A Study To Determine The Effect Of Ocrelizumab On Leptomeningeal Inflammation In Multiple Sclerosis

NCT05208840 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: ML42302
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

This study will evaluate the evolution of leptomeningeal lesions via leptomeningeal contrast enhancement (LMCE) presence/disappearance after treatment administration in patients with active progressive multiple sclerosis (MS). In addition, this study will investigate if the presence of leptomeningeal inflammation is associated with alterations of B cell repertoire and whether therapy with ocrelizumab will lead to change of B cell repertoire in LMCE-positive patients.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline, Month 24

Secondary Outcomes (8)

• The change from the Baseline visit in LMCE foci at the Month 12 visit in the LMCE- positive group.

  Baseline, Month 12

• The change from the Baseline visit in LMCE foci at the Month 12 visit in the LMCE-negative group

  Baseline, Month 12

• The change from the Baseline visit in LMCE foci at the Month 24 visit in the LMCE-negative group

  Baseline, Month 24

• Time until 3-months composite confirmed disability progression in the LMCE-positive group and the LMCE-negative group

  Baseline to 3 months

• Time until 3-months confirmed disability progression in the LMCE-positive group and the LMCE-negative group

  Baseline to 3 months

Study Arms (2)

LMCE-positive

EXPERIMENTAL

LMCE-positive participants enrolled in the study will receive therapy with ocrelizumab for 2 years.

Drug: Ocrelizumab

LMCE-negative

EXPERIMENTAL

LMCE-negative participants enrolled in the study will receive therapy with ocrelizumab for 2 years.

Drug: Ocrelizumab

Interventions

Ocrelizumab DRUG

Ocrelizumab will be given as slow intravenous infusion. Each treatment cycle has a duration of 6 months (5 cycles are planned in the study). The first cycle will consist of 2 infusions of 300 mg ocrelizumab (second infusion will be performed 14 days after first infusion). Cycles 2 through 5 will consist of one infusion of 600 mg ocrelizumab administered on Day 1 of each cycle.

Also known as: RO4964913

LMCE-negative; LMCE-positive

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (2)

City Clinical Hospital #24; Multipal Sclerosis department

Moskva, Moscow Oblast, 127015, Russia

Location

National Center of Socially Significant Diseases

Saint Petersburg, Sankt-Peterburg, 197110, Russia

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

ocrelizumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2022
• First Posted: January 26, 2022
• Study Start: September 15, 2023
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2026
• Last Updated: January 23, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share

Locations

RU (2)