Norwegian Study of Oral Cladribine and Rituximab in Multiple Sclerosis (NOR-MS) A Prospective Randomized Open-label Blinded Endpoint (PROBE) Multicenter Non-inferiority Study

Official Summary

The main aim and overall objective of the study is to assess whether rituximab is non-inferior to cladribine for the treatment of relapsing MS. Secondly, the investigators will test specific blood and MRI biomarkers that may contribute to future personalized treatment for MS patients. Furthermore, the investigators want to evaluate the health economic consequences of the two therapies.

Eligibility Requirements

• Minimum Age: 18 Years
• Maximum Age: 65 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: SINGLE
• Enrollment: 267 participants

Study Arms

• Rituximab (ACTIVE_COMPARATOR)
  Biosimilar rituximab concentrate for solution for infusion
• Cladribine (ACTIVE_COMPARATOR)
  Mavenclad oral cladribine tablets

Interventions

• BIOLOGICAL: Rituximab — Biosimilar rituximab concentrate for solution for infusion
• DRUG: Cladribine — Mavenclad oral cladribine tablets

Primary Outcomes

• Number of new or enlarging cerebral MRI T2 lesions (Week 12-96)

Secondary Outcomes

• T2 lesions after 48 weeks (Week 12-48)
• Annual clinical relapse rate (ARR) (Week -2 to 96)
• Relapse-free patients (Week -2 to 96)
• Disability progression (Week -2 to 96)
• Change in disability (Week -2 to 96)

Eligibility Criteria

Inclusion Criteria:

* Age between 18 and 65 years
* A diagnosis of relapsing MS according to the 2017 McDonald criteria
* Disease activity seen as either a clinical relapse or MRI activity during the last 12 months
* EDSS between 0 and 5.5
* Thrombocytes and leukocytes within normal range, and lymphocytes above 0.8 x10 9/L before first dose of study medication
* A) For women of childbearing potential: accepting to use adequate contraception in the trial period. If randomized to cladribine, women who use systemic hormonal contraception must accept to use additional barrier contraception during each treatment cycle and for four weeks after each treatment cycle.
* B) For men: If randomized to cladribine, accepting to use adequate contraception in the safety period of 6 months after each treatment cycle.
* Able to understand written and spoken Norwegian or English
* Able to complete treatment or follow-ups in the study (e.g. no contraindications for MRI, severe psychiatric disease, drug abuse or plans of moving)
* Signed informed consent

Exclusion Criteria:

* Any contraindication or increased risk of side-effects from rituximab or cladribine (such as ongoing acute or chronic infection, live vaccination less than 4 weeks before start of treatment or planned live vaccination, immunocompromised, previous or active malignant disease, ongoing glucocorticoid treatment or allergy against any products of the medication)
* Previous use of any of cladribine, rituximab, alemtuzumab, ocrelizumab, hematopoietic stem cell therapy (HSCT) or other immunosuppression with long lasting effects
* Fingolimod or natalizumab treatment within the last six months before inclusion
* Current pregnancy or lactation

Trial Locations

• Department of Neurology - Drammen, Vestre Viken HF, Drammen, Buskerud, Norway
• Department of Neurology - Lillehammer, SI Lillehammer, Lillehammer, Oppland, Norway
• Department of Neurology, Stavanger universitetssykehus, Stavanger, Rogaland, Norway
• Department of Neurology - Førde, Helse Førde HF, Førde, Sogn Og Fjordane, Norway
• Department of Neurology - Skien, Sykehuset Telemark, Skien, Telemark, Norway
• Department of Neurology - Tromsø, University Hospital of North Norway, Tromsø, Troms, Norway
• Department of Neurology - Kristiansand, Sørlandet sykehus HF, Kristiansand, Vest-Agder, Norway
• Department of Neurology - Tønsberg, Sykehuset i Vestfold HF, Tønsberg, Vestfold, Norway
• Department of Neurology, Oslo University Hospital, Oslo, Norway
• St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
• ...and 1 more locations

Study Officials

• Hanne Flistad Harbo, MD, PhD — STUDY_CHAIR
  Oslo University Hospital
• Gro Owren Nygaard, MD, PhD — PRINCIPAL_INVESTIGATOR
  Oslo University Hospital

More Relapsing Multiple Sclerosis Trials

View all Relapsing Multiple Sclerosis clinical trials