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

Immunogenicity and Safety of a Purified Vero Rabies Vaccine-Serum Free (VRVg) Assessed With the Institut Pasteur du Cambodge (IPC: 2-2-2-0-0) and the Thai Red Cross (TRC: 2-2-2-0-2) Intradermal Regimens as Simulated Rabies Post-exposure Prophylaxis in Healthy Subjects in Thailand

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.

Study Overview

• Status: Completed
• Conditions: Rabies (Healthy Volunteers)
• Intervention / Treatment: Biological: Purified vero rabies vaccine - serum free VRVg-2; Biological: Purified inactivated rabies vaccine; Biological: Equine rabies immunoglobulins (ERIG) (only Group 3 and Group 4); Biological: Human rabies immunoglobulins (HRIG) (only Group 5 and Group 6)

Detailed 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).

• Study Type: Interventional
• Enrollment (Actual): 403
• Phase: Phase 3

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand
    • Investigational Site Number :7640002
  • Bangkok, Thailand, 10400
    • Investigational Site Number :7640004
  • Khon Kaen, Thailand, 40002
    • Investigational Site Number :7640003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: pediatric participants; VRVg-2; VRVg-2 8 injections: 2 at Day 0, 2 at Day 3, 2 at Day 7, and 2 at Day 28	Biological: Purified vero rabies vaccine - serum free VRVg-2; Pharmaceutical form:freeze-dried Route of administration: intradermal
Active Comparator: Group 2: pediatric participants; Verorab; Verorab 8 injections: 2 at Day 0, 2 at Day 3, 2 at Day 7, and 2 at Day 28	Biological: Purified inactivated rabies vaccine; Pharmaceutical form:freeze-dried Route of administration: intradermal; Other Names: Verorab®
Experimental: Group 3: adult participants; VRVG-2 + ERIG; VRVg-2 8 injections: 2 at Day 0, 2 at Day 3 and 2 at Day 7 + ERIG at D0	Biological: Purified vero rabies vaccine - serum free VRVg-2; Pharmaceutical form:freeze-dried Route of administration: intradermal; Biological: Equine rabies immunoglobulins (ERIG) (only Group 3 and Group 4); Pharmaceutical form: liquid/solution in 5 mL vials Route of administration: intramuscular; Other Names: ERIG
Active Comparator: Group 4: adult participants; Verorab + ERIG; Verorab 8 injections: 2 at Day 0, 2 at Day 3 and 2 at Day 7 + ERIG at D0	Biological: Purified inactivated rabies vaccine; Pharmaceutical form:freeze-dried Route of administration: intradermal; Other Names: Verorab®; Biological: Equine rabies immunoglobulins (ERIG) (only Group 3 and Group 4); Pharmaceutical form: liquid/solution in 5 mL vials Route of administration: intramuscular; Other Names: ERIG
Experimental: Group 5: adult participants; VRVG-2 + HRIG; VRVg-2 8 injections: 2 at Day 0, 2 at Day 3, 2 at Day 7, and 2 at Day 28 + HRIG at D0	Biological: Purified vero rabies vaccine - serum free VRVg-2; Pharmaceutical form:freeze-dried Route of administration: intradermal; Biological: Human rabies immunoglobulins (HRIG) (only Group 5 and Group 6); Pharmaceutical form: liquid/solution in 2 mL vials Route of administration: intramuscular; Other Names: IMOGAM® Rabies-HT
Active Comparator: Group 6: adult participants; Verorab + HRIG; Verorab 8 injections: 2 at Day 0, 2 at Day 3, 2 at Day 7, and 2 at Day 28 + HRIG at D0	Biological: Purified inactivated rabies vaccine; Pharmaceutical form:freeze-dried Route of administration: intradermal; Other Names: Verorab®; Biological: Human rabies immunoglobulins (HRIG) (only Group 5 and Group 6); Pharmaceutical form: liquid/solution in 2 mL vials Route of administration: intramuscular; Other Names: IMOGAM® Rabies-HT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants in Group 1, Group 2, Group 5 and Group 6 achieving rabies virus neutralizing antibody (RVNA) titer greater than or equal to (≥) 0.5 IU/mL	RVNA titers will be measured by rapid fluorescent focus inhibition test (RFFIT)	Day 14 (post-vaccination)
Percentage of participants in Group 1, Group 2, Group 5 and Group 6 achieving RVNA titer greater than or equal to (≥) 0.5 IU/mL	RVNA titers will be measured by RFFIT	Day 42 (post-vaccination)
Number of Participants in Group 1, Group 2, Group 5 and Group 6 achieving RVNA titer greater than or equal to (≥) lower limit of quantification	RVNA titers will be measured by RFFIT Lower limit of quantification for RFFIT assay is 0.2 IU/mL	Day 14 (post-vaccination)
Number of Participants in Group 1, Group 2, Group 5 and Group 6 achieving RVNA titer greater than or equal to (≥) lower limit of quantification	RVNA titers will be measured by RFFIT Lower limit of quantification for RFFIT assay is 0.2 IU/mL	Day 42 (post-vaccination)
Geometric Mean Titer Ratio (GMTR) of individual RVNA titer: (post-/pre-vaccination) in Group 1, Group 2, Group 5 and Group 6 Participants	RVNA titers against rabies virus will be measured by RFFIT at Day 0 and Day 14 RVNA ratios Day14/Day0 will be calculated	Day 14 (post-vaccination)
Geometric Mean Titer Ratio (GMTR) of individual RVNA titer: (post-/pre-vaccination) in Group 1, Group 2, Group 5 and Group 6 Participants	RVNA titers against rabies virus will be measured by RFFIT at Day 0 and Day 42 RVNA ratios Day42/Day0 will be calculated	Day 42 (post-vaccination)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants reporting immediate adverse events (AEs)	Includes unsolicited (spontaneously reported) systemic AEs	Within 30 minutes post-vaccination
Percentage of participants reporting solicited injection site reactions	Solicited injection site reactions: tenderness, erythema, swelling in toddlers (aged ≥ 1 year to < 2 years); pain, erythema, and swelling in children (aged 2 years to < 12 years), in adolescents and adults (aged ≥ 12 years)	Within 7 days post-vaccination
Percentage of participants reporting solicited systemic reactions	Solicited systemic reactions: fever, vomiting, crying abnormal, drowsiness, appetite lost, irritability in toddlers (aged ≥ 1 year to < 2 years); fever, headache, malaise and myalgia in children (aged 2 years to < 12 years), adolescents or adults (aged ≥ 12 years)	Between Day 0 and Day 3, between Day 3 and Day 7, and during the 7 days following the remaining vaccinations
Number of participants reporting unsolicited injection site AEs	Unsolicited (spontaneously reported) injection site AEs	Within 28 days post-vaccination
Number of participants reporting unsolicited systemic AEs	Unsolicited (spontaneously reported) systemic AEs	Between each vaccination and up to 28 days after the last vaccination
Number of participants reporting serious adverse events (SAEs)	SAEs, including adverse event of special interest (AESIs)	Up to 6 months post-vaccination
Percentage of participants in Group 3 and Group 4 achieving rabies virus neutralizing antibody (RVNA) titer greater than or equal to (≥) 0.5 IU/mL	RVNA titers will be measured by RFFIT	Day 14 (post-vaccination)
Number of Participants in Group 3 and Group 4 achieving RVNA titer greater than or equal to (≥) lower limit of quantification	RVNA titers will be measured by RFFIT Lower limit of quantification for RFFIT assay is 0.2 IU/mL	Day 14 (post-vaccination)
Geometric Mean Titer Ratio (GMTR) of individual RVNA titer: (post-/pre-vaccination) in Group 3 and Group 4 Participants	RVNA titers against rabies virus will be measured by RFFIT at Day 0 and Day 14 RVNA ratios Day14/Day0 will be calculated	Day 14 (post-vaccination)
Percentage of participants in Group 1, Group 2, Group 5 and Group 6 achieving rabies virus neutralizing antibody (RVNA) titer greater than or equal to (≥) 0.5 IU/mL	RVNA titers will be measured by RFFIT	Day 90 (post-vaccination)
Number of Participants in Group 1, Group 2, Group 5 and Group 6 achieving RVNA titer greater than or equal to (≥) lower limit of quantification	RVNA titers will be measured by RFFIT Lower limit of quantification for RFFIT assay is 0.2 IU/mL	Day 90 (post-vaccination)
Geometric Mean Titer Ratio (GMTR) of individual RVNA titer: (post-/pre-vaccination) in Group 1, Group 2, Group 5 and Group 6 Participants	RVNA titers against rabies virus will be measured by RFFIT at Day 0 and Day 90 RVNA ratios Day90/Day0 will be calculated	Day 90 (post-vaccination)

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi Pasteur, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2020
• Primary Completion (Actual): March 19, 2022
• Study Completion (Actual): July 21, 2022

Study Registration Dates

• First Submitted: July 15, 2020
• First Submitted That Met QC Criteria: July 15, 2020
• First Posted (Actual): July 20, 2020

Study Record Updates

• Last Update Posted (Actual): July 13, 2023
• Last Update Submitted That Met QC Criteria: July 11, 2023
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Rabies Vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Mononegavirales Infections; Rhabdoviridae Infections; Rabies; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Vaccines; Immunoglobulins; Immunoglobulins, Intravenous
• Other Study ID Numbers: VRV09; U1111-1227-4143 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No