Clinical trial NCT06159712: Comparative Study of High-Efficacy Disease Modifying Treatment of Relapsing Multiple Sclerosis
Official title: Comparative Study of High-Efficacy Disease Modifying Treatment of Relapsing Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Relapsing Remitting Multiple Sclerosis
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
name: Gødstrup Hospital
name: Regionshospitalet Viborg, Skive
name: Sorbonne University
First posted: 2023-12-07
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in B cell populations
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
measure: Relapses
timeFrame: 1 year
measure: Annualized Relapse Rate
timeFrame: 1 year
measure: T-cells, B-cell subsets and monocyte-subsets
timeFrame: 1 year
measure: EBV
timeFrame: 1 year
measure: HERVs
timeFrame: 1 year
measure: Complement
timeFrame: 1 year
measure: MRI lesions
timeFrame: 1 year
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University
Study officials:
affiliation: University of Aarhus
name: Morten Stilund, MD
role: STUDY_DIRECTOR
References: