Clinical trial NCT03965962: Study of Purified Vero Rabies Vaccine Compared With Two Reference Rabies Vaccines in a Simulated Post-Exposure Regimen in Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rabies (Healthy Volunteers)
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2019-05-29
Enrollment: 640
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study was divided into 4 groups: groups 1 to 3 (VRVg-2 + HRIG; Verorab + HRIG; Imovax Rabies + HRIG) were modified double-blind and group 4 (VRVg-2 standalone) was open-label.
Primary purpose: PREVENTION

Brief 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).

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Day 28
Secondary outcomes:
measure: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL
timeFrame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42
measure: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (Lower Limit of Quantification [LLOQ])
timeFrame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42
measure: Rabies Virus Neutralizing Antibody (RVNA) Geometric Mean Titers (GMTs) Against Rabies Virus
timeFrame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42
measure: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers
timeFrame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42
measure: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization
timeFrame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42
measure: Number of Participants With Immediate Unsolicited Adverse Events (AEs)
timeFrame: Within 30 minutes after any and each vaccination (Vaccination 1, 2, 3, 4 and 5)
measure: Number of Participants With 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 Solicited Systemic Reactions
timeFrame: Up to 7 days after any and each vaccination (Vaccination 1, 2, 3, 4 and 5)
measure: Number of Participants With Unsolicited Adverse Events
timeFrame: Up to 28 days after any and each vaccination (Vaccination 1, 2, 3, 4 and 5)
measure: Number of Participants With Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
timeFrame: From Baseline (Day 0) up to 6 months after last vaccination (i.e., up to Month 7)
Other outcomes:
Locations:
city: Gieres
country: France
facility: Investigational Site Number 2500002
city: Rennes Cedex
country: France
facility: Investigational Site Number 2500001
Study officials:
affiliation: Sanofi Pasteur, a Sanofi Company
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: