A Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis

NCT04035005 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 3 other identifiers: WA404042018-001511-732023-505980-36-00
• Study Type: interventional
• Target: 1,013
• Locations: 23 countries
• Sites: 155

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 will consist of the following phases: screening, double-blind treatment, an optional post-double-progression ocrelizumab (PDP OCR) treatment, follow-up 1 (FU1), an optional open-label extension (OLE), and follow-up 2 (FU2).

Conditions

Multiple Sclerosis, Primary Progressive

Outcome Measures

Primary Outcomes (2)

• Time to Onset of 12-week Composite Confirmed Disability Progression (cCDP12) in FAS

  Time to onset of cCDP12=time from randomization to the first occurrence of at least one of the following progression events: 1) 20% worsening from baseline in 9-hole Peg Test (9-HPT) confirmed for at least 12 weeks; 2) increase of ≥ 1.0 point from baseline in Expanded Disability Status Scale (EDSS) score in participants with a baseline EDSS score ≤5.5 or an increase of ≥ 0.5 point in participants with a baseline EDSS score of \>5.5 that is confirmed for at least 12 weeks. EDSS disability scale is based on a standard neurological examination, incorporating functional systems \& ambulation, that ranges in 0.5-point steps from 0 \[normal\] to 10.0 \[death\]. 9-HPT is a quantitative measure of arm \& hand function, where participants placed \& removed pegs 1 by 1 into 9 holes arranged in a board \& complete 2 successful trials for each hand \& the total time (in seconds) required was recorded. The longer it took to complete the test, the higher the scores, indicating deterioration.

  Up to approximately 243 weeks

• Time to Onset of cCDP12 in Magnetic Resonance Imaging (MRI) Activity Analysis Set

  Time to onset of cCDP12 was defined as the time from randomization to the first occurrence of at least one of the following progression events: 1) 20% worsening from baseline in 9-HPT confirmed for at least 12 weeks; 2) increase of ≥ 1.0 point from baseline in EDSS score in participants with a baseline EDSS score ≤5.5 or an increase of ≥ 0.5 point in participants with a baseline EDSS score of \>5.5 that is confirmed for at least 12 weeks. EDSS disability scale is based on a standard neurological examination, incorporating functional systems \& ambulation, that ranges in 0.5-point steps from 0 \[normal\] to 10.0 \[death\]. 9-HPT is a quantitative measure of arm \& hand function, where participants placed \& removed pegs 1 by 1 into 9 holes arranged in a board \& complete 2 successful trials for each hand \& the total time (in seconds) required was recorded. The longer it took to complete the test, the higher the scores, indicating deterioration.

  Up to approximately 243 weeks

Secondary Outcomes (13)

• Time to 12-week CDP in 9-HPT

  Up to approximately 243 weeks

• Time to 12-week CDP in EDSS

  Up to approximately 243 weeks

• Time to 24-week CDP in 9-HPT

  Up to approximately 243 weeks

• Time to 24-week CDP in EDSS

  Up to approximately 243 weeks

• Annual Rate of Change From Baseline in Radius of Total Volume of T2 Lesions

  Up to approximately 120 weeks

Study Arms (2)

Ocrelizumab

EXPERIMENTAL

Participants will receive ocrelizumab by intravenous (IV) infusion every 24 weeks.

Drug: Ocrelizumab

Placebo

PLACEBO COMPARATOR

Participants will receive placebo matched to ocrelizumab by IV infusion every 24 weeks.

Drug: Placebo

Interventions

Ocrelizumab DRUG

The first dose of ocrelizumab will be administered as two 300 milligrams (mg), IV infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 600 mg infusion every 24 weeks. A minimum interval of 20 or 22 weeks, depending on if the previous dose was administered in one or two infusion, should be maintained between each infusion.

Also known as: Ocrevus

Ocrelizumab

Placebo DRUG

The first dose of placebo will be administered as two IV infusions given 14 days apart. For the subsequent doses, placebo will be administered as a single infusion every 24 weeks, with a minimum interval of 20 or 22 weeks, depending on if the previous dose was administered in one or two infusions, maintained between each infusion.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 participants with an EDSS score at screening 7.0 - 8.0 Less than 15 years in participants with an EDSS at screening 5.5 - 6.5 Less than 10 years in participants 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 immunoglobulin G (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
• Participants 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 participants without reproductive potential: Women may be enrolled if surgically sterile (i.e hysterectomy, complete bilateral oophorectomy) or post-menopausal unless the participant is receiving a hormonal therapy for her menopause or if surgically sterile

You may not qualify if:

• 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
• Participants 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.
• Participants requiring symptomatic treatment of MS and/or physiotherapy who are not on a stable regimen. Participants 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 participant from participating in the study
• Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (155)

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

MS and Neuromuscular Center of Excellence

Clearwater, Florida, 33761, United States

Location

Neurological Services of Orlando

Orlando, Florida, 32806, United States

Location

Vero Neurology

Vero Beach, Florida, 32960, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

The Boster Center for Multiple Sclerosis a Singlepoint Healthcare Company

Columbus, Ohio, 43235-5422, United States

Location

Columbus Neuroscience

Westerville, Ohio, 43082-6910, United States

Location

Albert Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

Brain and Mind Research Institute

Camperdown, New South Wales, 2050, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

UZ Antwerpen

Edegem, Antwerpen, 2650, Belgium

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

MS & Neurologisch Revalidatie Centrum

Overpelt, 3900, Belgium

Location

Military Medical Academy HBAT

Pleven, 5800, Bulgaria

Location

Multiprofile Hospital For Active Treatment Avis Medica

Pleven, 5800, Bulgaria

Location

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

Sofia, 1113, Bulgaria

Location

University of Alberta

Edmonton, Alberta, T6G 2G3, Canada

Location

Dalhousie Multiple Sclerosis Research Unit

Halifax, Nova Scotia, B3H 4K4, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Recherche Sepmus Inc.

Greenfield Park, Quebec, J4V 2J2, Canada

Location

Instituto Neurologico de Colombia INDEC

Medellín, Antioquia, 50012, Colombia

Location

Clinica Colsanitas S.A. sede Clinica Universitaria Colombia

Bogotá, 111321, Colombia

Location

General Hospital Varazdin

Varaždin, 42000, Croatia

Location

Clinical Hospital Sestre Milosrdnice

Zagreb, 10000, Croatia

Location

University Hospital Center Zagreb

Zagreb, 10000, Croatia

Location

CHU de Bordeaux - Hôpital Pellegrin

Bordeaux, 33076, France

Location

Centre Hospitalier Universitaire de Clermont Ferrand

Clermont-Ferrand, 63003, France

Location

CHRU Nancy

Nancy, 54035, France

Location

Hopital Guillaume Et Rene Laennec

Nantes, 44805, France

Location

CHU de Nimes - Hopital Universitaire Caremeau

Nîmes, 30900, France

Location

Hopital Civil

Strasbourg, 67098, France

Location

Pineo Medical Ecosystem LTD

Tbilisi, 0114, Georgia

Location

The First University Clinic of Tbilisi State Medical University

Tbilisi, 0141, Georgia

Location

Khechinashvili University Hospital

Tbilisi, 179, Georgia

Location

AOU dell Universita degli Studi della Campania Luigi Vanvitelli Piazza Luigi Miraglia 2

Naples, Campania, 80138, Italy

Location

Fondazione PTV Policlinico Tor Vergata

Rome, Lazio, 00133, Italy

Location

Azienda Ospedaliera Sant'andrea

Rome, Lazio, 00189, Italy

Location

IRCCS AOM Azienda Ospedaliera Metropolitana

Genoa, Liguria, 16132, Italy

Location

Ospedale San Raffaele S.r.l. - PPDS

Milan, Lombardy, 20132, Italy

Location

Fondazione Istituto Neurologico Mondino IRCCS

Pavia, Lombardy, 27100, Italy

Location

Azienda Ospedaliero-Universitaria San Luigi Gonzaga

Orbassano, Piedmont, 10043, Italy

Location

Fondazione Istituto G. Giglio di Cefalu

Cefalù, Sicily, 90015, Italy

Location

Hotel Dieu de France

Achrafieh Beirut, 000000, Lebanon

Location

Saint George University Medical Hospital

El Achrafiyé, DUMMY_VALUE, Lebanon

Location

Grupo Medico Camino

Mexico City, Mexico CITY (federal District), 03310, Mexico

Location

Neurociencias Estudios Clinicos S.C.

Culiacán, Sinaloa, 80020, Mexico

Location

Hospital Angeles Chihuahua

Chihuahua City, 31238, Mexico

Location

Unidad de Investigacion en Salud de Chihuahua

Mexico City, 14050, Mexico

Location

Clinical Research Institute

Tlalnepantla, 54055, Mexico

Location

CHU Mohammed VI

Marrakesh, 40080, Morocco

Location

Centre Hospitalier Ibn Sina CHIS - Hopital des Specialites

Rabat, 10100, Morocco

Location

New Zealand Clinical Research - Christchurch

Christchurch, 8011, New Zealand

Location

Dunedin Hospital

Dunedin, New Zealand

Location

Neurocentrum Bydgoszcz sp z o.o

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796, Poland

Location

Przychodnia EuroMediCare

Wroclaw, Lower Silesian Voivodeship, 50-220, Poland

Location

Rejdak Konrad Indywidualna Praktyka Lekarska dr hab. Konrad Rejdak

Lublin, Lublin Voivodeship, 20-410, Poland

Location

Centrum Medyczne Medyk

Rzeszów, Podkarpackie Voivodeship, 35-055, Poland

Location

SPZOZ Wojewodzki Szpital Specjalistyczny nr 3

Rybnik, Silesian Voivodeship, 44-200, Poland

Location

Uniwersytecki Szpital Kliniczny w Bialymstoku Marii Sklodowskiej Curie 24a

Bia?ystok, 15-276, Poland

Location

Copernicus Podmiot Leczniczy Sp z o o

Gda?sk, 80-803, Poland

Location

Mazowieckie Centrum Badan Klinicznych

Grodzisk Mazowiecki, 05-825, Poland

Location

MA-LEK Clinical Sp. Z o.o.

Katowice, 40-571, Poland

Location

Novo-Med Zielinski i wsp SpJ

Katowice, 40-584, Poland

Location

NEURO-MEDIC Sp. z o. o.

Katowice, 40-686, Poland

Location

Specjalistyczna Praktyka Lekarska Dr n.med. Stanislaw Ochudlo

Katowice, 40-752, Poland

Location

Szpital Uniwersytecki w Krakowie

Krakow, 31-503, Poland

Location

Centrum Neurologii Krzysztof Selmaj

Lodz, 90-324, Poland

Location

Galen Clinic

Lublin, 20-064, Poland

Location

Wojewodzki Szpital Specjalistyczny

Olsztyn, 10-561, Poland

Location

Med-Polonia Sp. z o.o.

Poznan, 60-693, Poland

Location

EUROMEDIS Sp z o o

Szczecin, 70-215, Poland

Location

Centrum Medyczne NeuroProtect Zablocinska 10

Warsaw, 01-684, Poland

Location

RESMEDICA Spolka z o.o.

Kielce, Świętokrzyskie Voivodeship, 25-726, Poland

Location

ULS de Loures-Odivelas, EPE - Hospital de Loures

Loures, Lisbon District, 2674-514, Portugal

Location

Hospital Garcia de Orta

Almada, 2805-267, Portugal

Location

Hospital de Braga

Braga, 4710-243, Portugal

Location

Hospital de Santo Antonio

Porto, 4099-001, Portugal

Location

Campus Neurologico Senior

Torres Vedras, 2560-280, Portugal

Location

Spitalul Judetean de Urgenta Deva

Deva, Hunedoara County, 330084, Romania

Location

SC Clubul Sanatatii SRL

Campulung Muscel, 115100, Romania

Location

Cai Ferate Clinical Hospital

Constanța, 900123, Romania

Location

Targu Mures Clinical Emergency County Hospital

Târgu Mure?, 540136, Romania

Location

Krasnoyarsk State Medical Academy

Krasnoyarsk, Krasnoyarsk Krai, 660022, Russia

Location

City Clinical Hospital a n Buyanov V M

Moscow, Moscow Oblast, 115516, Russia

Location

City Clinical Hospital #24

Moscow, Moscow Oblast, 127015, Russia

Location

Moscow Regional Research Clinical Institute Na Mfvladimirskiy

Moscow, Moscow Oblast, 129110, Russia

Location

Research Center of Neurology of RAMS

Moskva, Moscow Oblast, 125367, Russia

Location

Neftyanik Medical and Sanitary Unit

Tumen, Moscow Oblast, 625000, Russia

Location

Nizhegorodskaya Regional Clinical Hospital n.a. Semashko

Nizhny Novgorod, Niznij Novgorod, 603126, Russia

Location

MEDIS Limited Liability Company

Nizhny Novgorod, Niznij Novgorod, 603137, Russia

Location

SBHI of Nizhny Novgorod region City Clinical Hospital #3

Nizhny Novgorod, Niznij Novgorod, 603155, Russia

Location

National Center of Socially Significant Diseases

Saint Petersburg, Sankt-Peterburg, 197110, Russia

Location

City Hospital #40 of Kurortniy Administrative District

Saint Petersburg, Sankt-Peterburg, 197706, Russia

Location

City Clinical Hospital #4

Saransk, Saratov Oblast, 430032, Russia

Location

Sverdlovsk Regional Clinical Hospital 1

Yekaterinburg, Sverdlovsk Oblast, 620102, Russia

Location

Vertebronevrologiya LLC

Kazan', Tatarstan Republic, 420043, Russia

Location

Ulyanovsk Regional Clinical Hospital

Ulyanovsk, Ulyanovsk Oblast, 432063, Russia

Location

Belyayev Clinical Hospital of the Kuzbass

Kemerovo, 650066, Russia

Location

Kirov State Medical Academy

Kirov, 610027, Russia

Location

FSBIH Siberian Regional Medical Centre of FMBA of Russia

Novosibirsk, 630007, Russia

Location

Perm Regional Clinical Hospital of Znak Pocheta Medal

Perm, 614990, Russia

Location

Siberian State Medical University of Roszdrav

Tomsk, 634050, Russia

Location

Military Medical Academy

Belgrade, 11000, Serbia

Location

University Clinical Center of Serbia -PPDS

Belgrade, 11000, Serbia

Location

Clinical Hospital Centre Zemun

Belgrade, 11080, Serbia

Location

University Clinical Center Kragujevac

Kragujevac, 34000, Serbia

Location

Clinical Center Nis

Niš, 18000, Serbia

Location

Clinical Centre of Vojvodina

Nova Sad, 21000, Serbia

Location

General Hospital Uzice

Užice, 31000, Serbia

Location

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital Universitario Virgen de La Arrixaca

El Palmar, Murcia, 30120, Spain

Location

Complejo Hospitalario Universitario de Vigo

Vigo, Pontevedra, 36312, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Puerta de Hierro - Majadahonda

Madrid, 28222, Spain

Location

Complejo Asistencial Universitario de Salamanca ? H. Clinico

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Hopital Razi

LA Mannouba, 2010, Tunisia

Location

Fattouma Bourguiba University Hospital

Monastir, 5000, Tunisia

Location

Hospital Habib Bourguiba

Sfax, 3029, Tunisia

Location

Military Hospital of Tunis

Tunis, 1008, Tunisia

Location

Treatment and diagnostic Center Neuro Global of LLC Neuro Global

Krykhivtsi, Ivano-Frankivsk Oblast, 76493, Ukraine

Location

Communal noncommercial enterprise of Lviv Regional Council Lviv Regional Clinical Hospital

