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
Condition: Rabies (Healthy Volunteers)
MeSH terms: Rabies
Intervention: Purified vero rabies vaccine - serum free - VRVg-2; Purified inactivated rabies vaccine - Verorab®; Purified inactivated rabies vaccine - Imovax® Rabies
Intervention description: Pharmaceutical form: Freeze-dried Route of administration: Intramuscular; Pharmaceutical form:Freeze-dried Route of administration: Intramuscular; Pharmaceutical form: Freeze-dried Route of administration: Intramuscular
Intervention MeSH terms: Vaccines
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Primary series will be observer-blinded for both Cohort 1 (3-dose pre-exposure prophylaxis [PrEP] regimen) and Cohort 2 (one week 2-dose PrEP regimen).
Booster phase will be conducted in a blinded manner (vaccine received in the primary series) with an adult subset from Cohort 1 and hereafter referred as "Booster Phase Cohort 1" (with booster dose 1 year after the 1st primary series vaccine injection).
Evaluation of immunogenicity persistence after primary series and a booster phase will be conducted in an open label manner with an adult subset from Cohort 2 and hereafter referred as "Immunogenicity Persistence and Booster Phase Cohort 2" (including blood samples collection at Month 6, Month 12, Month 18, pre-booster between Month 24 up to Month 36, and post-booster between Month 24 up to Month 36+Day 14; and a booster dose between Month 24 up to Month 36).
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: For cohort 1 primary series and booster dose and cohort 2 primary series. The study is conducted in an observer-blind manner. Unblinded staff members, independent of the safety evaluation and other study evaluations, prepare and administer the vaccine. The Investigator or delegate in charge of safety assessment as well as the participants are blinded and do not know which vaccine is administered.
In addition to the participants, health care providers, data collectors, outcome assessors (e.g., Investigator who assess the safety), the Sponsor personnel (e.g., Clinician, Data Management, Biostatistician) will remain blinded until the first statistical analysis.
For cohort 2 immunogenicity persistence and booster phase: this phase is open label, however, the laboratory analysts who will be involved in the blood sample testing will remain blinded during the whole study.
Enrollment: 1708.0
Sex: All
Minimum age: 1 Year
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The primary objective of this study is:

      To demonstrate the Purified Vero Rabies Vaccine - Serum Free (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 pre-exposure prophylaxis (PrEP) regimen, in terms of proportion of
      participants achieving a rabies virus neutralizing antibody (RVNA) titer greater than or
      equal to (>=) 0.5 IU/mL at Day (D) 42, i.e., 14 days after the 3rd injection (for Primary
      Series Cohort 1).

      The secondary objectives of this study are: First 1-5 with hypotheses testing will be
      evaluated sequentially - only if the previous objective is achieved, will the next objective
      be tested.

      To demonstrate that:

        -  the observed proportion of participants in the VRVg-2 (VRVg) group at D42 is at least
           99% with a lower limit of the 95% confidence interval (CI) of at least 97%

        -  VRVg is non-inferior (NI) to Verorab and Imovax Rabies vaccines (Imovax) in each age
           group at D28

        -  2-dose VRVg at D28 is NI to 3-dose Imovax at D42 in each age group

        -  the observed proportion of participants in the VRVg group at D28 is at least 99% with a
           lower limit of the 95% CI of at least 97%

        -  2-dose Imovax at D28 is NI to 3-dose Imovax at D42 in overall participants (Cohort 1)

      To describe:

        -  the immune response induced by VRVg versus Verorab and Imovax at D28 and at D42 in all
           age groups

        -  the immune response induced by VRVg at D14 after a booster dose of VRVg administered at
           Month (M) 12 (Cohort 1) and between M24 up to M36 (Cohort 2)

        -  the persistence of immune response at M6,12,18, and pre-booster between M24 up to M36
           post-primary series vaccination (Cohort 2)

        -  safety profile of VRVg versus Verorab and Imovax in primary series and after a booster
           dose of VRVg.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Aged >=1 year on the day of inclusion

               -  Cohort 1 - pediatrics (>=1 to 17 years old) and adults (>=18 years old)

               -  Cohort 2 - all adults (>=18 years old)

          -  Informed consent form has been signed and dated by the participant and /or and
             parent(s) or legally acceptable representative (LAR) 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 less than
             [<]18 years) are able to attend all scheduled visits and to comply with all study
             procedures.

        Exclusion Criteria:

          -  Participant is pregnant, or lactating, or of childbearing potential and not using an
             effective method of contraception or abstinence from at least 4 weeks prior to the
             first vaccination until 1 month after each vaccination. To be considered of
             non-childbearing potential, a female must be pre-menarche or post-menopausal for at
             least 1 year, or surgically sterile.

          -  Participation at the time of study enrollment or, planned participation during the
             present study period in another clinical study investigating a vaccine, drug, medical
             device, or medical procedure.

          -  Receipt of any vaccine in the 4 weeks (28 days) preceding the first study vaccination
             or planned receipt of any vaccine prior to Visit 5 for pediatric participants and
             adult participants in Cohort 1, and prior to Visit 4 for adult participants in Cohort
             2.

          -  Previous vaccination against rabies (in pre- or post-exposure regimen) with either the
             study vaccines or another vaccine.

          -  Bite by, or exposure to a potentially rabid animal in the previous 6 months with or
             without post-exposure prophylaxis.

          -  Receipt of immune globulins, blood or blood-derived products in the past 3 months.

          -  Known or suspected congenital or acquired immunodeficiency; or receipt of
             immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy,
             within the preceding 6 months; or long-term systemic corticosteroid therapy
             (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).

          -  At high risk for rabies exposure during the study.

          -  Known systemic hypersensitivity to any of the study/control vaccine components, or
             history of a life-threatening reaction to the vaccines used in the study or to a
             vaccine containing any of the same substances.

          -  Self-reported thrombocytopenia, contraindicating intramuscular vaccination.

          -  Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion,
             contraindicating intramuscular vaccination.

          -  Deprived of freedom by an administrative or court order, or in an emergency setting,
             or hospitalized involuntarily.

          -  Current alcohol or substance abuse that, in the opinion of the investigator, might
             interfere with the study conduct or completion.

          -  Chronic illness(1) that, in the opinion of the Investigator, is at a stage where it
             might interfere with study conduct or completion.

          -  Moderate or severe acute illness/infection (according to Investigator judgment) on the
             day of vaccination or febrile illness (temperature >=38.0°C). A prospective
             participant should not be included in the study until the condition has resolved or
             the febrile event has subsided.

          -  Personal history of Guillain-Barré syndrome.

          -  Identified as an Investigator or employee of the Investigator or study center with
             direct involvement in the proposed study, or identified as an immediate family member
             (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with
             direct involvement in the proposed study.

               1. Chronic illness may include, but is not limited to, neurological,
                  cardiopulmonary, gastrointestinal, renal, genitourinary, metabolic, hematologic,
                  auto-immune, or psychiatric disorders or infection