Multiple SclerosisPhase 3Noisy RebelsNCT05834855
Non-inferiority Study of Rituximab Compared to Ocrelizumab in Relapsing MS
A Phase 3 study testing Rituximab in people with Multiple Sclerosis and Multiple Sclerosis, Relapsing-Remitting, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
Rationale: Ocrelizumab is widely and effectively used to treat relapsing multiple sclerosis (RMS). Phase II studies and data from large patient cohorts indicate that rituximab, another anti-CD20 monoclonal antibody, is probably equally effective and safe as ocrelizumab in the treatment of RMS. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Demyelinating Autoimmune Diseases, CNS
- What is being tested?
- Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteNetherlands
- Study dates
- Apr 2023to May 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women aged 18 years and older
- A diagnosis of relapsing MS according to the 2017 revised diagnostic criteria
- Indication to start treatment with anti-CD20 therapy according to the treating neurologist and the relevant label in the Netherlands for treatment of relapsing MS
- Able to understand written and spoken Dutch or English
- Capable of giving signed informed consent including compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- Screening EDSS score ≤ 6.5 .
Who cannot join
- Medical Conditions
- A known allergy or other intolerability to RTX, OCR, gadolinium-based MRI contrast agents, or corticosteroids.
- A diagnosis of primary progressive MS according to the diagnostic criteria.
- A diagnosis of not-active secondary progressive MS.
- Chronic infectious diseases such as tuberculosis, VZV, hepatitis virus or HIV, as well as hepatitis B surface antigen positivity and/or hepatitis C PCR positivity verified at screening visit.
- A history of proven inflammatory bowel disease such as M. Crohn or ulcerative colitis
Show all 29Show fewer
- Prior or current psychiatric illness, mental deficiency or cognitive dysfunction influencing the patient ability to make an informed consent or comply with the treatment and follow-up phases of this protocol.
- Cardiac disease that makes treatment with OCR or RTX contra-indicated as stated by the most recent SmPC
- Active malignancy or prior history of malignancy that makes treatment with OCR or RTX contra-indicated as stated by the most recent SmPC.
- WBC < 1.5 x 109/L if not caused by a reversible effect of documented ongoing medication. If caused by a reversible effect of documented ongoing medication the WBC count must be > 1,5 x 109/L before start of study treatment.
- Platelet (thrombocyte) count < 100 x 109/L
- ALAT and/or ASAT more than 2 times the upper normal reference limit (ULN)
- Serum creatinine > 200 μmol/L
- Serum bilirubin > ULN
- Serum IgG < LLN
- Pregnant or breast-feeding women
- Women of childbearing potential (WOCBP) not able or willing to use highly effective methods of birth control per ICH M3 (R2) that result in failure rate of ≤ 1% per year when used consistently and correctly for the duration of the study OR until 3 months after last dose administered.
- History of serious or life-threatening infusion reaction to OCR or RTX
- Treatment with glucocorticoids or ACTH within one month prior to start of study treatment
- Prior/Concomitant Therapy
- Previous use of second line MS-therapies cladribine, RTX, alemtuzumab, OCR, ofatumumab, hematopoietic stem cell therapy (HSCT) or other immunosuppression therapies with long lasting effects. Mitoxantrone is allowed if used > 1 year before enrolment. If any of these medications have been used for indications other than MS, patients can be included if the medications have not been used the year before enrolment. Previous treatment with natalizumab is allowed if the reason to switch was disease activity (so not allowed in for example cases that switch from natalizumab to anti-CD20 therapy because of JCV positivity).
- Concomitant use of systemic immunosuppressive medication (except corticosteroids for symptomatic treatment of relapses).
- Prior/Concurrent Clinical Study Experience
- Currently enrolled in another investigational device or drug study, or less than 30 days since ending of another investigational device or drug study (s), or receiving other investigational treatment(s). Patients participating in a purely observational studies will be allowed to participate.
- Lifestyle
- Current alcohol or drug dependencies.
- Diagnostic assessments
- Presence of metallic objects implanted in the body, that would preclude the ability of the patient to safely have MRI exams.
- Not willing to undergo MRI scans with i.v. gadolinium injections
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam UMC, location VUmc
Amsterdam, 1081 HV
B. van Oosten, Dr.
E. Strijbis, Dr.
About this study
Official title: Non-inferiority Study of Rituximab Compared to Ocrelizumab in Relapsing Multiple Sclerosis
Rationale: Ocrelizumab is widely and effectively used to treat relapsing multiple sclerosis (RMS). Phase II studies and data from large patient cohorts indicate that rituximab, another anti-CD20 monoclonal antibody, is probably equally effective and safe as ocrelizumab in the treatment of RMS. An advantage of rituximab is a considerably lower price. Therefore we will start a study aimed at demonstrating non-inferiority of rituximab compared to ocrelizumab in RMS. If non-inferiority of rituximab can be shown, important reductions in the cost of treatment of RMS will be possible, without loss of efficacy.
Objective: Evaluating the efficacy and safety of ritixumab compared to ocrelizumab in the treatmens of RMS.
