Study of Purified Vero Rabies Vaccine Compared With Two Reference Rabies Vaccines in a Simulated Post-Exposure Regimen in Adults

Rabies (Healthy Volunteers) Clinical Trial

Official title:

Immunogenicity and Safety of a Purified Vero Rabies Vaccine - Serum Free in Comparison With Verorab® and Imovax® Rabies, in a Simulated Rabies Post-exposure Regimen in Healthy Adults in France

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03965962
• Other study ID #: VRV13
• Secondary ID: 2018-004055-20U1
• Status: Completed
• Phase: Phase 3
• Start date: July 1, 2019
• Est. completion date: July 1, 2021

Study information

• Verified date: June 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

To demonstrate that Purified Vero Rabies Vaccine - Serum Free Vaccine generation 2 (VRVg-2) was non-inferior to Verorab and Imovax Rabies vaccines when co-administered with human rabies immunoglobulin (HRIG), in terms of proportion of participants achieving a rabies virus neutralizing antibody (RVNA) titer greater than or equal to (>=) 0.5 international units per milliliter (IU/mL) at Day 28, i.e., 14 days after the fourth vaccine injection.

Secondary Objective:

• To describe the safety profile of VRVg-2 versus Verorab and Imovax Rabies vaccines when co-administered with HRIG, as well as that of VRVg-2, after each vaccine injection.

• To demonstrate that the proportion of participants in the VRVg-2 + HRIG group achieving an RVNA titer >= 0.5 IU/mL at Day 28 was at least 95 percent (%).

• To describe the immune response induced by VRVg-2 versus Verorab and Imovax Rabies vaccines when co-administered with HRIG, as well as that induced by VRVg-2, at Day 14 (7 days after the third injection), at Day 28 (14 days after the fourth injection) and at Day 42 (14 days after the last injection).

Description:

Study duration per participant was approximately 7 months including: 1 day of screening and vaccination, a total of 5 vaccine injections over a 28-day period, 1 safety-follow up visit at Day 42, 1 safety follow-up/end of study visit at Day 56 and a 6-month safety follow-up call after last vaccine administration.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 640
• Est. completion date: July 1, 2021
• Est. primary completion date: December 22, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria :

• Men or women aged >=18 years on the day of inclusion (>= 18 years means from the day of the 18th birthday onwards, with no upper age limit).

• Able to attend all scheduled visits and to comply with all trial procedures.

• Body Mass Index (BMI): 18.5 kilograms per square meter (kg/m^2) less than or equal to (<=) BMI <=30 kg/m^2.

Exclusion criteria:

• 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 7.

• Previous vaccination against rabies (in pre- or post-exposure regimen) with either the trial vaccines 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 exposure during the trial (veterinarians and their staff, animal handlers, rabies researchers, and certain laboratory workers, persons whose activities bring them into frequent contact with rabies virus or potentially rabid bats, raccoons, skunks, cats, dogs, or other species at risk for having rabies, people travelling where rabies was enzootic).

• Known systemic hypersensitivity to any of the vaccine or 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.

• Current alcohol or substance abuse that, in the opinion of the investigator, might interfere with the trial conduct of completion.

• Chronic illness that, in the opinion of the investigator, was 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 degree Celsius). A prospective participant should not be included in the study until the condition had resolved or the febrile event had subsided.

• Personal history of Guillain-Barré syndrome.

• 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 (ie, parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Rabies
• Rabies (Healthy Volunteers)

Intervention

Biological:
• VRVg-2
Pharmaceutical form: Powder and solvent for suspension for injection; Route of administration: IM
• Purified Inactivated Rabies Vaccine
Pharmaceutical form: Powder and solvent for suspension for injection; Route of administration: IM
• Human Diploid Cell Vaccine (HDCV)
Pharmaceutical form: Powder and solvent for suspension for injection; Route of administration: IM
• Rabies immune globulin (human)
Pharmaceutical form: Solution for injection; Route of administration: IM

Locations

Country	Name	City	State
France	Investigational Site Number 2500002	Gieres
France	Investigational Site Number 2500001	Rennes Cedex

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Rabies Virus Neutralizing Antibody (RVNA) Titers Greater Than or Equal to (>=) 0.5 International Units Per Milliliter (IU/mL)-Non-Inferiority Analysis	RVNA titer against rabies virus was assessed using the Rapid Fluorescent Focus Inhibition test (RFFIT) assay method.	Day 28
Secondary	Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL	RVNA titer against rabies virus was assessed using the RFFIT assay method. Immune response of VRVg-2 was considered sufficient if the lower limit of the 95% CI for percentage of participants in Group 1 with RVNA titers >=0.5 IU/mL was not less than 95% at Day 28, when the primary non-inferiority objective was achieved at Day 28.	Day 0 (pre-vaccination), Day 14, Day 28 and Day 42
Secondary	Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (Lower Limit of Quantification [LLOQ])	RVNA titer against rabies virus was assessed using the RFFIT assay method. Lower limit of quantitation (LLOQ) for the RFFIT assay was 0.2 IU/mL.	Day 0 (pre-vaccination), Day 14, Day 28 and Day 42
Secondary	Rabies Virus Neutralizing Antibody (RVNA) Geometric Mean Titers (GMTs) Against Rabies Virus	RVNA GMT against rabies virus was assessed using the RFFIT assay method.	Day 0 (pre-vaccination), Day 14, Day 28 and Day 42
Secondary	Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers	RVNA titer against rabies virus was assessed using the RFFIT assay method. GMTRs were calculated as the ratio of GMTs post vaccination (i.e., on Day 14, 28 and Day 42) and pre-vaccination on Day 0.	Day 0 (pre-vaccination), Day 14, Day 28 and Day 42
Secondary	Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization	Virus neutralization was defined as complete (absence of fluorescent cells) and incomplete (presence of fluorescent cells) at the participant/timepoint level at the starting dilution (1/5) of RFFIT assay. Percentage of participants with determined complete and determined incomplete virus neutralization were reported.	Day 0 (pre-vaccination), Day 14, Day 28 and Day 42
Secondary	Number of Participants With Immediate Unsolicited Adverse Events (AEs)	An AE was defined as any untoward medical occurrence in a participant who received study vaccine and does not necessary had 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 book (CRB) 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 CRB. Immediate AEs considered as related to vaccination were recorded as immediate unsolicited adverse reactions (ARs).	Within 30 minutes after any and each vaccination (Vaccination 1, 2, 3, 4 and 5)
Secondary	Number of Participants With Solicited Injection Site Reactions	A solicited reaction (SR) was an expected AR observed and reported under conditions (nature and onset) prelisted (i.e., solicited) in the protocol and CRB 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.	Within 7 days after any and each vaccination (Vaccination 1, 2, 3, 4 and 5)
Secondary	Number of Participants With Solicited Systemic Reactions	SR was an expected AR observed and reported under conditions (nature and onset) prelisted (i.e., solicited) in the protocol and CRB 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.	Up to 7 days after any and each vaccination (Vaccination 1, 2, 3, 4 and 5)
Secondary	Number of Participants With Unsolicited Adverse Events	An AE was defined as any untoward medical occurrence in a participant who received study vaccine and does not necessary had to have a causal relationship with treatment. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the CRB in terms of diagnosis and/or onset post-vaccination.	Up to 28 days after any and each vaccination (Vaccination 1, 2, 3, 4 and 5)
Secondary	Number of Participants With Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)	An AE was defined as any untoward medical occurrence in a participant who received study vaccine and does not necessary had 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. An AESI was defined as one of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was appropriate. All SAEs and AESIs occurring during the study that were related to the product administered were reported by the Investigator to the Independent Ethics Committee/Institutional Review Board. Relatedness to study vaccine was based on Investigator's discretion.	From Baseline (Day 0) up to 6 months after last vaccination (i.e., up to Month 7)