Comparative Study of High-Efficacy Disease Modifying Treatment of Relapsing Multiple Sclerosis

NCT ID: NCT06159712

Last Updated: 2023-12-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-11-27

Study Completion Date

2025-11-30

Brief Summary

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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

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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.

Conditions

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Relapsing Remitting Multiple Sclerosis

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Ocrelizumab

Patients with active multiple sclerosis starting standard treatment with ocrelizumab

Group Type OTHER

Blood samples

Intervention Type OTHER

Extra blood samples

Rituximab

Patients with active multiple sclerosis starting standard treatment with rituximab

Group Type OTHER

Blood samples

Intervention Type OTHER

Extra blood samples

Ofatumumab

Patients with active multiple sclerosis starting standard treatment with ofatumumab

Group Type OTHER

Blood samples

Intervention Type OTHER

Extra blood samples

Natalizumab

Patients with active multiple sclerosis starting standard treatment with natalizumab

Group Type OTHER

Blood samples

Intervention Type OTHER

Extra blood samples

Healthy controls

An age and gender matched healthy control group

Group Type OTHER

Blood samples

Intervention Type OTHER

Extra blood samples

Interventions

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Blood samples

Extra blood samples

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Aarhus University Hospital

OTHER

Sponsor Role collaborator

Gødstrup Hospital

OTHER

Sponsor Role collaborator

Regionshospitalet Viborg, Skive

OTHER

Sponsor Role collaborator

Sorbonne University

OTHER

Sponsor Role collaborator

University of Aarhus

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Morten Stilund, MD

Role: STUDY_DIRECTOR

University of Aarhus

Locations

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Aarhus University

Aarhus, , Denmark

Site Status RECRUITING

Countries

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Denmark

Central Contacts

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Camilla Mærsk-Møller, MD

Role: CONTACT

Phone: +4521392792

Email: [email protected]

Morten Stilund, MD

Role: CONTACT

Phone: +4578430926

Email: [email protected]

Facility Contacts

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Helene Nørrelund

Role: primary

Camilla Mærsk-Møller, MD

Role: backup

Other Identifiers

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CoSHED

Identifier Type: -

Identifier Source: org_study_id