Read more
Study design: Randomized double blind multi-centre non-inferiority study of rituximab compared to ocrelizumab in 200 patients with RMS. The trial duration will be 30 months
Study population: The study population consists of 200 adult RMS patiens with an indication to start anti-CD20 monoclonal antibody treatment.
Intervention: Patients will be randomized 1:1 into the standard group (ocrelizumab treatment) or the experimental group (rituximab treatment).
Main study parameters: To conclude non-inferiority of rituximab there will be one primary endpoint: the proportion of patients free of inflammatory disease activity (defined as: new or enlarged T2 lesions) between week 24 (M6) and week 96 (M24) of treatment in each arm. Secondary trial endpoints are presence and number of clinical relapses,T2 and contrast enhancing lesion volumes, brain volume and brain volume changes, disease progression (defined as clinically relevant change on any of the measures: EDSS, T25FW, 9HPT, SDMT), biochemical parameters such as lipidomics and neurofilament light (NfL), immunological parameters, safety as measured by the number of (serious) adverse events ((S)AE), quality of life (EQ-5D-L) and treatment satisfaction (TSQM) and patient reported measures of MS impact (MSIS-29) and well-being (questionnaire on physical complaints)
Nature and extent of the burden and risk: Patients included in this study will be treated and monitored by MRI, clinical tests and laboratory tests according to existing protocols and will not be exposed to extra or unknown risks. They will have extra annual questionnaires and larger blood samples at some time points. There is extensive experience with both rituximab and ocrelizumab as efficacious and safe treatments of RMS.
- Conditions
- Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Demyelinating Autoimmune Diseases, CNS, Autoimmune Diseases of the Nervous System, Nervous System Diseases, Demyelinating Diseases
- Being tested
- Rituximab
- Keywords
- ocrelizumab, rituximab, non-inferiority
- Medical subject headings
- Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Demyelinating Autoimmune Diseases, CNS, Autoimmune Diseases of the Nervous System, Nervous System Diseases, Demyelinating Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called MabThera, Truxima, Ruxience, Rixathon
Treatment with rituximab
| Study group | Role | What they receive |
|---|---|---|
| Ocrelizumab | No intervention | The standard group will receive ocrelizumab (600 mg, the first dosage given in two infusion of 300 mg with a two week interval) following the current treatment protocol |
| Rituximab | Experimental | The experimental group will receive rituximab (1000 mg). Rituximab will be given intravenously. To ensure blinding of treatment allocation two dosages of 500 mg with a two week interval will be given instead of one initial dosage of 1000 mg of rituximab to mimic the ocrelizumab protocol Receives: Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients free of inflammatory disease activity
Proportion of patients with no new or enlarged T2 lesions on brain MRI between month 6 and month 24
Measured: between month 6 and month 24
Secondary outcomes (7)
Presence and number of clinical relapses
Clinical relapses during treatment
Measured: Baseline, month 6, month 24
Contrast enhancing lesions
Proportion of patients with no contrast enhancing lesions on brain MRI
Measured: Baseline, month 6, month 24
Average number of T2 lesions on brain MRI
The average number of new/enlarged T2 lesions between baseline, month 6 and month 24 on brain MRI
Measured: Baseline, month 6, month 24
Disability progression during follow-up
Disability progression measured on the Expanded Disability Status Scale (EDSS)
Measured: Baseline, month 6, month 24
Disability progression during follow-up
Disability progression measured on the timed 25 foot walk test (T25FW)
Measured: Baseline, month 6, month 24
Disability progression during follow-up
Disability progression measured on the Nine Hole Peg Test (9HPT)
Measured: Baseline, month 6, month 24
Disability progression during follow-up
Disability progression measured on the Symbol Digit Modalities Test(SDMT)
Measured: Baseline, month 6, month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2023
- Study startApr 2023 (estimated)
- Primary completionMay 2027 (estimated)
- Study completionMay 2027 (estimated)
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 Amsterdam UMC, location VUmcThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multicenter randomized controlled double-blind non-inferiority trial in The Netherlands
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Collaborators
- Stichting Treatmeds
- Responsible party
- Principal investigator, Eva M.M. Strijbis, Amsterdam UMC, location VUmc
- Investigators
- Bob van Oosten, Dr, Principal investigator, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05834855
- Sponsor's protocol ID
- Anti-CD20 in RMS
- Acronym
- Noisy Rebels
- Status last verified
- Apr 2023
- First submitted
- 3 Apr 2023
- Last updated
- 28 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-inferiority Study of Rituximab Compared to Ocrelizumab in Relapsing Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT05834855
- Acronym / sponsor ID
- Noisy Rebels / Anti-CD20 in RMS
- Conditions
- Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Demyelinating Autoimmune Diseases, CNS, Autoimmune Diseases of the Nervous System, Nervous System Diseases, Demyelinating Diseases
- Keywords
- ocrelizumab, rituximab, non-inferiority
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Collaborators
- Stichting Treatmeds
- Study start
- Apr 2023 (estimated)
- Primary completion
- May 2027 (estimated)
- Study completion
- May 2027 (estimated)
- First posted
- 28 Apr 2023 (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.
