Imovax® Rabies and VERORAB® Immunogenicity and Safety After One Week 2-sites Intradermal or 1-site Intramuscular Pre-Exposure Prophylaxis Regimens, Followed by a Simulated Post-Exposure Prophylaxis Regimen at One Year

Study Overview
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Brief Summary
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The primary objective of the study is to demonstrate that a short intramuscular (IM) pre-exposure prophylaxis (PrEP) regimen is non-inferior to the reference IM PrEP regimen in terms of seroconversion rate. The secondary objectives of the study are: To describe the immunogenicity of the PrEP regimen in each group To describe the antibody persistence in each group 6 months and 1 year after the last PrEP vaccination To describe the immunogenicity of the simulated post-exposure prophylaxis (PEP) regimen in each group To describe the safety profile of study vaccines administered as PrEP regimen and as a simulated PEP regimen in each group

Detailed Description
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Study duration per participant is approximately 403 to 436 days

Official Title
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Imovax® Rabies and VERORAB® Immunogenicity and Safety After One Week 2-sites Intradermal or 1-site Intramuscular Pre-Exposure Prophylaxis Regimens, Followed by a Simulated Intradermal or Intramuscular Post-Exposure Prophylaxis Regimen at One Year

Conditions
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Healthy Volunteers (Rabies Immunization)

Intervention / Treatment
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* Biological: HDCV
* Biological: HDCV
* Biological: PVRV
* Biological: PVRV


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Aged ≥ 2 years on the day of inclusion Participant aged < 18 years: Assent form has been signed and dated by the subject (as appropriate, according to country-specific institution requirements), and informed consent form (ICF) signed and dated by the parent or another legally acceptable representative Participant aged ≥ 18 years: ICF signed and dated by the subject The participant (and parent/legally acceptable representative, if applicable) is able to attend all scheduled visits and to comply with all trial procedures Exclusion criteria: 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 at least 4 weeks after the last 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 in the 4 weeks preceding the first trial vaccination) 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 preceding the first trial vaccination or planned receipt of any vaccine in the 4 weeks following any trial vaccination except for influenza vaccination, which may be received at least 2 weeks before study vaccines. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines. Previous vaccination at any time against rabies with either the trial vaccine 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) Known systemic hypersensitivity to any of the vaccine 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 Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily Current alcohol abuse or drug addiction Chronic illness that, in the opinion of the investigator, is 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 C). A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided 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 (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study History of Guillain-Barré syndrome Receipt of chloroquine or other medications used for malaria chemoprophylaxis, with or without other anti-malarial treatment, for more than 4 weeks (duration of anti-malarial course) and part of the treatment received within the 2 weeks before vaccination, contraindicating intradermal vaccination The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>1 IM dose of human diploid cell vaccine (HDCV) on D0 and D7 (short HDCV IM PrEP regimen), followed by 1 IM dose of HDCV on Year (Y)1 and Y1 + 3 days | Biological: HDCV<br>* Pharmaceutical form:Solution for injection Route of administration: Intramuscular<br>|
| Active Comparator: Group 2<br>1 IM dose of HDCV on D0, D7, and D21 (reference), followed by 1 IM dose of HDCV on Y1 and Y1 + 3 days | Biological: HDCV<br>* Pharmaceutical form:Solution for injection Route of administration: Intramuscular<br>|
| Experimental: Group 3<br>2 intradermal (ID) doses of HDCV on D0 and D7 (short HDCV ID PrEP regimen), followed by 1 ID dose of HDCV on Y1 and Y1 + 3 days | Biological: HDCV<br>* Pharmaceutical form:Solution for injection Route of administration: Intradermal<br>|
| Experimental: Group 4<br>1 IM dose of purified Vero cell rabies vaccine (PVRV) on D0 and D7 (short PVRV IM PrEP regimen), followed by 1 IM dose of PVRV on Y1 and Y1 + 3 days | Biological: PVRV<br>* Pharmaceutical form:Solution for injection Route of administration: Intramuscular<br>|
| Experimental: Group 5<br>2 ID doses of PVRV on D0 and D7 (short PVRV ID PrEP regimen), followed by 1 ID dose of PVRV on Y1 and Y1 + 3 days | Biological: PVRV<br>* Pharmaceutical form:Solution for injection Route of administration: Intradermal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion of participant | Rabies virus neutralizing antibodies (RVNA) titer ≥ 0.5 IU/mL | 14 days after the last PrEP vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant RVNA titer |  | Day 0 and 14 days after the last PrEP vaccination | 
| Persistence of RVNA titer |  | 6 months and 1 year after the last PrEP vaccination | 
| Participant RVNA titer after simulated PEP vaccination |  | 7 and 14 days after the first simulated PEP vaccination | 
| Seroconversion of participant | RVNA titer ≥ 0.5 IU/mL | Day 0 and 14 days after the last PrEP vaccination | 
| Persistence of seroconversion | RVNA titer ≥ 0.5 IU/mL | 6 months and 1 year after the last PrEP vaccination | 
| Seroconversion of participant after simulated PEP vaccination - | RVNA titer ≥ 0.5 IU/mL | 7 and 14 days after the first simulated PEPvaccination | 
| Seropositivity of participant | RVNA titer ≥ the lower limit of quantitation (LLOQ) | Day 0 and 14 days after the last PrEP vaccination | 
| Persistence of seropositivity | RVNA titer ≥ the LLOQ | 6 months and 1 year after the last PrEP vaccination | 
| Seropositivity of participant after simulated PEP vaccination | RVNA titer ≥ the LLOQ | 7 and 14 days after the first simulated PEP vaccination | 
| Participant RVNA titer ratios | Titer 14 days after the last PrEP vaccination / titer at D0 | 14 days after last PrEP vaccination | 
| Participant RVNA titer ratios (persistence assessment) | RVNA titer ratios are assessed 6 months / 14 days after the last PrEP vaccination, and 1 year / 14 days after the last PrEP vaccination | 6 months and 1 year after the last PrEP vaccination | 
| Participant RVNA titer after simulated PEP vaccination | Ratio of titers measured 7 and 14 days after the first simulated PEP vaccination / 1 year after the last PrEP vaccination | 1 year after the last PrEP vaccination | 
| Solicited injection site and systemic reactions after PrEP vaccination | Injection site reactions: injection site pain, erythema, and swelling. Systemic reactions: fever, headache, malaise and myalgia. | 7 days after PrEP vaccination | 
| Solicited injection site and systemic reactions after simulated PEP vaccination | Injection site reactions: injection site pain, erythema, and swelling. Systemic reactions: fever, headache, malaise and myalgia. Solicited systemic reactions are collected between the first and second PEP injection and within 7 days after the second PEP injection. | 7 days after simulated PEP vaccination |