on-inferiority study of ocrelizumab and rituximab in active multiple sclerosis.

Phase 1

Conditions: Multiple sclerosis.
MedDRA version: 21.1Level: PTClassification code 10063400Term: Secondary progressive multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders
MedDRA version: 21.1Level: PTClassification code 10063399Term: Relapsing-remitting multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders
MedDRA version: 21.1Level: PTClassification code 10063401Term: Primary progressive multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2020-002981-15-DK

Lead Sponsor: Danish Multiple Sclerosis Center, Rigshospitalet

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 594

Inclusion Criteria

•Age =18 and =65 years
•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:

oTreatment naïve RRMS patients (never treated, or no DMT the previous 3 months):
? =2 relapse previous 12 months
OR ? =1 relapse previous 12 months AND =9 T2 lesions on brain and/or spinal MRI AND =1 contrast-enhancing lesion or =1 new or enlarging T2 lesion on brain and/or spinal MRI previous 12 month

oPreviously treated RRMS patients:
? =1 relapse previous 12 months
OR ? =1 contrast-enhancing lesion or =2 new/enlarging T2 lesions on brain MRI previous 12 months

oProgressive MS patients:
? =1 relapse previous 12 months
OR ? =1 contrast-enhancing lesion previous 12 months or =1 new/enlarging T2 lesions on brain MRI previous 12 months or =2 new or enlarging T2 lesion on brain MRI previous 24 months
OR? Increased levels of neurofilament light chain in serum or cerebrospinal on 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):
o18 to 40 years >560 ng/l
o41 to 60 years >890 ng/l
o61 to 65 years >1850 ng/l

?sNFL level (measured with Simoa™ NF-light® Advantage Kit)
o18 to 20 years >7.4 ng/l
o21 to 30 years >9.9 ng/l
o31 to 40 years >13.1 ng/l
o41 to 50 years >17.5 ng/l
o51 to 60 years >23.3 ng/l
o61 to 75 years >30.9 ng/l

•Signed written informed consent

long-term follow-up phase of the study:

Standard dosing:
•Completed the first 24 months of the study
•No signs of active disease the previous 18 months

Inclusion criteria for extended interval dosing sub-study though randomisation
•Completed the first 24 months of the study
•No signs of active disease the previous 18 months
•Signed written informed consent

Inclusion criteria for extended interval dosing outside the randomisation process

•Completed the first 24 months of the study
•Recommended by physician to switch to extended interval dosing due to Low IgG (<6,1 g/L) or Frequent infections
•No signs of active disease the previous 18 months
•Signed written informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 584
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

•Pregnancy or breast feeding
•Lack of effective contraception for women of child-bearing potential
Effective contraception includes:
?Oral contraception (combined and progestogen-only)
?Intrauterine devices and intrauterine hormone-releasing system
?Bilateral tubal occlusion
?Vasectomised partner (provided that partner is the sole sexual partner)
?Sexual abstinence (refraining from heterosexual intercourse during the study period; sexual abstinence should be evaluated in relation to the participants preferred and usual lifestyle)
?Other forms of contraception with failure rate <1%
•Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization
•Active malignant disease in the previous 5 years
•Positive test for HIV, hepatitis B or C, or tuberculosis
•Negative test for varicella zoster
•Lymphopenia grade 2 (0.5 to 0.8 × 109/L) or higher grades of lymphopenia (in case of switching from fingolimod, siponimod or ozanimod lymphopenia is accepted at screening visit (note that treatment with interferon-beta can induce transient lymphopenia)
•Neutropenia grade 2 (1.0 to 1.5 × 109/L) or higher grades
•Thrombocytopenia grade 2 (50 to 75 × 109/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 4 weeks within baseline visit and baseline MRI scan
•Findings on the screening MRI (for patients without MRI scan of the brain the previous 12 months the baseline MRI scan is also used as 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