Rationale: Ocrelizumab is widely and effectively used to treat relapsing multiple sclerosis (RMS). Phase II studies and data from large patient cohorts indicate that rituximab, another anti-CD20 monoclonal antibody, is probably equally effective and safe as ocrelizumab in the treatment of RMS. An advantage of rituximab is a considerably lower price. Therefore we will start a study aimed at demonstrating non-inferiority of rituximab compared to ocrelizumab in RMS. If non-inferiority of rituximab can be shown, important reductions in the cost of treatment of RMS will be possible, without loss of efficacy.
Objective: Evaluating the efficacy and safety of ritixumab compared to ocrelizumab in the treatmens of RMS.
Study design: Randomized double blind multi-centre non-inferiority study of rituximab compared to ocrelizumab in 200 patients with RMS. The trial duration will be 30 months
Study population: The study population consists of 200 adult RMS patiens with an indication to start anti-CD20 monoclonal antibody treatment.
Intervention: Patients will be randomized 1:1 into the standard group (ocrelizumab treatment) or the experimental group (rituximab treatment).
Main study parameters: To conclude non-inferiority of rituximab there will be one primary endpoint: the proportion of patients free of inflammatory disease activity (defined as: new or enlarged T2 lesions) between week 24 (M6) and week 96 (M24) of treatment in each arm. Secondary trial endpoints are presence and number of clinical relapses,T2 and contrast enhancing lesion volumes, brain volume and brain volume changes, disease progression (defined as clinically relevant change on any of the measures: EDSS, T25FW, 9HPT, SDMT), biochemical parameters such as lipidomics and neurofilament light (NfL), immunological parameters, safety as measured by the number of (serious) adverse events ((S)AE), quality of life (EQ-5D-L) and treatment satisfaction (TSQM) and patient reported measures of MS impact (MSIS-29) and well-being (questionnaire on physical complaints)
Nature and extent of the burden and risk: Patients included in this study will be treated and monitored by MRI, clinical tests and laboratory tests according to existing protocols and will not be exposed to extra or unknown risks. They will have extra annual questionnaires and larger blood samples at some time points. There is extensive experience with both rituximab and ocrelizumab as efficacious and safe treatments of RMS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Multicenter randomized controlled double-blind non-inferiority trial in The Netherlands
| Arm | Type | Receives |
|---|---|---|
| Ocrelizumab | No intervention | –The standard group will receive ocrelizumab (600 mg, the first dosage given in two infusion of 300 mg with a two week interval) following the current treatment protocol |
| Rituximab | Experimental | Drug: RituximabThe experimental group will receive rituximab (1000 mg). Rituximab will be given intravenously. To ensure blinding of treatment allocation two dosages of 500 mg with a two week interval will be given instead of one initial dosage of 1000 mg of rituximab to mimic the ocrelizumab protocol |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Men and women aged 18 years and older
- A diagnosis of relapsing MS according to the 2017 revised diagnostic criteria
- Indication to start treatment with anti-CD20 therapy according to the treating neurologist and the relevant label in the Netherlands for treatment of relapsing MS
- Able to understand written and spoken Dutch or English
- Capable of giving signed informed consent including compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Key exclusion criteria (29 listed)
- Medical Conditions
- A known allergy or other intolerability to RTX, OCR, gadolinium-based MRI contrast agents, or corticosteroids.
- A diagnosis of primary progressive MS according to the diagnostic criteria.
- A diagnosis of not-active secondary progressive MS.
- Chronic infectious diseases such as tuberculosis, VZV, hepatitis virus or HIV, as well as hepatitis B surface antigen positivity and/or hepatitis C PCR positivity verified at screening visit.
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 |
|---|---|---|
| RituximabAlso: MabThera, Truxima, Ruxience, RixathonTreatment with rituximab | Drug | Rituximab |
Primary outcome
Proportion of patients free of inflammatory disease activity
Time frame: between month 6 and month 24
Proportion of patients with no new or enlarged T2 lesions on brain MRI between month 6 and month 24
7 secondary outcomes
Presence and number of clinical relapses
Time frame: Baseline, month 6, month 24
Contrast enhancing lesions
Time frame: Baseline, month 6, month 24
Average number of T2 lesions on brain MRI
Time frame: Baseline, month 6, month 24
Disability progression during follow-up
Time frame: Baseline, month 6, month 24
Disability progression during follow-up
Time frame: Baseline, month 6, month 24
Disability progression during follow-up
Time frame: Baseline, month 6, month 24
Disability progression during follow-up
Time frame: Baseline, month 6, month 24
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2023.
- Individual participant dataSharing planned: Yes
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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.
Bob van Oosten, Dr principal investigator
Amsterdam UMC, location VUmc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rituximab in people with Multiple Sclerosis and Multiple Sclerosis, Relapsing-Remitting, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
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 29 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: looking for participants now, as of the sponsor's last update on 28 Apr 2023. 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 Netherlands. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lisa Schoof, Msc (650087853 ext. +31, l.g.schoof@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients free of inflammatory disease activity (time frame: between month 6 and 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 28 Apr 2023.