Rabies Prophylaxis Boostability After Priming With Inactivated Rabies Virus Strain Flury LEP Vaccination Regimens in Healthy Volunteers

The primary objective is to assess whether the boostability of three rabies pre-exposure prophylaxis regimens is non-inferior to a theoretical 99% response when a single-dose intramuscular booster is administered at least 5 years after priming. This evaluates the capacity of prior vaccination to elicit an adequate anamnestic immune response after a long interval, which is clinically relevant for post-exposure management. The secondary objectives are to determine the proportion of participants with an adequate immune response, defined as RFFIT levels ≥ 0.5 IU/mL, on Day 0 and Day 14 after the booster; the proportion with good/robust protection, defined as RFFIT levels ≥ 3.0 IU/mL, on Day 7 and Day 14; the proportion with long-lasting immunity, defined as RFFIT levels ≥ 10 IU/mL, on Day 7 and Day 14; the estimation of geometric mean titers by visit and their change from the booster baseline within each regimen; and the proportion of solicited adverse events, unsolicited adverse events, and severe adverse events occurring during the study period.

The sponsor did not provide the total number of participants or a detailed description of the study population. The trial population was selected from healthy volunteers of both sexes, with an age range of 18 to 60 years at inclusion. Participants had previously received rabies vaccination through a 2x1 IM, 2²ID, or 1²ID regimen at least 5 years before study start. Written informed consent was required. No relevant lifestyle considerations were provided.

This multicentre, open-label trial in healthy volunteers is designed to assess the boostability of three rabies pre-exposure prophylaxis regimens after administration of a single-dose, intramuscular booster vaccination at least 5 years after priming. The study compares a two-visit intramuscular regimen, a two-visit intradermal regimen, and a one-visit intradermal regimen. The main objective is to determine whether each regimen is non-inferior to a theoretical 99% boostability. The planned study period extends from 15 May 2026 to 15 June 2027. Participant involvement is expected to last from screening through the end-of-study visit, with follow-up visits on Day 7 and Day 14 after the booster. The screening visit is used to confirm eligibility, including age, informed consent, and prior rabies vaccination history. The booster vaccination is administered on Day 0, followed by visits for assessment of immune response and safety. The end-of-study visit occurs after completion of the scheduled follow-up assessments. Early termination from the study may occur if eligibility criteria are no longer met, if participation is withdrawn, or if the study procedures cannot be completed as planned.

The investigational treatment was rabies virus (inactivated) strain Flury LEP, supplied as Rabipur in a solution for injection. It was administered as a 1 mL dose by the intramuscular route. In the trial, a single-dose intramuscular vaccination was given as simulated post-exposure prophylaxis at least 5 years after the priming regimen.

The study evaluated three different pre-exposure prophylaxis regimens: a two-visit intramuscular regimen, a two-visit intradermal regimen, and a one-visit intradermal regimen. No other non-experimental treatment was specified in the source data. Administration followed the defined dosing schedule for each regimen, and boostability was assessed after the later single-dose intramuscular vaccination.

Efficacy will be assessed by the proportion of participants with an adequate immune response, defined as Rapid Fluorescent Focus Inhibition Test (RFFIT) levels of at least 0.5 IU/mL according to the WHO standard on Day 7 after the booster. Additional efficacy assessments will include the proportion of participants with RFFIT levels of at least 0.5 IU/mL on Day 14 after the booster and on Day 0, as well as the proportions with RFFIT levels of at least 3.0 IU/mL and 10 IU/mL on Days 7 and 14 after the booster. Geometric mean titers will also be evaluated at all visits for all arms, together with the ratio to baseline GMTs per arm.