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Relapsing Remitting Multiple SclerosisPhase 3DanNORMSNCT04688788

Non-inferiority Study of Ocrelizumab and Rituximab in Active Multiple Sclerosis

A Phase 3 study testing Rituximab, Ocrelizumab and Fexofenadine in people with Relapsing Remitting Multiple Sclerosis and Secondary Progressive Multiple Sclerosis, run by Copenhagen University Hospital, Rigshospitalet at 11 sites in Denmark.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The DanNORMS study is a phase 3, non-inferiority clinical trial examining whether treatment of active multiple sclerosis with rituximab is non-inferior to ocrelizumab regarding efficacy and safety. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Rituximab, Ocrelizumab and Fexofenadine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
600 participants
Where
11 sitesDenmark
Study dates
28 Apr 2021to 10 Jun 2029
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 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • MS diagnosis and definition of disease course according to the 2017 McDonald criteria
  • Expanded disability status scale (EDSS) ≤6.5
  • Fulfilling criteria for active MS:
  • Treatment naïve relapsing remitting multiple sclerosis (RRMS) patients (never treated, or no DMT the previous 2 years):
  • ▪≥2 relapse previous 12 months OR
  • 1 relapse previous 12 months with severe residual symptoms and EDSS ≥ 3.0 OR
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  • 1 relapse previous 12 months AND ≥9 T2 lesions on brain and/or spinal cord MRI AND
  • 1 contrast-enhancing lesion or ≥1 new or enlarging T2 lesion on brain and/or spinal cord MRI previous 12 month
  • Previously treated RRMS patients:
  • ≥1 relapse previous 12 months OR
  • ≥1 contrast-enhancing lesion or ≥2 new/enlarging T2 lesions on brain and/or spinal cord MRI previous 12 months
  • Progressive MS patients:
  • ≥1 relapse previous 12 months OR
  • ≥1 contrast-enhancing lesion previous 12 months or ≥1 new/enlarging T2 lesions on brain and/or spinal cord MRI previous 12 months or ≥2 new or enlarging T2 lesion on brain and/or spinal cord MRI previous 24 months OR
  • Increased levels of neurofilament light chain (NFL) in serum or cerebrospinal fluid (CSF) in sample collected previous 12 months. Progressive MS patients not fulfilling the clinical/MRI criteria for active disease, may qualify for inclusion in the study if:
  • CSF NFL level (measured with NF-Light® ELISA assay from Uman Diagnostics or Simoa):
  • 18 to 40 years >560 ng/l
  • 41 to 60 years >890 ng/l
  • 61 to 65 years >1850 ng/l
  • or
  • Serum NFL level (measured with Simoa™ NF-light® Advantage Kit)
  • o Increased sNFL based on individual age-determined cut-off: >4.19 × 1.029^age ng/L
  • OR
  • o Increased sNFL based age-partitioned cut-offs:
  • 18 to 20 years >7.4 ng/L
  • 21 to 30 years >9.9 ng/L
  • 31 to 40 years >13.1 ng/L
  • 41 to 50 years >17.5 ng/L
  • 51 to 60 years >23.3 ng/L
  • 61 to 65 years >30.9 ng/L
  • Signed written informed consent

Who cannot join

  • Pregnancy or breast feeding
  • Lack of effective contraception for women of child-bearing potential (effective contraception include oral contraception, intrauterine devices and other forms of contraception with failure rate <1%)
  • Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization
  • Known active malignant disease
  • Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
  • Positive test for HIV, hepatitis B or C, or symptoms or signs of active tuberculosis in a patient with a positive Quantiferon test.
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  • Negative test for varicella zoster
  • Lymphopenia grade 2 (0.5 to 0.8 × 10^9/L) or higher grades of lymphopenia. In case of switching from fingolimod, siponimod or ozanimod lymphopenia is accepted at screening visit. Patients switching from dimethylfumarate who have persistent lymphopenia 5 to 6 weeks after stopping dimethylfumarate can be included if lymphopenia is grade 2 or lower, and treating phycisian judge CD20-depleting therapy safe.
  • Neutropenia grade 2 (1.0 to 1.5 × 10^9/L) or higher grades
  • Thrombocytopenia grade 2 (50 to 75 × 10^9/L) or higher grades
  • Previous treatment with alemtuzumab or hematopoietic stem-cell transplantation
  • Previous treatment with cladribine, CD20-depleting antibodies, daclizumab or other immune suppressive treatment which is judged to still exert immune suppressive effect by treating physician
  • Methylprednisolone treatment within 1 month of baseline visit
  • Findings on the screening MRI judged to preclude participation by the treating physician
  • Other diseases judged to be relevant by the treating physician
  • Contraindication to MRI
  • Known allergy or hypersensitivity to rituximab or ocrelizumab

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

Denmark11 sites

  • Department of Neurology, Aalborg University Hospital

    Aalborg, 9000

  • Department of Neurology, Aarhus University Hospital

    Aarhus, 8200

  • Department of Neurology, Hospital of South West Jutland, Esbjerg

    Esbjerg, 6700

  • Danish Multiple Sclerosis Center, Rigshospitalet

    Glostrup Municipality, Copenhagen, 2600

  • Department of Neurology, Herlev Hospital

    Herlev, 2730

  • Department of Neurology, Nordsjællands Hospital i Hillerød

    Hillerød, 3400

  • Department of Neurology, Regionshospitalet Holstebro

    Holstebro, 7500

  • Department of Neurology, Kolding Hospital

    Kolding, 6000

  • Department of Neurology, Odense University Hospital

    Odense, 5000

  • Department of Neurology, Hospital of Southern Jutland, Sønderborg

    Sønderborg, 6400

  • Department of neurology, Regionshospitalet Viborg

    Viborg, 8800

Other trials in Denmark

About this study

Official title: Danish Non-inferiority Study of Ocrelizumab and Rituximab in MS (DanNORMS): A Randomized Study Comparing the Efficacy of Ocrelizumab and Rituximab in Active Multiple Sclerosis

The DanNORMS study is a phase 3, non-inferiority clinical trial examining whether treatment of active multiple sclerosis with rituximab is non-inferior to ocrelizumab regarding efficacy and safety.

Read the detailed description

The DanNORMS study will include patients with active multiple sclerosis aged 18-65 years. Patients will be randomized in a 2:1 ratio to either rituximab or ocrelizumab. The study duration is 24 months for the core-phase, and patients can continue in a long-term follow-up phase for additional 36 months with possibility for extended interval dosing guided by CD19+ B cell count.

The primary endpoint is the percentage of patients without new or enlarging T2 white matter lesions on brain MRI scans from month 6 to month 24, which will be assessed by radiologists blinded to the treatments status. The study will evaluate a number of efficacy and safety endpoints using clinical, MRI, routine blood samples and research biomarkers.

Being tested
Rituximab, Ocrelizumab, Fexofenadine, Paracetamol, Methylprednisolone
Keywords
Magnetic resonance imaging, Rituximab, Ocrelizumab
Medical subject headings
Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Chronic Progressive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RituximabDrug

    Also called Ruxience, Rixathon® or other biosimilar rituximab

    Rituximab is a chimeric mouse/human monoclonal immunoglobulin gamma-1 (IgG1) antibody which depletes cluster of differentiation antigen 20 (CD20)-positive cells. Rituximab is approved for non-hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangitis and microscopic polyangitis, and pemphigus vulgaris.

  • OcrelizumabDrug

    Also called Ocrevus

    Ocrelizumab is a recombinant humanised monoclonal IgG1 antibody which depletes CD20-positive cells. Ocrelizumab is approved for multiple sclerosis.

  • FexofenadineDrug

    Premedication with oral fexofenadine 360 mg is given before every infusion to reduce frequency and intensity of infusion related reactions.

  • ParacetamolDrug

    Premedication with oral. paracetamol 1000 mg is given before every infusion to reduce frequency and intensity of infusion related reactions.

  • MethylprednisoloneDrug

    Premedication with oral methylprednisolone 100 mg is given before every infusion to reduce frequency and intensity of infusion related reactions.

Study groups in NCT04688788
Study groupRoleWhat they receive
RituximabExperimentalIntravenous biosimilar rituximab (Ruxience®, Rixathon® or other biosimilar rituximab) 1000 mg given every 6th month (first 2 infusions 1000mg/1000 mg given 2 weeks apart).
Receives: Drug: Rituximab; Drug: Fexofenadine; Drug: Paracetamol; Drug: Methylprednisolone
OcrelizumabActive comparatorIntravenous ocrelizumab (Ocrevus®) 600 mg every 6th month (first 2 infusions 300 mg/300 mg given 2 weeks apart).
Receives: Drug: Ocrelizumab; Drug: Fexofenadine; Drug: Paracetamol; Drug: Methylprednisolone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of patients without new or enlarging T2 white matter lesions on brain MRI scans

    MRI outcome

    Measured: Month 6 to month 24

Secondary outcomes (14)

  1. Percentage of patients with 6-month confirmed disability progression (CDP) in Expanded Disability Status Scale (EDSS)

    Clinical outcome

    Measured: Baseline to month 24

  2. Annualised relapse rate based on cumulative number of confirmed relapses from baseline to months 24

    Clinical outcome

    Measured: Baseline to month 24

  3. Percentage of patients with 6-months CDP in Timed 25 Foot Walk (T25FW)

    Clinical outcome

    Measured: Baseline to month 24

  4. Percentage of patients with 6-months CDP in 9-Hole-Peg Test (9HPT)

    Clinical outcome

    Measured: Baseline to month 24

  5. Percentage of patients with 6-months CDP in Symbol Digit Modalities Test (SDMT)

    Clinical outcome

    Measured: Baseline to month 24

  6. Change in Multiple Sclerosis Impact Scale (MSIS-29)

    Patient related outcome measure (PROM). A 29 item questionnaire with values ranging from 29 (good) to 145 (worse).

    Measured: Baseline to month 24

  7. Change in Fatigue Scale for Motor and Cognitive Functions (FSMC)

    PROM. A 20 item questionnaire with values ranging from 20 (no fatigue at all) and 100 (severest grade of fatigue.

    Measured: Baseline to month 24

  8. EuroQol- 5 Dimension (EQ-5D)

    PROM. A 5 item questionnaire with values ranging from 5 (good) to 15 (worse).

    Measured: Baseline to month 24

  9. Percentage of patients without gadolinium-enhancing lesions (GdEL)

    MRI outcome

    Measured: Month 6 and month 24 MRI scans

  10. Change in T2 white matter lesion volume

    MRI outcome

    Measured: From month 6 to month 24

  11. Change in T1 white matter lesion volume

    MRI outcome

    Measured: From month 6 to month 24

  12. Percentage brain volume change (PBVC) from month 6 to month 24

    MRI outcome

    Measured: From month 6 to month 24

  13. Change in serum neurofilament light chain level

    Blood biomarker

    Measured: From baseline to month 24

  14. Blood levels of cluster of differentiation antigen 19 (CD19)+ B cells

    Blood biomarker

    Measured: At month 6 and month 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Dec 2020
  2. Study start28 Apr 2021
  3. Primary completion10 Jun 2026
  4. Study completion10 Jun 2029 (estimated)

Resources

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, 2:1 randomized, open-label, multi-centre, phase 3 non-inferiority clinical trial with blinded primary endpoint.
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
600 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04688788
Sponsor's protocol ID
DanNORMS_version 3.3
Acronym
DanNORMS
Status last verified
Aug 2026
First submitted
22 Dec 2020
Last updated
17 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Rituximab, Ocrelizumab and Fexofenadine in people with Relapsing Remitting Multiple Sclerosis and Secondary Progressive Multiple Sclerosis, run by Copenhagen University Hospital, Rigshospitalet at 11 sites in Denmark.

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 31 inclusion and 17 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: under way, not looking for participants, as of the sponsor's last update on 17 Aug 2026. 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 Denmark. 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?

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?

Percentage of patients without new or enlarging T2 white matter lesions on brain MRI scans (time frame: Month 6 to month 24). 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 NCT04688788.

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 Aug 2026.

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