Lviv, Kharkiv Governorate, 79010, Ukraine

Location

Municipal Non-profit Enterprise Kherson City Clinical Hospital named after Ye.Ye. Karabelesh

Kherson, Kherson Governorate, 73000, Ukraine

Location

Treatment and Diagnostic Center of LLC MRT Elit

Kropyvnytskyi, KIEV Governorate, 25005, Ukraine

Location

Medical Centre of PE First Private Clinic

Kyiv, KIEV Governorate, 03037, Ukraine

Location

Kyiv City Clinical Hospital #4

Kyiv, KIEV Governorate, 03110, Ukraine

Location

Communal Non-Commercial Enterprise Clinical Hospital #15 of the Podilskyi District ofthe Kyiv City

Kyiv, KIEV Governorate, 04070, Ukraine

Location

Municipal NPE Regional Clinical Center of Neurosurgery and Neurology of Transcarpathian RC

Uzhhorod, KIEV Governorate, 88018, Ukraine

Location

Medical Center Artes Medicum LLC

Kyiv, Kyiv Oblast, 02002, Ukraine

Location

Communal noncommercial enterprise of Lviv Regional Council Lviv Regional Clinical Hospital

Lviv, Lviv Oblast, 79010, Ukraine

Location

Medical Center Salutem

Vinnytsia, Podolia Governorate, 21009, Ukraine

Location

LLC Medical Center Health Clinic

Vinnytsia, Volhynian Governorate, 21009, Ukraine

Location

LLC Medical Center Unimed

Zaporizhzhia, Zaporizhzhia Oblast, 69000, Ukraine

Location

University hospital of Dnipro State Medical University

Dnipro, 49089, Ukraine

Location

LLC Medical Center Family Medicine Clinic

Dnipro, 49600, Ukraine

Location

Communal Non-commercial Enterprise of Kharkiv Regional Council Regional Clinical Hospital

Kharkiv, 61022, Ukraine

Location

Medical Center of LLC Medical Center Dopomoga Plus

Kyiv, 02000, Ukraine

Location

Private Enterprise Clinic Medicom

Kyiv, 04219, Ukraine

Location

Volyn Regional Clinical Hospital

Lutsk, 43005, Ukraine

Location

LLC Medical Center INET 09

Zaporizhzhia, 69035, Ukraine

Location

Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council

Zaporizhzhia, 69600, Ukraine

Location

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

Location

Queen Elizabeth University Hospital - PPDS

Glasgow, G51 4TF, United Kingdom

Location

Raigmore Hospital - PPDS

Inverness, IV2 3JH, United Kingdom

Location

The Royal London Hospital

London, E1 1BB, United Kingdom

Location

The National Hospital for Neurology & Neurosurgery

London, GT LON, WC1N 3BG, United Kingdom

Location

University of Nottingham

Nottingham, NG7 2UH, United Kingdom

Location

Peninsula College of Medicine and Dentistry

Plymouth, PL6 8BX, United Kingdom

Location

Salford Royal Hospital

Salford, M6 8HD, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, S10 2JF, United Kingdom

Location

Morriston Hospital

Swansea, SA6 6NL, United Kingdom

Location

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive

Interventions

ocrelizumab

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: July 29, 2019
• Study Start: August 12, 2019
• Primary Completion: January 15, 2025
• Study Completion (Estimated): January 19, 2028
• Last Updated: February 23, 2026
• Results First Posted: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

CO (2); IT (8); BU (3); CA (4); AU (3); FR (6); ME (5); MO (2); PL (20); TU (4); RO (4); ES (10); LE (2); CR (3); BE (3); GE (3); PT (5); RU (20); SE (7); UA (21); US (8); NZ (2); GB (10)