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

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: NCT05208840
Recruitment Status : Recruiting
First Posted : January 26, 2022
Last Update Posted : June 9, 2022
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Drug: Ocrelizumab Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-Label Multicenter Study To Determine The Effect Of Ocrelizumab On Leptomeningeal Inflammation In Multiple Sclerosis
Estimated Study Start Date : September 29, 2022
Estimated Primary Completion Date : January 31, 2025
Estimated Study Completion Date : January 31, 2026

Resource links provided by the National Library of Medicine

Drug Information available for: Ocrelizumab

Arm Intervention/treatment
Experimental: LMCE-positive
LMCE-positive participants enrolled in the study will receive therapy with ocrelizumab for 2 years.
Drug: Ocrelizumab
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.
Other Name: RO4964913

Experimental: LMCE-negative
LMCE-negative participants enrolled in the study will receive therapy with ocrelizumab for 2 years.
Drug: Ocrelizumab
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.
Other Name: RO4964913




Primary Outcome Measures :
  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 [ Time Frame: Baseline, Month 24 ]

Secondary Outcome Measures :
  1. The change from the Baseline visit in LMCE foci at the Month 12 visit in the LMCE- positive group. [ Time Frame: Baseline, Month 12 ]
  2. The change from the Baseline visit in LMCE foci at the Month 12 visit in the LMCE-negative group [ Time Frame: Baseline, Month 12 ]
  3. The change from the Baseline visit in LMCE foci at the Month 24 visit in the LMCE-negative group [ Time Frame: Baseline, Month 24 ]
  4. Time until 3-months composite confirmed disability progression in the LMCE-positive group and the LMCE-negative group [ Time Frame: Baseline to 3 months ]
  5. Time until 3-months confirmed disability progression in the LMCE-positive group and the LMCE-negative group [ Time Frame: Baseline to 3 months ]
  6. Time until 3-months confirmed 20% worsening in arm function (9-HPT) in the LMCE-positive group and the LMCE-negative group [ Time Frame: Baseline to 3 months ]
  7. Time until 3-months confirmed 20% worsening of gait function (T25FWT) in the LMCE-positive group and the LMCE-negative group [ Time Frame: Baseline to 3 months ]
  8. Percentage of Participants with Adverse Events [ Time Frame: Baseline up to 2 years ]
    Incidence and severity of adverse events, with severity determined according to NCI CTCAE v5.0.



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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:

  • 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

Exclusion Criteria:

  • 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 cyclophosphamide, azathioprine, mycophenolate mofetil (MMF), cyclosporine, methotrexate or natalizumab within 24 months prior to screening.
  • Treatment with fingolimod or other S1P receptor modulator within 24 weeks prior to screening.
  • Treatment with intravenous immunoglobulin within 12 weeks prior to baseline.
  • Positive screening tests for hepatitis B (hepatitis B surface antigen [HBsAg] positive, or positive hepatitis B core antibody [total HBcAb] confirmed by a positive viral deoxyribonucleic acid [DNA] polymerase chain reaction [PCR]) or hepatitis C (HepCAb).
  • Positive syphilis (RPR) test
  • Positive HIV infection serological test

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): NCT05208840


Contacts
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Contact: Reference Study ID Number: ML42302, https://forpatients.roche.com/ 888-662-6728 global-roche-genentech-trials@gene.com

Locations
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Russian Federation
City Clinical Hospital #24; Multipal Sclerosis department Recruiting
Moskva, Moskovskaja Oblast, Russian Federation, 127015
National Center of Socially Significant Diseases Recruiting
Saint-Petersburg, Sankt Petersburg, Russian Federation, 197110
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: NCT05208840    
Other Study ID Numbers: ML42302
First Posted: January 26, 2022    Key Record Dates
Last Update Posted: June 9, 2022
Last Verified: June 2022
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.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). 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
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Inflammation
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