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

NCT04127786 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: VRV12U1111-1217-32412019-000973-22
• Study Type: interventional
• Target: 1,708
• Locations: 1 country
• Sites: 4

Brief Summary

The primary objective of this study is: To demonstrate the 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 PrEP regimen, in terms of proportion of participants achieving a rabies virus neutralizing antibody (RVNA) titer ≥ 0.5 IU/mL at Day 42, ie. 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 VRVg2(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 (Cohort1) 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 M12 (Cohort1) and between M24 up to M36 (Cohort2)
• the persistence of immune response at M6,12,18, and pre-booster between M24 up to M36 post-primary series vaccination (Cohort2)
• safety profile of VRVg versus Verorab and Imovax in primary series and after a booster dose of VRVg

Conditions

Healthy Volunteers; Rabies

Outcome Measures

Primary Outcomes (1)

• Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody (RVNA) Titer Greater Than or Equal to (>=) 0.5 IU/mL

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

  Day 42 (post-vaccination)

Secondary Outcomes (34)

• Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL

  Cohort 1: Day 0 (pre-vaccination), Day 28 and Day 42 (post-vaccination)

• Primary Series: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population

  Cohort 1: Day 0 (pre-vaccination), Day 28 (post-vaccination); Cohort 2: Day 0 (pre-vaccination) and Day 28 (post-vaccination)

• Primary Series: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population (Groups 1 and 4) Versus Cohort 1: Group 3: Non-inferiority Analysis

  Pooled Groups 1 and 4: Day 28 (post-vaccination) and Primary Series: Cohort-1 Group 3: Day 42 (post-vaccination)

• Primary Series: Groups 1 and 4: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population - Superiority Analysis

  Day 28 (post-vaccination)

• Primary Series Cohort 1 Group 3: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Non-Inferiority Analysis

  Cohort 1: Day 28 and Day 42 (post-vaccination)

Study Arms (6)

Group1:VRVg2 Cohort1(C1)-1ry Series:pediatric&adult participants-Booster:102 adult participants

EXPERIMENTAL

VRVg-2, 3 injections at Day 0, Day 7, and Day 28 Booster dose of VRVg-2 for a subset of 102 adult participants at Month 12

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

Group 2:Verorab C1-1ry Series:pediatric&adult participants-Booster Phase:34 adult participants

ACTIVE COMPARATOR

Verorab, 3 injections at Day 0, Day 7, and Day 28 Booster dose of VRVg-2 for a subset of 34 adult participants at Month 12

Biological: Purified vero rabies vaccine - serum free - VRVg-2; Biological: Purified inactivated rabies vaccine - Verorab®

Group 3:Imovax Rabies C1-1ry Series:pediatric&adult participants-Booster Phase:34 adult participants

ACTIVE COMPARATOR

Imovax Rabies, 3 injections at Day 0, Day 7, and Day 28 Booster dose of VRVg-2 for a subset of 34 adult participants at Month 12

Biological: Purified vero rabies vaccine - serum free - VRVg-2; Biological: Purified inactivated rabies vaccine - Imovax® Rabies

Group 4:VRVg-2 Cohort 2(C2)-1ry Series:Adult participants-Booster Phase:138 adult participants

EXPERIMENTAL

VRVg-2, 2 injections at Day 0 and Day 7 Booster dose of VRVg-2 for a subset of 138 adult participants between Month 24 up to Month 36

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

Group 5:Verorab C2-1ry Series:adult participants-Booster Phase:46 adult participants

ACTIVE COMPARATOR

Verorab, 2 injections at Day 0 and Day 7 Booster dose of VRVg-2 for a subset of 46 adult participants between Month 24 up to Month 36

Biological: Purified vero rabies vaccine - serum free - VRVg-2; Biological: Purified inactivated rabies vaccine - Verorab®

Group 6:Imovax Rabies C2-1ry Series:adult participants-Booster Phase:46 adult participants

ACTIVE COMPARATOR

Imovax Rabies, 2 injections at Day 0 and Day 7 Booster dose of VRVg-2 for a subset of 46 adult participants between Month 24 up to Month 36

Biological: Purified vero rabies vaccine - serum free - VRVg-2; Biological: Purified inactivated rabies vaccine - Imovax® Rabies

Interventions

Purified inactivated rabies vaccine - Verorab® BIOLOGICAL

Pharmaceutical form:Freeze-dried Route of administration: Intramuscular

Group 2:Verorab C1-1ry Series:pediatric&adult participants-Booster Phase:34 adult participants; Group 5:Verorab C2-1ry Series:adult participants-Booster Phase:46 adult participants

Purified inactivated rabies vaccine - Imovax® Rabies BIOLOGICAL

Pharmaceutical form: Freeze-dried Route of administration: Intramuscular

Group 3:Imovax Rabies C1-1ry Series:pediatric&adult participants-Booster Phase:34 adult participants; Group 6:Imovax Rabies C2-1ry Series:adult participants-Booster Phase:46 adult participants

Purified vero rabies vaccine - serum free - VRVg-2 BIOLOGICAL

Pharmaceutical form: Freeze-dried Route of administration: Intramuscular

Group 2:Verorab C1-1ry Series:pediatric&adult participants-Booster Phase:34 adult participants; Group 3:Imovax Rabies C1-1ry Series:pediatric&adult participants-Booster Phase:34 adult participants; Group 4:VRVg-2 Cohort 2(C2)-1ry Series:Adult participants-Booster Phase:138 adult participants; Group 5:Verorab C2-1ry Series:adult participants-Booster Phase:46 adult participants; Group 6:Imovax Rabies C2-1ry Series:adult participants-Booster Phase:46 adult participants; Group1:VRVg2 Cohort1(C1)-1ry Series:pediatric&adult participants-Booster:102 adult participants

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohort 1 - pediatrics (\>1 to 17 years old) and adult (≥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 \<18 years) are able to attend all scheduled visits and to comply with all study procedures.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (4)

Investigational Site Number : 7640001

Bangkok, 10330, Thailand

Location

Investigational Site Number : 7640004

Bangkok, 10400, Thailand

Location

Investigational Site Number : 7640003

Bangkok, 10700, Thailand

Location

Investigational Site Number : 7640002

Khon Kaen, 40002, Thailand

Location

Related Publications (1)

• Chokephaibulkit K, Huoi C, Tantawichien T, Mootsikapun P, Kosalaraksa P, Kiertiburanakul S, Ratanasuwan W, Vangelisti M, Laot T, Huang Y, Petit C, Pineda-Pena AC, Frago C. Noninferiority Study of Purified Vero Rabies Vaccine-Serum Free in 3-dose and 2-dose Preexposure Prophylaxis Regimens in Comparison With Licensed Rabies Vaccines. Clin Infect Dis. 2025 Oct 6;81(3):654-666. doi: 10.1093/cid/ciae581.

  PMID: 39587931 DERIVED

Related Links

• VRV12 Plain Language Results Summary

MeSH Terms

Conditions

Rabies

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi Pasteur

Contact-US@sanofi.com

8006331610

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: 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 (eg, Investigator who assess the safety), the Sponsor personnel (eg, 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: October 11, 2019
• First Posted: October 16, 2019
• Study Start: October 21, 2019
• Primary Completion: March 25, 2020
• Study Completion: April 24, 2025
• Last Updated: February 10, 2026
• Results First Posted: February 9, 2024

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

TH (4)