E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10048393 |
E.1.2 | Term | Multiple sclerosis relapse |
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 |
Demonstrate the effectiveness of ofatumumab 20 mg s.c. administered every 4 weeks in subjects with relapsing forms of MS who had breakthrough disease on fumarates or fingolimod |
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E.2.2 | Secondary objectives of the trial |
Evaluate the safety of ofatumumab 20 mg s.c. administrated every 4 weeks in subjects with relapsing forms of MS who had breakthrough disease on fumarates or fingolimod |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Diagnosis of MS according to the 2017 Revised McDonald criteria • Relapsing MS: relapsing forms of MS (RMS) including RMS and secondary progressive MS (SPMS) (Lublin et al 2014) • Disability status at screening defined by Expanded Disability Status Scale (EDSS) score of 0 to 4 (inclusive) • MS treatment history with a maximum of 3 Disease Modifying Therapies (DMTs), where all fumarates are considered as one DMT • Subject transitioning from either any fumarate-based RMS approved therapies, such as dimethyl fumarate (DMF) or diroximel fumarate (DRF), or fingolimod which was administered for a period of at least 6 months, as their last DMT before first study drug administration • Breakthrough disease activity while the participant was adequately using fumarates or fingolimod prior to transitioning for a minimum of 6 months as evidenced by one or more clinically reported relapses or one or more signs of Magnetic Resonance Imaging (MRI) activity (e.g. Gd+ enhancement, new or enlarging T2 lesions) • Neurologically stable within one month prior to first study drug administration
Please see protocol for complete detailed list of inclusion criteria. |
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E.4 | Principal exclusion criteria |
• Subjects with primary progressive MS (Polman et al 2011) or SPMS without disease activity (Lublin et al 2014) • Subjects meeting criteria for neuromyelitis optica (Wingerchuk et al 2015) • Disease duration of more than 10 years since diagnosis • Pregnant or nursing(lactating) women • Women of child-bearing potential unless they are using highly effective forms of contraception during dosing and for at least 6 months after stopping study medication • Subjects with active chronic disease of the immune system other than MS or with immunodeficiency syndrome • Subjects with active systemic bacterial, fungal or viral infections (such as hepatitis, HIV, COVID-19), or known to have Acquired Immunodeficiency Syndrome (AIDS) • Subjects with neurological symptoms consistent with Progressive Multifocal Leukoencephalopathy (PML) or with confirmed PML • Subjects at risk of developing or having reactivation of syphilis or tuberculosis (e.g. subjects with known exposure to, or history of syphilis, or active or latent tuberculosis, even if previously treated), as confirmed by medical history or per local practice • Subjects with active hepatitis B and C disease, assessed locally • Have received any live or live-attenuated vaccines within 4 weeks prior to first study drug administration • Have been treated with medications as specified or within timeframes specified (e.g. corticosteroids, ofatumumab, rituximab, ocrelizumab, alemtuzumab, natalizumab, daclizumab, cyclophosphamide, teriflunomide etc.) • Subjects suspected of not being able or willing to cooperate or comply with study protocol requirements in the opinion of the investigator
Please see protocol for complete detailed list of exclusion criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Annual relapse rate (ARR, based on confirmed relapses) measured over the 96 weeks |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Proportion of subjects with adverse events, including injection related reactions • Proportion of patients with laboratory or vital signs results meeting abnormal criteria • The proportion of subjects discontinuing treatment due to insufficient effectiveness (lack of efficacy) or tolerability/safety reasons |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 85 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Canada |
Lebanon |
Mexico |
Saudi Arabia |
United States |
Austria |
Estonia |
France |
Latvia |
Poland |
Bulgaria |
Spain |
Switzerland |
Czechia |
Germany |
Greece |
Italy |
Belgium |
Hungary |
Norway |
Portugal |
Russian Federation |
Slovakia |
Slovenia |
Turkey |
United Kingdom |
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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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Study completion is defined as when the last subject finishes their Study Completion visit and any repeat assessments associated with this visit have been documented and followed-up appropriately by the Investigator or, in the event of an early study termination decision, the date of that decision. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |