E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapse Remitting Multiple Sclerosis |
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E.1.1.1 | Medical condition in easily understood language |
A chronic, autoimmune, inflammatory disease characterized by demyelination of central nervous system areas and consecutive neurologic deficits which is typically chronic but aggravated during flairs |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028245 |
E.1.2 | Term | Multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063399 |
E.1.2 | Term | Relapsing-remitting multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint, the annualized relapse rate, will be calculated during the final visit. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
48 weeks after first infusion |
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E.5.2 | 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
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E.5.2.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Final Visit of the Last Patient |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |