Multiple SclerosisPhase 4LEGATONCT05208840
A Study To Determine The Effect Of Ocrelizumab On Leptomeningeal Inflammation In Multiple Sclerosis
A Phase 4 study testing Ocrelizumab in people with Multiple Sclerosis, run by Hoffmann-La Roche at 2 sites in Russia.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Ocrelizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesRussia
- Study dates
- 15 Sep 2023to 31 Jan 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
2 sites in 1 country.
Russia2 sites
City Clinical Hospital #24; Multipal Sclerosis department
Moskva, Moscow Oblast, 127015
National Center of Socially Significant Diseases
Saint Petersburg, Sankt-Peterburg, 197110
About this study
Official title: Open-Label Multicenter Study To Determine The Effect Of Ocrelizumab On Leptomeningeal Inflammation In Multiple Sclerosis
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
- Being tested
- Ocrelizumab
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OcrelizumabDrug
Also called RO4964913
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.
| Study group | Role | What they receive |
|---|---|---|
| LMCE-positive | Experimental | LMCE-positive participants enrolled in the study will receive therapy with ocrelizumab for 2 years. Receives: Drug: Ocrelizumab |
| LMCE-negative | Experimental | LMCE-negative participants enrolled in the study will receive therapy with ocrelizumab for 2 years. Receives: Drug: Ocrelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: Baseline, Month 12
The change from the Baseline visit in LMCE foci at the Month 12 visit in the LMCE-negative group
Measured: Baseline, Month 12
The change from the Baseline visit in LMCE foci at the Month 24 visit in the LMCE-negative group
Measured: Baseline, Month 24
Time until 3-months composite confirmed disability progression in the LMCE-positive group and the LMCE-negative group
Measured: Baseline to 3 months
Time until 3-months confirmed disability progression in the LMCE-positive group and the LMCE-negative group
Measured: Baseline to 3 months
Time until 3-months confirmed 20% worsening in arm function (9-HPT) in the LMCE-positive group and the LMCE-negative group
Measured: Baseline to 3 months
Time until 3-months confirmed 20% worsening of gait function (T25FWT) in the LMCE-positive group and the LMCE-negative group
Measured: Baseline to 3 months
Percentage of Participants with Adverse Events
Incidence and severity of adverse events, with severity determined according to NCI CTCAE v5.0.
Measured: Baseline up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2022
- Study start15 Sep 2023 (estimated)
- Primary completion31 Jan 2025 (estimated)
- Study completion31 Jan 2026 (estimated)
Why it stopped: Due to deterioration of the geopolitical situation and escalation of conflict between Russia and Ukraine ML42302 study was put on hold.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05208840
- Sponsor's protocol ID
- ML42302
- Acronym
- LEGATO
- Status last verified
- Jan 2024
- First submitted
- 12 Jan 2022
- Last updated
- 23 Jan 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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).
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-Label Multicenter Study To Determine The Effect Of Ocrelizumab On Leptomeningeal Inflammation In Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT05208840
- Acronym / sponsor ID
- LEGATO / ML42302
- Conditions
- Multiple Sclerosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Due to deterioration of the geopolitical situation and escalation of conflict between Russia and Ukraine ML42302 study was put on hold.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 15 Sep 2023 (estimated)
- Primary completion
- 31 Jan 2025 (estimated)
- Study completion
- 31 Jan 2026 (estimated)
- First posted
- 26 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LMCE-positive | Experimental | Drug: OcrelizumabLMCE-positive participants enrolled in the study will receive therapy with ocrelizumab for 2 years. |
| LMCE-negative | Experimental | Drug: OcrelizumabLMCE-negative participants enrolled in the study will receive therapy with ocrelizumab for 2 years. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (30 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OcrelizumabAlso: RO4964913Ocrelizumab 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. | Drug | LMCE-negative, LMCE-positive |
Primary outcome
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
8 secondary outcomes
The change from the Baseline visit in LMCE foci at the Month 12 visit in the LMCE- positive group.
Time frame: Baseline, Month 12
The change from the Baseline visit in LMCE foci at the Month 12 visit in the LMCE-negative group
Time frame: Baseline, Month 12
The change from the Baseline visit in LMCE foci at the Month 24 visit in the LMCE-negative group
Time frame: Baseline, Month 24
Time until 3-months composite confirmed disability progression in the LMCE-positive group and the LMCE-negative group
Time frame: Baseline to 3 months
Time until 3-months confirmed disability progression in the LMCE-positive group and the LMCE-negative group
Time frame: Baseline to 3 months
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
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
Percentage of Participants with Adverse Events
Time frame: Baseline up to 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2024.
- Individual participant dataSharing planned: Yes. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ocrelizumab in people with Multiple Sclerosis, run by Hoffmann-La Roche at 2 sites in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 23 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2024.