Immunogenicity and Safety of Verorab® in a One-week Intradermal Post-exposure Prophylaxis Regimen

Study Overview
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Brief Summary
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The purpose of this study is to assess the 4-site one-week post-exposure prophylaxis (PEP) regimen as a possible alternative to the 2-site updated Thai Red Cross (TRC) PEP regimen. Primary objective: To demonstrate that PEP using the new one-week, 4-site (4-4-4-0-0) intradermal (ID) vaccination regimen is non-inferior to PEP using the updated TRC (2-2-2-0-2) ID vaccination regimen. Secondary objectives: Primary immunization: To describe the immune response in each group at Day 0, Day 14 and Day 90. Antibody persistence: To describe rabies virus-neutralizing antibody persistence during the 5 years after completion of PEP in each group. Booster vaccination: To describe the immune response induced by a single-visit 4-site intradermal booster vaccination in each group at Year 5. Safety: To describe the safety profile of each group after the primary and booster vaccinations.

Detailed Description
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Participants with WHO Category II exposure will receive PEP, using one-week, 4-site ID vaccination regimen. Participants with WHO Category III exposure will receive PEP, using one-week, 4-site (4-4-4-0-0) ID vaccination regimen and pERIG Favirab® or using the updated 2-site TRC (2-2-2-0-2) ID vaccination regimen and pERIG Favirab®. All participants will receive a single-visit, 4-site booster vaccination five years later.

Official Title
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Verorab® Immunogenicity and Safety After a One-week, 4-site, Intradermal (ID) Post-exposure Prophylaxis Regimen (4-4-4-0-0) Followed by a One-visit, 4-site, ID Booster at Five Years

Conditions
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Rabies

Intervention / Treatment
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* Biological: PVRV
* Biological: PVRV and pERIG Favirab®
* Biological: PVRV and pERIG Favirab®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For all patients: Patient aged ≤50 years, with WHO category II or III contacts happened within 48 hours before appearance at site. For adults: Informed consent form has been signed and dated. Able to attend all scheduled visits and to comply with all trial procedures. For children: For children under 18 years of age, informed consent form has been signed and dated by the parent(s) or another legally acceptable representative. For children under 18 years, assent form or informed consent form has been signed and dated by the appropriate age-range patient, according to country specific institution requirement as detailed in each country specific assent form or informed consent form. Patient and parent/guardian are able to attend all scheduled visits and to comply with all trial procedures. Exclusion Criteria: For all patients: 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. Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the first trial immunization Planned participation in another clinical trial during the present trial period Receipt of any vaccine in the 4 weeks preceding the first trial vaccination, except for influenza vaccination and tetanus immunization (related only to current animal bite exposure Planned receipt of any vaccine in the 4 weeks following the trial primary and booster vaccination Previous immunization against rabies at any time in the past with either the trial vaccine and immunoglobulin or another rabies immunobiological product (in pre-or post-exposure regimen) Receipt of blood or blood-derived products in the past 3 months, which might interfere with assessment of the immune response 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) Self-reported seropositivity for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus Patient with clinical signs of encephalitis Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion Identified as employees of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members (i.e., immediate, husband, wife and their children, adopted or natural) of the employees or the Investigator Febrile illness (temperature ≥38.0°C) or moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination Prior history of mammal animal bite within the past 5 years. For infants or toddlers : Known personal or maternal seropositivity for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus, as reported by the parent/guardian Prior history of seizures .

Ages Eligible for Study
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Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Patients with WHO Category II exposure receive PEP with PVRV using one-week, 4-site (4-4-4-0-0) ID vaccination regimen, and a single-visit, 4-site booster vaccination with PVRV 5 years later | Biological: PVRV<br>* 0.1 mL, 4 site 'one week' (4-4-4-0-0) administered intradermally<br>* Other names: VERORAB®;|
| Experimental: Group 2<br>Patients with WHO Category III exposure receive PEP with PVRV using one-week, 4-site (4-4-4-0-0) ID vaccination regimen and pERIG Favirab®, and a single-visit, 4-site booster vaccination with PVRV 5 years later | Biological: PVRV and pERIG Favirab®<br>* 0.1 mL of vaccine administered intradermally in 4 site 'one week' (4-4-4-0-0) regimen, and pERIG Favirab® (volume to be calculated according to the patient' body weight) infiltrated into and around wound(s)<br>* Other names: VERORAB®; pERIG Favirab®;|
| Active Comparator: Group 3<br>Patients with WHO Category III exposure receive PEP with PVRV using the updated 2-site TRC (2-2-2-0-2) ID vaccination regimen and pERIG Favirab®, and a single-visit, 4-site booster vaccination with PVRV 5 years later | Biological: PVRV and pERIG Favirab®<br>* 0.1 mL of vaccine administered intradermally in 2-site TRC (2-2-2-0-2) regimen, and pERIG Favirab® (volume to be calculated according to the patient' body weight) infiltrated into and around wound(s)<br>* Other names: VERORAB®; pERIG Favirab®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with seroconversion on Day 14 | Seroconversion is defined as rabies virus neutralizing antibody titers ≥ 0.5 IU/mL | Day 14 post vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with seroconversion before and after primary vaccination | Seroconversion is defined as rabies virus neutralizing antibody titers ≥ 0.5 IU/mL | Day 0, Day 14, Day 90 | 
| Percentage of participants with seroconversion after primary vaccination (antibody persistence) | Seroconversion is defined as rabies virus neutralizing antibody titers ≥ 0.5 IU/mL | Year 1 to Year 5 | 
| Percentage of participants with seroconversion after booster vaccination | Seroconversion is defined as rabies virus neutralizing antibody titers ≥ 0.5 IU/mL | Year 5 + 11 days | 
| Geometric mean titers (GMTs) before and after primary vaccination | Titers of rabies virus-neutralizing antibodies were assessed by the rapid fluorescent focus inhibition test | Day 0, Day 14, Day 90 | 
| GMTs after primary vaccination (antibody persistence) | Titers of rabies virus-neutralizing antibodies were assessed by the rapid fluorescent focus inhibition test | Year 1 to Year 5 | 
| GMTs after booster vaccination | Titers of rabies virus-neutralizing antibodies were assessed by the rapid fluorescent focus inhibition test | Year 5 + 11 days | 
| Number of participants reporting solicited injection site reactions following primary and booster vaccination | Solicited injection site reactions are tenderness (for participants aged ≤ 23 months), pain (for participants aged ≥ 2 years), redness and swelling (for all participants) | 7 days after each and any injection | 
| Number of participants reporting solicited systemic reactions following primary and booster vaccination | Solicited systemic reactions are Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, and Irritability for participants aged ≤ 23 months and Fever (Temperature), Headache, Malaise, and Myalgia for participants aged ≥ 2 years | From Day 0 up to 7 days after injection 3, and 7 days after subsequent injections | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rabies, Verorab®, Favirab®