Study of Purified Vero Rabies Vaccine Compared with Two Reference Rabies Vaccines, Given in a Pre-exposure Regimen to Children and Adults and as Single Booster Dose to a Subset of Adults

INTERVENTION: Product Name: VRVg Product Code: 382 Pharmaceutical Form: Powder and solvent for suspension for injection INN or Proposed INN: Purified vero rabies vaccine ‐ serum free Other descriptive name: RABIES VIRUS (INACTIVATED) STRAIN WISTAR (PM/WI 38‐1503‐3M) Concentration unit: IU international unit(s) Concentration type: not less then Concentration number: 2.5‐ Trade Name: Verorab® Pharmaceutical Form: Powder and solvent for suspension for injection INN or Proposed INN: Purified inactivated rabies vaccine Other descriptive name: RABIES VIRUS (INACTIVATED) STRAIN WISTAR (PM/WI 38‐1503‐3M) Concentration unit: IU international unit(s) Concentration type: not less then Concentration number: 2.5‐ Trade Name: Imovax® Rabies Pharmaceutical Form: Powder and solvent for suspension for injection INN or Proposed INN: Purified inactivated rabies vaccine Other descriptive name: RABIES VIRUS (INACTIVATED) STRAIN WISTAR (PM/WI 38‐1503‐3M) Concentration unit: IU international unit(s) Concentration type: not less then Concentration number: 2.5‐ CONDITION: Rabies ; MedDRA version: 20.0 Level: PT Classification code 10037742 Term: Rabies System Organ Class: 10021881 ‐ Infections and infestations Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: Main Objective: To demonstrate the VRVg‐2 is non‐inferior to Verorab and Imovax Rabies vaccines in each age group (pediatric and adult populations) when administered as a 3‐dose PrEP regimen, in terms of proportion of participants achieving a RVNA titer = 0.5 IU/mL at Day 42, ie. 14 days after the 3rd injection. Primary end point(s): Participant with RVNA titer = 0.5 IU/mL ‐ Percentage of participants with RVNA titer above threshold (= 0.5 IU/mL). RVNA titers are measured by the rapid fluorescent focus inhibition test (RFFIT) assay Secondary Objective: ‐To describe the safety profile of VRVg‐2 versus Verorab and Imovax Rabies vaccines (2 comparator vaccines) after each vaccination, per age group; ‐To describe the safety of a booster dose of VRVg‐2 in a subset of adults at month 12 after 3‐dose primary series (Cohort 1) and between 24 to 36 months after 2‐dose primary series (Cohort 2); ‐To demonstrate that the observed proportion of participants in the VRVg‐2 group achieving an RVNA titer = 0.5 IU/mL at Day 42 is at least 99%, with a lower limit of the 95% confidence interval of at least 97%; ‐To demonstrate that VRVg‐2 is non‐inferior to comparator vaccines per age group, in terms of proportion of participants achieving a RVNA titer = 0.5 IU/mL at Day 28; ‐To describe the immune response induced by VRVg‐2 versus comparator vaccines among subset of adults at Day 28 and Day 42; and 14 days after booster dose (Month 12 in cohort 1 and between 24‐36 months in cohort 2) regardless of the vaccine received in primary series Timepoint(s) of evaluation of this end point: Day 42 for participants in Primary Series Cohort 1 INCLUSION CRITERIA: ‐ Aged =1 year on the day of inclusion ‐ Informed consent form has been signed and dated by the participant and /or and the parent(s) or Legally Acceptable Representative and by an independent witness (if required by local regulations), as necessary; and Assent form has been signed and dated by the participant, as required ‐ Participant (adult = 18 years) or participant and parent/LAR (1 year to <18 years) are able to attend all scheduled visits and to comply with all studyprocedures. Are the trial subjects under 18? yes Number of subjects for this age range: 505 F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 1162 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 33 SECONDARY OUTCOME: Secondary end point(s): 1) Number of participants with immediate adverse events ‐ Percentage of participants reporting systemic unsolicited adverse events in the 30 minutes after vaccination; ; 2) Number of participants with solicited injection site or systemic reactions ‐ Percentage of participants reporting‐ injection site reactions in participants aged <=23 months: tenderness, erythema, and swelling; in participants aged 2 years and above: pain, erythema and swelling or in participants aged <=23 months: fever, vomiting, crying abnormal, drowsiness, appetite lost, and irritability; in participants aged 2 years and above: fever, headache, malaise, and myalgia ; ; 3) Number of participants with unsolicited adverse events ‐ Percentage of subjecs with unsolicited (spontaneously reported) injection site reactions occurring within 28 days after each injection and unsolicited systemic AEs between each injection and up to 28 days after the last injection ; ; 4) Number of participants with serious adverse events (SAEs) and adverse events of special interest (AESIs) ‐ Percentage of participants with SAEs, including AESIs, throughout the study; ; 5) RVNA titer ‐ RVNA titers are measured by RFFIT and expressed as geometric mean titers (GMT); ; 6) RVNA titer = 0.5 IU/mL ‐ Percentage of participants witth RVNA titers above threshold (= 0.5 IU/mL). RVNA titers are measured by RFFIT; ; 7) RVNA titer above lower limit of quantification (LLOQ) IU/Ml ‐ Percentage of participants with RVNA titers above LLOQ IU/ml are measured by RFFIT; ; 8) RVNA titer ratio ‐ Individual RVNA titer ratio; ; 9) Participant with complete or incomplete neutralization at the starting dilution of the RFFIT assay ‐ Percentage of participants with complete or incomplete neutralization at the dilution of 1/5 in RFFIT. Timepoint(s) of evaluation of this end point: 1) Within 30 minutes after vaccination; ; 2) Within 7 days after vaccination; ; 3) Within 28 days after vaccination; ; 4) Up to 6 months after last vaccination; ; 5) 6) 7) 9) Day 0 and Day 28 for participants in Primary Series Cohort 1 and Cohort 2; Day 42 for participants in Primary Series Cohort 1; Month 12 and Month 12+Day 14 for the Booster Phase Cohort 1; Between Month 24 up to Month36 and between Month 24 up to Month 36+Day 14 for the Booster Phase Cohort 2; ; 8) Day 28/Day 0 on Primary Series Cohort 1 and Cohort 2, and Day 42/Day 0 in Primary Series Cohort 1