Multiple Sclerosis, Relapsing-RemittingPhase 4NCT04261790
Effects of Ocrelizumab on B-cell Tolerance Defect in Relapsing Multiple Sclerosis
A Phase 4 study testing Ocrelizumab in people with Multiple Sclerosis, Relapsing-Remitting, run by Johns Hopkins University at 1 site in United States.
Trial summary
B-cells have an important role in the pathogenesis of multiple sclerosis (MS). Ocrelizumab, a medication that targets B-cells have been found to be highly effective in stopping the disease activity in relapsing-remitting MS. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting
- What is being tested?
- Ocrelizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2020to 1 Nov 2024
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of relapsing remitting multiple sclerosis (RRMS) based on revised McDonald criteria
- At least one Gd-enhancing lesions on the brain or spinal cord MRI done in the prior three months OR at least one new T2/FLAIR lesion on the brain or spinal cord MRI done in the prior three months (compared to a prior MRI performed within 18 months of the most recent MRI)
- Naïve to Disease modifying therapy (DMT) or at least off these DMTs (natalizumab, fingolimod, DMF) for three months or on an injectable DMT (interferons or glatiramer acetate)
- Expanded Disability Status Scale (EDSS) score at the time of screening =<3
- Negative urine or serum pregnancy test must be available for premenopausal women and for women <12 months after the onset of menopause unless these women have undergone surgical sterilization
- Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use one method of contraception with a failure rate of <1% per year or a barrier method supplemented with spermicide. Contraception must continue for the duration of study treatment and for at least 24 weeks after the last dose of study treatment
Who cannot join
- Contraindication to treatment with an anti- cluster of differentiation antigen 20 (CD20) antibodies, including being seropositive for HBsAg
- Active hepatitis B virus infection
- Ever received B-cell depleting antibodies (rituximab, ocrelizumab, ofatumumab), alemtuzumab, daclizumab, mitoxantrone or hematopoietic stem-cell transplant
- Pregnant or lactating women
- Hypersensitivity to ocrelizumab
- Treatment with steroids in the past 30 days
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluating the Effects of Ocrelizumab on B-cell Tolerance Defect in Relapsing Multiple Sclerosis
B-cells have an important role in the pathogenesis of multiple sclerosis (MS). Ocrelizumab, a medication that targets B-cells have been found to be highly effective in stopping the disease activity in relapsing-remitting MS.
The efficacy of ocrelizumab might be related to the specific pattern of B-cell tolerance defect in patients with MS and the potential of its normalization with treatment with ocrelizumab. By analyzing the reactivity of recombinant antibodies expressed from single B-cells, the investigators' collaborators have demonstrated that the pattern of B-cell tolerance defect is different in people with MS who only display an impaired removal of developing autoreactive B-cells in the periphery while central B-cell tolerance in the bone marrow is functional in most patients. In contrast, patients with rheumatoid arthritis (RA), type-1 diabetes (T1D) or Sjögren's syndrome (SS) show defective central and peripheral B-cell tolerance checkpoints. As a consequence, while anti-B-cell therapy does not correct defective early B-cell tolerance checkpoints in T1D and only temporarily slows down autoimmune processes before newly generated autoreactive B-cells likely induce patient relapse, the investigators postulate that the efficacy of ocrelizumab in MS may be linked to normal central B-cell tolerance and the production of a normal B-cell and T-cell compartment after ocrelizumab therapy.
In an open-label study, 10 patients with relapsing MS will be treated with two courses of ocrelizumab and will be followed clinically and radiologically for at least two and a half years. Assessment of T and B-cell phenotypes and function at baseline and 18-24 months post-B-cell depletion will be the primary outcome of the study.
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Being tested
- Ocrelizumab
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OcrelizumabDrug
Also called Ocrevus
Patients will be treated with two courses of ocrelizumab (Ocrevus) 600mg/course, for one year and then will stop the medication and will be monitored for the return of the disease activity. Those who experience the return of the disease activity can go back on the medication.
| Study group | Role | What they receive |
|---|---|---|
| Ocrelizumab | Other | Patients will be treated with two courses of ocrelizumab (Ocrevus) for one year and then will stop the medication and will be monitored for the return of the disease activity. Those who experience the return of the disease activity can go back on the medication. Receives: Drug: Ocrelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Peripheral B-cell Tolerance Checkpoints in People With MS Before and After Ocrelizumab Therapy.
By assessing the antibodies produced by isolated B-cells, changes in the frequencies (percentage) of polyreactive, and anti-nuclear clones of new emigrant/transitional and mature naive B-cells will be determined.
