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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01194570




Registration number
NCT01194570
Ethics application status
Date submitted
28/08/2010
Date registered
3/09/2010
Date last updated
10/01/2024

Titles & IDs
Public title
A Study of Ocrelizumab in Participants With Primary Progressive Multiple Sclerosis
Scientific title
A Phase III, Multicentre, Randomized, Parallel-group, Double-blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis
Secondary ID [1] 0 0
2010-020338-25
Secondary ID [2] 0 0
WA25046
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis, Primary Progressive 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ocrelizumab
Other interventions - Placebo

Experimental: Placebo - Participants with primary progressive multiple sclerosis (PPMS) received placebo matched to ocrelizumab at a schedule interval of 24 weeks up to at least 120 weeks.

Placebo comparator: Ocrelizumab 600 mg - Participants with PPMS received ocrelizumab as two IV infusions of 300 mg separated by 14 days at a scheduled interval of every 24 weeks up to at least 120 weeks.


Treatment: Drugs: Ocrelizumab
Two IV infusions of 300 mg in each treatment cycle of double blind treatment period; two IV infusions of ocrelizumab 300 mg for Cycle 1 and single IV infusion of ocrelizumab 600 mg for subsequent cycles in OLE phase.

Other interventions: Placebo
Two IV infusions of placebo matched to ocrelizumab in each treatment cycle of double blind treatment period.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to Onset of Clinical Disability Progression (CDP) Sustained for at Least 12 Weeks During the Double-Blind Treatment Period
Timepoint [1] 0 0
Maximal follow up: 216 weeks for Placebo arm and 217 weeks for Ocrelizumab arm
Secondary outcome [1] 0 0
Time to Onset of Clinical Disability Progression (CDP) Sustained for at Least 24 Weeks During the Double-Blind Treatment Period
Timepoint [1] 0 0
Maximal follow up: 216 weeks for Placebo arm and 217 weeks for Ocrelizumab arm
Secondary outcome [2] 0 0
Percent Change From Baseline in Timed 25-Foot Walk (T25-FW) at Week 120
Timepoint [2] 0 0
Baseline, Week 120
Secondary outcome [3] 0 0
Percent Change From Baseline in Total Volume of T2 Lesions at Week 120
Timepoint [3] 0 0
From Baseline to Week 120
Secondary outcome [4] 0 0
Percent Change in Total Brain Volume From Week 24 to Week 120
Timepoint [4] 0 0
From Week 24 to Week 120
Secondary outcome [5] 0 0
Change in From Baseline Physical Component Summary Score (PCS) SF- 36 Health Survey (SF-36) at Week 120
Timepoint [5] 0 0
From Baseline to Week 120
Secondary outcome [6] 0 0
Number of Participants With at Least One Adverse Event (AE)
Timepoint [6] 0 0
From baseline to 9 years

