Status:
ACTIVE_NOT_RECRUITING
Non-inferiority Study of Ocrelizumab and Rituximab in Active Multiple Sclerosis
Lead Sponsor:
Rigshospitalet, Denmark
Collaborating Sponsors:
Odense University Hospital
Aarhus University Hospital
Conditions:
Relapsing Remitting Multiple Sclerosis
Secondary Progressive Multiple Sclerosis
Eligibility:
All Genders
18-65 years
Phase:
PHASE3
Brief 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.
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...
Eligibility Criteria
Inclusion
- 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
- 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:
- (A) 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
- (B) 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
Exclusion
- 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.
- 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
Key Trial Info
Start Date :
April 28 2021
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
May 5 2029
Estimated Enrollment :
600 Patients enrolled
Trial Details
Trial ID
NCT04688788
Start Date
April 28 2021
End Date
May 5 2029
Last Update
July 28 2025
Active Locations (11)
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1
Danish Multiple Sclerosis Center, Rigshospitalet
Glostrup Municipality, Copenhagen, Denmark, 2600
2
Department of Neurology, Aalborg University Hospital
Aalborg, Denmark, 9000
3
Department of Neurology, Aarhus University Hospital
Aarhus, Denmark, 8200
4
Department of Neurology, Hospital of South West Jutland, Esbjerg
Esbjerg, Denmark, 6700