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A Study of Ocrelizumab in Participants With Primary Progressive Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT01194570
Recruitment Status : Active, not recruiting
First Posted : September 3, 2010
Results First Posted : December 26, 2017
Last Update Posted : May 25, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

August 28, 2010
September 3, 2010
March 30, 2017
December 26, 2017
May 25, 2018
March 2, 2011
July 23, 2015   (Final data collection date for primary outcome measure)
Time to Onset of Clinical Disability Progression (CDP) Sustained for at Least 12 Weeks During the Double-Blind Treatment Period [ Time Frame: 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 (normal) to 10 (death due to multiple sclerosis). The randomized participants who did not receive any treatment were censored at days 0 in each Arm.
Efficacy: Time to onset of sustained disability progression, defined as an increase in Expanded Disability Status Scale (EDSS) score that is sustained for at least 12 weeks [ Time Frame: from baseline to sustained disability progression over a 3-year period ]
Complete list of historical versions of study NCT01194570 on ClinicalTrials.gov Archive Site
  • Time to Onset of Clinical Disability Progression (CDP) Sustained for at Least 24 Weeks During the Double-Blind Treatment Period [ Time Frame: 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 (normal) to 10 (death due to multiple sclerosis). The randomized participants who did not receive any treatment were censored at days 0 in each Arm.
  • Percent Change From Baseline in Timed 25-Foot Walk (T25-FW) at Week 120 [ Time Frame: Baseline, Week 120 ]
  • Percent Change From Baseline in Total Volume of T2 Lesions at Week 120 [ Time Frame: From Baseline to Week 120 ]
  • Percent Change in Total Brain Volume From Week 24 to Week 120 [ Time Frame: From Week 24 to Week 120 ]
  • Change in From Baseline Physical Component Summary Score (PCS) SF- 36 Health Survey (SF-36) at Week 120 [ Time Frame: 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 (a) multiplying each health domain z score by a scale-specific physical factor score coefficient, (b) summing the resulting products, (c) converting the product total to T score. The total score ranges from 0-100, higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
  • Percentage of Participants With at Least One Adverse Event (AE) [ Time Frame: From the first infusion up to the study clinical cut-off date 24 July 2015 (up to 229 weeks) ]
    AEs included infusion related reactions (IRRs) and serious multiple sclerosis (MS) relapses, but excluded non-serious MS relapses.
  • Time to sustained disability progression, defined as an increase in EDSS score that is sustained for at least 24 weeks [ Time Frame: from baseline to sustained disability progression over a 3-year period ]
  • Change in timed 25-foot walk [ Time Frame: from baseline to Week 120 ]
  • Change in total volume of T2 lesions on magnetic resonance imaging (MRI) scans of the brain [ Time Frame: from baseline to Week 180 ]
  • Safety and tolerability: Adverse events, laboratory parameters, vital signs, ECG, neurological examination, MRI [ Time Frame: up to 3 years ]
Not Provided
Not Provided
 
A Study of Ocrelizumab in Participants With Primary Progressive Multiple Sclerosis
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
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. The blinded treatment period will be at least 120 weeks, followed by an Open Label Extension (OLE) treatment for participants in both groups who in the opinion of the investigator could benefit from further or newly initiated ocrelizumab treatment. Unless terminated early, all participants will continue their treatment with open-label ocrelizumab until the last participant who entered the OLE phase reaches 4 years of open-label ocrelizumab treatment.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Multiple Sclerosis, Primary Progressive
  • Drug: 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: Placebo
    Two IV infusions of placebo matched to ocrelizumab in each treatment cycle of double blind treatment period.
  • 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.
    Interventions:
    • Drug: Ocrelizumab
    • Other: Placebo
  • 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.
    Intervention: Drug: Ocrelizumab
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
732
630
April 29, 2021
July 23, 2015   (Final data collection date for primary outcome measure)

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

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
Sexes Eligible for Study: All
18 Years to 55 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Austria,   Belgium,   Brazil,   Bulgaria,   Canada,   Czechia,   Denmark,   Finland,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Lithuania,   Mexico,   Netherlands,   New Zealand,   Norway,   Peru,   Poland,   Portugal,   Romania,   Russian Federation,   Spain,   Switzerland,   Turkey,   Ukraine,   United Kingdom,   United States,   Uruguay
Czech Republic
 
NCT01194570
WA25046
2010-020338-25 ( EudraCT Number )
Yes
Not Provided
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP