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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 : Completed
First Posted : September 3, 2010
Results First Posted : December 26, 2017
Last Update Posted : May 22, 2023
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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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.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis, Primary Progressive Drug: Ocrelizumab Other: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 735 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : March 2, 2011
Actual Primary Completion Date : July 23, 2015
Actual Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Ocrelizumab

Arms and Interventions
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Arm Intervention/treatment
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.
 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.
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.
 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.


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. Percent Change From Baseline in Timed 25-Foot Walk (T25-FW) at Week 120 [ Time Frame: Baseline, Week 120 ]
  3. Percent Change From Baseline in Total Volume of T2 Lesions at Week 120 [ Time Frame: From Baseline to Week 120 ]
  4. Percent Change in Total Brain Volume From Week 24 to Week 120 [ Time Frame: From Week 24 to Week 120 ]
  5. 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.

  6. 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.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01194570


Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01194570    
Other Study ID Numbers: WA25046
2010-020338-25 ( EudraCT Number )
First Posted: September 3, 2010    Key Record Dates
Results First Posted: December 26, 2017
Last Update Posted: May 22, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Additional relevant MeSH terms:
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Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
 Autoimmune Diseases
Immune System Diseases
Chronic Disease
Disease Attributes
Ocrelizumab
Immunologic Factors
Physiological Effects of Drugs