Clinical trial NCT04035005: A Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis
Official title: A Phase IIIb Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Multiple Sclerosis, Primary Progressive
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2019-07-29
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy and safety of ocrelizumab ( Ocrevus®) compared with placebo in participants with primary progressive multiple sclerosis (PPMS), including participants later in their disease course. This study focuses on upper limit disability progression. This study will consist of the following phases: screening, double-blind treatment, follow-up 1 (FU1), an optional open-label extension (OLE), follow-up 2 (FU2), and B-cell monitoring (BCM).

Detailed description: The screening phase will last up to 24 weeks. In the double-blind treatment phase, participants will undergo at least 120 weeks of study treatment. Study drug (ocrelizumab or placebo) will be administered every 24 weeks. In the FU1 phase, all participants who discontinue prematurely from the double-blind treatment phase will enter the FU1 phase, including participants who receive post-double progression ocrelizumab (PDP OCR) treatment, other immunomodulatory or immunosuppressive treatment(s) for MS, commercial ocrelizumab, or no treatment. The FU1 phase will run in parallel with the double-blind treatment phase until the primary analysis is performed. If the primary analysis is positive, an optional OLE phase is planned for eligible participants who either have remained in the double-blind treatment phase or are on PDP OCR treatment at the time of the primary analysis and, in the opinion of the investigator, could benefit from ocrelizumab treatment. The follow-up 2 (FU2) phase will begin after the primary analysis is performed. The following participants will move into the FU2 phase: participants who are ongoing in the FU1 and not on PDP OCR treatment at the time of primary analysis; participants who are ongoing in the double-blind treatment phase or receiving PDP OCR at the time of the primary analysis and do not enter the OLE phase; participants who complete or withdraw from the OLE phase. At the end of the FU2, all participants will move into B-cell monitoring (BCM) phase until the end of the study. This study will end when all participants who are not being treated with an alternative B-cell depleting therapy have repleted his or her B-cells.

Eligibility criteria: Inclusion Criteria:

* EDSS score at screening and baseline \>= 3.0 to 8.0, inclusive
* Disease duration from the onset of MS symptoms relative to randomization date:

Less than 20 years in patients with an EDSS score at screening 7.0 - 8.0 Less than 15 years in patients with an EDSS at screening 5.5 - 6.5 Less than 10 years in patients with an EDSS at screening \<= 5.0

* Documented history or presence at screening of at least one of the following laboratory findings in a cerebrospinal fluid specimen: Elevated IgG index or one or more IgG oligoclonal bands detected by isoelectric focusing
* Screening and baseline 9-HPT completed in \> 25 seconds (average of the two hands)
* Neurological stability for ≥ 30 days prior to baseline
* Ability to complete the 9-HPT within 240 seconds with each hand at screening and baseline
* Neurological stability for \>/= 30 days prior to baseline
* Patients previously treated with immunosuppressants, immunomodulators, or other immunomodulatory therapies must undergo an appropriate washout period according to the local label of the immunosuppressant/immunomodulatory drug used
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraceptive methods during the treatment period and for 6 or 12 months after the final dose of ocrelizumab. Adherence to local requirements, if more stringent, is required.
* For female patients without reproductive potential: Women may be enrolled if surgically sterile (i.e hysterectomy, complete bilateral oophorectomy) or post-menopausal unless the patient is receiving a hormonal therapy for her menopause or if surgically sterile

Exclusion Criteria:

* History of relapsing-remitting or secondary progressive MS at screening
* Confirmed serious opportunistic infection including: active bacterial, viral, fungal, mycobacterial infection or other infection, including tuberculosis or atypical mycobacterial disease
* Patients who have or have had confirmed or a high degree of suspicion of progressive multifocal leukoencephalopathy (PML)
* Known active malignancy or are being actively monitored for recurrence of malignancy
* Immunocompromised state
* Receipt of a live-attenuated vaccine within 6 weeks prior to randomization
* Inability to complete an MRI or contraindication to Gd administration.
* Patients requiring symptomatic treatment of MS and/or physiotherapy who are not on a stable regimen. Patients must not initiate symptomatic treatment of MS or physiotherapy within 4 weeks of randomization.
* Contraindications to mandatory premedications for infusion-related reactions, including:

uncontrolled psychosis for corticosteroids and closed-angle glaucoma for antihistamines

* Known presence of other neurologic disorders
* Pregnant or breastfeeding, or intending to become pregnant during the study and for 6 or 12 months after last infusion of the study drug
* Lack of peripheral venous access
* Significant, uncontrolled disease, such as cardiovascular, pulmonary, renal, hepatic, endocrine or gastrointestinal, or any other significant disease that may preclude patient from participating in the study
* Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
* History of alcohol or other drug abuse
* History of primary or secondary immunodeficiency
* Treatment with any investigational agent within 24 weeks prior to screening (Visit 1) or 5 half-lives of the investigational drug (whichever is longer), or treatment with any experimental procedure for MS
* Previous treatment with B-cell targeting therapies
* Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation
* Any previous history of transplantation or anti-rejection therapy
* Treatment with IV Ig or plasmapheresis within 12 weeks prior to randomization
* Systemic corticosteroid therapy within 4 weeks prior to screening
* Positive serum hCG measured at screening or positive urine β-hCG at baseline
* Positive screening tests for hepatitis B
* Any additional exclusionary criterion as per ocrelizumab (Ocrevus®) local label, if more stringent than the above
* Lack of MRI activity at screening/baseline if more than 650 patients without MRI activity have already been enrolled, as defined by T1 Gd+ lesion(s) and/or new and/or enlarged T2 lesion(s) in the screening, to ensure that at least 350 patients with MRI activity will be randomized

Eligibility Criteria for Open-Label Extension Phase:

* Completed the double-blind treatment phase of the trial or have received PDP OCR in the FU1 phase, and who, in the opinion of the investigator, may benefit from treatment with Ocrelizumab. Patients who withdrew from study treatment and received another disease-modifying therapy (DMT) or commercial ocrelizumab will not be allowed to enter in the OLE phase.
* Meet the re-treatment criteria for ocrelizumab
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraceptive methods during the treatment period and for 6 or 12 months after the final dose of ocrelizumab. Adherence to local requirements, if more stringent, is required.
* For female patients without reproductive potential: Women may be enrolled if surgically sterile (i.e. hysterectomy, complete bilateral oophorectomy) or post-menopausal unless the patient is receiving a hormonal therapy for her menopause or if surgically sterile

