Study of Purified Vero Rabies Vaccine Compared With Two Reference Rabies Vaccines in a Simulated Post-Exposure Regimen in Adults
- Conditions
- Rabies (Healthy Volunteers)
- Interventions
- Biological: VRVg-2Biological: Purified Inactivated Rabies VaccineBiological: Human Diploid Cell Vaccine (HDCV)Biological: Rabies immune globulin (human)
- Registration Number
- NCT03965962
- Lead Sponsor
- Sanofi Pasteur, a Sanofi Company
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 640
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 2: Verorab + HRIG Rabies immune globulin (human) Participants received 0.5 mL IM injection of Verorab on Days 0, 3, 7, 14 and 28 along with HRIG injection at Day 0. Group 3: Imovax Rabies + HRIG Rabies immune globulin (human) Participants received 1 mL IM injection of Imovax Rabies on Days 0, 3, 7, 14 and 28 along with HRIG injection at Day 0. Group 1: VRVg-2 + HRIG VRVg-2 Participants received 0.5 milliliters (mL) intramuscular (IM) injection of VRVg-2 formulation on Days 0, 3, 7, 14 and 28 along with HRIG injection at Day 0. Group 1: VRVg-2 + HRIG Rabies immune globulin (human) Participants received 0.5 milliliters (mL) intramuscular (IM) injection of VRVg-2 formulation on Days 0, 3, 7, 14 and 28 along with HRIG injection at Day 0. Group 2: Verorab + HRIG Purified Inactivated Rabies Vaccine Participants received 0.5 mL IM injection of Verorab on Days 0, 3, 7, 14 and 28 along with HRIG injection at Day 0. Group 3: Imovax Rabies + HRIG Human Diploid Cell Vaccine (HDCV) Participants received 1 mL IM injection of Imovax Rabies on Days 0, 3, 7, 14 and 28 along with HRIG injection at Day 0. Group 4: VRVg-2 VRVg-2 Participants received 0.5 mL IM injection of VRVg-2 formulation on Days 0, 3, 7, 14 and 28.
- Primary Outcome Measures
Name Time Method 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 Day 28 RVNA titer against rabies virus was assessed using the Rapid Fluorescent Focus Inhibition test (RFFIT) assay method.
- Secondary Outcome Measures
Name Time Method Rabies Virus Neutralizing Antibody (RVNA) Geometric Mean Titers (GMTs) Against Rabies Virus Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 RVNA GMT against rabies virus was assessed using the RFFIT assay method.
Number of Participants With Solicited Injection Site Reactions Within 7 days after any and each vaccination (Vaccination 1, 2, 3, 4 and 5) 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.
Number of Participants With Solicited Systemic Reactions Up to 7 days after any and each vaccination (Vaccination 1, 2, 3, 4 and 5) 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.
Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 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.
Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (Lower Limit of Quantification [LLOQ]) Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 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.
Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 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.
Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 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.
Number of Participants With Immediate Unsolicited Adverse Events (AEs) Within 30 minutes after any and each vaccination (Vaccination 1, 2, 3, 4 and 5) 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).
Number of Participants With Unsolicited Adverse Events Up to 28 days after any and each vaccination (Vaccination 1, 2, 3, 4 and 5) 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.
Number of Participants With Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) From Baseline (Day 0) up to 6 months after last vaccination (i.e., up to Month 7) 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.
Trial Locations
- Locations (2)
Investigational Site Number 2500001
🇫🇷Rennes Cedex, France
Investigational Site Number 2500002
🇫🇷Gieres, France