E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Myasthenia gravis Lambert-Eaton myasthenic syndrome |
Myasthenia gravis Lambert-Eaton myastheen syndroom |
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E.1.1.1 | Medical condition in easily understood language |
Myasthenia Lambert-Eaton myasthenic syndrome |
Myasthenie Lambert-Eaton myastheen syndroom |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the effectiveness of the humeral and cellular immune response after tetanus revaccination in patients with AChR MG, MuSK MG, or LEMS. |
Het vaststellen van de effectiviteit van de humorale en cellulaire immunreactie na een tetanus revaccinatie in patienten met AChR MG, MuSK MG of LEMS. |
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E.2.2 | Secondary objectives of the trial |
To determine if revaccination induces immunological or clinical exacerbation in patients with AChR MG, MuSK MG, or LEMS |
Het vaststellen of revaccinatie een immunologische of klinische exacerbatie induceert in patiënten met AChR MG, MuSK MG of LEMS. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The validation of the MG-QOL15 in Dutch |
Het valideren van de MG-QOL15 in het Nederlands |
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E.3 | Principal inclusion criteria |
1. Males and females aged between 18 years and 65 years at the time of the injection. 2. Patient with ocular or generalized AChR MG, MuSK MG or LEMS; and 3. A positive serologic test for AChR antibodies > 3 nmol/l or MuSK antibodies >0.1 nmol/l or VGCC antibodies >20 fmol/l. 4. Patient with prednisone dose lower than 30mg and stable (dose +/- 5mg) during the 3 months before participation; other immunosuppressive should be stable/unchanged.
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1. Mannen en vrouwen tussen de 18 en 65 jaar op het moment van injectie 2. Patienten met oculaire of gegeneraliseerde AChR MG, MuSK MG of LEMS; en 3. Een positieve serologie test voor AChR antistoffen >3 nmol/l of MuSK antistoffen >0.1 nmol/l of VGCC antistoffen >20 fmol/l. 4. Patienten met prednisondosering lager dan 30mg en deze moet stabiel zijn (+/- 5mg) gedurende de 3 maanden voor deelname; andere immunosuppresiva moeten stabiel/onveranderd zijn. |
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E.4 | Principal exclusion criteria |
1. Received no previous tetanus vaccination in the childhood age or received a revaccination in de past year. 2. MG patients of Grade 4 or 5 based on MGFA classification. 3. Myasthenic crisis in the last 3 months 4. Presence of a thymoma. 5. Planned thymectomy during the study period or within 12 months prior of the tetanus toxoid booster immunization. 6. Any confirmed or suspected immunosuppressive or immunodeficient condition not related to the treatment of MG, including human immunodeficiency virus (HIV) infection, or a family history of congenital or hereditary immunodeficiency. 7. History or evidence of administration of immunoglobulins within 3 months prior to the tetanus revaccination. 8. History or evidence of plasmapheresis within 3 months prior to the tetanus revaccination. 9. At high risk for aspiration. 10. Pulmonary: forced vital capacity reduced to less than 70% of predicted capacity. 11. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. 12. History of relevant chronic degenerative, psychiatric, or neurological disorder other than MG. 13. Severe hepatic, renal or cardiac insufficiency. 14. Major congenital defects or serious chronic illness other than MG. 15. Positive pregnancy test or desire to become pregnant during the study. 16. Influenza vaccination 1 month before the tetanus revaccination 17. The use of vitamine K antagonist or new coagulantia (NOAC's) 18. The patient is unable to fill out the study questionnaires or be interviewed in Dutch, or is unable to undergo the tests needed for the study, or is unable to give informed consent for participation in the study. 19. The investigator can exclude patients for this trial which are deemed not suitable for any reason.
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1. Niet voor tetanus gevaccineerd op kinderleeftijd of nog binnen het afgelopen jaar een revaccinatie ontvangen. 2. MG patiënten met graad 4 of 5 volgens de MGFA classificatie 3. Myasthene crisis in de afgelopen 3 maanden 4. Aanwezigheid van een thymoom. 5. Geplande thymectomy gedurende de studie of binnen 12 maanden voor de tetanus revaccinatie. 6. Een bevestigde of verdenking op een immunosuppresiva of immunodeficiente aandoening die niet gerelateerd is aan de behandeling voor MG, inclusief infectie met het human immunodeficiency virus (HIV), of een familaire voorgeschiedenis van congenitale of overerfbare immunodeficientie. 7. Voorgeschiedenis of bewijs van toediening van immunoglobulines in de 3 maanden voor de tetanus revaccinatie. 8. Voorgeschiedenis of bewijs van plasmaferese in de 3 maanden voor de tetanus revaccinatie. 9. Verhoogd risico op aspiratie 10. Pulmonaal: forced vital capacity afgenomen tot minder dan 70% van de verwachte capaciteit. 11. Voorgeschiedenis van allergische ziekten/reacties die uitgelokt kunnen worden door een van de componenten van het vaccin 12. Voorgeschiedenis van relevante chronisch degeneratieve, psychiatrische of neurologische aandoeningen anders dan MG 13. Ernstige lever, nier of cardiale insufficiëntie 14. Ernstige congenitale defecten of ernstige chronische ziekten anders dan MG. 15. Positieve zwangerschapstest of het verlangen om zwanger te worden gedurende de studie. 16. Griepvaccinatie 1 maand voor deelname aan de studie. 17. Het gebruik van vitamine K antagonisten of nieuwe coagulantia (NOAC's) 18. De patiënt is niet in staat om de vragenlijsten in het Nederlands in te vullen, of is niet in staat om de testen die voor de studie nodig zijn te ondergaan, of is niet in staat om informed consent te geven voor deelname aan de studie. 19. De onderzoeker kan patiënten excluderen voor deze studie die voor welke reden dan ook niet geschikt zijn. |
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E.5 End points |
E.5.1 | Primary end point(s) |
-Change in total tetanus specific serum IgG titer in patients with AChR MG, MuSK MG, or LEMS -Change in MG composite score at 4 weeks after revaccination
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- Verandering van de totaal tetanus specifieke serum IgG titer in patienten met AChR MG, MuSK MG of LEMS - Verandering in de MG composite score 4 weken na revaccinatie.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
4 weeks after the revaccination |
4 weken na de revaccinatie |
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E.5.2 | Secondary end point(s) |
- Change in MG composite score at 12 weeks after revaccination - Change in MG-ADL 4 and/or 12 weeks after revaccination - Increase in the dose of any of the immunosuppressive drugs for treatment of the MG or LEMS during the 12 weeks of the study - Change in tetanus specific serum IgG subclass titers in patients with AChR MG, MuSK MG, or LEMS -Change in autoimmune antibody titers against AChR, MuSK or VGCC at 4 weeks after revaccination -Change in tetanus specific T-cell immune response at 4 weeks after revaccination - Validation of the MG-QOL15 in Dutch
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- Verandering in MG composite score 12 weken na de revaccinatie - Verandering in de MG-ADL 4 en/of 12 weken na revaccinatie. - Verhoogde dosering van een van de immunosuppressieve medicatie voor de behandeling van de MG of LEMS gedurende de 12 weken van de studie - Verandering in de tetanus specifieke serum IgG sublclass titers in patienten met AChR MG, MuSK MG of LEMS. - Validatie van de MG-QOL15 in het Nederlands |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
4 and 12 weeks after the revaccination |
4 en 12 weken na de revaccinatie |
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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 | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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.8.3 |
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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12 weeks after the last subject is received the revaccination |
12 weken nadat de laatste proefpersoon de revaccinatie heeft gehad. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |