Boostability Assessment of Three Rabies Pre-Exposure Regimens in Healthy Volunteers 5 Years Following Priming. (BAZOOKA_221)

A Multicentre, Open-label Trial in Healthy Volunteers to Assess the Boostability of Three Different Rabies Pre-exposure Prophylaxis Regimens When Administering a Single-dose, Intramuscular Vaccination as Simulated Post-exposure Prophylaxis at Least Five Years Following Priming.

A multicentre, open label trial in healthy volunteers to assess the boostability of three different rabies pre-exposure prophylaxis regimens (2 x 1IM regimen, 2 x 2 ID regimen, 1 x 2 ID regimen) when administering a single-dose, intramuscular vaccination as simulated post-exposure prophylaxis at least five years following priming.

Study Overview

• Status: Not yet recruiting
• Conditions: Rabies (Healthy Volunteers)
• Intervention / Treatment: Biological: Booster vaccination

Detailed Description

This multicentre clinical trial will include 561 participants, allocated evenly across 3 groups (187 per group). Participants are assigned to one of three groups according to their prior PrEP regimen, provided their last dose was given at least 5 years prior to enrollment.

• Group 1: 21IM regimen, (N = 187): received PrEP at least 5 years ago through 1 x 1,0 mL IM injection (Day 0 and Day 7), with a 7-day interval between visits (interval of 5 to 56 days is allowed).

• Group 2: 2²ID regimen (N = 187): received PrEP at least 5 years ago through 2 x 0,1 mL ID injections (Day 0 and Day 7) with a 7-day interval between visits (interval of 5 to 56 days is allowed).

• Group 3: 1²ID regimen (N = 187): received PrEP at least 5 years ago through 2 x 0,1 mL ID injections on Day 0

All subjects will receive 1 x 1,0 mL IM injection of purified chick-embryo cell-culture rabies vaccine as sPEP (booster) at least five years after primary vaccination (PrEP).

Neutralizing antibody titers against rabies virus will be measured using the Rapid Fluorescent Focus Inhibition Test (RFFIT) on Day 0 (before administration of sPEP) and on Days 7 and 14 after sPEP vaccination.

A titre of ≥ 0.5 IU/mL is defined as adequate (WHO standard).

• Study Type: Interventional
• Enrollment (Estimated): 561
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Thomas Hendrickx, MsC; Phone Number: 000000000000000000000000000000; Email: thendrickx@itg.be
• Study Contact Backup: Name: Clinical Trial Unit Clinical Trial Unit Insitute of Tropical Medicine Antwerp, MsC; Phone Number: 000000000000000000000000000000; Email: ctu@itg.be

Study Locations

• Belgium
  • Antwerp, Belgium, 2000
    • Clinical Trial Site Insitute of Tropical Medicine
  • Brussels, Belgium, 1200
    • Cliniques Universitaires de Saint Luc
  • Ghent, Belgium, 9000
    • Centrum voor vaccinologie (CEVAC)
  • Jette, Belgium, 1090
    • UZ Brussel
  • Liège, Belgium, 4000
    • Centre Hospitalier Universitaire de Liège
  • Neder-Over-Heembeek, Belgium, 1120
    • Military Hospital Queen Astrid

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ≥ 18 to ≤ 60 years of age at time of inclusion
2. Willingness to provide written informed consent
3. Having received PrEP with a 21IM, 2²ID or 1²ID regimen at least 5 years before starting the study. For 21IM and 2²ID interval of 5 days to 56 days between the 2 visits is allowed.

Exclusion Criteria:

1. Known allergy to one of the components of the vaccine.

2. Subjects, who received immunomodulating therapy within the last 3 months (12 weeks).

   Note: See Section 6.3 for detailed guidance on immunomodulating therapies.

3. Planned vaccination with any inactivated vaccine within 2 weeks before or after vaccination in the study or with any live attenuated vaccine within 1 month before or after each vaccination in the study.
4. Ongoing pregnancy or active child wish at the time of booster vaccination (D0).
5. Any other PrEP rabies vaccine schedule/vaccination than mentioned in the inclusion criteria.
6. Previous rabies (s)PEP
7. Inability or unwillingness to comply with study procedures, including protocol-defined visits, assessments, or interventions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: 2 x 1IM regimen, (N = 187): Healthy volunteers that received Pre-Exposure Prohphylaxis (PrEP) (a rabies vaccination) at least 5 years ago through 1 x 1,0 mL IM injection (Day 0 and Day 7), with a 7-day interval between visits (interval of 5 to 56 days is allowed).	Biological: Booster vaccination; To investigate whether the boostability of a (A) two-visit IM, (B) two-visit ID and (C) one-visit ID pre-exposure vaccination regimen is non-inferior to a theoretical 99% boostability by administering a single-dose IM booster to simulate exposure to rabies at least 5 years after the pre-exposure regimens regimen.
Experimental: Group 2: 2²ID regimen (N = 187): Received PrEP vaccination (Pre-Exposure prophylaxis usinga rabies vaccine) at least 5 years ago through 2 x 0,1 mL ID injections (Day 0 and Day 7) with a 7-day interval between visits (interval of 5 to 56 days is allowed).	Biological: Booster vaccination; To investigate whether the boostability of a (A) two-visit IM, (B) two-visit ID and (C) one-visit ID pre-exposure vaccination regimen is non-inferior to a theoretical 99% boostability by administering a single-dose IM booster to simulate exposure to rabies at least 5 years after the pre-exposure regimens regimen.
Experimental: Group 3: 1²ID regimen (N = 187); received PrEP (Pre-Exposure prophylaxis using a rabies vaccine) at least 5 years ago through 2 x 0,1 mL ID injections on Day 0	Biological: Booster vaccination; To investigate whether the boostability of a (A) two-visit IM, (B) two-visit ID and (C) one-visit ID pre-exposure vaccination regimen is non-inferior to a theoretical 99% boostability by administering a single-dose IM booster to simulate exposure to rabies at least 5 years after the pre-exposure regimens regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary: boostability	To investigate whether the boostability of a (A) two-visit IM, (B) two-visit ID and (C) one-visit ID Pre-exposure Prophylaxis (PrEP) regimen is non-inferior to a theoretical 99% boostability when a single-dose IM simulated Post Exposure Prophylaxis (sPEP) is administered at least 5 years after the PrEP regimen. Primary Endpoint: Proportion of participants that have an adequate immune response (Rapid Fluorescent Focus Inhibition Test (RFFIT) level, WHO standard) on Day 7 after the booster.	13 months - from First Patient In (FPI) to Last Patient Out (LPO)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RFFIT levels ≥ 0.5 IU/mL Day 14	To estimate per arm the proportion of participant with adequate immune response on Day 14 after the booster. RFFIT levels ≥ 0.5 IU/mL is the WHO standard for adequate immune response.	14 days following booster vaccination
FFIT levels ≥ 0.5 IU/mL on the day of the booster (Day 0).	To estimate per arm the proportion of participant with RFFIT levels ≥ 0.5 IU/mL on the day of the booster (Day 0). RFFIT levels ≥ 0.5 IU/mL is the WHO standard for adequate immune response.	Day 0 - on day of booster vaccination
RFFIT levels ≥ 3.0 IU/mL on Day 7 after the booster	To estimate per arm the proportion of participant with RFFIT levels ≥ 3.0 IU/mL on Day 7 after the booster. A titre ≥ 3.0 IU/ml is considered to be a proxy for good/robust protection.	Day 7 - following booster vaccination
RFFIT levels ≥ 3.0 IU/mL on Day 14 after the booster.	To estimate per arm the proportion of participants with RFFIT levels ≥ 3.0 IU/mL on Day 14 after the booster. A titre ≥ 3.0 IU/ml is considered to be a proxy for good/robust protection.	Day 14 after the booster vaccination
RFFIT levels ≥ 10 IU/mL on Day 7 after the booster.	To estimate per arm the proportion of participants with RFFIT levels ≥ 10 IU/mL on Day 7 after the booster. A titre ≥ 10 IU/ml is considered to be a proxy for long-lasting immunity.	Day 14 following the booster vaccination
RFFIT levels ≥ 10 IU/mL on Day 14 after the booster.	To estimate per arm the proportion of participants with RFFIT levels ≥ 10 IU/mL on Day 14 after the booster. A titre ≥ 10 IU/ml is considered to be a proxy for long-lasting immunity.	Day 14 following the booster vaccination.
Safety objectives	Safety objectives; To estimate the proportion of solicited AEs (local reactions and general symptoms) occurring within 7 days after the sPEP vaccination session.; To estimate the proportion of unsolicited AEs occurring within 7 days after the sPEP vaccination session.; To estimate the proportion of Severe Adverse Events (SAE) occurring throughout the study period after sPEP vaccination session.	1. & 2. Day 7 following the booster vaccination. 3. 13 months - entire study duration FPI to LPO

Collaborators and Investigators

• Sponsor: Institute of Tropical Medicine, Belgium

Study record dates

Study Major Dates

• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: February 23, 2026
• First Submitted That Met QC Criteria: March 2, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: prophylaxis; vaccination; Rabies; Vaccination regimens; rabies pre-exposure prophylaxis; boostability
• Additional Relevant MeSH Terms: Infections; RNA Virus Infections; Virus Diseases; Mononegavirales Infections; Rhabdoviridae Infections; Rabies; Investigative Techniques; Therapeutics; Biological Therapy; Immunologic Techniques; Immunomodulation; Immunization; Immunotherapy; Immunization, Secondary
• Other Study ID Numbers: BAZOOKA_221; 2025-524765-24-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No