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NCT01194570

A Study of Ocrelizumab in Participants With Primary Progressive Multiple Sclerosis

Completed Phase 3 Results posted Last updated 10 January 2024
What this trial tests

Phase 3 trial testing Ocrelizumab in Multiple Sclerosis, Primary Progressive in 735 participants. Completed in 31 December 2022.

Timeline
2 March 2011
Primary endpoint
23 July 2015
31 December 2022

Quick facts

Lead sponsorHoffmann-La Roche
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment735
Start date2 March 2011
Primary completion23 July 2015
Estimated completion31 December 2022
Sites184 locations across Italy, Finland, Poland, New Zealand, Netherlands, Russia, Belgium, Mexico

Drugs / interventions tested

Conditions studied

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

Adults 18 to 55, any sex, with Multiple Sclerosis, Primary Progressive. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Time to Onset of Clinical Disability Progression (CDP) Sustained for at Least 12 Weeks During the Double-Blind Treatment Period Primary · Maximal follow up: 216 weeks for Placebo arm and 217 weeks for Ocrelizumab arm

The time to onset of CDP was defined as time from baseline to first disability progression, which is confirmed at next regularly scheduled visit \>=12 weeks (\>=84 days) after initial disability progression. Baseline for time to onset of CDP is the date of randomization, independent of the first day of dosing. Disability progression is defined as an increase of \>= 1.0 point from baseline expanded disability status scale (EDSS) score, if baseline EDSS value is \<=5.5 points (inclusive), or an increase of \>=0.5 points, if baseline EDSS is \>5.5 points. The total EDSS score ranges from 0 (norma

GroupValue95% CI
PlaceboNA0 – NA
Ocrelizumab 600 mgNA0 – NA
Time to Onset of Clinical Disability Progression (CDP) Sustained for at Least 24 Weeks During the Double-Blind Treatment Period Secondary · Maximal follow up: 216 weeks for Placebo arm and 217 weeks for Ocrelizumab arm

The time to onset of CDP was defined as time from baseline to first disability progression, which is confirmed at next regularly scheduled visit \>=12 weeks (\>=84 days) after initial disability progression. Baseline for time to onset of CDP is the date of randomization, independent of the first day of dosing. Disability progression is defined as an increase of \>= 1.0 point from baseline expanded disability status scale (EDSS) score, if baseline EDSS value is \<=5.5 points (inclusive), or an increase of \>=0.5 points, if baseline EDSS is \>5.5 points. The total EDSS score ranges from 0 (norma

GroupValue95% CI
PlaceboNA0 – NA
Ocrelizumab 600 mgNA0 – NA
Percent Change From Baseline in Timed 25-Foot Walk (T25-FW) at Week 120 Secondary · Baseline, Week 120
GroupValue95% CI
Placebo55.09739.855 – 71.999
Ocrelizumab 600 mg38.93329.222 – 49.374
Percent Change From Baseline in Total Volume of T2 Lesions at Week 120 Secondary · From Baseline to Week 120
GroupValue95% CI
Placebo7.4264.967 – 9.942
Ocrelizumab 600 mg-3.366-4.987 – -1.718
Percent Change in Total Brain Volume From Week 24 to Week 120 Secondary · From Week 24 to Week 120
GroupValue95% CI
Placebo-1.093-1.236 – -0.951
Ocrelizumab 600 mg-0.902-1.004 – -0.799
Change in From Baseline Physical Component Summary Score (PCS) SF- 36 Health Survey (SF-36) at Week 120 Secondary · From Baseline to Week 120

The SF-36v2 is a 36-item, self- reported, generic measure of quality of life that has been widely used in multiple disease areas. It is composed of 8 health domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The PCS score was derived based on the SF-36 V2 User's Manual. Scoring for PCS involves (a) recoding item response values, (b) summing recoded response values for all items in a given scale to obtain the scale raw score, (c) transforming scale raw score to a 0-100 score. The PCS score was computed by (

GroupValue95% CI
Placebo-1.108-2.394 – 0.177
Ocrelizumab 600 mg-0.731-1.655 – 0.193
Number of Participants With at Least One Adverse Event (AE) Secondary · From baseline to 9 years

AEs included infusion related reactions (IRRs) and serious multiple sclerosis (MS) relapses, but excluded non-serious MS relapses.

Serious Adverse Events
GroupValue95% CI
Placebo53
Ocrelizumab 600 mg99
Placebo (Open Label Extension)59
Ocrelizumab (Open Label Extension)167
Adverse Events
GroupValue95% CI
Placebo215
Ocrelizumab 600 mg462
Placebo (Open Label Extension)148
Ocrelizumab (Open Label Extension)354

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to 615 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

DB PLACEBO
Serious: 58/239 (24%)
Deaths: 3/239
DB OCRELIZUMAB
Serious: 104/486 (21%)
Deaths: 3/486
OLE PLACEBO
Serious: 59/158 (37%)
Deaths: 4/158
OLE OCRELIZUMAB
Serious: 167/369 (45%)
Deaths: 19/369

Serious adverse events (330 terms)

ReactionSystemDB PLACEBODB OCRELIZUMABOLE PLACEBOOLE OCRELIZUMAB
COVID-19 PNEUMONIAInfections and infestations
URINARY TRACT INFECTIONInfections and infestations
PNEUMONIAInfections and infestations
COVID-19Infections and infestations
SEPSISInfections and infestations
UROSEPSISInfections and infestations
CELLULITISInfections and infestations
INFUSION RELATED REACTIONInjury, poisoning and procedural complications
PULMONARY EMBOLISMRespiratory, thoracic and mediastinal disorders
ASTHENIAGeneral disorders
PYELONEPHRITIS ACUTEInfections and infestations
BACK PAINMusculoskeletal and connective tissue disorders
MULTIPLE SCLEROSISNervous system disorders
MULTIPLE SCLEROSIS RELAPSENervous system disorders
CARDIAC ARRESTCardiac disorders
APPENDICITISInfections and infestations
ERYSIPELASInfections and infestations
PNEUMONIA ASPIRATIONInfections and infestations
PYELONEPHRITISInfections and infestations
MUSCLE SPASTICITYNervous system disorders
SUICIDE ATTEMPTPsychiatric disorders
URINARY RETENTIONRenal and urinary disorders
DEEP VEIN THROMBOSISVascular disorders
MYOCARDIAL INFARCTIONCardiac disorders
CATARACTEye disorders
Other adverse events (33 terms — click to expand)

ReactionSystemDB PLACEBODB OCRELIZUMABOLE PLACEBOOLE OCRELIZUMAB
INFUSION RELATED REACTIONInjury, poisoning and procedural complications
URINARY TRACT INFECTIONInfections and infestations
NASOPHARYNGITISInfections and infestations
COVID-19Infections and infestations
PNEUMONIAInfections and infestations
HEADACHENervous system disorders
UPPER RESPIRATORY TRACT INFECTIONInfections and infestations
BACK PAINMusculoskeletal and connective tissue disorders
INFLUENZAInfections and infestations
ARTHRALGIAMusculoskeletal and connective tissue disorders
DIARRHOEAGastrointestinal disorders
FALLInjury, poisoning and procedural complications
COUGHRespiratory, thoracic and mediastinal disorders
PAIN IN EXTREMITYMusculoskeletal and connective tissue disorders
DEPRESSIONPsychiatric disorders
BRONCHITISInfections and infestations
FATIGUEGeneral disorders
INSOMNIAPsychiatric disorders
HYPERTENSIONVascular disorders
DIZZINESSNervous system disorders
CONSTIPATIONGastrointestinal disorders
INFLUENZA LIKE ILLNESSGeneral disorders
CONTUSIONInjury, poisoning and procedural complications
PYREXIAGeneral disorders
RASHSkin and subcutaneous tissue disorders
OEDEMA PERIPHERALGeneral disorders
ASTHENIAGeneral disorders
SINUSITISInfections and infestations
TOOTH INFECTIONInfections and infestations
MUSCLE SPASMSMusculoskeletal and connective tissue disorders
ECZEMASkin and subcutaneous tissue disorders
SKIN LACERATIONInjury, poisoning and procedural complications
TRIGEMINAL NEURALGIANervous system disorders

Most-reported serious reactions: COVID-19 PNEUMONIA, URINARY TRACT INFECTION, PNEUMONIA, COVID-19, SEPSIS, UROSEPSIS, CELLULITIS, INFUSION RELATED REACTION.

Data from ClinicalTrials.gov NCT01194570 adverse events section.

Sponsor's own description

This randomized, parallel group, double-blind, placebo controlled study will evaluate the efficacy and safety of ocrelizumab in participants with primary progressive multiple sclerosis. Eligible participants will be randomized 2 : 1 to receive either ocrelizumab or placebo.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis.
    Montalban X, Hauser SL, Kappos L, Arnold DL, et al · · 2017 · cited 1296× · PMID 28002688 · DOI 10.1056/nejmoa1606468
  2. Epstein-Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies.
    Bar-Or A, Pender MP, Khanna R, Steinman L, et al · · 2020 · cited 199× · PMID 31862243 · DOI 10.1016/j.molmed.2019.11.003
  3. Antibodies to watch in 2017.
    Reichert JM. · · 2017 · cited 194× · PMID 27960628 · DOI 10.1080/19420862.2016.1269580
  4. Chronic white matter lesion activity predicts clinical progression in primary progressive multiple sclerosis.
    Elliott C, Belachew S, Wolinsky JS, Hauser SL, et al · · 2019 · cited 166× · PMID 31497864 · DOI 10.1093/brain/awz212
  5. Clinical trials in progressive multiple sclerosis: lessons learned and future perspectives.
    Ontaneda D, Fox RJ, Chataway J. · · 2015 · cited 161× · PMID 25772899 · DOI 10.1016/s1474-4422(14)70264-9
  6. Slowly expanding/evolving lesions as a magnetic resonance imaging marker of chronic active multiple sclerosis lesions.
    Elliott C, Wolinsky JS, Hauser SL, Kappos L, et al · · 2019 · cited 156× · PMID 30566027 · DOI 10.1177/1352458518814117
  7. Antibodies to watch in 2016.
    Reichert JM. · · 2016 · cited 135× · PMID 26651519 · DOI 10.1080/19420862.2015.1125583
  8. Safety of Ocrelizumab in Patients With Relapsing and Primary Progressive Multiple Sclerosis.
    Hauser SL, Kappos L, Montalban X, Craveiro L, et al · · 2021 · cited 131× · PMID 34475123 · DOI 10.1212/wnl.0000000000012700

Verify or expand the search:

Other trials of Ocrelizumab

Trials testing the same drug.

Other recruiting trials for Multiple Sclerosis, Primary Progressive

Currently open trials in the same condition.

Other Hoffmann-La Roche trials

Trials by the same sponsor.

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Data sources for this page

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing