Study of Purified Vero Rabies Vaccine Compared With Two Reference Rabies Vaccines in a Simulated Post-Exposure Regimen in Adults
Condition: Rabies (Healthy Volunteers)
MeSH terms: Rabies
Intervention: VRVg-2; Purified Inactivated Rabies Vaccine; Human Diploid Cell Vaccine (HDCV); Rabies immune globulin (human)
Intervention description: Pharmaceutical form: Powder and solvent for suspension for injection;
Route of administration: IM; Pharmaceutical form: Powder and solvent for suspension for injection;
Route of administration: IM; Pharmaceutical form: Powder and solvent for suspension for injection;
Route of administration: IM; Pharmaceutical form: Solution for injection;
Route of administration: IM
Intervention MeSH terms: Vaccines; Immunoglobulins; Antibodies; gamma-Globulins; Immunoglobulins, Intravenous; Rho(D) Immune Globulin
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The study was divided into 4 groups: groups 1 to 3 (VRVg-2 + HRIG; Verorab + HRIG; Imovax Rabies + HRIG) were modified double-blind and group 4 (VRVg-2 standalone) was open-label.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Modified double-blind: the participant (or legally acceptable representative) and the Investigator remain unaware of the treatment assignments throughout the study. An unblinded qualified trial staff member administered the appropriate vaccine but was not involved in the immunogenicity and safety evaluations.
Enrollment: 640.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Primary Objective:

      To demonstrate that Purified Vero Rabies Vaccine - Serum Free Vaccine generation 2 (VRVg-2)
      was non-inferior to Verorab and Imovax Rabies vaccines when co-administered with human rabies
      immunoglobulin (HRIG), in terms of proportion of participants achieving a rabies virus
      neutralizing antibody (RVNA) titer greater than or equal to (>=) 0.5 international units per
      milliliter (IU/mL) at Day 28, i.e., 14 days after the fourth vaccine injection.

      Secondary Objective:

        -  To describe the safety profile of VRVg-2 versus Verorab and Imovax Rabies vaccines when
           co-administered with HRIG, as well as that of VRVg-2, after each vaccine injection.

        -  To demonstrate that the proportion of participants in the VRVg-2 + HRIG group achieving
           an RVNA titer >= 0.5 IU/mL at Day 28 was at least 95 percent (%).

        -  To describe the immune response induced by VRVg-2 versus Verorab and Imovax Rabies
           vaccines when co-administered with HRIG, as well as that induced by VRVg-2, at Day 14 (7
           days after the third injection), at Day 28 (14 days after the fourth injection) and at
           Day 42 (14 days after the last injection).
    

Eligibility criteria:

        Inclusion criteria :

          -  Men or women aged >=18 years on the day of inclusion (>= 18 years means from the day
             of the 18th birthday onwards, with no upper age limit).

          -  Able to attend all scheduled visits and to comply with all trial procedures.

          -  Body Mass Index (BMI): 18.5 kilograms per square meter (kg/m^2) less than or equal to
             (<=) BMI <=30 kg/m^2.

        Exclusion criteria:

          -  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 at least 4 weeks after the last vaccination. To be considered of
             non-childbearing potential, a female must be post-menopausal for at least 1 year, or
             surgically sterile.

          -  Participation at the time of study enrollment or, planned participation during the
             present trial period in another clinical trial investigating a vaccine, drug, medical
             device, or medical procedure.

          -  Receipt of any vaccine in the 4 weeks (28 days) preceding the first trial vaccination
             or planned receipt of any vaccine prior to Visit 7.

          -  Previous vaccination against rabies (in pre- or post-exposure regimen) with either the
             trial vaccines or another vaccine.

          -  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 trial (veterinarians and their staff,
             animal handlers, rabies researchers, and certain laboratory workers, persons whose
             activities bring them into frequent contact with rabies virus or potentially rabid
             bats, raccoons, skunks, cats, dogs, or other species at risk for having rabies, people
             travelling where rabies was enzootic).

          -  Known systemic hypersensitivity to any of the vaccine or HRIG components, or history
             of a life-threatening reaction to the vaccines used in the trial or to a vaccine
             containing any of the same substances.

          -  Self-reported thrombocytopenia, contraindicating IM vaccination.

          -  Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion,
             contraindicating IM vaccination.

          -  Current alcohol or substance abuse that, in the opinion of the investigator, might
             interfere with the trial conduct of completion.

          -  Chronic illness that, in the opinion of the investigator, was at a stage where it
             might interfere with trial conduct or completion.

          -  Moderate or severe acute illness/infection (according to investigator judgment) on the
             day of vaccination or febrile illness (temperature >=38.0 degree Celsius). A
             prospective participant should not be included in the study until the condition had
             resolved or the febrile event had 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
             (ie, parent, spouse, natural or adopted child) of the Investigator or employee with
             direct involvement in the proposed study.

        The above information was not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.