Relapsing Multiple SclerosisPhase 3NOR-MSNCT04121403
Norwegian Study of Oral Cladribine and Rituximab in Multiple Sclerosis (NOR-MS)
A Phase 3 study testing Rituximab and Cladribine in people with Relapsing Multiple Sclerosis and Multiple Sclerosis, run by Oslo University Hospital at 11 sites in Norway.
Trial summary
The main aim and overall objective of the study is to assess whether rituximab is non-inferior to cladribine for the treatment of relapsing MS. Secondly, the investigators will test specific blood and MRI biomarkers that may contribute to future personalized treatment for MS patients. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Relapsing Multiple Sclerosis, Multiple Sclerosis
- What is being tested?
- Rituximab and Cladribine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 267 participants
- Where
- 11 sitesNorway
- Study dates
- 16 Oct 2019to 31 Aug 2024
- Phase
- Phase 3
- 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
- Age between 18 and 65 years
- A diagnosis of relapsing MS according to the 2017 McDonald criteria
- Disease activity seen as either a clinical relapse or MRI activity during the last 12 months
- EDSS between 0 and 5.5
- Thrombocytes and leukocytes within normal range, and lymphocytes above 0.8 x10 9/L before first dose of study medication
- A) For women of childbearing potential: accepting to use adequate contraception in the trial period. If randomized to cladribine, women who use systemic hormonal contraception must accept to use additional barrier contraception during each treatment cycle and for four weeks after each treatment cycle.
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- B) For men: If randomized to cladribine, accepting to use adequate contraception in the safety period of 6 months after each treatment cycle.
- Able to understand written and spoken Norwegian or English
- Able to complete treatment or follow-ups in the study (e.g. no contraindications for MRI, severe psychiatric disease, drug abuse or plans of moving)
- Signed informed consent
Who cannot join
- Any contraindication or increased risk of side-effects from rituximab or cladribine (such as ongoing acute or chronic infection, live vaccination less than 4 weeks before start of treatment or planned live vaccination, immunocompromised, previous or active malignant disease, ongoing glucocorticoid treatment or allergy against any products of the medication)
- Previous use of any of cladribine, rituximab, alemtuzumab, ocrelizumab, hematopoietic stem cell therapy (HSCT) or other immunosuppression with long lasting effects
- Fingolimod or natalizumab treatment within the last six months before inclusion
- Current pregnancy or lactation
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
Norway11 sites
Department of Neurology - Drammen, Vestre Viken HF
Drammen, Buskerud, 3004
Department of Neurology - Førde, Helse Førde HF
Førde, Sogn Og Fjordane, 6807
Department of Neurology - Kristiansand, Sørlandet sykehus HF
Kristiansand, Vest-Agder, 4604
Department of Neurology - Lillehammer, SI Lillehammer
Lillehammer, Oppland, 2629
Department of Neurology, Oslo University Hospital
Oslo, 0424
Department of Neurology - Kalnes, Sykehuset Østfold HF
Sarpsborg, Østfold fylke, 1714
Department of Neurology - Skien, Sykehuset Telemark
Skien, Telemark, 3710
Department of Neurology, Stavanger universitetssykehus
Stavanger, Rogaland, 4068
Department of Neurology - Tønsberg, Sykehuset i Vestfold HF
Tønsberg, Vestfold, 3103
Department of Neurology - Tromsø, University Hospital of North Norway
Tromsø, Troms, 9038
St. Olavs Hospital, Trondheim University Hospital
Trondheim, 7006
About this study
Official title: Norwegian Study of Oral Cladribine and Rituximab in Multiple Sclerosis (NOR-MS) A Prospective Randomized Open-label Blinded Endpoint (PROBE) Multicenter Non-inferiority Study
The main aim and overall objective of the study is to assess whether rituximab is non-inferior to cladribine for the treatment of relapsing MS. Secondly, the investigators will test specific blood and MRI biomarkers that may contribute to future personalized treatment for MS patients. Furthermore, the investigators want to evaluate the health economic consequences of the two therapies.
Read the detailed description
Multiple sclerosis (MS) is a demyelinating and neurodegenerative inflammatory disease of the central nervous system, affecting more than 12 000 patients in Norway and more than 2.2 mill patients worldwide.
Oral cladribine is one of the first choices for highly efficient disease modulatory treatment (DMT), while Rituximab is used off-label as DMT in relapsing MS. Large observational studies indicate good tolerance and treatment effect of rituximab in MS and studies from other diseases indicate a good safety profile. However, no phase 3 studies have been performed to test whether rituximab is as efficient as established MS treatments. Formal safety data is also lacking for the treatment with rituximab in MS.
The investigators will perform a prospective randomized open-label blinded endpoint multicenter non-inferiority study. The primary objective is to test whether rituximab is non-inferior to oral cladribine in the treatment of relapsing MS. 264 MS patients aged 18-65 years with relapsing MS will be recruited from 10 centers and followed for 96 weeks. The primary endpoint is difference in new T2 lesions between the groups. Furthermore, the investigators will test novel blood sample and MRI biomarkers to provide tools for personalized MS treatments. Finally, the health economic consequences of these treatment options will be evaluated.
This study will guide clinicians and patients in the future treatment choice for MS and can potentially make a huge impact on the costs of future MS treatment.
- Conditions
- Relapsing Multiple Sclerosis, Multiple Sclerosis
- Being tested
- Rituximab, Cladribine
- Keywords
- multiple sclerosis, ms, rms, rituximab, cladribine, probe
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabBiological
Biosimilar rituximab concentrate for solution for infusion
CladribineDrug
Also called Mavenclad
Mavenclad oral cladribine tablets
| Study group | Role | What they receive |
|---|---|---|
| Rituximab | Active comparator | Biosimilar rituximab concentrate for solution for infusion Receives: Biological: Rituximab |
| Cladribine | Active comparator | Mavenclad oral cladribine tablets Receives: Drug: Cladribine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of new or enlarging cerebral MRI T2 lesions
The primary outcome is the number of new or enlarging cerebral MRI T2 lesions per patient from week 12 to week 96
Measured: Week 12-96
Secondary outcomes (5)
T2 lesions after 48 weeks
Number of new or enlarging cerebral MRI T2 lesions per patient from week 12 to week 48
Measured: Week 12-48
Annual clinical relapse rate (ARR)
Annual clinical relapse rate (ARR) at 24, 48 and 96 weeks
Measured: Week -2 to 96
Relapse-free patients
Proportion of relapse-free patients at 24, 48 and 96 weeks
Measured: Week -2 to 96
Disability progression
Proportion of patients with 24 weeks confirmed disability progression (24-CDP) on EDSS at 48 and 96 weeks
Measured: Week -2 to 96
Change in disability
Change in disability on the Expanded Disability Status Scale (EDSS) from week -2 to 48 and 96 weeks. Disability progression is defined as an increase in EDSS of at least 1.5 points if baseline EDSS was 0, 1 point with baseline EDSS 0.5-4.5 and 0.5 point with baseline EDSS 5-5.5. EDSS is a scale from 0-10 measuring neurological disability.
Measured: Week -2 to 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2019
- Study start16 Oct 2019
- Primary completion31 Aug 2024
- Study completion31 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsing Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe 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
- A prospective randomized open-label blinded endpoint (PROBE) multicenter non-inferiority study, designed to establish non-inferiority of the test treatment rituximab compared with the comparator oral cladribine for consecutively included patients with active RMS. Randomization rituximab:cladribine is 1:1.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 267 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oslo, Sykehuset Ostfold, Sykehuset Telemark, Vestre Viken Hospital Trust, Sorlandet Hospital HF, Helse Stavanger HF, Sykehuset Innlandet HF, Sykehuset i Vestfold HF, University Hospital of North Norway, St. Olavs Hospital
- Responsible party
- Principal investigator, Gro Owren Nygaard, Oslo University Hospital
- Investigators
- Hanne Flistad Harbo, MD, PhD, Study chair, Oslo University HospitalGro Owren Nygaard, MD, PhD, Principal investigator, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04121403
- Sponsor's protocol ID
- 11383
- Acronym
- NOR-MS
- Status last verified
- Dec 2024
- First submitted
- 23 Sep 2019
- Last updated
- 16 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Norwegian Study of Oral Cladribine and Rituximab in Multiple Sclerosis (NOR-MS) A Prospective Randomized Open-label Blinded Endpoint (PROBE) Multicenter Non-inferiority Study
- ClinicalTrials.gov ID
- NCT04121403
- Acronym / sponsor ID
- NOR-MS / 11383
- Conditions
- Relapsing Multiple Sclerosis, Multiple Sclerosis
- Keywords
- multiple sclerosis, ms, rms, rituximab, cladribine, probe
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 267 participants (actual)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- University of Oslo, Sykehuset Ostfold, Sykehuset Telemark, Vestre Viken Hospital Trust, Sorlandet Hospital HF, Helse Stavanger HF, Sykehuset Innlandet HF, Sykehuset i Vestfold HF, University Hospital of North Norway, St. Olavs Hospital
- Study start
- 16 Oct 2019 (actual)
- Primary completion
- 31 Aug 2024 (actual)
- Study completion
- 31 Aug 2024 (actual)
- First posted
- 9 Oct 2019 (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.
The main aim and overall objective of the study is to assess whether rituximab is non-inferior to cladribine for the treatment of relapsing MS. Secondly, the investigators will test specific blood and MRI biomarkers that may contribute to future personalized treatment for MS patients. Furthermore, the investigators want to evaluate the health economic consequences of the two therapies.
Detailed description
Multiple sclerosis (MS) is a demyelinating and neurodegenerative inflammatory disease of the central nervous system, affecting more than 12 000 patients in Norway and more than 2.2 mill patients worldwide.
Oral cladribine is one of the first choices for highly efficient disease modulatory treatment (DMT), while Rituximab is used off-label as DMT in relapsing MS. Large observational studies indicate good tolerance and treatment effect of rituximab in MS and studies from other diseases indicate a good safety profile. However, no phase 3 studies have been performed to test whether rituximab is as efficient as established MS treatments. Formal safety data is also lacking for the treatment with rituximab in MS.
The investigators will perform a prospective randomized open-label blinded endpoint multicenter non-inferiority study. The primary objective is to test whether rituximab is non-inferior to oral cladribine in the treatment of relapsing MS. 264 MS patients aged 18-65 years with relapsing MS will be recruited from 10 centers and followed for 96 weeks. The primary endpoint is difference in new T2 lesions between the groups. Furthermore, the investigators will test novel blood sample and MRI biomarkers to provide tools for personalized MS treatments. Finally, the health economic consequences of these treatment options will be evaluated.
This study will guide clinicians and patients in the future treatment choice for MS and can potentially make a huge impact on the costs of future MS treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- A prospective randomized open-label blinded endpoint (PROBE) multicenter non-inferiority study, designed to establish non-inferiority of the test treatment rituximab compared with the comparator oral cladribine for consecutively included patients with active RMS. Randomization rituximab:cladribine is 1:1.
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Active comparator | Biological: RituximabBiosimilar rituximab concentrate for solution for infusion |
| Cladribine | Active comparator | Drug: CladribineMavenclad oral cladribine tablets |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age between 18 and 65 years
- A diagnosis of relapsing MS according to the 2017 McDonald criteria
- Disease activity seen as either a clinical relapse or MRI activity during the last 12 months
- EDSS between 0 and 5.5
- Thrombocytes and leukocytes within normal range, and lymphocytes above 0.8 x10 9/L before first dose of study medication
Key exclusion criteria (4 listed)
- Any contraindication or increased risk of side-effects from rituximab or cladribine (such as ongoing acute or chronic infection, live vaccination less than 4 weeks before start of treatment or planned live vaccination, immunocompromised, previous or active malignant disease, ongoing glucocorticoid treatment or allergy against any products of the medication)
- Previous use of any of cladribine, rituximab, alemtuzumab, ocrelizumab, hematopoietic stem cell therapy (HSCT) or other immunosuppression with long lasting effects
- Fingolimod or natalizumab treatment within the last six months before inclusion
- Current pregnancy or lactation
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 |
|---|---|---|
| RituximabBiosimilar rituximab concentrate for solution for infusion | Biological | Rituximab |
| CladribineAlso: MavencladMavenclad oral cladribine tablets | Drug | Cladribine |
Primary outcome
Number of new or enlarging cerebral MRI T2 lesions
Time frame: Week 12-96
The primary outcome is the number of new or enlarging cerebral MRI T2 lesions per patient from week 12 to week 96
5 secondary outcomes
T2 lesions after 48 weeks
Time frame: Week 12-48
Annual clinical relapse rate (ARR)
Time frame: Week -2 to 96
Relapse-free patients
Time frame: Week -2 to 96
Disability progression
Time frame: Week -2 to 96
Change in disability
Time frame: Week -2 to 96
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2024.
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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.
Hanne Flistad Harbo, MD, PhD study chair
Oslo University Hospital
Gro Owren Nygaard, MD, PhD principal investigator
Oslo University Hospital
11 sites 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 and Cladribine in people with Relapsing Multiple Sclerosis and Multiple Sclerosis, run by Oslo University Hospital at 11 sites in Norway.
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 10 inclusion and 4 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 16 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Norway. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of new or enlarging cerebral MRI T2 lesions (time frame: Week 12-96). 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 16 Dec 2024.