot Walk Test (T25FWT) in <150 seconds.
  • For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs.
  • For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm.

OLE Inclusion Criteria:

  • Completed the Double-Blind Treatment (DBT) phase of the study (remaining on study treatment; no other Disease-Modifying Therapy (DMT) administered) and who, in the opinion of the investigator, may benefit from treatment with fenebrutinib.
  • For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs.
  • For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm.
Exclusion Criteria
  • For participants enrolled in Germany and in Italy only: Presence of gadolinium-enhancing lesions on T1-weighted MRI (T1Gd +) lesion on the screening MRI
  • Any known or suspected active infection (excluding onychomycosis) at screening, including but not limited to a positive screening test for Hepatitis B and C, an active or latent or inadequately treated infection with tuberculosis (TB), a confirmed or suspected progressive multifocal leukoencephalopathy (PML).
  • Participants with a previous history of a serious Infusion-Related Reaction (IRR) (Common Terminology Criteria for Adverse Events [CTCAE] Grade >= 4) and/or any hypersensitivity reaction to ocrelizumab.
  • History of cancer including hematologic malignancy and solid tumors within 10 years of screening. Exceptions: Basal/squamous cell carcinoma of skin cured by excision. In situ carcinoma of the cervix successfully treated by curative therapy >1 year prior to screening.
  • Known presence of other neurological disorders, that could interfere with the diagnosis of MS or assessments of efficacy or safety during the study, clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal disease.
  • Presence of cirrhosis (Child-Pugh Class A, B, or C)
  • Chronic liver disease unless considered stable for >6 months
  • Acute liver disease
  • Any concomitant disease that may require chronic treatment with systemic corticosteroids, immunosuppressants or specific medication that could impact the primary evaluation of the study.
  • History of alcohol or other drug abuse within 12 months prior to screening.
  • Female participants who are pregnant or breastfeeding or intending to become pregnant during the study or 6 or 12 months (as applicable from the local label for ocrelizumab) after final dose of study drug.
  • Male participants intending to father a child during the study or for 28 days after final dose of study drug.
  • Lack of peripheral venous access.
  • Any previous treatment with immunomodulatory or immunosuppressive medication without an appropriate washout period.
  • Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization.
  • Immunocompromised state, history of primary or secondary (non-drug related) immunodeficiency, or history of transplantation or antirejection therapy
  • Known bleeding diathesis, anemia, or history of hospitalization or transfusion for gastrointestinal (GI) bleed
  • Any previous treatment with cladribine, mitoxantrone, daclizumab, alemtuzumab, or cyclophosphamide

OLE Exclusion Criteria:

  • Chronic liver disease unless considered stable for > 6 months
  • Acute liver disease

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
FenebrutinibPlacebo matched to ocrelizumabParticipants will receive oral fenebrutinib and intravenous (IV) ocrelizumab-matching placebo.
OcrelizumabPlacebo matched to fenebrutinibParticipants will receive intravenous (IV) ocrelizumab and oral fenebrutinib-matching placebo.
FenebrutinibFenebrutinibParticipants will receive oral fenebrutinib and intravenous (IV) ocrelizumab-matching placebo.
OcrelizumabOcrelizumabParticipants will receive intravenous (IV) ocrelizumab and oral fenebrutinib-matching placebo.
Primary Outcome Measures
NameTimeMethod
Time to Onset of Composite 12-week Confirmed Disability Progression (cCDP12)Minimum of 120 weeks
Secondary Outcome Measures
NameTimeMethod
Time to Onset of 12-week Confirmed 4-point Worsening in Symbol Digit Modality Test (SDMT) ScoreMinimum of 120 weeks

The SDMT is used for detecting the presence of cognitive impairment and changes in cognitive functioning over time and in response to treatment. The SDMT is brief, easy to administer test, and involves a simple substitution task. Using a reference key, the examinee has 90 seconds to pair specific numbers with given geometric figures. Responses will be collected only orally, and administration time is approximately 5 minutes. The number of correct responses in 90 seconds will be considered the SDMT score. A decrease by 4 points on the SDMT score from baseline represents a clinically meaningful change in cognitive processing. The SDMT score ranges from 0 to 110. The higher the results, the better processing speed/working memory.

