The efficacy of treatment of patients with multiple sclerosis, a chronic, inflammatory, autoimmune, disease that leads to neurologic deficits and aggravates with flairs, with low doses of rituximab, an antibody directed against the CD20 epitope on B Lymphocytes, specific cells of the immune system contributing to the progression of the disease - a pilot trial

• Register: EUCTR
• Last refreshed on: 10 September 2018
• Main ID: EUCTR2017-000426-35-AT
• Date of registration: 12/03/2018
• Prospective Registration: Yes
• Primary sponsor: Medical University of Vienna - Department of Neurology
• Public title: The efficacy of treatment of patients with multiple sclerosis, a chronic, inflammatory, autoimmune, disease that leads to neurologic deficits and aggravates with flairs, with low doses of rituximab, an antibody directed against the CD20 epitope on B Lymphocytes, specific cells of the immune system contributing to the progression of the disease - a pilot trial
• Scientific title: Efficacy of Rituximab at low doses in Multiple Sclerosis – A prospective, randomized, double-blind, active controlled, pilo trial - Low-dose Rituximab in MS
• Date of first enrolment: 17/04/2018
• Target sample size: 70
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000426-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria

Contacts

• Name: Office of the Dept. of Neurology
• Affiliation: Medical University of Vienna - Department of Neurology

• Name: Office of the Dept. of Neurology
• Affiliation: Medical University of Vienna - Department of Neurology

Key inclusion & exclusion criteria

Inclusion criteria:
• Signed informed consent obtained before any trial related activities
• Ability to understand the nature and the purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the trial
• In female subjects either childbearing potential terminated by surgery or one year post- menopausal, or a negative urine pregnancy test during screening and the willingness not to become pregnant during the entire study period by practicing reliable methods of contraception
• Normal findings in medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant
• Normal laboratory values unless the investigator considers an abnormality to be clinically irrelevant
• Diagnosis of RR-MS and existing or planned rituximab treatment

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
• Patients with HepBc antibodies
• Clinically relevant infection (<1 week)
• Relevant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, hematological, endocrine, inflammatory or neurological diseases, that may interfere with the aim of the study
• Ascertained or presumed hypersensitivity to the active principle and/or formulations' ingredients; history of anaphylaxis to drugs or major allergic reactions in general, which the investigator considers may compromise the safety of the participants
• Use of medication during 2 weeks before the start of the study, which the investigator considers may affect the validity of the study
• Drug abuse, alcohol (>1 drinks/day, defined according to USDA Dietary Guidelines)
• Pregnancy (positive pregnancy test at screening or during study phase), lactation or unreliable contraception in female subjects with child-bearing potential



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Relapse Remitting Multiple Sclerosis
MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Trade Name: Mabthera or biosimilar rituximab product
Product Name: Rituximab
Product Code: Rituximab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Current Sponsor code: Rituximab
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Mabthera or biosimilar rituximab product
Product Name: Rituximab
Product Code: Rituximab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Current Sponsor code: Rituximab
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Secondary Objective: To investigate the number of new gadolinium enhancing MRI lesions within 48 weeks.
To investigate the number of new T2-weighted MRI lesions within 48 weeks.
To investigate the changes in the Expanded Disability Status Scale (EDSS).
To investigate the CD19/CD20+ cell counts in the course of the trial.
To investigate the immunogenicity of both treatments by measuring neutralizing anti-drug antibodies (NADA) and human anti-chimeric antibodies (HACA).
To calculate the reduction in drug costs.
To assess the safety and adverse events of very low doses of rituximab.

Main Objective: The main objective of this trial is to investigate whether 100mg rituximab every 10-12 weeks are equally effective compared to other, currently used dosing regimens. This will be evaluated by the annualized relapse rate at 48 weeks

Timepoint(s) of evaluation of this end point: 48 weeks after first infusion

Primary end point(s): The primary endpoint, the annualized relapse rate, will be calculated during the final visit.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: EDSS, CD19/20+ cell counts, no of relapses, relapse rate annualized: at all visits
MRI and Immunogenicity: screening and final visit

Secondary end point(s): - Annualized relapse rate at other time points (each infusion day)
- CD19/20+ cell counts
- MRI lesions (both gadolinium enhancing and T2-weighted)
- Number of relapses (total and relative)
- Immunogenicity (HACA and NADA)
- EDSS

Secondary ID(s)

1.0

Source(s) of Monetary Support

Medical University of Vienna