Rabies VirusPhase 2NCT03145766

Immunogenicity and Safety of a Purified Vero Rabies Vaccine

A Phase 2 study testing VRVg 2, VRVg 1 and Imovax Rabies in people with Rabies Virus, run by Sanofi Pasteur, a Sanofi Company at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This multicenter, observer-blind, controlled, randomized, Phase II study was designed to evaluate different formulations of the Purified Vero Rabies Cell vaccine VRVg. Read more about this study

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Rabies Virus
What is being tested?: VRVg 2, VRVg 1 and Imovax Rabies
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 320 participants
Where: 5 sitesUnited States
Study dates: 17 Apr 2017to 8 Jan 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

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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.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

Investigational Site
Las Vegas, Nevada, 89104
Investigational Site
Omaha, Nebraska, 68134
Investigational Site
Redding, California, 96001
Investigational Site
San Diego, California, 92117
Investigational Site
South Miami, Florida, 33143

Other trials in United States

About this study

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

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

Read the 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.

Conditions: Rabies Virus
Being tested: VRVg 2, VRVg 1, Imovax Rabies, Human Rabies Immunoglobulins (HRIG)
Keywords: Rabies virus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VRVg 2Biological
Modified formulation 1 (Low) of Purified Vero Rabies Vaccine Serum Free
VRVg 1Biological
Initial formulation of Purified Vero Rabies Vaccine Serum Free
Imovax RabiesBiological
Purified inactivated rabies vaccine prepared on human diploid cell cultures
VRVg 2Biological
Modified formulation 2 (Medium) of Purified Vero Rabies Vaccine Serum Free
VRVg 2Biological
Modified formulation 3 (High) of Purified Vero Rabies Vaccine Serum Free
Human Rabies Immunoglobulins (HRIG)Biological
Commercialized formulation of HRIG

Study groups in NCT03145766
Study group	Role	What they receive
Group 1: VRVg-2 Formulation 1	Experimental	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. Receives: Biological: VRVg 2; Biological: Human Rabies Immunoglobulins (HRIG)
Group 2: VRVg-2 Formulation 2	Experimental	VRVg-2 formulation 2, IM injection on Days 0, 3, 7, 14 and 28. Concomitant administration of HRIG on Day 0. Receives: Biological: VRVg 2; Biological: Human Rabies Immunoglobulins (HRIG)
Group 3: VRVg-2 Formulation 3	Experimental	VRVg-2 formulation 3, IM injection on Days 0, 3, 7, 14 and 28. Concomitant administration of HRIG on Day 0. Receives: Biological: VRVg 2; Biological: Human Rabies Immunoglobulins (HRIG)
Group 4: VRVg-1	Experimental	VRVg-1 initial formulation, IM injection on Days 0, 3, 7, 14 and 28. Concomitant administration of HRIG on Day 0. Receives: Biological: VRVg 1; Biological: Human Rabies Immunoglobulins (HRIG)
Group 5: Imovax Rabies	Active comparator	Imovax Rabies, IM injection on Days 0, 3, 7, 14 and 28. Concomitant administration of HRIG on Day 0. Receives: Biological: Imovax Rabies; Biological: Human Rabies Immunoglobulins (HRIG)

What is being measured

The primary outcome is the main question the study is designed to answer.

Rabies Virus Neutralizing Antibody (RVNA) Geometric Mean Titers (GMTs) Against Rabies Virus at Day 0
RVNA GMT against rabies virus was assessed using the rapid fluorescent focus inhibition test (RFFIT) assay method.
Measured: Day 0
Rabies Virus Neutralizing Antibody Geometric Mean Titers Against Rabies Virus at Day 14
RVNA GMT against rabies virus was assessed using the RFFIT assay method.
Measured: Day 14
Rabies Virus Neutralizing Antibody Geometric Mean Titers Against Rabies Virus at Day 28
RVNA GMT against rabies virus was assessed using the RFFIT assay method.
Measured: Day 28
Rabies Virus Neutralizing Antibody Geometric Mean Titers Against Rabies Virus at Day 42
RVNA GMT against rabies virus was assessed using the RFFIT assay method.
Measured: Day 42
Rabies Virus Neutralizing Antibody Geometric Mean Titers Against Rabies Virus at Month 7
RVNA GMT against rabies virus was assessed using the RFFIT assay method.
Measured: Month 7
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
RVNA titer against rabies virus was assessed using the RFFIT assay method. Participants with RVNA titer >=0.2 IU/mL were considered as seropositive.
Measured: Day 0
Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL and >=0.5 IU/mL at Day 14
RVNA titer against rabies virus was assessed using the RFFIT assay method. Participants with RVNA titer >=0.2 IU/mL were considered as seropositive.
Measured: Day 14
Percentage of Participants With RVNA Titers >=0.2 IU/mL and >=0.5 IU/mL at Day 28
RVNA titer against rabies virus was assessed using the RFFIT assay method. Participants with RVNA titer >=0.2 IU/mL were considered as seropositive.
Measured: Day 28
Percentage of Participants With RVNA Titers >=0.2 IU/mL and >=0.5 IU/mL at Day 42
RVNA titer against rabies virus was assessed using the RFFIT assay method. Participants with RVNA titer >=0.2 IU/mL were considered as seropositive.
Measured: Day 42
Percentage of Participants With RVNA Titers >=0.2 IU/mL and >=0.5 IU/mL at 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.
Measured: Month 7
Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody 7 Days Following Vaccination 3 (Day 14/Day 0)
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.
Measured: Day 0 (pre-dose) and Day 14 (7 days post-dose 3)
Geometric Mean Titer Ratio of Rabies Virus Neutralizing Antibody 14 Days Following Vaccination 4 (Day 28/Day 0)
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.
Measured: Day 0 (pre-dose) and Day 28 (14 days post-dose 4)
Geometric Mean Titer Ratio of Rabies Virus Neutralizing Antibody 14 Days Following Vaccination 5 (Day 42/Day 0)
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.
Measured: Day 0 (Pre-dose) and Day 42 (14 days Post-dose 5)
Geometric Mean Titer Ratio of Rabies Virus Neutralizing Antibody 6 Months Following Last Vaccination (Month 7/Day 0)
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.
Measured: Day 0 (Pre-dose) and Month 7 (6 Months Post Last Vaccination)
Percentage of Participants With Complete Virus Neutralization at Starting Dilution (1/5) of Rapid Fluorescent Focus Inhibition Test Assay at Day 0
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.
Measured: Day 0
Percentage of Participants With Complete Virus Neutralization at Starting Dilution (1/5) of Rapid Fluorescent Focus Inhibition Test Assay at Day 14
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.
Measured: Day 14
Percentage of Participants With Complete Virus Neutralization at Starting Dilution (1/5) of Rapid Fluorescent Focus Inhibition Test Assay at Day 28
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.
Measured: Day 28
Percentage of Participants With Complete Virus Neutralization at Starting Dilution (1/5) of Rapid Fluorescent Focus Inhibition Test Assay at 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.
Measured: Day 42
Percentage of Participants With Complete Virus Neutralization at Starting Dilution (1/5) of Rapid Fluorescent Focus Inhibition Test Assay at 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.
Measured: Month 7
Number of Participants With Immediate Unsolicited Adverse Events
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).
Measured: Within 30 Minutes After any Vaccination
Number of Participants With at Least One Solicited Injection Site Reactions
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.
Measured: Within 7 Days After any and each vaccination (Vaccination 1, 2, 3, 4 and 5)
Number of Participants With at Least One Solicited Systemic Reactions
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.
Measured: Within 7 Days After any and each vaccination (Vaccination 1, 2, 3, 4 and 5)
Number of Participants With at Least One Unsolicited Adverse Events
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.
Measured: Within 28 Days After any vaccination
Number of Participants With Serious Adverse Events (SAEs)
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.
Measured: From Day 0 up to Month 7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

17 Apr 20178 Jan 2018

First posted9 May 2017
Study start17 Apr 2017
Primary completion8 Jan 2018
Study completion8 Jan 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Rabies VirusStudies of the same condition, open and under way.
More trials run by Sanofi Pasteur, a Sanofi CompanyThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 320 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03145766
Sponsor's protocol ID: VRV11
Other IDs: U1111-1174-4976
Status last verified: Mar 2022
First submitted: 3 May 2017
Last updated: 19 Apr 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: 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

Publications

Pichon S, Guinet-Morlot F, Saleh J, Essink B, Pineda-Pena AC, Moureau A, Petit C, Minutello AM. Safety and immunogenicity of three dose levels of an investigational, highly purified Vero cell rabies vaccine: A randomized, controlled, observer-blinded, Phase II study with a simulated post-exposure regimen in healthy adults. Hum Vaccin Immunother. 2023 Dec 15;19(3):2275453. doi: 10.1080/21645515.2023.2275453. Epub 2023 Nov 3.
PubMed 37921410

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 19 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03145766
Acronym / sponsor ID: VRV11
Conditions: Rabies Virus
Keywords: Rabies virus
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 320 participants (actual)
Lead sponsor: Sanofi Pasteur, a Sanofi CompanyIndustry (pharma, biotech, devices)
Study start: 17 Apr 2017 (actual)
Primary completion: 8 Jan 2018 (actual)
Study completion: 8 Jan 2018 (actual)
First posted: 9 May 2017 (actual)
Results: Posted 28 Jan 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 5

Arm	Type	Receives
Group 1: VRVg-2 Formulation 1	Experimental	Biological: VRVg 2, Biological: Human Rabies Immunoglobulins (HRIG)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.
Group 2: VRVg-2 Formulation 2	Experimental	Biological: VRVg 2, Biological: Human Rabies Immunoglobulins (HRIG)VRVg-2 formulation 2, IM injection on Days 0, 3, 7, 14 and 28. Concomitant administration of HRIG on Day 0.
Group 3: VRVg-2 Formulation 3	Experimental	Biological: VRVg 2, Biological: Human Rabies Immunoglobulins (HRIG)VRVg-2 formulation 3, IM injection on Days 0, 3, 7, 14 and 28. Concomitant administration of HRIG on Day 0.
Group 4: VRVg-1	Experimental	Biological: VRVg 1, Biological: Human Rabies Immunoglobulins (HRIG)VRVg-1 initial formulation, IM injection on Days 0, 3, 7, 14 and 28. Concomitant administration of HRIG on Day 0.
Group 5: Imovax Rabies	Active comparator	Biological: Imovax Rabies, Biological: Human Rabies Immunoglobulins (HRIG)Imovax Rabies, IM injection on Days 0, 3, 7, 14 and 28. Concomitant administration of HRIG on Day 0.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (17 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
VRVg 2Modified formulation 1 (Low) of Purified Vero Rabies Vaccine Serum Free	Biological	Group 1: VRVg-2 Formulation 1
VRVg 1Initial formulation of Purified Vero Rabies Vaccine Serum Free	Biological	Group 4: VRVg-1
Imovax RabiesPurified inactivated rabies vaccine prepared on human diploid cell cultures	Biological	Group 5: Imovax Rabies
VRVg 2Modified formulation 2 (Medium) of Purified Vero Rabies Vaccine Serum Free	Biological	Group 2: VRVg-2 Formulation 2
VRVg 2Modified formulation 3 (High) of Purified Vero Rabies Vaccine Serum Free	Biological	Group 3: VRVg-2 Formulation 3
Human Rabies Immunoglobulins (HRIG)Commercialized formulation of HRIG	Biological	Group 1: VRVg-2 Formulation 1, Group 2: VRVg-2 Formulation 2, Group 3: VRVg-2 Formulation 3, Group 4: VRVg-1, Group 5: Imovax Rabies

Primary outcome

Rabies Virus Neutralizing Antibody (RVNA) Geometric Mean Titers (GMTs) Against Rabies Virus at Day 0
Time frame: Day 0
RVNA GMT against rabies virus was assessed using the rapid fluorescent focus inhibition test (RFFIT) assay method.
Rabies Virus Neutralizing Antibody Geometric Mean Titers Against Rabies Virus at Day 14
Time frame: Day 14
RVNA GMT against rabies virus was assessed using the RFFIT assay method.
Rabies Virus Neutralizing Antibody Geometric Mean Titers Against Rabies Virus at Day 28
Time frame: Day 28
RVNA GMT against rabies virus was assessed using the RFFIT assay method.
Rabies Virus Neutralizing Antibody Geometric Mean Titers Against Rabies Virus at Day 42
Time frame: Day 42
RVNA GMT against rabies virus was assessed using the RFFIT assay method.
Rabies Virus Neutralizing Antibody Geometric Mean Titers Against Rabies Virus at Month 7
Time frame: Month 7
RVNA GMT against rabies virus was assessed using the RFFIT assay method.
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
RVNA titer against rabies virus was assessed using the RFFIT assay method. Participants with RVNA titer >=0.2 IU/mL were considered as seropositive.
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
RVNA titer against rabies virus was assessed using the RFFIT assay method. Participants with RVNA titer >=0.2 IU/mL were considered as seropositive.
Percentage of Participants With RVNA Titers >=0.2 IU/mL and >=0.5 IU/mL at Day 28
Time frame: Day 28
RVNA titer against rabies virus was assessed using the RFFIT assay method. Participants with RVNA titer >=0.2 IU/mL were considered as seropositive.
Percentage of Participants With RVNA Titers >=0.2 IU/mL and >=0.5 IU/mL at Day 42
Time frame: Day 42
RVNA titer against rabies virus was assessed using the RFFIT assay method. Participants with RVNA titer >=0.2 IU/mL were considered as seropositive.
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.
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)
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.
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.
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)
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.
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)
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.
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
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.
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
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.
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
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.
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.
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.
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).
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)
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.
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.
Number of Participants With at Least One Unsolicited Adverse Events
Time frame: Within 28 Days After any vaccination
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.
Number of Participants With Serious Adverse Events (SAEs)
Time frame: From Day 0 up to Month 7
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.

Results and safety

Results posted to the registry on 28 Jan 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group 1: VRVg-2 Formulation 1	80	74
Group 2:VRVg-2 Formulation 2	80	77
Group 3: VRVg-2 Formulation 3	80	78
Group 4: VRVg-1	40	33
Group 5: Imovax Rabies	40	37

Primary outcome: Rabies Virus Neutralizing Antibody (RVNA) Geometric Mean Titers (GMTs) Against Rabies Virus at Day 0

Time frame: Day 0. Geometric mean (95% Confidence Interval). Unit: international units per milliliter

Measure	Group 1: VRVg-2 Formulation 1 n = 72	Group 2:VRVg-2 Formulation 2 n = 75	Group 3: VRVg-2 Formulation 3 n = 71	Group 4: VRVg-1 n = 35	Group 5: Imovax Rabies n = 34
Value	0.101 (0.099 to 0.102)	0.100 (NA to NA)	0.102 (0.099 to 0.104)	0.101 (0.099 to 0.103)	0.100 (NA to NA)

Population analysed: Per-Protocol Analysis Set (PPAS): participants who received at least one dose of the study vaccine without protocol deviations before Day 14 (i.e., 7 days after the 3rd vaccine injection).

Primary outcome: Rabies Virus Neutralizing Antibody Geometric Mean Titers Against Rabies Virus at Day 14

Time frame: Day 14. Geometric mean (95% Confidence Interval). Unit: international units per milliliter

Measure	Group 1: VRVg-2 Formulation 1 n = 72	Group 2:VRVg-2 Formulation 2 n = 75	Group 3: VRVg-2 Formulation 3 n = 71	Group 4: VRVg-1 n = 35	Group 5: Imovax Rabies n = 34
Value	1.28 (0.944 to 1.73)	1.79 (1.33 to 2.41)	2.52 (1.93 to 3.28)	1.38 (0.936 to 2.05)	1.56 (1.06 to 2.29)

Population analysed: Analysis was performed on PPAS.

Primary outcome: Rabies Virus Neutralizing Antibody Geometric Mean Titers Against Rabies Virus at Day 28

Time frame: Day 28. Geometric mean (95% Confidence Interval). Unit: international units per milliliter

Measure	Group 1: VRVg-2 Formulation 1 n = 66	Group 2:VRVg-2 Formulation 2 n = 73	Group 3: VRVg-2 Formulation 3 n = 68	Group 4: VRVg-1 n = 29	Group 5: Imovax Rabies n = 33
Value	3.22 (2.48 to 4.17)	4.64 (3.53 to 6.10)	6.81 (5.52 to 8.39)	3.04 (1.86 to 4.95)	4.86 (3.56 to 6.65)

Population analysed: Analysis was performed on PPAS. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Primary outcome: Rabies Virus Neutralizing Antibody Geometric Mean Titers Against Rabies Virus at Day 42

Time frame: Day 42. Geometric mean (95% Confidence Interval). Unit: international units per milliliter

Measure	Group 1: VRVg-2 Formulation 1 n = 69	Group 2:VRVg-2 Formulation 2 n = 72	Group 3: VRVg-2 Formulation 3 n = 65	Group 4: VRVg-1 n = 30	Group 5: Imovax Rabies n = 31
Value	8.14 (6.60 to 10.0)	9.68 (7.50 to 12.5)	15.6 (12.7 to 19.1)	6.98 (4.69 to 10.4)	8.99 (6.48 to 12.5)

Population analysed: Analysis was performed on PPAS. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Adverse events

Time frame: AE data were collected from Day 0 (post-vaccination 1) up to 28 days post any vaccination. SR data were collected within 7 days post any vaccination. SAE data were collected throughout the study (up to 6 months after last vaccination, i.e., up to Month 7).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group 1: VRVg-2 Formulation 1	0 of 80 (0%)	40 of 80 (50%)	0 of 80
Group 2: VRVg-2 Formulation 2	0 of 80 (0%)	39 of 80 (48.8%)	0 of 80
Group 3: VRVg-2 Formulation 3	1 of 80 (1.3%)	45 of 80 (56.3%)	0 of 80
Group 4: VRVg-1	0 of 39 (0%)	22 of 39 (56.4%)	0 of 39
Group 5: Imovax Rabies	0 of 41 (0%)	28 of 41 (68.3%)	0 of 41

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37921410Pichon S, Guinet-Morlot F, Saleh J, Essink B, Pineda-Pena AC, Moureau A, Petit C, Minutello AM. Safety and immunogenicity of three dose levels of an investigational, highly purified Vero cell rabies vaccine: A randomized, controlled, observer-blinded, Phase II study with a simulated post-exposure regimen in healthy adults. Hum Vaccin Immunother. 2023 Dec 15;19(3):2275453. doi: 10.1080/21645515.2023.2275453. Epub 2023 Nov 3.
Individual participant dataSharing planned: Yes. 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

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing VRVg 2, VRVg 1 and Imovax Rabies in people with Rabies Virus, run by Sanofi Pasteur, a Sanofi Company at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rabies Virus Neutralizing Antibody (RVNA) Geometric Mean Titers (GMTs) Against Rabies Virus at Day 0 (time frame: Day 0). The study lists 24 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03145766, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2022.