Study of Purified Vero Rabies Vaccine Compared With a Reference Rabies Vaccine as Simulated Rabies Post-Exposure Prophylaxis in Adult and Pediatric Population in Thaïland

Sanofi

Status and phase: Completed; Phase 3

Conditions: Rabies (Healthy Volunteers)

Treatments: Biological: Equine rabies immunoglobulins (ERIG) (only Group 3 and Group 4); Biological: Purified inactivated rabies vaccine; Biological: Human rabies immunoglobulins (HRIG) (only Group 5 and Group 6); Biological: Purified vero rabies vaccine - serum free VRVg-2

Study type: Interventional

Funder types: Industry

Identifiers

NCT04478084

U1111-1227-4143 (Other Identifier)

VRV09

Details and patient eligibility

About

Primary Objective:

To describe the immune response induced by VRVg-2 and Verorab vaccine at Day 14 (to assess the immune response after 3 doses [2-2-2]) and Day 42 (to assess the immune response after 4 doses [2-2-2-0-2]) when administered as standalone in healthy pediatric population or co-administered with HRIG (Group 5 and Group 6) at Day 0 in healthy adults.

Secondary Objectives:

• To describe the immune response induced by VRVg-2 and Verorab vaccine at Day 14 (to assess the immune response after 3 doses [2-2-2]) when co-administered with ERIG (Group 3 and Group 4) at Day 0 in healthy adults
• To describe the immune response induced by VRVg-2 and Verorab vaccine at D90 (to assess the immune response 90 days post-rabies simulated exposure) when administered as standalone in healthy pediatric population or co-administered with HRIG (Group 5 and Group 6) at Day 0 in healthy adults
• To describe the safety profile of VRVg-2 and Verorab vaccine as standalone in pediatric population or when co-administered with ERIG (Group 3 and Group 4) or HRIG (Group 5 and Group 6) at Day 0 in adults, after each vaccination.

Full description

The duration of each participant's participation in the study is approximately 7 months (28 day-vaccination period followed by 6 month safety follow-up period).

Enrollment: 403 patients

Sex: All

Ages: 1+ year old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Inclusion criteria :

• Aged ≥ 1 year on the day of inclusion
• Participant (adult ≥ 18 years without upper age limit) or participant and participant's parent/LAR (child ≥ 1 to < 18 years) are able to attend all scheduled visits and to comply with all study procedures

The following criterion only applies to healthy adults ≥ 18 years:

- Body Mass Index (BMI): 18.5 kg/m2 ≤ BMI ≤ 30 kg/m2

Exclusion criteria

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 and 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 8 (D90)
• 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 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
• Known systemic hypersensitivity to any of the study/control vaccine components or, for adults, to ERIG Group 3 and Group 4) or HRIG (Group 5 and Group 6), or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances
• Positive skin test to ERIG at Visit 1 for only adult participants enrolled in Group 3 and Group 4 as per superseded Protocol version 5.0
• Self-reported thrombocytopenia
• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion
• 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 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 subject 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 (ie, parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study
• Receipt of chloroquine or hydroxychloroquine up to 2 months prior to the study or through to study until Visit 8

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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403 participants in 6 patient groups

Group 1: pediatric participants; VRVg-2

Experimental group

Description:

VRVg-2 8 injections: 2 at Day 0, 2 at Day 3, 2 at Day 7, and 2 at Day 28

Treatment:

Biological: Purified vero rabies vaccine - serum free VRVg-2

Group 2: pediatric participants; Verorab

Active Comparator group

Description:

Verorab 8 injections: 2 at Day 0, 2 at Day 3, 2 at Day 7, and 2 at Day 28

Treatment:

Biological: Purified inactivated rabies vaccine

Group 3: adult participants; VRVG-2 + ERIG

Experimental group

Description:

VRVg-2 8 injections: 2 at Day 0, 2 at Day 3 and 2 at Day 7 \+ ERIG at D0

Treatment:

Biological: Purified vero rabies vaccine - serum free VRVg-2

Biological: Equine rabies immunoglobulins (ERIG) (only Group 3 and Group 4)

Group 4: adult participants; Verorab + ERIG

Active Comparator group

Description:

Verorab 8 injections: 2 at Day 0, 2 at Day 3 and 2 at Day 7 \+ ERIG at D0

Treatment:

Biological: Purified inactivated rabies vaccine

Biological: Equine rabies immunoglobulins (ERIG) (only Group 3 and Group 4)

Group 5: adult participants; VRVG-2 + HRIG

Experimental group

Description:

VRVg-2 8 injections: 2 at Day 0, 2 at Day 3, 2 at Day 7, and 2 at Day 28 \+ HRIG at D0

Treatment:

Biological: Purified vero rabies vaccine - serum free VRVg-2

Biological: Human rabies immunoglobulins (HRIG) (only Group 5 and Group 6)

Group 6: adult participants; Verorab + HRIG

Active Comparator group

Description:

Verorab 8 injections: 2 at Day 0, 2 at Day 3, 2 at Day 7, and 2 at Day 28 \+ HRIG at D0

Treatment:

Biological: Human rabies immunoglobulins (HRIG) (only Group 5 and Group 6)

Biological: Purified inactivated rabies vaccine