Norwegian Study of Oral Cladribine and Rituximab in Multiple Sclerosis (NOR-MS)

NCT04121403 | Completed Phase 3 DMC

• 1 other identifier: 11383
• Study Type: interventional
• Target: 267
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Relapsing Multiple Sclerosis; Multiple Sclerosis

Keywords

multiple sclerosis; ms; rms; rituximab; cladribine; probe

Outcome Measures

Primary Outcomes (1)

• Number of new or enlarging cerebral MRI T2 lesions

  The primary outcome is the number of new or enlarging cerebral MRI T2 lesions per patient from week 12 to week 96

  Week 12-96

Secondary Outcomes (5)

• 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

Other Outcomes (23)

• MRI from baseline

  Week -6 - 96

• No evidence of disease activity (NEDA 3)

  Week -2 - 96

• MRI contrast enhancing lesions

  Week 12-96

Study Arms (2)

Rituximab

ACTIVE COMPARATOR

Biosimilar rituximab concentrate for solution for infusion

Biological: Rituximab

Cladribine

ACTIVE COMPARATOR

Mavenclad oral cladribine tablets

Drug: Cladribine

Interventions

Rituximab BIOLOGICAL

Biosimilar rituximab concentrate for solution for infusion

Rituximab

Cladribine DRUG

Mavenclad oral cladribine tablets

Also known as: Mavenclad

Cladribine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Current pregnancy or lactation

Sponsors & Collaborators

• Oslo University Hospital: lead
• University of Oslo: collaborator
• Sykehuset Ostfold: collaborator
• Sykehuset Telemark: collaborator
• Vestre Viken Hospital Trust: collaborator
• Sorlandet Hospital HF: collaborator
• Helse Stavanger HF: collaborator
• Sykehuset Innlandet HF: collaborator
• Sykehuset i Vestfold HF: collaborator
• University Hospital of North Norway: collaborator
• St. Olavs Hospital: collaborator

Study Sites (11)

Department of Neurology - Drammen, Vestre Viken HF

Drammen, Buskerud, 3004, Norway

Location

Department of Neurology - Lillehammer, SI Lillehammer

Lillehammer, Oppland, 2629, Norway

Location

Department of Neurology, Stavanger universitetssykehus

Stavanger, Rogaland, 4068, Norway

Location

Department of Neurology - Førde, Helse Førde HF

Førde, Sogn Og Fjordane, 6807, Norway

Location

Department of Neurology - Skien, Sykehuset Telemark

Skien, Telemark, 3710, Norway

Location

Department of Neurology - Tromsø, University Hospital of North Norway

Tromsø, Troms, 9038, Norway

Location

Department of Neurology - Kristiansand, Sørlandet sykehus HF

Kristiansand, Vest-Agder, 4604, Norway

Location

Department of Neurology - Tønsberg, Sykehuset i Vestfold HF

Tønsberg, Vestfold, 3103, Norway

Location

Department of Neurology, Oslo University Hospital

Oslo, 0424, Norway

Location

St. Olavs Hospital, Trondheim University Hospital

Trondheim, 7006, Norway

Location

Department of Neurology - Kalnes, Sykehuset Østfold HF

Sarpsborg, Østfold fylke, 1714, Norway

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Rituximab; Cladribine

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; 2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Hanne Flistad Harbo, MD, PhD

  Oslo University Hospital

  STUDY CHAIR

• Gro Owren Nygaard, MD, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Two independent blinded radiologists assess the primary endpoint, New or enlarging T2 lesions. The blinding is asserted by transfer of deidentified MRIs to a Research server, from where the assessment is performed, so that the radiologists know only the ID, not the treatment allocation of the patients from whom the assess MRIs.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Gro Owren Nygaard, MD, PhD

Model Details: A prospective randomized open-label blinded endpoint (PROBE) multicenter non-inferiority study, designed to establish non-inferiority of the test treatment rituximab compared with the comparator oral cladribine for consecutively included patients with active RMS. Randomization rituximab:cladribine is 1:1.

Study Record Dates

• First Submitted: September 23, 2019
• First Posted: October 9, 2019
• Study Start: October 16, 2019
• Primary Completion: August 31, 2024
• Study Completion: August 31, 2024
• Last Updated: December 16, 2024

Record last verified: 2024-12

Locations

NO (11)