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Clinical Trials in the UK / NCT04035005
Active, not recruiting Phase 3

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

NCT04035005 · tracked via the Priya Life Science UK tracker
Sponsor
Hoffmann-La Roche
Phase
Phase 3
Started
2019-08-12
Last updated
2026-02-23

Condition(s) studied

Multiple Sclerosis, Primary Progressive

Investigational drug(s) / intervention(s)

OcrelizumabPlacebo

Ocrelizumab: 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.

Placebo: 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.

Study 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).

Eligibility

Sex
ALL
Min age
18 Years
Max age
65 Years
Healthy volunteers
No
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 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 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 * 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 * 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 human chorionic gonadotropin (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 participants 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 participants with MRI activity will be randomized Eligibility Criteria for OLE Phase: * Completed the 144 weeks of double-blind treatment phase of the trial or are ongoing in the double blind treatment phase at the time of the primary analysis, and who, in the opinion of the investigator, may benefit from treatment with Ocrelizumab. Participants who withdrew from study treatment and received another DMT or commercial ocrelizumab will not be allowed to enter in the OLE phase. * 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

Primary outcome measure(s)

Trial sites (155)

FacilityCityRegionStatus
Georgetown University Medical Center Washington D.C. District of Columbia
MS and Neuromuscular Center of Excellence Clearwater Florida
Neurological Services of Orlando Orlando Florida
Vero Neurology Vero Beach Florida
University of Kansas Medical Center Kansas City Kansas
The Boster Center for Multiple Sclerosis a Singlepoint Healthcare Company Columbus Ohio
Columbus Neuroscience Westerville Ohio
Albert Einstein Medical Center Philadelphia Pennsylvania
Brain and Mind Research Institute Camperdown New South Wales
Austin Hospital Heidelberg Victoria
Royal Melbourne Hospital Parkville Victoria
UZ Antwerpen Edegem Antwerpen
Cliniques Universitaires St-Luc Brussels Belgium
MS & Neurologisch Revalidatie Centrum Overpelt Belgium
Military Medical Academy HBAT Pleven Bulgaria
Multiprofile Hospital For Active Treatment Avis Medica Pleven Bulgaria
Multiprofile Hospital for Active Treatment of Neurology and Psychiatry Sv. Naum EAD Sofia Bulgaria
University of Alberta Edmonton Alberta
Dalhousie Multiple Sclerosis Research Unit Halifax Nova Scotia
St. Michael's Hospital Toronto Ontario
Recherche Sepmus Inc. Greenfield Park Quebec
Instituto Neurologico de Colombia INDEC Medellín Antioquia
Clinica Colsanitas S.A. sede Clinica Universitaria Colombia Bogotá Colombia
General Hospital Varazdin Varaždin Croatia
Clinical Hospital Sestre Milosrdnice Zagreb Croatia
University Hospital Center Zagreb Zagreb Croatia
CHU de Bordeaux - Hôpital Pellegrin Bordeaux France
Centre Hospitalier Universitaire de Clermont Ferrand Clermont-Ferrand France
CHRU Nancy Nancy France
Hopital Guillaume Et Rene Laennec Nantes France
CHU de Nimes - Hopital Universitaire Caremeau Nîmes France
Hopital Civil Strasbourg France
Pineo Medical Ecosystem LTD Tbilisi Georgia
The First University Clinic of Tbilisi State Medical University Tbilisi Georgia
Khechinashvili University Hospital Tbilisi Georgia
AOU dell Universita degli Studi della Campania Luigi Vanvitelli Piazza Luigi Miraglia 2 Naples Campania
Fondazione PTV Policlinico Tor Vergata Rome Lazio
Azienda Ospedaliera Sant'andrea Rome Lazio
IRCCS AOM Azienda Ospedaliera Metropolitana Genoa Liguria
Ospedale San Raffaele S.r.l. - PPDS Milan Lombardy

+ 115 more sites — see the full list on the official registry below.

On this site

📄 Ocrevus (ocrelizumab) drug profile →

More Hoffmann-La Roche trials in the UK

Other trials for the same condition

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT04035005 on ClinicalTrials.gov ↗ ← All trials in the UK