Percentage of Participants with Adverse Events (AEs)Up to 4.7 years
Plasma Concentrations of Fenebrutinib at Specified TimepointsUp to 4.7 years
Percent Change from Screening in Blood Neurofilament Light Chain (NfL) LevelsUp to Week 120
Time to Onset of Composite 24-week CDP (cCDP24)Minimum of 120 weeks
Time to Onset of 12-week CDP (CDP12)Minimum of 120 weeks
Time to Onset of 24-week CDP (CDP24)Minimum of 120 weeks
Percentage Change in Total Brain Volume Assessed by Magnetic Resonance Imaging (MRI)From Week 24 to Week 120
Change from Baseline in Participant-Reported Physical Impacts of Multiple Sclerosis (MS) Measured by the Multiple Sclerosis Impact Scale, 29-Item [MSIS-29] Physical ScaleBaseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120

The MSIS-29, Version 2 is a 29-item patient-reported measure of the physical and psychological impacts of MS. Participants are asked to rate how much their functioning and well-being has been impacted over the past 14 days on a 4-point scale, from "Not at all" (1) to "Extremely" (4). The physical score is the sum of items 1-20, which is then transformed to a 0-100 scale. The psychological score is the sum of items 21-29, transformed to a 0-100 scale. Higher scores indicate a greater impact of MS.

Trial Locations

Locations (189)

Fundacion Rosarina de Neurorehabilitacion

🇦🇷

Rosario, Argentina

UMHAT Dr. Georgi Stranski

🇧🇬

Pleven, Bulgaria

Instituto Neurologico de Colombia INDEC

🇨🇴

Medellin, Colombia

Aarhus Universitetshospital

🇩🇰

Aarhus N, Denmark

Groupe Hospitalier Pellegrin

🇫🇷

Bordeaux, France

Hopital Pierre Wertheimer

🇫🇷

Bron, France

CHRU de Montpellier, Hopital Gui de Chauliac

🇫🇷

Montpellier, France

Hopital Guillaume Et Rene Laennec

🇫🇷

Nantes, France

Hôpital Pasteur

🇫🇷

Nice, France

Hopitaux Universitaires de Strasbourg

🇫🇷

Strasbourg, France

Charite - Universitatsmedizin Berlin

🇩🇪

Berlin, Germany

Studienzentrum Dr. Bischof GmbH

🇩🇪

Böblingen, Germany

Klinikum rechts der Isar der TU Muenchen

🇩🇪

München, Germany

Universitaetsklinikum Tuebingen

🇩🇪

Tuebingen, Germany

Deutsche Klinik für Diagnostik

🇩🇪

Wiesbaden, Germany

Hospital Eginition

🇬🇷

Athens, Greece

401 Military Hospital of Athens

🇬🇷

Athens, Greece

AHEPA Univ. General Hospital of Thessaloniki

🇬🇷

Thessaloniki, Greece

Clinexpert Kft.

🇭🇺

Budapest, Hungary

S-Medicon Egeszsegugyi Szolgaltato Kft.

🇭🇺

Budapest, Hungary

Markhot Ferenc Oktatokorhaz és Rendelointezet

🇭🇺

Eger, Hungary

Pest Megyei Flor Ferenc Korhaz

🇭🇺

Kistarcsa, Hungary

Rambam Medical Center

🇮🇱

Haifa, Israel

The Chaim Sheba Medical Center

🇮🇱

Ramat-Gan, Israel

Hospital Geral de Santo Antonio

🇵🇹

Porto, Portugal

Hospital de Sao Joao

🇵🇹

Porto, Portugal

San Juan MS Center

🇵🇷

Guaynabo, Puerto Rico

Volyn Regional Clinical Hospital

🇺🇦

Lutsk, Ukraine

Odesa Regional Clinical Hospital

🇺🇦

Odesa, Ukraine

Queen Elizabeth University Hospital

🇬🇧

Glasgow, United Kingdom

Charing Cross Hospital

🇬🇧

London, United Kingdom

Ondokuz Mayis Univ. Med. Fac.

🇹🇷

Samsun, Turkey

Karadeniz Tecnical Uni. Med. Fac.

🇹🇷

Trabzon, Turkey

Van Yuzuncu Yil University Hospital

🇹🇷

Van, Turkey

Baskent Universitesi Ankara Hastanesi

🇹🇷

Çankaya, Turkey

Neurology Associates PA

🇺🇸

Maitland, Florida, United States

Neurological Services of Orlando

🇺🇸

Orlando, Florida, United States

Neurology Clinic PC

🇺🇸

Cordova, Tennessee, United States

Hope Neurology

🇺🇸

Knoxville, Tennessee, United States

Alabama Neurology Associates

🇺🇸

Homewood, Alabama, United States

Sutter East Bay Medical Foundation

🇺🇸

Berkeley, California, United States

Fullerton Neurology and Headache Center

🇺🇸

Fullerton, California, United States

Palo Alto Medical Foundation Research Center

🇺🇸

Sunnyvale, California, United States

University of Colorado Denver

🇺🇸

Aurora, Colorado, United States

Yale University School Of Medicine

🇺🇸

Fairfield, Connecticut, United States

Georgetown University Medical Center

🇺🇸

Washington, District of Columbia, United States

University of South Florida

🇺🇸

Tampa, Florida, United States

Josephson Wallack Munshower Neurology PC

🇺🇸

Indianapolis, Indiana, United States

University of Kansas Medical Center

🇺🇸

Kansas City, Kansas, United States

Johns Hopkins University School Of Medicine

🇺🇸

Baltimore, Maryland, United States

Dragonfly Research, LLC

🇺🇸

Wellesley, Massachusetts, United States

Wayne State University

🇺🇸

Detroit, Michigan, United States

Minneapolis Clinic of Neurology

🇺🇸

Golden Valley, Minnesota, United States

Washington University

🇺🇸

Saint Louis, Missouri, United States

Cleveland Clinic Lou Ruvo

🇺🇸

Las Vegas, Nevada, United States

Hackensack U Med Ctr

🇺🇸

Hackensack, New Jersey, United States

Barnabas Health Ambulatory Care Center

🇺🇸

Livingston, New Jersey, United States

Jersey Shore University Medical Centre

🇺🇸

Neptune, New Jersey, United States

Rutgers New Jersey Medical School

🇺🇸

Newark, New Jersey, United States

Holy Name Hospital

🇺🇸

Teaneck, New Jersey, United States

Dent Neurological Institute

🇺🇸

Amherst, New York, United States

Columbia University Medical Center

🇺🇸

New York, New York, United States

University of Rochester

🇺🇸

Rochester, New York, United States

Stony Brook University Medical Center

🇺🇸

Stony Brook, New York, United States

SUNY Upstate Medical University

🇺🇸

Syracuse, New York, United States

Atrium Health Neurosciences Institute ? Charlotte

🇺🇸

Charlotte, North Carolina, United States

Raleigh Neurology Associates

🇺🇸

Raleigh, North Carolina, United States

Miami Valley Hospital South

🇺🇸

Centerville, Ohio, United States

UC Health, LLC.

🇺🇸

Cincinnati, Ohio, United States

OhioHealth Riverside Methodist Hospital

🇺🇸

Columbus, Ohio, United States

Providence Brain and Spine Institute

🇺🇸

Portland, Oregon, United States

Vanderbilt University Medical Center

🇺🇸

Nashville, Tennessee, United States

Uni of Texas Health Science Center At Houston

🇺🇸

Houston, Texas, United States

Texas Institute for Neurological Disorders

🇺🇸

Sherman, Texas, United States

Evergreen MS Center

🇺🇸

Kirkland, Washington, United States

Swedish Medical Center

🇺🇸

Seattle, Washington, United States

West Virginia University

🇺🇸

Morgantown, West Virginia, United States

Medical College of Wisconsin, Inc.

🇺🇸

Milwaukee, Wisconsin, United States

Centro de Especialidades Neurológicas y Rehabilitación - CENyR

🇦🇷

Buenos Aires, Argentina

Focus CECIC

🇦🇷

Buenos Aires, Argentina

Instituto Reumatológico Strusberg

🇦🇷

Cordoba, Argentina

Centro de Investigaciones Médicas Tucuman

🇦🇷

San Miguel, Argentina

Brain and Mind Research Institute

🇦🇺

Camperdown, New South Wales, Australia

Liverpool Hospital

🇦🇺

Liverpool, New South Wales, Australia

John Hunter Hospital

🇦🇺

New Lambton, New South Wales, Australia

Princess Alexandra Hospital

🇦🇺

Woolloongabba, Queensland, Australia

Box Hill Hospital

🇦🇺

Box Hill, Victoria, Australia

Austin Hospital

🇦🇺

Heidelberg, Victoria, Australia

Royal Melbourne Hospital

🇦🇺

Parkville, Victoria, Australia

Kepler Universitätsklinikum GmbH - Neuromed Campus

🇦🇹

Linz, Austria

Medizinische Universität Wien

🇦🇹

Wien, Austria

Santa Casa de Misericordia

🇧🇷

Belo Horizonte, Minas Gerais, Brazil

Instituto de Neurologia de Curitiba

🇧🇷

Curitiba, Paraná, Brazil

IMV Pesquisa Neurológica

🇧🇷

Porto Alegre, Rio Grande Do Sul, Brazil

Núcleo de Pesquisa do Rio Grande do Sul

🇧🇷

Porto Alegre, Rio Grande Do Sul, Brazil

Clinica Neurologica

🇧🇷

Joinville, Santa Catarina, Brazil

Centro de Pesquisas Clinicas

🇧🇷

Sao Paulo, São Paulo, Brazil

Hospital Universitario Gaffree e Guinle

🇧🇷

Rio de Janeiro, Brazil

Multiprofile Hospital for Active Treatment of Neurology and Psychiatry Sv. Naum EAD

