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A Study to Evaluate Ocrelizumab Treatment in Participants With Progressive Multiple Sclerosis (CONSONANCE)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03523858
Recruitment Status : Recruiting
First Posted : May 14, 2018
Last Update Posted : October 6, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This study is a prospective, multicenter, open-label, single-arm effectiveness and safety study in participants with progressive multiple sclerosis (PMS).

Condition or disease Intervention/treatment Phase
Progressive Multiple Sclerosis (PMS) Drug: Ocrelizumab Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 900 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Single-Arm 4-Year Study to Evaluate Effectiveness and Safety of Ocrelizumab Treatment in Patients With Progressive Multiple Sclerosis
Actual Study Start Date : May 28, 2018
Estimated Primary Completion Date : March 27, 2024
Estimated Study Completion Date : September 25, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Ocrelizumab

Arm Intervention/treatment
Experimental: Ocrelizumab
Ocrelizumab will be administered via intravenous (IV) infusion.
Drug: Ocrelizumab
Ocrelizumab will be administered via intravenous (IV) infusion at an initial dose of two 300-mg infusions separated by 14 days (on Days 1 and 15), and then 600 mg at every subsequent dose every 24 weeks for the remainder of the study treatment period (approximately 192 weeks)




Primary Outcome Measures :
  1. Proportion of Participants with No Evidence of Progression (NEP) [ Time Frame: From Baseline to Week 96, Week 96 to Week 192 and Baseline to Week 192 ]
    NEP is defined as no progression sustained for at least 24 weeks on all of the following three components (confirmed disability progression [CDP]; ≥20% increase in timed 25-foot walk test [T25FWT]; ≥20% increase in nine-hole peg test [9HPT])

  2. Proportion of Participants with no evidence of progression and no active disease (NEPAD) [ Time Frame: From Baseline to Week 96, Week 96 to Week 192 and Baseline to Week 192 ]
    NEPAD is defined as no progression sustained for at least 24 weeks on all of the three components of NEP (CDP, T25FWT, 9HPT), no protocol-defined relapse, no enlarging or new T2 lesion, and no T1 gadolinium (Gd+)-enhancing lesion


Secondary Outcome Measures :
  1. Change from Baseline in Cognitive Function, as Measured by the Symbol Digit Modalities Test (SDMT) [ Time Frame: Baseline to end of study (Week 192) ]
  2. Mean Change from Baseline in the Expanded Disability Status Scale (EDSS) score over the course of the study [ Time Frame: Baseline to end of study (Week 192) ]
  3. Time to Onset of First Confirmed Disability Progression (CDP) Sustained for at least 24 and 48 Weeks [ Time Frame: Baseline to onset of first CDP (as measured by EDSS) sustained for at least 24 and 48 weeks ]
  4. Time to Onset of First >=20% Increase in Timed 25-foot Walk Test (T25FWT) Sustained for at least 24 Weeks [ Time Frame: Baseline to onset of first >=20% increase in T25FWT sustained for at least 24 weeks ]
  5. Time to Onset of First >=20% Increase in 9 Hole Peg Test (9HPT) Sustained For At Least 24 Weeks [ Time Frame: Baseline to onset of first >=20% increase in 9HPT sustained for at least 24 weeks ]
  6. Proportion of Participants with NEP [ Time Frame: Week 24 to Week 96, Week 24 to Week 192, and Week 48 to Week 192 ]
  7. Proportion of Participants with NEPAD [ Time Frame: Week 24 to Week 96, Week 24 to Week 192, Week 48 to Week 192 ]
  8. Change from Baseline in Patient-Reported Outcomes (PROs) [ Time Frame: Baseline to end of study (Week 192) ]
    PROs collected in this study will be the Multiple Sclerosis Impact Scale (MSIS-29), the Multiple Sclerosis Walking scale (MSWS-12), the ABILHAND-56 Questionnaire, Fatigue Scale for Motor and Cognitive function (FSMC), SymptoMScreen, 88-item Multiple Sclerosis Spasticity Scale (MSSS-88), Numerical Pain Rating Scale (NPRS), and the Patient Global Impression of Severity (PGIS) for upper limb, lower limb and cognitive function

  9. Change from Baseline in the number of falls and near-falls [ Time Frame: Baseline to end of study (Week 192) ]
  10. Change in Whole Brain Volume (Whole, Cerebral White Matter, Cortical Grey Matter) [ Time Frame: Baseline to end of study (Week 192) ]
  11. Change in thalamic and hippocampal volumes [ Time Frame: Baseline to end of study (Week 192) ]
  12. Change in cerebellar volume (whole, grey matter, white matter) [ Time Frame: Baseline to end of study (Week 192) ]
  13. Change in cervical cord cross-sectional area (total, white matter and grey matter) [ Time Frame: Baseline to end of study (Week 192) ]
  14. Change in number of new/enlarging T2 lesionsand total T2 Lesion Volume [ Time Frame: Baseline to end of study (Week 192) ]
  15. Change in number of T1 Gadolinium (Gd)+ Lesions and total volume [ Time Frame: 'Baseline to end of study (Week 192) ]
  16. Change in Slowly Evolving Lesions (SEL) [ Time Frame: Baseline to end of study (Week 192) ]
  17. Measurement of T1 Gd+ enhancement in New Focal T2 Lesions, SELs, Persistent Areas of Non-SEL T2 Lesions, and Normal-Appearing Brain Tissue [ Time Frame: Baseline to end of study (Week 192) ]
  18. Change in Gd-enhancing late-Fluid-Attenuated Inversion-Recovery (FLAIR) Meningeal Lesions [ Time Frame: Baseline to end of study (Week 192) ]
  19. Change in the number of cortical lesions (subpial, intracortical, and leucocortical) [ Time Frame: Baseline to end of study (Week 192) ]
  20. Change in the number/ spatial distribution of lesions in the cervical spinal cord [ Time Frame: Baseline to end of study (Week 192) ]
  21. Spectroscopic MR: Measure of the Relative Signal Amplitude of N-Acetyl Aspartate (NAA), and Choline to Creatine [ Time Frame: Baseline to end of study (Week 192) ]
    Only in centers with 1.5-Tesla MRI capable to perform it

  22. Measure of Phase Rim Lesions by T2* sequence [ Time Frame: Baseline to end of study (Week 192) ]
    Only in centers with 3-Tesla MRI capable to perform it, where this sequence would replace the spectroscopic MR in the acquisition flow

  23. Change in number of white mater lesions with central veins, using T2* sequences [ Time Frame: Baseline to end of study (Week 192) ]
  24. Measure of cortical and periventricular magnetization transfer ratio (MTR) gradients [ Time Frame: Baseline to end of study (Week 192) ]
  25. Measure of mean lesional magnetization transfer ratio (MTR) and mean MTR in normal-appearing white matter (NAWM) and grey matter (NAGM) [ Time Frame: Baseline to end of study (Week 192) ]
  26. Precentage of Participants with Adverse Events (AEs) [ Time Frame: Baseline to end of study (Week 192) ]
  27. Time to Study Treatment Discontinuation due to Adverse Events [ Time Frame: Baseline to Week 192 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have a definite diagnosis of PMS (as per the revised McDonald 2010 criteria for PPMS or Lublin et al. 2014 criteria for PMS)
  • EDSS (Expanded Disability Status Scale) </ =6.5 at screening
  • Have a length of disease duration since Progressive Multiple Sclerosis (PMS) disease symptom onsent </= 10 years if baseline Expanded Disability Status Scale (EDSS) </=5.0 and </=15 years if baseline EDSS >5.0
  • Have a documented evidence of disability progression independent of relapse at any point over the 2 years prior to the screening visit. In case relapse(s) have occurred in the last 2 years, disability progression will have to be considered as independent of relapse activity as per treating physician's judgment
  • Fulfill at least one of the 21 criteria assessing the evidence of disability progression independent of relapse activity in the last 2 years using the pre-baseline disability progression rating system checklist
  • Have experience of having used a smartphone and connecting a smartphone to Wi-Fi network providers
  • For women of childbearing potential: agreement to remain abstinent or use acceptable contraceptive methods during the treatment period and for at least 6 months, or longer if the local label is more stringent after the last dose of study drug

Exclusion Criteria:

  • Relapsing-remitting multiple sclerosis (RRMS) at screening
  • Inability to complete an MRI
  • Gadolinium (Gd) intolerance
  • Known presence of other neurological disorders

Exclusions Related to General Health:

  • Positive screening tests for hepatitis B
  • Pregnancy confirmed by positive serum β human chorionic gonadotropin (hCG) measured at screening
  • Lactation
  • Any concomitant disease that may require chronic treatment of systemic corticosteroids or immunosuppressants during the course of the study
  • History or currently active primary or secondary immunodeficiency
  • Lack of peripheral venous access
  • Significant or uncontrolled somatic disease or any other significant disease that may preclude participant from participating in the study.
  • Active infections must be treated and resolved before possible inclusion in the study.
  • Participants in a severely immunocompromised state until the condition resolves
  • Participants with known active malignancies or being actively monitored for recurrence of malignancy
  • Participants who have or have had confirmed progressive multifocal leukoencephalopathy (PML)

Exclusions Related to Medications:

  • Hypersensitivity to ocrelizumab or to any of its excipients
  • Previous treatment with B-cell targeted therapies (i.e., rituximab, ocrelizumab, atacicept, tabalumab, belimumab, ofatumumab, or obinutizumab)
  • Any previous treatment with alemtuzumab (Campath/Mabcampath/Lemtrada), total body irradiation, or bone marrow transplantation
  • Previous treatment with natalizumab where PML has not been excluded according to specific algorithm
  • Contraindications to or intolerance of oral or intravenous (IV) corticosteroids, including methylprednisolone administered IV, according to the country label
  • Systemic corticosteroid therapy within 4 weeks prior to screening
  • All vaccines should be given at least 6 weeks before the first infusion of ocrelizumab. Live/live attenuated vaccines should be avoided during treatment and safety follow-up period until B cells are peripherally repleted
  • Previous treatment with daclizumab or figolimod in the last 8 weeks
  • Treatment with fampridine/dalfampridine (Fampyra)/Ampyra) or other symptomatic MS treatment unless on stable dose for ≥30 days prior to screening
  • Previous treatment with natalizumab in the last 12 weeks
  • Previous treatment with azathioprine, cyclophosphamide, mycophenolate mofetil or methotrexate in the last 12 weeks
  • Treatment with any investigational agent within 24 weeks of screening (Visit 1) or five half-lives of the investigational drug (whichever is longer) or treatment with any experimental procedures for MS
  • Previous treatment with mitoxantrone, cyclosporine or cladribine in the last 96 weeks
  • Participants previously treated with teriflunomide within the last two years, unless measured plasma concentrations are less than 0.02 mg/l. If above or not known, an accelerated elimination procedure should be implemented before screening visit

Exclusions for Participants in the Optical Coherence Tomography (OCT) Assessments:

- Participants with clinically relevant ocular pathologies, potentially interfering with clinical and instrumental evaluations

Exclusions for Participants Participating in the Measurement of Motor Evoked Potentials:

  • History of seizures
  • Prior craniotomy or skull fracture
  • Movable metallic implant in the head
  • Implanted stimulators (e.g. cochlear implant or cardiac pacemaker, deep brain stimulator)
  • Known history of high intracranial pressure

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): NCT03523858


Contacts
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Contact: Reference Study ID Number: MN39159 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
Show Show 134 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03523858    
Other Study ID Numbers: MN39159
First Posted: May 14, 2018    Key Record Dates
Last Update Posted: October 6, 2020
Last Verified: October 2020
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.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). 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).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
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
Ocrelizumab
Immunologic Factors
Physiological Effects of Drugs