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

NCT03965962 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: VRV132018-004055-20U1111-1216-6151
• Study Type: interventional
• Target: 640
• Locations: 1 country
• Sites: 2

Brief 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).

Conditions

Rabies (Healthy Volunteers)

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Rabies Virus Neutralizing Antibody (RVNA) Titers Greater Than or Equal to (>=) 0.5 International Units Per Milliliter (IU/mL)-Non-Inferiority Analysis

  RVNA titer against rabies virus was assessed using the Rapid Fluorescent Focus Inhibition test (RFFIT) assay method.

  Day 28

Secondary Outcomes (10)

• Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL

  Day 0 (pre-vaccination), Day 14, Day 28 and Day 42

• Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (Lower Limit of Quantification [LLOQ])

  Day 0 (pre-vaccination), Day 14, Day 28 and Day 42

• Rabies Virus Neutralizing Antibody (RVNA) Geometric Mean Titers (GMTs) Against Rabies Virus

  Day 0 (pre-vaccination), Day 14, Day 28 and Day 42

• Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers

  Day 0 (pre-vaccination), Day 14, Day 28 and Day 42

• Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization

  Day 0 (pre-vaccination), Day 14, Day 28 and Day 42

Study Arms (4)

Group 1: VRVg-2 + HRIG

EXPERIMENTAL

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.

Biological: VRVg-2; Biological: Rabies immune globulin (human)

Group 2: Verorab + HRIG

ACTIVE COMPARATOR

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

Biological: Purified Inactivated Rabies Vaccine; Biological: Rabies immune globulin (human)

Group 3: Imovax Rabies + HRIG

ACTIVE COMPARATOR

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

Biological: Human Diploid Cell Vaccine (HDCV); Biological: Rabies immune globulin (human)

Group 4: VRVg-2

EXPERIMENTAL

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

Biological: VRVg-2

Interventions

VRVg-2 BIOLOGICAL

Pharmaceutical form: Powder and solvent for suspension for injection; Route of administration: IM

Group 1: VRVg-2 + HRIG; Group 4: VRVg-2

Purified Inactivated Rabies Vaccine BIOLOGICAL

Pharmaceutical form: Powder and solvent for suspension for injection; Route of administration: IM

Also known as: Verorab®

Group 2: Verorab + HRIG

Human Diploid Cell Vaccine (HDCV) BIOLOGICAL

Pharmaceutical form: Powder and solvent for suspension for injection; Route of administration: IM

Also known as: IMOVAX® Rabies

Group 3: Imovax Rabies + HRIG

Rabies immune globulin (human) BIOLOGICAL

Pharmaceutical form: Solution for injection; Route of administration: IM

Also known as: IMOGAM® Rabies-HT

Group 1: VRVg-2 + HRIG; Group 2: Verorab + HRIG; Group 3: Imovax Rabies + HRIG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (2)

Investigational Site Number 2500002

Gières, 38610, France

Location

Investigational Site Number 2500001

Rennes, 35000, France

Location

Related Publications (1)

• Pineda-Pena AC, Jiang Q, Petit C, Korejwo-Peyramond J, Donazzolo Y, Latreille M, Homery MC, Babin V, Benamor S, Pichon S, Guinet-Morlot F, Minutello AM. Immunogenicity and Safety of a Purified Vero Rabies Vaccine-Serum Free, Compared With 2 Licensed Vaccines, in a Simulated Rabies Post-Exposure Regimen in Healthy Adults in France: A Randomized, Controlled, Phase 3 Trial. Clin Infect Dis. 2024 Jun 14;78(6):1748-1756. doi: 10.1093/cid/ciae137.

  PMID: 38478634 DERIVED

Related Links

• VRV13 Plain Language Results Summary

MeSH Terms

Conditions

Rabies

Interventions

Rabies Vaccines

Condition Hierarchy (Ancestors)

Rhabdoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi Pasteur

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi Pasteur, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 24, 2019
• First Posted: May 29, 2019
• Study Start: July 1, 2019
• Primary Completion: December 22, 2020
• Study Completion: July 1, 2021
• Last Updated: September 18, 2025
• Results First Posted: March 11, 2022

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

FR (2)