Primary outcomes:
measure: Time to Upper Limb Disability Progression Confirmed For at Least 12 Weeks
timeFrame: Baseline up to approximately 5.5 years
Secondary outcomes:
measure: Time to Upper Limb Disability Progression Confirmed For at Least 24 Weeks
timeFrame: Baseline up to approximately 5.5 years
measure: Time to Disability Progression Confirmed For at Least 12 Weeks
timeFrame: Baseline up to approximately 5.5 years
measure: Time to Disability Progression Confirmed For at Least 24 Weeks
timeFrame: Baseline up to approximately 5.5 years
measure: Percent Change in Total Volume of T2 Lesions on MRI
timeFrame: Baseline up to week 120
measure: Percent Change in Total Brain Volume on MRI Scans
timeFrame: Week 24 to Week 120
measure: Percentage of Participants with Adverse Events
timeFrame: Baseline up to 8.5 years
measure: Percentage of Participants With Serious Adverse Events
timeFrame: Baseline up to 8.5 years
measure: Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab
timeFrame: Baseline, Weeks 2, 12, 24, 48, 60, 72, and every 12 weeks till the end of the double-blind period and Weeks 0 and 48 of the OLE period
measure: Evaluation of Ocrelizumab Pharmacodynamics, as measured by B-Cell Levels in Blood
timeFrame: Baseline, Weeks 2, 24, 48, 72 and every 12 weeks till the end of the double-blind period and Weeks 0, 22, 46, 70 and 96 of the OLE period
Other outcomes:
Locations:
city: Laguna Hills
country: United States
facility: Multiple Sclerosis Center of California
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Clearwater
country: United States
facility: MS and Neuromuscular Center of Excellence
state: Florida
city: Orlando
country: United States
facility: Neurological Services of Orlando
state: Florida
city: Vero Beach
country: United States
facility: Vero Neurology
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Clinton Township
country: United States
facility: Michigan Neurology Associates P.C.
state: Michigan
city: Columbus
country: United States
facility: The Boster Center for MS
state: Ohio
city: Westerville
country: United States
facility: Columbus Neuroscience
state: Ohio
city: Philadelphia
country: United States
facility: Albert Einstein Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: Maxine Mesinger MS Clinic/Baylor College of Medicine
state: Texas
city: Camperdown
country: Australia
facility: Brain and Mind Research Institute
state: New South Wales
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Edegem
country: Belgium
facility: UZ Antwerpen
state: Antwerpen
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Overpelt
country: Belgium
facility: MS & Neurologisch Revalidatie Centrum
city: Pleven
country: Bulgaria
facility: Military Medical Academy HBAT
city: Pleven
country: Bulgaria
facility: Multiprofile Hospital For Active Treatment Avis Medica
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment of Neurology and Psychiatry Sv. Naum EAD
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Halifax
country: Canada
facility: Dalhousie Multiple Sclerosis Research Unit
state: Nova Scotia
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Greenfield Park
country: Canada
facility: Recherche Sepmus Inc.
state: Quebec
city: Medellin
country: Colombia
facility: Instituto Neurologico de Colombia INDEC
state: Antioquia
city: Bogota
country: Colombia
facility: Clinica Colsanitas S.A. sede Clinica Universitaria Colombia
city: Osijek
country: Croatia
facility: Clinical Hospital Centre Osijek
city: Varaždin
country: Croatia
facility: General Hospital Varazdin
city: Zagreb
country: Croatia
facility: Clinical Hospital Sestre Milosrdnice
city: Zagreb
country: Croatia
facility: University Hospital Center Zagreb
city: Bordeaux
country: France
facility: CHU de Bordeaux - Hôpital Pellegrin
city: Clermont ferrand
country: France
facility: Centre Hospitalier Universitaire de Clermont Ferrand
city: Nancy
country: France
facility: CHRU Nancy
city: Nantes
country: France
facility: Hopital Guillaume Et Rene Laennec
city: Nimes
country: France
facility: CHU de Nimes - Hopital Universitaire Caremeau
city: Strasbourg
country: France
facility: Hopital Civil
city: Tbilisi
country: Georgia
facility: Pineo Medical Ecosystem LTD
city: Tbilisi
country: Georgia
facility: The First University Clinic of Tbilisi State Medical University
city: Tbilisi
country: Georgia
facility: Khechinashvili University Hospital
city: Napoli
country: Italy
facility: AOU dell Universita degli Studi della Campania Luigi Vanvitelli Piazza Luigi Miraglia 2
state: Campania
city: Rome
country: Italy
facility: Fondazione PTV Policlinico Tor Vergata
state: Lazio
city: Rome
country: Italy
facility: Azienda Ospedaliera Sant'andrea
state: Lazio
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino
state: Liguria
city: Milano
country: Italy
facility: Ospedale San Raffaele S.r.l. - PPDS
state: Lombardia
city: Pavia
country: Italy
facility: Fondazione Istituto Neurologico Mondino IRCCS
state: Lombardia
city: Orbassano
country: Italy
facility: Azienda Ospedaliero-Universitaria San Luigi Gonzaga
state: Piemonte
city: Cefalù
country: Italy
facility: Fondazione Istituto G. Giglio di Cefalu
state: Sicilia
city: Achrafieh Beirut
country: Lebanon
facility: Hotel Dieu de France
city: Achrafieh
country: Lebanon
facility: Saint George University Medical Hospital
city: Mexico city
country: Mexico
facility: Grupo Medico Camino
state: Mexico CITY (federal District)
city: Culiacán
country: Mexico
facility: Neurociencias Estudios Clinicos S.C.
state: Sinaloa
city: Chihuahua
country: Mexico
facility: Hospital Angeles Chihuahua
city: Mexico City
country: Mexico
facility: Unidad de Investigacion en Salud de Chihuahua
city: Tlalnepantla de Baz
country: Mexico
facility: Clinical Research Institute
city: Marrakech
country: Morocco
facility: CHU Mohammed VI
city: Rabat
country: Morocco
facility: Centre Hospitalier Ibn Sina CHIS - Hopital des Specialites
city: Rabat
country: Morocco
facility: Hopital Militaire d'Instruction Mohamed V
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research - Christchurch
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Wroclaw
country: Poland
facility: Przychodnia EuroMediCare
state: Dolnoslaskie
city: Bydgoszcz
country: Poland
facility: Neurocentrum Bydgoszcz sp z o.o
state: Kujawsko-pomorskie
city: Lublin
country: Poland
facility: Rejdak Konrad Indywidualna Praktyka Lekarska dr hab. Konrad Rejdak
state: Lubelskie
city: Rzeszów
country: Poland
facility: Centrum Medyczne Medyk
state: Podkarpackie
city: Rybnik
country: Poland
facility: SPZOZ Wojewodzki Szpital Specjalistyczny nr 3
state: Slaskie
city: Kielce
country: Poland
facility: RESMEDICA Spolka z o.o.
state: Swietokrzyskie
city: Bia?ystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Bialymstoku Marii Sklodowskiej Curie 24a
city: Gdansk
country: Poland
facility: Copernicus Podmiot Leczniczy Sp z o o
city: Grodzisk Mazowiecki
country: Poland
facility: Mazowieckie Centrum Badan Klinicznych
city: Katowice
country: Poland
facility: MA-LEK Clinical Sp. Z o.o.
city: Katowice
country: Poland
facility: Novo-Med Zielinski i wsp SpJ
city: Katowice
country: Poland
facility: NEURO-MEDIC Sp. z o. o.
city: Katowice
country: Poland
facility: Specjalistyczna Praktyka Lekarska Dr n.med. Stanislaw Ochudlo
city: Kraków
country: Poland
facility: SP ZOZ Szpital Uniwersytecki w Krakowie
city: Lodz
country: Poland
facility: Centrum Neurologii Krzysztof Selmaj
city: Lublin
country: Poland
facility: Galen Clinic
city: Olsztyn
country: Poland
facility: Wojewodzki Szpital Specjalistyczny
city: Poznan
country: Poland
facility: Med-Polonia Sp. z o.o.
city: Szczecin
country: Poland
facility: EUROMEDIS Sp z o o
city: Warsaw
country: Poland
facility: Centrum Medyczne NeuroProtect Zablocinska 10
city: Loures
country: Portugal
facility: ULS de Loures-Odivelas, EPE - Hospital de Loures
state: Lisboa
city: Almada
country: Portugal
facility: Hospital Garcia de Orta
city: Braga
country: Portugal
facility: Hospital de Braga
city: Porto
country: Portugal
facility: Hospital de Santo Antonio
city: Torres Vedras
country: Portugal
facility: Campus Neurologico Senior
city: Deva
country: Romania
facility: Spitalul Judetean de Urgenta Deva
state: Hunedoara
city: Campulung
country: Romania
facility: SC Clubul Sanatatii SRL
city: Constanta
country: Romania
facility: Cai Ferate Clinical Hospital
city: Târgu Mure?
country: Romania
facility: Targu Mures Clinical Emergency County Hospital
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk State Medical Academy
state: Krasnojarsk
city: Moscow
country: Russian Federation
facility: City Clinical Hospital a n Buyanov V M
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: City Clinical Hospital #24
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: Moscow Regional Research Clinical Institute Na Mfvladimirskiy
state: Moskovskaja Oblast
city: Moskva
country: Russian Federation
facility: Research Center of Neurology of RAMS
state: Moskovskaja Oblast
city: Tumen
country: Russian Federation
facility: Neftyanik Medical and Sanitary Unit
state: Moskovskaja Oblast
city: Nizhnij Novgorod
country: Russian Federation
facility: SBHI of Nizhny Novgorod region City Clinical Hospital #3
state: Niznij Novgorod
city: Nizhny Novgorod
country: Russian Federation
facility: Nizhegorodskaya Regional Clinical Hospital n.a. Semashko
state: Niznij Novgorod
city: Nizhny Novgorod
country: Russian Federation
facility: MEDIS Limited Liability Company
state: Niznij Novgorod
city: Saint-Petersburg
country: Russian Federation
facility: National Center of Socially Significant Diseases
state: Sankt Petersburg
city: St. Petersburg
country: Russian Federation
facility: City Hospital #40 of Kurortniy Administrative District
state: Sankt Petersburg
city: Saransk
country: Russian Federation
facility: City Clinical Hospital #4
state: Saratov
city: Yekaterinburg
country: Russian Federation
facility: Sverdlovsk Regional Clinical Hospital 1
state: Sverdlovsk
city: Kazan
country: Russian Federation
facility: Vertebronevrologiya LLC
state: Tatarstan
city: Ulyanovsk
country: Russian Federation
facility: Ulyanovsk Regional Clinical Hospital
state: Uljanovsk
city: Kemerovo
country: Russian Federation
facility: Belyayev Clinical Hospital of the Kuzbass
city: Kirov
country: Russian Federation
facility: Kirov State Medical Academy
city: Novosibirsk
country: Russian Federation
facility: FSBIH Siberian Regional Medical Centre of FMBA of Russia
city: Perm
country: Russian Federation
facility: Perm Regional Clinical Hospital of Znak Pocheta Medal
city: Tomsk
country: Russian Federation
facility: Siberian State Medical University of Roszdrav
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia -PPDS
city: Belgrade
country: Serbia
facility: Clinical Hospital Centre Zemun
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac
city: NIS
country: Serbia
facility: Clinical Center Nis
city: Nova Sad
country: Serbia
facility: Clinical Centre of Vojvodina
city: Uzice
country: Serbia
facility: General Hospital Uzice
city: Pozuelo de Alarcón
country: Spain
facility: Hospital Universitario Quironsalud Madrid
state: Madrid
city: El Palmar
country: Spain
facility: Hospital Universitario Virgen de La Arrixaca
state: Murcia
city: Vigo
country: Spain
facility: Complejo Hospitalario Universitario de Vigo
state: Pontevedra
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca ? H. Clinico
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: LA Mannouba
country: Tunisia
facility: Hopital Razi
city: Monastir
country: Tunisia
facility: Fattouma Bourguiba University Hospital
city: Sfax
country: Tunisia
facility: Hospital Habib Bourguiba
city: Tunis
country: Tunisia
facility: Military Hospital of Tunis
city: Krykhivtsi
country: Ukraine
facility: Treatment and diagnostic Center Neuro Global of LLC Neuro Global
state: Ivano-Frankivs'ka Oblast
city: Lviv
country: Ukraine
facility: Communal noncommercial enterprise of Lviv Regional Council Lviv Regional Clinical Hospital
state: Kharkiv Governorate
city: Kherson
country: Ukraine
facility: Municipal Non-profit Enterprise Kherson City Clinical Hospital named after Ye.Ye. Karabelesh
state: Kherson Governorate
city: Kropyvnytskyi
country: Ukraine
facility: Treatment and Diagnostic Center of LLC MRT Elit
state: KIEV Governorate
city: Kyiv
country: Ukraine
facility: Medical Centre of PE First Private Clinic
state: KIEV Governorate
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Hospital #4
state: KIEV Governorate
city: Kyiv
country: Ukraine
facility: Communal Non-Commercial Enterprise Clinical Hospital #15 of the Podilskyi District ofthe Kyiv City
state: KIEV Governorate
city: Uzhhorod
country: Ukraine
facility: Municipal NPE Regional Clinical Center of Neurosurgery and Neurology of Transcarpathian RC
state: KIEV Governorate
city: Kyiv
country: Ukraine
facility: Medical Center Artes Medicum LLC
state: Kyiv Oblast
city: Lviv
country: Ukraine
facility: Communal noncommercial enterprise of Lviv Regional Council Lviv Regional Clinical Hospital
state: L'vivs'ka Oblast
city: Vinnytsia
country: Ukraine
facility: Medical Center Salutem
state: Podolia Governorate
city: Vinnytsia
country: Ukraine
facility: LLC Medical Center Health Clinic
state: Volhynian Governorate
city: Zaporizhzhia
country: Ukraine
facility: LLC Medical Center Unimed
state: Zaporiz'ka Oblast
city: Dnipro
country: Ukraine
facility: University hospital of Dnipro State Medical University
city: Dnipro
country: Ukraine
facility: LLC Medical Center Family Medicine Clinic
city: Kharkiv
country: Ukraine
facility: Communal Non-commercial Enterprise of Kharkiv Regional Council Regional Clinical Hospital
city: Kyiv
country: Ukraine
facility: Medical Center of LLC Medical Center Dopomoga Plus
city: Kyiv
country: Ukraine
facility: Private Enterprise Clinic Medicom
city: Lutsk
country: Ukraine
facility: Volyn Regional Clinical Hospital
city: Zaporizhzhia
country: Ukraine
facility: LLC Medical Center INET 09
city: Zaporizhzhia
country: Ukraine
facility: Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital - PPDS
city: Inverness
country: United Kingdom
facility: Raigmore Hospital - PPDS
city: London, GT LON
country: United Kingdom
facility: The National Hospital for Neurology & Neurosurgery
city: London
country: United Kingdom
facility: The Royal London Hospital
city: Nottingham
country: United Kingdom
facility: University of Nottingham
city: Plymouth
country: United Kingdom
facility: Peninsula College of Medicine and Dentistry
city: Salford
country: United Kingdom
facility: Salford Royal Hospital
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
city: Swansea
country: United Kingdom
facility: Morriston Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: