E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Healthy volunteers |
Gezonde vrijwilligers |
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E.1.1.1 | Medical condition in easily understood language |
Rabies vaccination |
Vaccinatie tegen hondsdolheid |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10069589 |
E.1.2 | Term | Rabies immunization |
E.1.2 | System Organ Class | 100000004865 |
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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 demonstrate the presence of a rapid and adequate anamnestic antibody response against rabies virus vaccine five years after primary vaccination with a single intramuscular dose (1.0 mL) of rabies vaccine. The rate of increase in geometric mean concentrations of RVNA observed at day 8 after a standard 2-dose PEP vaccination schedule should be non-inferior to that of the reference group who received primary vaccination with 2-dose PrEP. |
We vergelijken de langdurige werking en veiligheid van een enkele vaccinatie tegen hondsdolheid met twee vaccinaties tegen hondsdolheid. Vijf jaar na pre-exposure profylaxe kijken we of de stijging in RVNA titers op dag 8 na post-exposure profylaxe non-inferior is bij mensen die 1 vaccinatie hebben ontvangen vergeleken met mensen die 2 vaccinaties hebben ontvangen. |
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E.2.2 | Secondary objectives of the trial |
1. To describe the kinetics of rabies virus neutralizing antibody levels in healthy young adults, who received single-visit single-dose rabies PrEP or two-visit PrEP, during a five-year follow-up.
2. To describe the kinetics of rabies-specific memory B-cells in healthy young adults, who received single-visit single-dose rabies PrEP or two-visit PrEP, during a five-year follow-up.
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1. De kinetiek beschrijven van RVNA titers in gezonde jongvolwassenen gedurende een follow-up van vijf jaar na ofwel een enkele ofwel twee vaccinaties tegen hondsdolheid.
2. De kinetiek beschrijven van rabies-specifieke B-geheugencellen in gezonde jongvolwassenen gedurende een follow-up van vijf jaar na ofwel een enkele ofwel twee vaccinaties tegen hondsdolheid.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age ≥18 years and ≤40 years • Good health according to investigator • Willingness and ability to adhere to the study regimen • Able to provide informed consent • Naïve to rabies exposure or vaccination • Willing to comply to a follow-up of 5 years • Unlikely to require rabies PrEP in next 5 years |
• Minimaal 18 en maximaal 40 jaar oud • Goede gezondheid • Bereid en in staat tot het volhouden van de studieplanning • In staat om informed consent te verlenen • Niet eerder blootgesteld aan of gevaccineerd tegen rabies • Bereid om aan een follow-up van vijf jaar deel te nemen • Waarschijnlijk geen PEP nodig in de komende vijf jaar |
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E.4 | Principal exclusion criteria |
• History of previous rabies vaccination • Suspected previous vaccination against rabies • Known or suspected severe allergy against egg protein • Known or suspected allergy against any of the other vaccine components • History of unusual or severe reactions to any previous vaccination • History of (pre)syncope associated with medical procedures involving needles • Immunocompromized state due to illness or medication • Administration of plasma or blood products three months prior to inclusion • (hydroxy)chloroquine or mefloquine use • History of any neurological disorder including epilepsy • Pregnancy during study visits in which the participant is vaccinated • Breastfeeding during and up to 4 weeks after study visits in which the participant is vaccinated • Any current infectious disease other than seasonal cold • Bleeding disorders or use of anticoagulants |
• Eerder gevaccineerd tegen rabies • Vermoeden van eerdere vaccinatie tegen rabies • Bekende of vermoede ernstige allergie tegen eiwit • Bekende of vermoede allergie tegen overige vaccincomponenten • Voorgeschiedenis van ongebruikelijke of ernstige reacties op eerdere vaccinaties • Voorgeschiedenis van (pre)syncope bij medische procedures met naalden • Immunogecompromitteerd door ziekte of medicatie • Toedeniening van plasma of bloedproducten in de drie maanden voor inclusie • Gebruik van (hydroxy)chloroquine of mefloquine • Voorgeschiedenis van een neurologische aandoening, waaronder epilepsie • Zwangerschap tijdens studiebezoeken waarbij de deelnemer gevaccineerd wordt • Borstvoeding geven tijdens en tot 4 weken na studiebezoeken waarbij de deelnemer gevaccineerd wordt • Elke andere infectieziekte dan seizoensverkoudheid • Bloedziekten of het gebruik van anticoagulantia |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the rate of increase of geometric mean concentrations (GMC) of rabies neutralizing antibodies between day 1 and day 8 after revaccination. |
De stijging van geometrisch gemiddelde concentraties (GMC) van rabies-neutraliserende antistoffen tussen dag 1 en 8 na revaccinatie. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
5 years after pre-exposure immunization. |
Vijf jaar na pre-exposure profylaxe. |
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E.5.2 | Secondary end point(s) |
Percentage of subjects with RVNA titer >0.5 IU/mL at D1, D57 or D64, Y1, Y2 and Y5 after primary vaccination. Percentage of subjects with RVNA titers>0.5 IU/mL at D1, D8 and D15, after the simulated post-exposure vaccination. Percentage of subjects with RVNA titers>3 IU/mL, and percentage of subjects with RVNA titers >5 IU/mL at day 8 after simulated PEP. GMCs at D1, D57 or D64, Y1, Y2 and Y5 after primary vaccination, and at D1, D8 and D15 after the simulated post-exposure vaccination.
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Percentage proefpersonen met RVNA titer >0.5 IU/mL op D1, D57 of D64, Y1, Y2 en Y5 na primaire vaccinatie. Percentage proefpersonen met RVNA titers>0.5 IU/mL op D1, D8 en D15, na gesimuleerde post-exposure vaccinatie. Percentage proefpersonen met RVNA titers>3 IU/mL, en percentage proefpersonen met >5 IU/mL op dag 8 na gesimuleerde post-exposure post-exposure vaccinatie. GMCs op D1, D57 of D64, Y1, Y2 en Y5 na primaire vaccinatie, en op D1, D8 en D15 na gesimuleerde post-exposure vaccinatie. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Percentage of subjects with RVNA titer >0.5 IU/mL at D1, D57 or D64, Y1, Y2 and Y5 after primary vaccination. Percentage of subjects with RVNA titers>0.5 IU/mL at D1, D8 and D15, after the simulated post-exposure vaccination. Percentage of subjects with RVNA titers>3 IU/mL, and percentage of subjects with RVNA titers >5 IU/mL at day 8 after simulated PEP. GMCs at D1, D57 or D64, Y1, Y2 and Y5 after primary vaccination, and at D1, D8 and D15 after the simulated post-exposure vaccination. Some timepoints contain a margin in which it is acceptable that the study visit takes place. For D57/D64, this margin is -2 days and +7 days. For year 1, year 2 and year 5, this margin is -7 days and +7 days. |
Percentage proefpersonen met RVNA titer >0.5 IU/mL op D1, D57 of D64, Y1, Y2 en Y5 na primaire vaccinatie. Percentage proefpersonen met RVNA titers>0.5 IU/mL op D1, D8 en D15, na gesimuleerde post-exposure vaccinatie. Percentage proefpersonen met RVNA titers>3 IU/mL, en percentage proefpersonen met >5 IU/mL op dag 8 na gesimuleerde post-exposure post-exposure vaccinatie. GMCs op D1, D57 of D64, Y1, Y2 en Y5 na primaire vaccinatie, en op D1, D8 en D15 na gesimuleerde post-exposure vaccinatie. Rondom enkele tijdpunten zit een marge waarin het studiebezoek plaats mag vinden. Voor D57/D64is dat -2 dagen en +7 dagen. Voor jaar 1, jaar 2 en jaar 5 is dat -7 dagen en +7 dagen. |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
Laboratorium (analyse) geblindeerd betreft allocatie |
Laboratory blinded from allocation |
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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 |
Standaard pre-exposure profylaxe (2 vaccinaties) |
Standard pre-exposure prophylaxis (2 vaccinations) |
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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
| 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |