Clinical trial NCT03145766: Immunogenicity and Safety of a Purified Vero Rabies Vaccine
Official title: Immunogenicity and Safety of a Purified Vero Rabies Vaccine - Serum Free When Administered According to a Simulated Rabies Post-exposure Regimen in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rabies Virus
Keywords: Rabies virus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2017-05-09
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This multicenter, observer-blind, controlled, randomized, Phase II study was designed to evaluate different formulations of the Purified Vero Rabies Cell vaccine VRVg.

Detailed description: This study assessed different formulations of the modified formulation of VRVg (VRVg 2- formulations 1 \[low\], 2 \[medium\] and 3 \[high\]) tested in parallel to the initial VRVg formulation (VRVg-1) and Imovax Rabies. Immune responses were assessed at Day 14, Day 28, Day 42, and at Month 7. Safety events were also reported.

Eligibility criteria: Inclusion Criteria:

An individual must fulfill all of the following criteria in order to be eligible for trial enrollment:

1. Aged 18 to less than 65 years on the day of inclusion.
2. Informed consent form had been signed and dated.
3. Able to attend all scheduled visits and to complied with all trial procedures.
4. Body Mass Index (BMI): 18.5 kilograms per meter square (Kg/m\^2) less than or equal to (\<=) BMI \<= 30 Kg/m\^2.

Exclusion Criteria:

An individual fulfilling any of the following criteria was to be excluded from trial enrollment:

1. Participant was 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 post-menopausal for at least 1 year, or surgically sterile.
2. Participation at the time of study enrollment or, planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure.
3. Receipt of any vaccine in the 4 weeks (28 days) preceding the first trial vaccination or planned receipt of any vaccine prior to Visit 6.
4. Previous vaccination against rabies (in pre- or post-exposure regimen) with either the trial vaccine or another vaccine.
5. Receipt of immune globulins, blood or blood-derived products in the past 3 months.
6. 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).
7. At high risk for rabies infection during the trial (e.g., veterinarians and staff, animal handlers, rabies researchers, or any others whose activities may bring them into frequent contact with rabies virus or animals who had the rabies virus).
8. Known systemic hypersensitivity to any of the vaccine or human rabies immunoglobulins (HRIG) 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.
9. Self-reported thrombocytopenia, contraindicating IM vaccination.
10. Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM vaccination.
11. Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
12. Current alcohol abuse or drug addiction.
13. Chronic illness that, in the opinion of the investigator, was at a stage where it might interfere with trial conduct or completion (e.g., cardiac disorders, renal disorders, auto immune disorders, diabetes, psychiatric disorders or chronic infection).
14. Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature greater than or equal to \[\>=\] 100.4 Fahrenheit \>=38.0 Celsius). A prospective participant should not be included in the study until the condition had resolved or the febrile event had subsided.
15. 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.
16. History of Guillain-Barré syndrome.

Primary outcomes:
measure: Rabies Virus Neutralizing Antibody (RVNA) Geometric Mean Titers (GMTs) Against Rabies Virus at Day 0
timeFrame: Day 0
measure: Rabies Virus Neutralizing Antibody Geometric Mean Titers Against Rabies Virus at Day 14
timeFrame: Day 14
measure: Rabies Virus Neutralizing Antibody Geometric Mean Titers Against Rabies Virus at Day 28
timeFrame: Day 28
measure: Rabies Virus Neutralizing Antibody Geometric Mean Titers Against Rabies Virus at Day 42
timeFrame: Day 42
measure: Rabies Virus Neutralizing Antibody Geometric Mean Titers Against Rabies Virus at Month 7
timeFrame: Month 7
measure: Percentage of Participants With Rabies Virus Neutralizing Antibody Titer Greater Than or Equal to (>=) 0.2 IU/mL and >=0.5 IU/mL at Day 0
timeFrame: Day 0
measure: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL and >=0.5 IU/mL at Day 14
timeFrame: Day 14
measure: Percentage of Participants With RVNA Titers >=0.2 IU/mL and >=0.5 IU/mL at Day 28
timeFrame: Day 28
measure: Percentage of Participants With RVNA Titers >=0.2 IU/mL and >=0.5 IU/mL at Day 42
timeFrame: Day 42
measure: Percentage of Participants With RVNA Titers >=0.2 IU/mL and >=0.5 IU/mL at Month 7
timeFrame: Month 7
measure: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody 7 Days Following Vaccination 3 (Day 14/Day 0)
timeFrame: Day 0 (pre-dose) and Day 14 (7 days post-dose 3)
measure: Geometric Mean Titer Ratio of Rabies Virus Neutralizing Antibody 14 Days Following Vaccination 4 (Day 28/Day 0)
timeFrame: Day 0 (pre-dose) and Day 28 (14 days post-dose 4)
measure: Geometric Mean Titer Ratio of Rabies Virus Neutralizing Antibody 14 Days Following Vaccination 5 (Day 42/Day 0)
timeFrame: Day 0 (Pre-dose) and Day 42 (14 days Post-dose 5)
measure: Geometric Mean Titer Ratio of Rabies Virus Neutralizing Antibody 6 Months Following Last Vaccination (Month 7/Day 0)
timeFrame: Day 0 (Pre-dose) and Month 7 (6 Months Post Last Vaccination)
measure: Percentage of Participants With Complete Virus Neutralization at Starting Dilution (1/5) of Rapid Fluorescent Focus Inhibition Test Assay at Day 0
timeFrame: Day 0
measure: Percentage of Participants With Complete Virus Neutralization at Starting Dilution (1/5) of Rapid Fluorescent Focus Inhibition Test Assay at Day 14
timeFrame: Day 14
measure: Percentage of Participants With Complete Virus Neutralization at Starting Dilution (1/5) of Rapid Fluorescent Focus Inhibition Test Assay at Day 28
timeFrame: Day 28
measure: Percentage of Participants With Complete Virus Neutralization at Starting Dilution (1/5) of Rapid Fluorescent Focus Inhibition Test Assay at Day 42
timeFrame: Day 42
measure: Percentage of Participants With Complete Virus Neutralization at Starting Dilution (1/5) of Rapid Fluorescent Focus Inhibition Test Assay at Month 7
timeFrame: Month 7
measure: Number of Participants With Immediate Unsolicited Adverse Events
timeFrame: Within 30 Minutes After any Vaccination
measure: Number of Participants With at Least One Solicited Injection Site Reactions
timeFrame: Within 7 Days After any and each vaccination (Vaccination 1, 2, 3, 4 and 5)
measure: Number of Participants With at Least One Solicited Systemic Reactions
timeFrame: Within 7 Days After any and each vaccination (Vaccination 1, 2, 3, 4 and 5)
measure: Number of Participants With at Least One Unsolicited Adverse Events
timeFrame: Within 28 Days After any vaccination
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From Day 0 up to Month 7
Secondary outcomes:
Other outcomes:
Locations:
city: Redding
country: United States
facility: Investigational Site
state: California
city: San Diego
country: United States
facility: Investigational Site
state: California
city: South Miami
country: United States
facility: Investigational Site
state: Florida
city: Omaha
country: United States
facility: Investigational Site
state: Nebraska
city: Las Vegas
country: United States
facility: Investigational Site
state: Nevada
Study officials:
References: