- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03145766
Immunogenicity and Safety of a Purified Vero Rabies Vaccine
March 30, 2022 updated by: Sanofi Pasteur, a Sanofi Company
Immunogenicity and Safety of a Purified Vero Rabies Vaccine - Serum Free When Administered According to a Simulated Rabies Post-exposure Regimen in Healthy Adults
This multicenter, observer-blind, controlled, randomized, Phase II study was designed to evaluate different formulations of the Purified Vero Rabies Cell vaccine VRVg.
Study Overview
Status
Completed
Conditions
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.
Study Type
Interventional
Enrollment (Actual)
320
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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California
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Redding, California, United States, 96001
- Investigational Site
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San Diego, California, United States, 92117
- Investigational Site
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Florida
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South Miami, Florida, United States, 33143
- Investigational Site
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Nebraska
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Omaha, Nebraska, United States, 68134
- Investigational Site
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Nevada
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Las Vegas, Nevada, United States, 89104
- Investigational Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 63 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
An individual must fulfill all of the following criteria in order to be eligible for trial enrollment:
- Aged 18 to less than 65 years on the day of inclusion.
- Informed consent form had been signed and dated.
- Able to attend all scheduled visits and to complied with all trial procedures.
- 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:
- 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.
- 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.
- 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.
- Previous vaccination against rabies (in pre- or post-exposure regimen) 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).
- 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).
- 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.
- Self-reported thrombocytopenia, contraindicating IM vaccination.
- Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM 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, 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).
- 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.
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group 1: VRVg-2 Formulation 1
VRVg-2 formulation 1, intramuscular (IM) injection on Days 0, 3, 7, 14 and 28.
Concomitant administration of human rabies immunoglobulins (HRIG) on Day 0.
|
Modified formulation 1 (Low) of Purified Vero Rabies Vaccine Serum Free
Modified formulation 2 (Medium) of Purified Vero Rabies Vaccine Serum Free
Modified formulation 3 (High) of Purified Vero Rabies Vaccine Serum Free
Commercialized formulation of HRIG
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Experimental: Group 2: VRVg-2 Formulation 2
VRVg-2 formulation 2, IM injection on Days 0, 3, 7, 14 and 28.
Concomitant administration of HRIG on Day 0.
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Modified formulation 1 (Low) of Purified Vero Rabies Vaccine Serum Free
Modified formulation 2 (Medium) of Purified Vero Rabies Vaccine Serum Free
Modified formulation 3 (High) of Purified Vero Rabies Vaccine Serum Free
Commercialized formulation of HRIG
|
Experimental: Group 3: VRVg-2 Formulation 3
VRVg-2 formulation 3, IM injection on Days 0, 3, 7, 14 and 28.
Concomitant administration of HRIG on Day 0.
|
Modified formulation 1 (Low) of Purified Vero Rabies Vaccine Serum Free
Modified formulation 2 (Medium) of Purified Vero Rabies Vaccine Serum Free
Modified formulation 3 (High) of Purified Vero Rabies Vaccine Serum Free
Commercialized formulation of HRIG
|
Experimental: Group 4: VRVg-1
VRVg-1 initial formulation, IM injection on Days 0, 3, 7, 14 and 28.
Concomitant administration of HRIG on Day 0.
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Commercialized formulation of HRIG
Initial formulation of Purified Vero Rabies Vaccine Serum Free
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Active Comparator: Group 5: Imovax Rabies
Imovax Rabies, IM injection on Days 0, 3, 7, 14 and 28.
Concomitant administration of HRIG on Day 0.
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Commercialized formulation of HRIG
Purified inactivated rabies vaccine prepared on human diploid cell cultures
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rabies Virus Neutralizing Antibody (RVNA) Geometric Mean Titers (GMTs) Against Rabies Virus at Day 0
Time Frame: Day 0
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RVNA GMT against rabies virus was assessed using the rapid fluorescent focus inhibition test (RFFIT) assay method.
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Day 0
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Rabies Virus Neutralizing Antibody Geometric Mean Titers Against Rabies Virus at Day 14
Time Frame: Day 14
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RVNA GMT against rabies virus was assessed using the RFFIT assay method.
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Day 14
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Rabies Virus Neutralizing Antibody Geometric Mean Titers Against Rabies Virus at Day 28
Time Frame: Day 28
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RVNA GMT against rabies virus was assessed using the RFFIT assay method.
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Day 28
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Rabies Virus Neutralizing Antibody Geometric Mean Titers Against Rabies Virus at Day 42
Time Frame: Day 42
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RVNA GMT against rabies virus was assessed using the RFFIT assay method.
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Day 42
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Rabies Virus Neutralizing Antibody Geometric Mean Titers Against Rabies Virus at Month 7
Time Frame: Month 7
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RVNA GMT against rabies virus was assessed using the RFFIT assay method.
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Month 7
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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
Time Frame: Day 0
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RVNA titer against rabies virus was assessed using the RFFIT assay method.
Participants with RVNA titer >=0.2 IU/mL were considered as seropositive.
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Day 0
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Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL and >=0.5 IU/mL at Day 14
Time Frame: Day 14
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RVNA titer against rabies virus was assessed using the RFFIT assay method.
Participants with RVNA titer >=0.2 IU/mL were considered as seropositive.
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Day 14
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Percentage of Participants With RVNA Titers >=0.2 IU/mL and >=0.5 IU/mL at Day 28
Time Frame: Day 28
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RVNA titer against rabies virus was assessed using the RFFIT assay method.
Participants with RVNA titer >=0.2 IU/mL were considered as seropositive.
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Day 28
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Percentage of Participants With RVNA Titers >=0.2 IU/mL and >=0.5 IU/mL at Day 42
Time Frame: Day 42
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RVNA titer against rabies virus was assessed using the RFFIT assay method.
Participants with RVNA titer >=0.2 IU/mL were considered as seropositive.
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Day 42
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Percentage of Participants With RVNA Titers >=0.2 IU/mL and >=0.5 IU/mL at Month 7
Time Frame: Month 7
|
RVNA titer against rabies virus was assessed using the RFFIT assay method.
Participants with RVNA titer >= 0.2 IU/mL were considered as seropositive.
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Month 7
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Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody 7 Days Following Vaccination 3 (Day 14/Day 0)
Time Frame: Day 0 (pre-dose) and Day 14 (7 days post-dose 3)
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RVNA titer against rabies virus was assessed using the RFFIT assay method.
GMTRs were calculated as the ratio of GMTs 7 days post 3rd vaccination (i.e., on Day 14) and pre-vaccination on Day 0.
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Day 0 (pre-dose) and Day 14 (7 days post-dose 3)
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Geometric Mean Titer Ratio of Rabies Virus Neutralizing Antibody 14 Days Following Vaccination 4 (Day 28/Day 0)
Time Frame: Day 0 (pre-dose) and Day 28 (14 days post-dose 4)
|
RVNA titer against rabies virus was assessed using the RFFIT assay method.
GMTRs were calculated as the ratio of GMTs 14 days post 4th vaccination (i.e., on Day 28) and pre-vaccination on Day 0.
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Day 0 (pre-dose) and Day 28 (14 days post-dose 4)
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Geometric Mean Titer Ratio of Rabies Virus Neutralizing Antibody 14 Days Following Vaccination 5 (Day 42/Day 0)
Time Frame: Day 0 (Pre-dose) and Day 42 (14 days Post-dose 5)
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RVNA titer against rabies virus was assessed using the RFFIT assay method.
GMTRs were calculated as the ratio of GMTs 14 days post 5th vaccination (i.e., on Day 42) and pre-vaccination on Day 0.
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Day 0 (Pre-dose) and Day 42 (14 days Post-dose 5)
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Geometric Mean Titer Ratio of Rabies Virus Neutralizing Antibody 6 Months Following Last Vaccination (Month 7/Day 0)
Time Frame: Day 0 (Pre-dose) and Month 7 (6 Months Post Last Vaccination)
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RVNA titer against rabies virus was assessed using the RFFIT assay method.
GMTRs were calculated as the ratio of GMTs 6 month post last vaccination on Month 7 and pre-vaccination on Day 0.
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Day 0 (Pre-dose) and Month 7 (6 Months Post Last Vaccination)
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Percentage of Participants With Complete Virus Neutralization at Starting Dilution (1/5) of Rapid Fluorescent Focus Inhibition Test Assay at Day 0
Time Frame: Day 0
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Complete virus neutralization was defined as absence of fluorescent cells at the participant/time point level at the starting dilution (1/5) of the RFFIT assay.
Percentage of participants with complete virus neutralization were reported.
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Day 0
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Percentage of Participants With Complete Virus Neutralization at Starting Dilution (1/5) of Rapid Fluorescent Focus Inhibition Test Assay at Day 14
Time Frame: Day 14
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Complete virus neutralization was defined as absence of fluorescent cells at the participant/time point level at the starting dilution (1/5) of the RFFIT assay.
Percentage of participants with complete virus neutralization were reported.
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Day 14
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Percentage of Participants With Complete Virus Neutralization at Starting Dilution (1/5) of Rapid Fluorescent Focus Inhibition Test Assay at Day 28
Time Frame: Day 28
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Complete virus neutralization was defined as absence of fluorescent cells at the participant/time point level at the starting dilution (1/5) of the RFFIT assay.
Percentage of participants with complete virus neutralization were reported.
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Day 28
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Percentage of Participants With Complete Virus Neutralization at Starting Dilution (1/5) of Rapid Fluorescent Focus Inhibition Test Assay at Day 42
Time Frame: Day 42
|
Complete virus neutralization was defined as absence of fluorescent cells at the participant/time point level at the starting dilution (1/5) of the RFFIT assay.
Percentage of participants with complete virus neutralization were reported.
|
Day 42
|
Percentage of Participants With Complete Virus Neutralization at Starting Dilution (1/5) of Rapid Fluorescent Focus Inhibition Test Assay at Month 7
Time Frame: Month 7
|
Complete virus neutralization was defined as absence of fluorescent cells at the participant/time point level at the starting dilution (1/5) of the RFFIT assay.
Percentage of participants with complete virus neutralization were reported.
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Month 7
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Number of Participants With Immediate Unsolicited Adverse Events
Time Frame: Within 30 Minutes After any Vaccination
|
An adverse event was defined as any untoward medical occurrence in a participant who received study drug and does not necessary have to have a causal relationship with treatment.
An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report form (CRF) in terms of diagnosis and/or onset post-vaccination.
All participants were observed for 30 minutes after any vaccination, and any unsolicited AEs occurred during that time were recorded as immediate unsolicited AEs in the CRF.
Immediate AEs considered as related to vaccination were recorded as immediate unsolicited adverse reactions (ARs).
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Within 30 Minutes After any Vaccination
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Number of Participants With at Least One Solicited Injection Site Reactions
Time Frame: Within 7 Days After any and each vaccination (Vaccination 1, 2, 3, 4 and 5)
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A solicited reaction (SR) was an AR observed and reported under conditions (symptoms and onset) prelisted (i.e., solicited) in the CRF and considered as related to vaccination.
An AR was all noxious and unintended responses to a medicinal product related to any dose.
Solicited injection site reactions included pain, erythema and swelling at and around the injection site.
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Within 7 Days After any and each vaccination (Vaccination 1, 2, 3, 4 and 5)
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Number of Participants With at Least One Solicited Systemic Reactions
Time Frame: Within 7 Days After any and each vaccination (Vaccination 1, 2, 3, 4 and 5)
|
A solicited reaction was an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the CRF and considered as related to vaccination.
An AR was all noxious and unintended responses to a medicinal product related to any dose.
Solicited systemic reactions included fever, headache, malaise and myalgia.
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Within 7 Days After any and each vaccination (Vaccination 1, 2, 3, 4 and 5)
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Number of Participants With at Least One Unsolicited Adverse Events
Time Frame: Within 28 Days After any vaccination
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An AE was defined as any untoward medical occurrence in a participant who received study drug and does not necessary have to have a causal relationship with treatment.
An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the CRF in terms of diagnosis and/or onset post-vaccination.
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Within 28 Days After any vaccination
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Number of Participants With Serious Adverse Events (SAEs)
Time Frame: From Day 0 up to Month 7
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An AE was defined as any untoward medical occurrence in a participant who received study drug and does not necessary have to have a causal relationship with treatment.
An SAE was any untoward medical occurrence that at any dose resulted in death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect or a medically important event.
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From Day 0 up to Month 7
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 17, 2017
Primary Completion (Actual)
January 8, 2018
Study Completion (Actual)
January 8, 2018
Study Registration Dates
First Submitted
May 3, 2017
First Submitted That Met QC Criteria
May 5, 2017
First Posted (Actual)
May 9, 2017
Study Record Updates
Last Update Posted (Actual)
April 19, 2022
Last Update Submitted That Met QC Criteria
March 30, 2022
Last Verified
March 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- VRV11
- U1111-1174-4976 (Other Identifier: UTN)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications.
Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants.
Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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