Eligibility
Key inclusion criteria
* Diagnosis of primary progressive multiple sclerosis (according to revised McDonald criteria)
* EDSS at screening from 3 to 6.5 points
* Disease duration from onset of MS symptoms less than (<) 15 years if EDSS greater than (>) 5.0; <10 years if EDSS greater than or equal to (>/=) 5.0
* Sexually active male and female participants of reproductive potential must use two methods of contraception throughout the study treatment phase and for 48 weeks after the last dose
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* History of relapsing remitting MS, secondary progressive, or progressive relapsing MS at screening
* Inability to complete an MRI (contraindications for MRI)
* Known presence of other neurologic disorders
* Known active infection or history of or presence of recurrent or chronic infection
* History of cancer, including solid tumors and hematological malignancies (except for basal cell, in situ squamous cell carcinomas of the skin and in situ carcinoma of the cervix that have been excised and resolved)
* Previous treatment with B-cell targeted therapies (e.g. rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab)
* Any previous treatment with lymphocyte trafficking blockers, with alemtuzumab, anti-cluster of differentiation 4 (CD4), cladribine, cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation, or bone marrow transplantation
* Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/03/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/12/2022
Sample size
Target
Accrual to date
Final
735
Recruitment in Australia
Recruitment state(s)
TAS,VIC
Recruitment hospital [1] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [2] 0 0
St Vincent's Hospital Melbourne; Clinical Neuroscience and Neurological Research - Fitzroy
Recruitment postcode(s) [1] 0 0
7000 - Hobart
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy
Recruitment outside Australia
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United States of America
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Arizona
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Madrid
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Malaga
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Sevilla
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Switzerland
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Basel
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Switzerland
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Lugano
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Ukraine
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Kherson Governorate
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Lviv
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Vinnytsya
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01194570
Trial related presentations / publications
Arnold DL, Sprenger T, Bar-Or A, Wolinsky JS, Kappos L, Kolind S, Bonati U, Magon S, van Beek J, Koendgen H, Bortolami O, Bernasconi C, Gaetano L, Traboulsee A. Ocrelizumab reduces thalamic volume loss in patients with RMS and PPMS. Mult Scler. 2022 Oct;28(12):1927-1936. doi: 10.1177/13524585221097561. Epub 2022 Jun 7.
Butzkueven H, Spelman T, Horakova D, Hughes S, Solaro C, Izquierdo G, Kubala Havrdova E, Grand'Maison F, Prat A, Girard M, Hupperts R, Onofrj M, Lugaresi A, Taylor B; MSBase Study Group; Giovannoni G, Kappos L, Hauser SL, Montalban X, Craveiro L, Freitas R, Model F, Overell J, Muros-Le Rouzic E, Sauter A, Wang Q, Wormser D, Wolinsky JS. Risk of requiring a wheelchair in primary progressive multiple sclerosis: Data from the ORATORIO trial and the MSBase registry. Eur J Neurol. 2022 Apr;29(4):1082-1090. doi: 10.1111/ene.14824. Epub 2021 May 6.
Wolinsky JS, Arnold DL, Brochet B, Hartung HP, Montalban X, Naismith RT, Manfrini M, Overell J, Koendgen H, Sauter A, Bennett I, Hubeaux S, Kappos L, Hauser SL. Long-term follow-up from the ORATORIO trial of ocrelizumab for primary progressive multiple sclerosis: a post-hoc analysis from the ongoing open-label extension of the randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2020 Dec;19(12):998-1009. doi: 10.1016/S1474-4422(20)30342-2. Epub 2020 Oct 29. Erratum In: Lancet Neurol. 2021 Jan;20(1):e1. doi: 10.1016/S1474-4422(20)30437-3.
Fox EJ, Markowitz C, Applebee A, Montalban X, Wolinsky JS, Belachew S, Fiore D, Pei J, Musch B, Giovannoni G. Ocrelizumab reduces progression of upper extremity impairment in patients with primary progressive multiple sclerosis: Findings from the phase III randomized ORATORIO trial. Mult Scler. 2018 Dec;24(14):1862-1870. doi: 10.1177/1352458518808189. Epub 2018 Nov 12.
Wolinsky JS, Montalban X, Hauser SL, Giovannoni G, Vermersch P, Bernasconi C, Deol-Bhullar G, Garren H, Chin P, Belachew S, Kappos L. Evaluation of no evidence of progression or active disease (NEPAD) in patients with primary progressive multiple sclerosis in the ORATORIO trial. Ann Neurol. 2018 Oct;84(4):527-536. doi: 10.1002/ana.25313.
Montalban X, Hauser SL, Kappos L, Arnold DL, Bar-Or A, Comi G, de Seze J, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Rammohan KW, Selmaj K, Traboulsee A, Sauter A, Masterman D, Fontoura P, Belachew S, Garren H, Mairon N, Chin P, Wolinsky JS; ORATORIO Clinical Investigators. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):209-220. doi: 10.1056/NEJMoa1606468. Epub 2016 Dec 21.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01194570