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A Study of Ocrelizumab in Participants With Primary Progressive Multiple Sclerosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01194570
Recruitment Status : Active, not recruiting
First Posted : September 3, 2010
Results First Posted : December 26, 2017
Last Update Posted : March 24, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE August 28, 2010
First Posted Date  ICMJE September 3, 2010
Results First Submitted Date  ICMJE March 30, 2017
Results First Posted Date  ICMJE December 26, 2017
Last Update Posted Date March 24, 2020
Actual Study Start Date  ICMJE March 2, 2011
Actual Primary Completion Date July 23, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 20, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 2, 2010)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2017)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 2, 2010)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Ocrelizumab in Participants With Primary Progressive Multiple Sclerosis
Official Title  ICMJE 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
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. 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 may continue their treatment with open-label ocrelizumab until 31 December 2020.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis, Primary Progressive
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 14, 2016)
732
Original Estimated Enrollment  ICMJE
 (submitted: September 2, 2010)
630
Estimated Study Completion Date  ICMJE December 9, 2021
Actual Primary Completion Date July 23, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Brazil,   Bulgaria,   Canada,   Czechia,   Finland,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Lithuania,   Mexico,   Netherlands,   New Zealand,   Norway,   Peru,   Poland,   Portugal,   Romania,   Russian Federation,   Spain,   Switzerland,   Ukraine,   United Kingdom,   United States,   Uruguay
Removed Location Countries Czech Republic,   Denmark,   Turkey
 
Administrative Information
NCT Number  ICMJE NCT01194570
Other Study ID Numbers  ICMJE WA25046
2010-020338-25 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date March 2020

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