Active progressive multiple sclerosis MedDRA version: 20.0 Level: HLT Classification code 10052785 Term: Multiple sclerosis acute and progressive System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders MedDRA version: 21.1 Level: PT Classification code 10053395 Term: Progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: OCREVUS
Product Name: OCRELIZUMAB
Product Code: RO4964913
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Ocrelizumab
CAS Number: 637334-45-3
Current Sponsor code: RO496491
PRO70769
Other descriptive name: Recombinant humanized anti-CD20 monoclonal antibody
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30 mg/1 ml-
Sponsors
F. Hoffmann-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Signed Informed Consent Form. •Age = 18 and = 65 years at time of signing Informed Consent Form. •Ability to comply with the study protocol. •Patients of both genders with active progressive multiple sclerosis, defined with Lublin 2013 classification: primary progressive multiple sclerosis with subsequent relapses or MRI activity (McDonald 2017 criteria), secondary progressive multiple sclerosis with relapses or MRI activity during 2 years prior to initiation of ocrelizumab. •It is indicated to treat patients with ocrelizumab according to local regulations. •EDSS = 6.0. •Readiness for blood sampling from peripheral vein puncture. •Neurological stability (no clinically significant worsening according to neurological examination) for =30 days prior to both screening and baseline. •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, as defined below: Women must remain abstinent or use contraceptive methods with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: •Inability to provide informed consent. •Inability to undergo MRI due to devices or metallic foreign bodies considered unsafe in the MRI magnet (contraindications for MRI include but are not restricted to claustrophobia, weight = 140 kg, pacemaker, cochlear implants, presence of foreign substances in the eye, intracranial vascular clips, surgery within 6 weeks of entry into the study, coronary stent implanted within 8 weeks prior to the time of the intended MRI, etc.). •Known presence of other neurological disorders which may mimic MS including but not limited to: neuromeylitis optica, Lyme disease, untreated vitamin B12 deficiency, neurosarcoidosis and cerebrovascular disorders. •Known allergies to contrast agent. •Pregnant or breastfeeding, or intending to become pregnant during the study or within 6 months after the final dose of ocrelizumab. Women of childbearing potential must have a negative serum pregnancy test result at screening. •Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study. •History or currently active primary or secondary immunodeficiency. •Moderately to severe kidney function decreased or severe kidney failure (Glomerular filtration rate <45 mL/min/1.73 m2 as calculated through use of the Chronic Kidney Disease Epidemiology Collaboration equation). •History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies. •Significant or uncontrolled somatic disease or any other significant disease that may preclude patient from participating in the study. •Congestive heart failure (NYHA III or IV functional severity). •Known active bacterial, viral, fungal, mycobacterial infection or other infection, excluding fungal infection of nail beds. •Infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks prior to the Baseline visit or oral antibiotics within 2 weeks prior to the Baseline visit. •History or known presence of recurrent or chronic infection (e.g., hepatitis B or C, HIV, syphilis, tuberculosis). •History of progressive multifocal leukoencephalopathy (PML). •History of malignancy, including solid tumors and hematological malignancies, except basal cell carcinoma, in situ squamous cell carcinoma of the skin, and in situ carcinoma of the cervix of the uterus that have been previously completely excised with documented, clear margins. •History of illicit drug or alcohol abuse within 24 weeks prior to screening, in the investigator’s judgment. •History or laboratory evidence of coagulation disorders. •Receipt of a live vaccine within 6 weeks prior to baseline. •Treatment with any investigational agent within screening period or five half-lives of the investigational drug (whichever is longer). •Contraindications to or intolerance of oral or intravenous corticosteroids, including methylprednisolone administered intravenously, according to the country label, including: psychosis not yet controlled by a treatment and hypersensitivity to any of the constituents. •Previous therapy with B-cell depleting agents (i.e. rituximab, ocrelizumab, atacicept, belimumab or ofatumumab). •Systemic corticosteroid therapy within 4 weeks prior to screening. •Any previous treatment with alemtuzumab, anti-CD4 antibodies, cladribine, mitoxantrone, daclizumab, dimethyl fumarate, teriflunomide, laquinimod, total body irradiation or bone marrow transplantation. •Treatment with cyclophosphamid
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary efficacy objective for this study is to determine the evolution of leptomeningeal lesions in patients with active progressive multiple sclerosis: •The number of LMCE foci at the Month 24 visit compared to the number of LMCE foci at the Baseline visit in the LMCE-positive group. The exploratory efficacy objective for this study is to investigate influence of leptomeningeal lesions evolution on brain atrophy estimates at 2 years with regard to LMCE-status: •Percentage of brain volume change (PBVC) after 2 years in the LMCE-positive group and the LMCE-negative group separately. The safety objective for this study is to evaluate the safety of ocrelizumab: •Incidence and severity of adverse events, with severity determined according to NCI CTCAE v5.0. •Change from baseline in vital signs (respiratory rate, pulse rate, and systolic and diastolic blood pressure). •Change from baseline in laboratory test results (hematology and chemistry panel). ;Secondary Objective: The secondary efficacy objective for this study is to determine the evolution of leptomeningeal lesions in patients with active progressive multiple sclerosis based on the following endpoints: •The change from the Baseline visit in LMCE foci at the Month 12 visit in the LMCE- positive group and in the LMCE-negative group. •The change from the Baseline visit in LMCE foci at the Month 24 visit in the LMCE-negative group. •Time until 3-months composite confirmed disability progression in the LMCE-positive group and the LMCE-negative group separately. •Time until 3-months confirmed disability progression in the LMCE-positive group and the LMCE-negative group separately. •Time until 3-months confirmed 20% worsening in arm function (9-HPT) in the LMCE-positive group and the LMCE-negative group separately. •Time until 3-months confirmed 20% worsening of gait function (T25FWT) in the LMCE-positive group and the LMCE-negative group separately.;Primary end point(s): The primary efficacy obj | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •The change from the Baseline visit in LMCE foci at the Month 12 visit in the LMCE- positive group. •The change from the Baseline visit in LMCE foci at the Month 12 visit in the LMCE-negative group. •The change from the Baseline visit in LMCE foci at the Month 24 visit in the LMCE-negative group. •Time until 3-months composite confirmed disability progression in the LMCE-positive group and the LMCE-negative group separately. •Time until 3-months confirmed disability progression in the LMCE-positive group and the LMCE-negative group separately. •Time until 3-months confirmed 20% worsening in arm function (9-HPT) in the LMCE-positive group and the LMCE-negative group separately. •Time until 3-months confirmed 20% worsening of gait function (T25FWT) in the LMCE-positive group and the LMCE-negative group separately. •B-cell repertoire at baseline in the LMCE-positive group and the LMCE-negative group separately. •The change in the B-cell repertoire at Month 24 compared to baseline in the LMCE-positive group and the LMCE-negative group separately. •The change in the B-cell repertoire at Month 24 compared to baseline in the subgroup of LMCE-positive patients with decreased amount of LMCE foci at Month 24 and subgroup of LMCE-positive patients with stable or increased amount of LMCE foci at Month 24 separately. ;Timepoint(s) of evaluation of this end point: Baseline, 3 months, 12 month, 24 month, 2 year | — |
Countries
Greece, Russian Federation
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd.
Outcome results
None listed