Clinical trial NCT04478084: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rabies (Healthy Volunteers)
Keywords: Rabies Vaccine
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2020-07-20
Enrollment: 403
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Day 14 (post-vaccination)
measure: 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
timeFrame: Day 42 (post-vaccination)
measure: 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
timeFrame: Day 14 (post-vaccination)
measure: 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
timeFrame: Day 42 (post-vaccination)
measure: Geometric Mean Titer Ratio (GMTR) of individual RVNA titer: (post-/pre-vaccination) in Group 1, Group 2, Group 5 and Group 6 Participants
timeFrame: Day 14 (post-vaccination)
measure: Geometric Mean Titer Ratio (GMTR) of individual RVNA titer: (post-/pre-vaccination) in Group 1, Group 2, Group 5 and Group 6 Participants
timeFrame: Day 42 (post-vaccination)
Secondary outcomes:
measure: Number of participants reporting immediate adverse events (AEs)
timeFrame: Within 30 minutes post-vaccination
measure: Percentage of participants reporting solicited injection site reactions
timeFrame: Within 7 days post-vaccination
measure: Percentage of participants reporting solicited systemic reactions
timeFrame: Between Day 0 and Day 3, between Day 3 and Day 7, and during the 7 days following the remaining vaccinations
measure: Number of participants reporting unsolicited injection site AEs
timeFrame: Within 28 days post-vaccination
measure: Number of participants reporting unsolicited systemic AEs
timeFrame: Between each vaccination and up to 28 days after the last vaccination
measure: Number of participants reporting serious adverse events (SAEs)
timeFrame: Up to 6 months post-vaccination
measure: 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
timeFrame: Day 14 (post-vaccination)
measure: Number of Participants in Group 3 and Group 4 achieving RVNA titer greater than or equal to (≥) lower limit of quantification
timeFrame: Day 14 (post-vaccination)
measure: Geometric Mean Titer Ratio (GMTR) of individual RVNA titer: (post-/pre-vaccination) in Group 3 and Group 4 Participants
timeFrame: Day 14 (post-vaccination)
measure: 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
timeFrame: Day 90 (post-vaccination)
measure: 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
timeFrame: Day 90 (post-vaccination)
measure: Geometric Mean Titer Ratio (GMTR) of individual RVNA titer: (post-/pre-vaccination) in Group 1, Group 2, Group 5 and Group 6 Participants
timeFrame: Day 90 (post-vaccination)
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Investigational Site Number :7640004
city: Bangkok
country: Thailand
facility: Investigational Site Number :7640002
city: Khon Kaen
country: Thailand
facility: Investigational Site Number :7640003
Study officials:
affiliation: Sanofi Pasteur, a Sanofi Company
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: