E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
relapsing multiple sclerosis |
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E.1.1.1 | Medical condition in easily understood language |
relapsing multiple sclerosis treated with ofatumumab |
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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 |
To estimate the proportion of RMS patients having established SARS-CoV-2-specific T cells after receiving a modRNA vaccine (initial vaccination cycle or booster vaccine) either before or after starting ofatumumab treatment. |
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E.2.2 | Secondary objectives of the trial |
To estimate: • the proportion of RMS patients maintaining for up to 18 months SARS-CoV-2-specific T cells after receiving a modRNA vaccine either before or after starting ofatumumab treatment • the proportion of RMS patients achieving seroconversion (i.e. having SARS-CoV-2 serum neutralizing antibodies) after receiving a modRNA vaccine either before or after starting ofatumumab treatment • the proportion of RMS patients maintaining for up to 18 months quantifiable levels of SARS-CoV-2 serum functional antibodies after receiving a modRNA vaccine either before or after starting ofatumumab treatment • the proportion of RMS patients with quantifiable SARS-CoV-2-specific T cells and functional antibodies after receiving an additional dose of modRNA vaccine (booster vaccine) Describing: • phenotypically the cellular response after receiving a modRNA vaccine either before or after starting ofatumumab treatment • safety and tolerability, incl. patients developing coronavirus disease 2019 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent must be obtained prior to participation in the study. 2. Patients eligible to start ofatumumab as per physician’s discretion and approved SmPC (exp. April, 2021; for cohort 2, patients may already be on ofatumumab, but most patients will start ofatumumab as part of this study). 3. Patients willing and eligible to receive a modRNA vaccine against SARS-CoV-2 as part of clinical routine |
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E.4 | Principal exclusion criteria |
1. History of COVID-19 or current COVID-19 symptoms 2. Patients who previously received a BTK inhibitor or an antiCD20 therapy other than ofatumumab 3. Patients likely not being able or willing to complete the study 4. Use of other investigational drugs within 5 half-lives of enrollment/initiation of study treatment (e.g. small molecules) or until the expected pharmacodynamic effect has returned to baseline (e.g. biologics), whichever is longer 5. Patients with any medical or psychological condition that, in the investigators opinion, renders the patient unable to understand the nature, scope, and possible consequences of the study 6. No person directly associated with the administration of the study is allowed to participate as a study subject 7. No family member of the investigational study staff is allowed to participate in this study 8. No previous vaccination with a non-modRNA SARS-CoV-2 vaccine. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of RMS patients having established SARS-CoV-2-specific T cells as defined by detection of SARS-CoV-2 reactive T-cells, measured by e.g. enzyme-linked immunosorbent spot (ELIspot) assay from T-cells that were stimulated with SARS-CoV-2 peptide mix, either one month after second dose of vaccine or one month after booster vaccine in participants who received the respective vaccine before or after starting ofatumumab treatment (yes/no) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
either one month after second dose of vaccine or one month after booster vaccine in participants who received the respective vaccine before or after starting ofatumumab treatment |
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E.5.2 | Secondary end point(s) |
• Proportion of RMS patients with detectable SARS-CoV-2 reactive T-cells one week, 6, 12 and 18 months after second dose of vaccine or 6 and 12 months after booster vaccine in participants who received the vaccine before or after starting ofatumumab treatment (yes/no) • Fold change of SARS-CoV-2 specific T-cell levels one week, 1 month, 6 months, 12 months and 18 months after the second dose of vaccine or 1 months, 6 months and 18 months after a booster vaccine compared to the last timepoint before the respective vaccine • Proportion of RMS patients achieving seroconversion (i.e. having SARS-CoV-2 serum neutralizing antibodies) after receiving a modRNA vaccine either before or after starting ofatumumab treatment (yes/no) • Proportion of RMS patients with quantifiable levels of SARS-CoV-2 serum functional antibodies one week, 1, 6, 12 and 18 months after receiving the second dose of modRNA vaccine or 1, 6 and 12 months after a booster shot either before or after starting ofatumumab treatment (yes/no) • Phenotypical characterization of peripheral blood mononuclear cells for CD45, CD3, CD4, CD8, CD62l, CD45RA, CD45R0, CCR7 • Immunophenotyping for naive, central memory, effector memory, and effector cells on CD4+ and CD8+ cells • Measuring cells positive for intracellular cytokine-staining for interferon-gamma and interleukin-4 • AEs, SAEs, incl. patients with clinical confirmed COVID-19 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Proportion of RMS patients with detectable SARS-CoV-2 reactive T-cells one week, 6, 12 and 18 months after second dose of vaccine or 6 and 12 months after booster vaccine in participants who received the vaccine before or after starting ofatumumab treatment • Fold change of SARS-CoV-2 specific T-cell levels one week, 1 month, 6 months, 12 months and 18 months after the second dose of vaccine or 1 months, 6 months and 18 months after a booster vaccine compared to the last timepoint before the respective vaccine • Proportion of RMS patients with quantifiable levels of SARS-CoV-2 serum functional antibodies one week, 1, 6, 12 and 18 months after receiving the second dose of modRNA vaccine or 1, 6 and 12 months after a booster shot either before or after starting ofatumumab treatment |
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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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
A major concern about B-cell depleting therapies in the context of vaccination is the potentially reduced immune response to vaccines. It has been shown for the approved SARS-CoV-2 mRNA vaccines that they induce a B-cell and a functional T-cell response. we evaluate the proportion of patients that elicit humoral and specific T-cell responses upon vaccination with modRNA vaccines in patients receiving vaccination before starting ofatumumab treatment or at least 4weeks after receiving ofatumumab. |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
RNA vaccination as part of clinical routine while already stable on Ofatumumab (OMB157) treatment |
RNA vaccination as part of clinical routine before starting Ofatumumab (OMB157) treatment |
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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
| 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 | 4 |
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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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 | 2 |
E.8.9.1 | In the Member State concerned days | |