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

Roche

Status and phase

Active, not recruiting

Phase 3

Conditions

Progressive Multiple Sclerosis (PMS)

Treatments

Drug: Ocrelizumab

Study type

Interventional

Funder types

Industry

Identifiers

NCT03523858

MN39159

Details and patient eligibility

About

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

Enrollment

927 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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 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:

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 prior to the first infusion of ocrelizumab
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 Laboratory Findings:

Positive screening tests for hepatitis B
CD4 count <250/μL
ANC <1.0 × 103/μL
AST/SGOT or ALT/SGPT ≥3.0 × ULN in combination with either an elevated total bilirubin (>2 X ULN) or clinical jaundice

Exclusions Related to Medications:

Hypersensitivity to ocrelizumab or to any of its excipients
Previous treatment with ocrelizumab
Previous treatment with B-cell targeted therapies (i.e., atacicept, tabalumab, belimumab, ofatumumab, or obinutuzumab). Note: previous treatment with rituximab is allowed as long as the last dose was administered more than 6 months before the ocrelizumab infusion AND if discontinuation was due to adverse events or immunogenicity AND if Bcell levels are above the lower limit of normal (LLN) prior to screening.
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, unless the local regulations allow for a shorter interval. Live/live attenuated vaccines should be avoided during treatment and safety follow-up period until B cells are peripherally repleted
Previous treatment with daclizumab, ozanimod or figolimod in the last 8 weeks
Previous treatment with siponimod in the last 2 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 teriflunomide in the last 12 weeks. This washout period can be shortened if an accelerated elimination procedure is implemented before screening visit. One of the following elimination procedures can be used:
Cholestyramine 8 g administered 3 times daily for a period of at least 7 days (cholestyramine 4 g three times a day can be used, if cholestyramine 8 g three times a day is not well tolerated)
Alternatively, 50 g of activated powdered charcoal is administered every 12 hours for a period of at least 7 days.
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