🇧🇬

Sofia, Bulgaria

University of Alberta Hospital

🇨🇦

Edmonton, Alberta, Canada

Fraser Health Authority - Fraser Health Multiple Sclerosis

🇨🇦

Burnaby, British Columbia, Canada

University of British Columbia

🇨🇦

Vancouver, British Columbia, Canada

London Health Sciences Centre Uni Campus

🇨🇦

London, Ontario, Canada

The Ottawa Hospital - General Campus

🇨🇦

Ottawa, Ontario, Canada

Sunnybrook Health Sciences Centre

🇨🇦

Toronto, Ontario, Canada

St. Michael's Hospital

🇨🇦

Toronto, Ontario, Canada

Clinique NeuroOutaouais

🇨🇦

Gatineau, Quebec, Canada

Recherche Sepmus Inc.

🇨🇦

Greenfield Park, Quebec, Canada

Montreal Neurological Institute and Hospital

🇨🇦

Montreal, Quebec, Canada

CeCim Biocinetic

🇨🇱

Santiago, Chile

Clinica Alemana

🇨🇱

Vitacura, Chile

Organizacion Sanitas Internacional

🇨🇴

Bogota, Colombia

Fundacion Clinica Valle del Lili

🇨🇴

Cali, Colombia

Rigshospitalet

🇩🇰

Glostrup, Denmark

Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften

🇩🇪

Dresden, Germany

Universitätsklinikum Freiburg, Klinik für Neurologie und Neurophysiologie

🇩🇪

Freiburg, Germany

Budapesti Jahn Ferenc Dél-pesti Kórház és Rendel?intézet

🇭🇺

Budapest, Hungary

Tel Aviv Sourasky Medical Center

🇮🇱

Tel Aviv, Israel

AOU Seconda Università degli Studi

🇮🇹

Napoli, Campania, Italy

A.O.U. di Parma

🇮🇹

Parma, Emilia-Romagna, Italy

Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla

🇮🇹

Roma, Lazio, Italy

Irccs A.O.U.San Martino Ist

🇮🇹

Genova, Liguria, Italy

IRCCS Ospedale San Raffaele

🇮🇹

Milano, Lombardia, Italy

Ospedale Civile di Montichiari

🇮🇹

Montichiari, Lombardia, Italy

IRCCS Istituto Neurologico Neuromed

🇮🇹

Pozzilli, Molise, Italy

A.R.N.A.S. Civico Di Cristina Benfratelli

🇮🇹

Palermo, Sicilia, Italy

Mexico Centre for Clinical Research

🇲🇽

Ciudad de México, Mexico CITY (federal District), Mexico

Hospital Juarez de Mexico

🇲🇽

Ciudad de México, Mexico CITY (federal District), Mexico

Clinstile S.A de C.V.

🇲🇽

Mexico City, Mexico CITY (federal District), Mexico

Grupo Médico Camino S.C.

🇲🇽

Mexico, Mexico CITY (federal District), Mexico

Clinical Research Institute

🇲🇽

Tialnepantla, Mexico

University Clinic of Neurology

🇲🇰

Skopje, North Macedonia

Hospital IV Alberto Sabogal Sologuren

🇵🇪

Bellavista, Peru

Clinica Internacional

🇵🇪

Lima, Peru

Instituto Nacional de Ciencias Neurológicas - Hospital Mogrovejo

🇵🇪

Lima, Peru

Neurocentrum Bydgoszcz sp. z o.o

🇵🇱

Bydgoszcz, Poland

Care Clinic

🇵🇱

Katowice, Poland

NEURO-CARE Sp. z o.o. Sp. Komandytowa

🇵🇱

Katowice, Poland

Centrum Neurologii Krzysztof Selmaj

🇵🇱

Lodz, Poland

Med Polonia

🇵🇱

Pozna?, Poland

Centrum Medyczne "MEDYK"

🇵🇱

Rzeszow, Poland

Nmedis sp. z o.o.

🇵🇱

Rzeszów, Poland

Centrum Medyczne NeuroProtect

🇵🇱

Warszawa, Poland

Wro Medica

🇵🇱

Wroc?aw, Poland

SPSK nr 1

🇵🇱

Zabrze, Poland

Hospital de Braga

🇵🇹

Braga, Portugal

Hospital Santo Antonio dos Capuchos

🇵🇹

Lisboa, Portugal

Hospital de Santa Maria

🇵🇹

Lisboa, Portugal

Krasnoyarsk State Medical Academy

🇷🇺

Krasnoyarsk, Krasnojarsk, Russian Federation

FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency

🇷🇺

Krasnoyarsk, Krasnojarsk, Russian Federation

National Center of Social Significant Disease

🇷🇺

Sankt-peterburg, Leningrad, Russian Federation

Federal center of brain research and neurotechnologies

🇷🇺

Moskva, Moskovskaja Oblast, Russian Federation

City Clinical Hospital #24

🇷🇺

Moskva, Moskovskaja Oblast, Russian Federation

City Hospital #40 of Resort Administrative District

🇷🇺

St. Petersburg, Sankt Petersburg, Russian Federation

Sverdlovsk Regional Clinical Hospital 1

🇷🇺

Yekaterinburg, Sverdlovsk, Russian Federation

Vertebronevrologiya LLC

🇷🇺

Kazan, Tatarstan, Russian Federation

Regional Multiple Sclerosis Centre b/o CC ECM Neftyanik

🇷🇺

Tyumen, Tjumen, Russian Federation

Center of Cardiology and Neurology

🇷🇺

Kirov, Russian Federation

State Novosibirsk Regional Clinical Hospital

🇷🇺

Novosibirsk, Russian Federation

Complejo Hospitalario Universitario A Coruña (CHUAC)

🇪🇸

Coruña, LA Coruna, Spain

Hospital Universitari Arnau de Vilanova de Lleida

🇪🇸

Lleida, Lerida, Spain

Hospital Quiron de Madrid

🇪🇸

Pozuelo de Alarcon, Madrid, Spain

Hospital Alvaro Cunqueiro

🇪🇸

Vigo, Pontevedra, Spain

Hospital Universitari Vall d'Hebron

🇪🇸

Barcelona, Spain

Hospital Puerta del Mar

🇪🇸

Cadiz, Spain

Hospital Ramon y Cajal

🇪🇸

Madrid, Spain

Hospital Regional Universitario de Malaga ? Hospital General

🇪🇸

Malaga, Spain

Hospital Universitario Virgen Macarena

🇪🇸

Sevilla, Spain

Universitätsspital Basel

🇨🇭

Basel, Switzerland

Inselspital Bern Medizin Neurologie

🇨🇭

Bern, Switzerland

Hacettepe University Medical Faculty

🇹🇷

Ankara, Turkey

Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi

🇹🇷

Istanbul, Turkey

Sancaktepe Training and Research Hospital

🇹🇷

Istanbul, Turkey

Selcuk University Medical Faculty

🇹🇷

Istanbul, Turkey

Kocaeli University Hospital

🇹🇷

Kocaeli, Turkey

Mersin University Medical Faculty

🇹🇷

Mersin, Turkey

CNPE City Clinical Hospital #3 of Chernivtsi City Council

🇺🇦

Chernivtsi, Chernihiv Governorate, Ukraine

Medical Centre of PE First Private Clinic

🇺🇦

Zhytomir, Crimean Regional Governmenta, Ukraine

Ams of Ukraine

🇺🇦

Kharkiv, Kharkiv Governorate, Ukraine

Municipal Institution Zaporizhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council

🇺🇦

Zaporizhzhia, Kharkiv Governorate, Ukraine

MEDBUD

🇺🇦

Kyiv, KIEV Governorate, Ukraine

Lviv Regional Clinical Hospital

🇺🇦

Lviv, KIEV Governorate, Ukraine

Salutem Medical Center

🇺🇦

Vinnytsia, KIEV Governorate, Ukraine

Medical Clinical Research Center of Medical Center LLC Health Clinic

🇺🇦

Vinnytsia, Podolia Governorate, Ukraine

Separated structural unit ?University hospital? of Dnipro State Medical University

🇺🇦

Dnipro, Tavria Okruha, Ukraine

MNE Lviv Territorial Medical Association Clinical Hospital for Palliative Care

🇺🇦

Lviv, Volhynian Governorate, Ukraine

Regional Clinical Hospital

🇺🇦

Ivano-Frankivsk, Ukraine

Nottingham University Hospitals NHS Trust

🇬🇧

Nottingham, United Kingdom

Morriston Hospital

🇬🇧

Swansea, United Kingdom

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