Study of Purified Vero Rabies Vaccine Compared With Two Reference Rabies Vaccines in a Simulated Post-Exposure Regimen in Adults

Sanofi

Status and phase: Completed; Phase 3

Conditions: Rabies (Healthy Volunteers)

Treatments: Biological: Human Diploid Cell Vaccine (HDCV); Biological: Purified Inactivated Rabies Vaccine; Biological: Rabies immune globulin (human); Biological: VRVg-2

Study type: Interventional

Funder types: Industry

Identifiers

NCT03965962

VRV13

2018-004055-20 (EudraCT Number)

U1111-1216-6151 (Other Identifier)

Details and patient eligibility

About

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).

Full description

Study duration per participant was approximately 7 months including: 1 day of screening and vaccination, a total of 5 vaccine injections over a 28-day period, 1 safety-follow up visit at Day 42, 1 safety follow-up/end of study visit at Day 56 and a 6-month safety follow-up call after last vaccine administration.

Enrollment: 640 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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640 participants in 4 patient groups

Group 1: VRVg-2 + HRIG

Experimental group

Description:

Participants received 0.5 milliliters (mL) intramuscular (IM) injection of VRVg-2 formulation on Days 0, 3, 7, 14 and 28 along with HRIG injection at Day 0.

Treatment:

Biological: VRVg-2

Biological: Rabies immune globulin (human)

Group 2: Verorab + HRIG

Active Comparator group

Description:

Participants received 0.5 mL IM injection of Verorab on Days 0, 3, 7, 14 and 28 along with HRIG injection at Day 0.

Treatment:

Biological: Rabies immune globulin (human)

Biological: Purified Inactivated Rabies Vaccine

Group 3: Imovax Rabies + HRIG

Active Comparator group

Description:

Participants received 1 mL IM injection of Imovax Rabies on Days 0, 3, 7, 14 and 28 along with HRIG injection at Day 0.

Treatment:

Biological: Rabies immune globulin (human)

Biological: Human Diploid Cell Vaccine (HDCV)

Group 4: VRVg-2

Experimental group

Description:

Participants received 0.5 mL IM injection of VRVg-2 formulation on Days 0, 3, 7, 14 and 28.

Treatment:

Biological: VRVg-2