Measured: Baseline and 18-24 months
Change in B-cell Subpopulations
Change in the frequency (percentage) of different B-cell subpopulation (assessed by flow cytometry) before and after treatment with ocrelizumab.
Measured: Baseline and 18-24 months
Change in Frequency of T-cell Phenotypes
Change in the frequency (percentage) of different T-cells subpopulation (assessed by flow cytometry) before and after treatment with ocrelizumab.
Measured: Baseline and 18-24 months
Change in the Production of Pro Inflammatory Cytokines Produced by Activated T-cells
Pro inflammatory cytokines, produced by Tregs and other T cell subsets after activating peripheral blood mononucleated cell with phorbol-12-myristate-13-acetate (PMA) and ionomycin will be measured by enzyme-linked immunosorbent assay.
Measured: Baseline and 18-24 months
Change in the Production of Anti-inflammatory Cytokines Produced by Activated T-cells
Anti-inflammatory cytokines, produced by Tregs and other T cell subsets after activating peripheral blood mononucleated cell with phorbol-12-myristate-13-acetate (PMA) and ionomycin will be measured by enzyme-linked immunosorbent assay
Measured: Baseline and 18-24 months
Secondary outcomes (3)
Patients With Return of Disease Activity
Patients with the return of disease activity after the third month post-first-infusion, objectively demonstrated by development of new T2 hyperintense lesions or Gd-enhancing lesions on the MRI or a clinical relapse that is confirmed with an objective change in the neurological examination.
Measured: Up to 30 months
Change in Disability as Assessed by Expanded Disability Status Scale (EDSS)
EDSS scores range from 0 to 10, with 0.5 steps. The higher the score, the worse the MS-related disability.
Measured: Screening visit and month 30 visit
Change in Quality of Life as Assessed by Neuro-QoL Fatigue T-score
T-score (standardized scores with a mean of 50 and a standard deviation (SD) of 10). A higher Neuro-QoL T-score represents more of the concept being measured. There is no specific upper or lower limit for this scoring
Measured: Screening visit and month 30 visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2020
- Study start1 Aug 2020
- Primary completion31 Oct 2024
- Study completion1 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Bardia Nourbakhsh, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04261790
- Sponsor's protocol ID
- IRB00230800
- Status last verified
- Jan 2025
- First submitted
- 6 Feb 2020
- Last updated
- 17 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Salazar-Camelo A, Vega L, Fadlallah Y, Bou Rjeily N, Balshi A, Morris B, Ghajarzadeh M, Mowry EM, Waubant E, Nourbakhsh B. Finite-course ocrelizumab in relapsing multiple sclerosis: Results of two prospective open-label trials with matched controls. Mult Scler. 2025 Oct;31(11):1338-1347. doi: 10.1177/13524585251375350. Epub 2025 Sep 19.
PubMed 40970353
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Effects of Ocrelizumab on B-cell Tolerance Defect in Relapsing Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT04261790
- Acronym / sponsor ID
- IRB00230800
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- 1 Aug 2020 (actual)
- Primary completion
- 31 Oct 2024 (actual)
- Study completion
- 1 Nov 2024 (actual)
- First posted
- 10 Feb 2020 (actual)
- Results
- Posted 17 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
B-cells have an important role in the pathogenesis of multiple sclerosis (MS). Ocrelizumab, a medication that targets B-cells have been found to be highly effective in stopping the disease activity in relapsing-remitting MS.
The efficacy of ocrelizumab might be related to the specific pattern of B-cell tolerance defect in patients with MS and the potential of its normalization with treatment with ocrelizumab. By analyzing the reactivity of recombinant antibodies expressed from single B-cells, the investigators' collaborators have demonstrated that the pattern of B-cell tolerance defect is different in people with MS who only display an impaired removal of developing autoreactive B-cells in the periphery while central B-cell tolerance in the bone marrow is functional in most patients. In contrast, patients with rheumatoid arthritis (RA), type-1 diabetes (T1D) or Sjögren's syndrome (SS) show defective central and peripheral B-cell tolerance checkpoints. As a consequence, while anti-B-cell therapy does not correct defective early B-cell tolerance checkpoints in T1D and only temporarily slows down autoimmune processes before newly generated autoreactive B-cells likely induce patient relapse, the investigators postulate that the efficacy of ocrelizumab in MS may be linked to normal central B-cell tolerance and the production of a normal B-cell and T-cell compartment after ocrelizumab therapy.
In an open-label study, 10 patients with relapsing MS will be treated with two courses of ocrelizumab and will be followed clinically and radiologically for at least two and a half years. Assessment of T and B-cell phenotypes and function at baseline and 18-24 months post-B-cell depletion will be the primary outcome of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ocrelizumab | Other | Drug: OcrelizumabPatients will be treated with two courses of ocrelizumab (Ocrevus) for one year and then will stop the medication and will be monitored for the return of the disease activity. Those who experience the return of the disease activity can go back on the medication. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosis of relapsing remitting multiple sclerosis (RRMS) based on revised McDonald criteria
- At least one Gd-enhancing lesions on the brain or spinal cord MRI done in the prior three months OR at least one new T2/FLAIR lesion on the brain or spinal cord MRI done in the prior three months (compared to a prior MRI performed within 18 months of the most recent MRI)
- Naïve to Disease modifying therapy (DMT) or at least off these DMTs (natalizumab, fingolimod, DMF) for three months or on an injectable DMT (interferons or glatiramer acetate)
- Expanded Disability Status Scale (EDSS) score at the time of screening =<3
- Negative urine or serum pregnancy test must be available for premenopausal women and for women <12 months after the onset of menopause unless these women have undergone surgical sterilization
Key exclusion criteria (6 listed)
- Contraindication to treatment with an anti- cluster of differentiation antigen 20 (CD20) antibodies, including being seropositive for HBsAg
- Active hepatitis B virus infection
- Ever received B-cell depleting antibodies (rituximab, ocrelizumab, ofatumumab), alemtuzumab, daclizumab, mitoxantrone or hematopoietic stem-cell transplant
- Pregnant or lactating women
- Hypersensitivity to ocrelizumab
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: OcrevusPatients will be treated with two courses of ocrelizumab (Ocrevus) 600mg/course, for one year and then will stop the medication and will be monitored for the return of the disease activity. Those who experience the return of the disease activity can go back on the medication. | Drug | Ocrelizumab |
Primary outcome
Change in Peripheral B-cell Tolerance Checkpoints in People With MS Before and After Ocrelizumab Therapy.
Time frame: Baseline and 18-24 months
By assessing the antibodies produced by isolated B-cells, changes in the frequencies (percentage) of polyreactive, and anti-nuclear clones of new emigrant/transitional and mature naive B-cells will be determined.
Change in B-cell Subpopulations
Time frame: Baseline and 18-24 months
Change in the frequency (percentage) of different B-cell subpopulation (assessed by flow cytometry) before and after treatment with ocrelizumab.
Change in Frequency of T-cell Phenotypes
Time frame: Baseline and 18-24 months
Change in the frequency (percentage) of different T-cells subpopulation (assessed by flow cytometry) before and after treatment with ocrelizumab.
Change in the Production of Pro Inflammatory Cytokines Produced by Activated T-cells
Time frame: Baseline and 18-24 months
Pro inflammatory cytokines, produced by Tregs and other T cell subsets after activating peripheral blood mononucleated cell with phorbol-12-myristate-13-acetate (PMA) and ionomycin will be measured by enzyme-linked immunosorbent assay.
Change in the Production of Anti-inflammatory Cytokines Produced by Activated T-cells
Time frame: Baseline and 18-24 months
Anti-inflammatory cytokines, produced by Tregs and other T cell subsets after activating peripheral blood mononucleated cell with phorbol-12-myristate-13-acetate (PMA) and ionomycin will be measured by enzyme-linked immunosorbent assay
3 secondary outcomes
Patients With Return of Disease Activity
Time frame: Up to 30 months
Change in Disability as Assessed by Expanded Disability Status Scale (EDSS)
Time frame: Screening visit and month 30 visit
Change in Quality of Life as Assessed by Neuro-QoL Fatigue T-score
Time frame: Screening visit and month 30 visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40970353Salazar-Camelo A, Vega L, Fadlallah Y, Bou Rjeily N, Balshi A, Morris B, Ghajarzadeh M, Mowry EM, Waubant E, Nourbakhsh B. Finite-course ocrelizumab in relapsing multiple sclerosis: Results of two prospective open-label trials with matched controls. Mult Scler. 2025 Oct;31(11):1338-1347. doi: 10.1177/13524585251375350. Epub 2025 Sep 19.
- Individual participant dataSharing planned: No
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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.
Bardia Nourbakhsh principal investigator
Johns Hopkins University
1 site 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, Relapsing-Remitting, run by Johns Hopkins University at 1 site in United States.
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 6 inclusion and 6 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: finished, as of the sponsor's last update on 17 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
Yes. Results are posted in the registry (first posted 17 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Peripheral B-cell Tolerance Checkpoints in People With MS Before and After Ocrelizumab Therapy. (time frame: Baseline and 18-24 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04261790, which also lists 1 linked publication.
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 17 Feb 2025.