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

Rabies (Healthy Volunteers) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04478084
• Other study ID #: VRV09
• Secondary ID: U1111-1227-4143
• Status: Completed
• Phase: Phase 3
• Start date: August 4, 2020
• Est. completion date: July 21, 2022

Study information

• Verified date: August 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 403
• Est. completion date: July 21, 2022
• Est. primary completion date: March 19, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Year and older

Eligibility

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.

Related Conditions & MeSH terms

• Rabies
• Rabies (Healthy Volunteers)

Intervention

Biological:
• Purified vero rabies vaccine - serum free VRVg-2
Pharmaceutical form:freeze-dried Route of administration: intradermal
• Purified inactivated rabies vaccine
Pharmaceutical form:freeze-dried Route of administration: intradermal
• Equine rabies immunoglobulins (ERIG) (only Group 3 and Group 4)
Pharmaceutical form: liquid/solution in 5 mL vials Route of administration: intramuscular
• Human rabies immunoglobulins (HRIG) (only Group 5 and Group 6)
Pharmaceutical form: liquid/solution in 2 mL vials Route of administration: intramuscular

Locations

Country	Name	City	State
Thailand	Investigational Site Number :7640002	Bangkok
Thailand	Investigational Site Number :7640004	Bangkok
Thailand	Investigational Site Number :7640003	Khon Kaen

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	Number of participants reporting immediate adverse events (AEs)	Includes unsolicited (spontaneously reported) systemic AEs	Within 30 minutes post-vaccination
Secondary	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
Secondary	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
Secondary	Number of participants reporting unsolicited injection site AEs	Unsolicited (spontaneously reported) injection site AEs	Within 28 days post-vaccination
Secondary	Number of participants reporting unsolicited systemic AEs	Unsolicited (spontaneously reported) systemic AEs	Between each vaccination and up to 28 days after the last vaccination
Secondary	Number of participants reporting serious adverse events (SAEs)	SAEs, including adverse event of special interest (AESIs)	Up to 6 months post-vaccination
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)