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

Korábbi kezelés

• Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization
• 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

Más betegség

• 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%)
• 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.
• Other diseases judged to be relevant by the treating physician
• Known allergy or hypersensitivity to rituximab or ocrelizumab

Laborértékek

• 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

Egyéb

• Pregnancy or breast feeding
• Negative test for varicella zoster
• Methylprednisolone treatment within 1 month of baseline visit
• Findings on the screening MRI judged to preclude participation by the treating physician
• Contraindication to MRI

• 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