The aim of this study is to demonstrate that a single dose of rabies vaccine can induce an equally rapid and adequate anamnestic antibody response as 2-dose PrEP to revaccination five years later.
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the rate of increase of geometric mean concentrations
(GMC) of rabies virus neutralizing antibodies between day 1 and day 8 after
revaccination.
Secondary outcome
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.
Background summary
The main purpose of prophylactic rabies pre-exposure immunization (PrEP) is to
induce an effective and rapid anamnestic antibody response after revaccination
that obviates the need for human rabies immunoglobulins (RIG) and simplifies
post-exposure immunization (PEP) to just 2 doses of rabies vaccine (D1, D4) in
case of high-risk bite wounds. Many travellers decline pre-travel PrEP because
of costs and insufficient time between visit at the travel clinic and
departure. If a single dose of rabies vaccine would be equally effective in
inducing a rapid and adequate anamnestic antibody response, guidelines on
pre-travel PrEP could be simplified. In particular, the induction of long-term
immunological memory might be an issue in the case of single-visit PrEP. To
evaluate if single-visit PrEP is a reasonable alternative for one of the
approved current standards, two-visit PrEP, we aim to study whether
single-visit priming results in non-inferior long-term immunological memory,
that is boostable by simulated post-exposure prophylaxis (PEP) after five
years.
Study objective
The aim of this study is to demonstrate that a single dose of rabies vaccine
can induce an equally rapid and adequate anamnestic antibody response as 2-dose
PrEP to revaccination five years later.
Study design
Randomized controlled non-inferiority trial.
Intervention
Participants will be randomized between standard 2-dose intramuscular PrEP (D1,
D8) or single-dose PrEP (standard intramuscular dose). After 5 years, all
subjects receive a simulated 2-dose post-exposure intramuscular vaccination
schedule (D1 and D4). Serum (all participants) and blood samples (50
participants) are collected after PrEP at D1, D57/D64 (depending on study
group), year 1, year 2 and year 5; and at D1, D8 and D15 after simulated PEP
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.
Study burden and risks
In total, 3 or 4 injections will be given with registered rabies vaccine
Rabipur. A maximum of 238 mL of blood will be collected during 7 sampling
moments. Depending on the study arm eight to nine visits are required for the
study. Participants are asked to complete a diary for safety evaluation during
the study, up to 7 days after each vaccination. The standard 2-dose PrEP (D1,
D8) has been endorsed by the WHO. No risks are associated with participation in
this study other than those of routine vaccination and minimal to moderate
physical discomfort that can be experienced after vaccination or the collection
of blood. Participants will receive financial compensation for their
participation.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
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
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
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-005564-21-NL |
| CCMO | NL79547.058.21 |
| OMON | NL-OMON22516 |