Prevention of Clinical Multiple Sclerosis in Individuals With Radiologically Isolated Disease.

• Status: Not yet recruiting
• Trial end date: 2028-07-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a multicenter, randomized, double-blind, placebo-controlled, Phase 4 study in which eligible patients with RADIOLOGICALLY ISOLATED SYNDROME (RIS) (as defined by meeting 2017 McDonald criteria for DIS) will be randomized 1:1 to receive ocrelizumab treatment or placebo (standard of care).

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Yale University
• Collaborator: Genentech, Inc.
• Treatments: Ocrelizumab

Criteria

Inclusion Criteria:

• Established RIS diagnosis (i.e. CNS lesions consistent with MS, meeting McDonald 2017 criteria for DIS), either diagnosed within the last 5 years or known to have had accumulation of CNS lesions within the last 5 years.

• No prior exposure to DMT or long-term immunomodulatory medications

Exclusion Criteria:

• Intolerance to gadolinium-based contrast agent

• Contraindications to MRI

• ≥5 years of radiologic stability since first known abnormal MRI for patients previously diagnosed with RIS

• History of remitting clinical symptoms consistent with MS lasting >24 hours prior to CNS imaging revealing anomalies suggestive of MS

• CNS MRI anomalies are better accounted for by another disease process

• Infection Related:

• Known presence of recurrent or chronic infection (e.g., HIV, syphilis, tuberculosis)

• History of recurrent aspiration pneumonia requiring antibiotic therapy

• History or known presence of infectious causes of myelopathy (e.g., syphilis, Lyme disease, HTLV-1, herpes zoster myelopathy)

• Known active bacterial, viral, fungal, mycobacterial infection, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to baseline visit or oral antibiotics within 2 weeks prior to baseline visit

• Cancer Related

• History of cancer, including solid tumors and hematological malignancies (except basal cell, in situ squamous cell carcinomas of the skin, and in situ carcinoma of the cervix or the uterus that have been excised and resolved with documented clean margins on pathology)

• Pregnant or lactating, or intending to become pregnant during the treatment phase and 6 months after the last infusion of study drug

• Women of childbearing potential must have a negative serum or urine pregnancy test result within 14 days prior to initiation of study drug

• Other Medical Conditions

• History of or currently active primary or secondary immunodeficiency

• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies

• History of alcohol or other drug abuse within 24 weeks prior to enrollment

• History or known presence of systemic autoimmune disorders associated with systemic symptoms (e.g., lupus, anti-phospholipid antibody syndrome, Sjögren's syndrome, Behçet's disease)

• Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study

• Significant, uncontrolled disease, as defined by AMA guidelines or similar, such as cardiovascular (including congestive heart failure - NYHA grade 3 or 4, cardiac arrhythmia), uncontrolled hypertension, pulmonary (including chronic obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), gastrointestinal, or any other significant disease

• Known presence or history of other neurologic disorders, including but not limited to, the following:

• Progressive multifocal leukoencephalopathy, CNS or spinal cord tumor, potential metabolic causes of myelopathy (e.g., untreated vitamin B12 deficiency)

• History of genetically inherited progressive CNS degenerative disorder (e.g., hereditary paraparesis; mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes [MELAS])

• Neuromyelitis optica spectrum disorders (NMOSD)

• Ischemic cerebrovascular disorders (e.g., stroke, transient ischemic attack) or ischemia of the spinal cord

• Severe, clinically significant brain or spinal cord trauma (e.g., cerebral contusion, spinal cord compression)

• Psychosis not yet controlled by a treatment

• Drug Related

• Systemic, high dose corticosteroid therapy within 4 weeks prior to screening

• Contraindications for, or intolerance to, oral or IV corticosteroids, including IV methylprednisolone, according to the country label, including hypersensitivity to any of the treatment drug constituents

• Prior exposure to immunomodulatory medications and/or DMT

• Prior treatment with any disease modifying therapy for MS including but not limited to: interferon (IFN-β-1a (Avonex, Rebif), IFN-β-1b (Betaseron/Betaferon), glatiramer acetate, dimethyl fumarate (DMF; Tecfidera), diroximel fumarate (Vumerity) fingolimod (Gilenya) or siponimod (Mayzent), ozanimod (Zeposia) natalizumab (Tysabri), alemtuzimab (Lemtrada), cladribine (Mavenclad), rituximab (Rituxan), and other anti-CD20 agents

• Previous treatment with cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation, or bone marrow transplantation

• Previous or concurrent treatment with any investigational agent or treatment with any experimental procedure for MS (e.g., treatment for chronic cerebrospinal venous insufficiency)

• Vaccinations: Receipt of a live or live-attenuated vaccine or an inactivated/non-live vaccine within 6 weeks prior to enrollment

• Laboratory: Certain laboratory abnormalities or findings at screening, including the following:

• Positive serum β-hCG

• Positive for hepatitis B (hepatitis B surface antigen [HBsAg] positive or hepatitis B core antibody [total HBcAb] confirmed by positive viral DNA polymerase chain reaction [PCR])

• AST or ALT ≥3.0 ×upper limit of normal

• Total white blood cell count, including differential counts, below lower limit of normal

• Absolute lymphocyte count below lower level of normal

• Absolute neutrophil count below lower limit of normal

• Platelet count below lower limit of normal