Relapsing Remitting Multiple Sclerosis
Conditions
Brief summary
The goal of this prospective, multi-center, non-blinded, non-randomized, non-intervention clinical trial is to compare immunologic, virologic and epigenetic factors in patients with active multiple sclerosis in standard 2.line treatment with ocrelizumab, rituximab, ofatumumab or natalizumab in Region Midt, Denmark. It aims to answer how the immunologic, virologic and epigenetic response in these patients are compared to healthy controls, and analyze their treatment effect in relation to this response. Participants will get an extra blood sample, when they have their routine blood samples taken.
Detailed description
The CoSHED RMS study will include patients with active multiple sclerosis aged 18-65 years fulfilling the criteria for 2. line treatment and starting treatment with one of the four high-efficacy disease modifying treatments ocrelizumab, rituximab, ofatumumab or natalizumab. Researchers will compare immunologic, virologic and epigenetic parameters in the four treatment groups to a age and gender matched healthy control group. The study duration is 12 months, and patients can continue in an extension phase for additional 12 month. The primary endpoint is changes in B cell populations between the four treatments within 12 months. The study will evaluate a number of efficacy and safety endpoints using clinical, MRI, routine blood samples and research biomarkers.
Interventions
OTHERBlood samples
Extra blood samples
Sponsors
Aarhus University Hospital
Gødstrup Hospital
Regionshospitalet Viborg, Skive
Sorbonne University
University of Aarhus
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Researchers compare immunologic, virologic and epigenetic factors in patients with multiple sclerosis in standard 2.line treatment with ocrelizumab, rituximab, ofatumumab and natalizumab by taking extra blood samples and compare it to a healthy control group.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Multiple sclerosis diagnosis and definition of disease course according to the 2017 McDonald criteria * Expanded disability status scale (EDSS) ≤6.5 * Signed written informed consent * 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
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 * 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 * 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, rituximab, ofatumumab or natalizumab
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in B cell populations | 1 year | Changes in B cell populations in the four treatment groups |
Other
| Measure | Time frame | Description |
|---|---|---|
| Annualized Relapse Rate | 1 year | Annualized Relapse Rate based on the total amount of relapses per year from baseline to 12 months |
| T-cells, B-cell subsets and monocyte-subsets | 1 year | Changes in frequency of T-cells, B-cell-subsets and monocyte-subsets from baseline, 6 months and to 12 months |
| EBV | 1 year | Changes in Epstein Barr-Virus DNA load from baseline, 6 months and to 12 months |
| Relapses | 1 year | Number of patients with relapse or relapses from start of treatment from baseline to 12 months |
| Complement | 1 year | Changes in complement system activity from baseline, 6 months and to 12 months |
| MRI lesions | 1 year | Changes in number of lesions on MRI scans of the brain from baseline, 6 months and to 12 months |
| HERVs | 1 year | Changes in Human Endogenous Retrovirus expression from baseline, 6 months and to 12 months |
Countries
Denmark
Contacts
Primary ContactCamilla Mærsk-Møller, MD
Backup ContactMorten Stilund, MD
Outcome results
None listed