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

  • STATUS
    Recruiting
  • End date
    Apr 28, 2028
  • participants needed
    594
  • sponsor
    Rigshospitalet, Denmark
Updated on 11 May 2022
rituximab
MRI
methylprednisolone
disease or disorder
myelopathies
ocrelizumab

Summary

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

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, and patients can continue in an extension phase for additional 36 month. 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.

Details
Condition Relapsing Remitting Multiple Sclerosis, Secondary Progressive Multiple Sclerosis, Primary Progressive Multiple Sclerosis
Treatment Rituximab, Methylprednisolone, Paracetamol, Ocrelizumab, Fexofenadine
Clinical Study IdentifierNCT04688788
SponsorRigshospitalet, Denmark
Last Modified on11 May 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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)
to 40 years >560 ng/l
Signed written informed consent
to 60 years >890 ng/l
to 65 years >1850 ng/l
or
(B) Serum NFL level (measured with Simoa™ NF-light® Advantage Kit)
to 20 years >7.4 ng/l
to 30 years >9.9 ng/l
to 40 years >13.1 ng/l
to 50 years >17.5 ng/l
to 60 years >23.3 ng/l
to 75 years >30.9 ng/l

Exclusion Criteria

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 tuberculosis
Negative test for varicella zoster
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
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
Lymphopenia grade 2 (0.5 to 0.8 × 10^9/L) or higher grades of lymphopenia (in case of switching from fingolimod lymphopenia grade 2 can be accepted if lymphocytes are rising markedly compared to on treatment levels)
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
Methylprednisolone treatment within 1 month of baseline visit
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