Phase 3
N=1,708
Study of Purified Vero Rabies Vaccine Compared With Two Reference Rabies Vaccines, Given in a Pre-exposure Regimen to Children and Adults and as Single Booster Dose to a Subset of Adults
Rabies · Healthy Volunteers
Bottom Line
View on ClinicalTrials.gov: NCT04127786 ↗Enrolled (actual)
1,708
Serious AEs
1.4%
Results posted
Feb 2024
Primary outcome: Primary: Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody (RVNA) Titer Greater Than or Equal to (>=) 0.5 IU/mL — 100; 100; 100; 100 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Purified vero rabies vaccine - serum free - VRVg-2 (Biological); Purified inactivated rabies vaccine - Verorab® (Biological); Purified inactivated rabies vaccine - Imovax® Rabies (Biological)
- Age
- Pediatric, Adult, Older Adult · 1+ yrs
- Sex
- All
- Sponsor
- Sanofi Pasteur, a Sanofi Company
- Primary completion
- Mar 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody (RVNA) Titer Greater Than or Equal to (>=) 0.5 IU/mL |
100; 100; 100; 100; 98.8; 100 | — |
| SECONDARY Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL |
0; 0; 0; 100; 99.4; 98.8 | — |
| SECONDARY Primary Series: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population |
100; 100; 100; 98.3; 98.5; 96.6 | — |
| SECONDARY Primary Series: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population (Groups 1 and 4) Versus Cohort 1: Group 3: Non-inferiority Analysis |
100; 100; 98.3; 100 | — |
| SECONDARY Primary Series: Groups 1 and 4: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population - Superiority Analysis |
98.8 | — |
| SECONDARY Primary Series Cohort 1 Group 3: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Non-Inferiority Analysis |
0; 98.8; 100 | — |
| SECONDARY Primary Series Cohort 1: Rabies Virus Neutralizing Antibody Geometric Mean Titers (GMTs) Against Rabies Virus |
0.100; 0.101; 0.101; 7.16; 4.90; 5.13 | — |
| SECONDARY Primary Series Cohort 2: Rabies Virus Neutralizing Antibody Geometric Mean Titers (GMTs) Against Rabies Virus |
0.101; 0.101; 0.100; 3.79; 2.92; 3.91 | — |
| SECONDARY Primary Series Cohort 2: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL |
0; 0; 0; 97.1; 98.3; 96.0 | — |
| SECONDARY Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (Lower Limit of Quantification [LLOQ]) |
0; 0; 0; 100; 99.4; 100 | — |
| SECONDARY Primary Series Cohort 2: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (Lower Limit of Quantification [LLOQ]) |
0; 0; 0; 99.7; 100; 98.4 | — |
| SECONDARY Primary Series Cohort 1: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers |
71.5; 48.7; 51.0; 240; 199; 163 | — |
| SECONDARY Primary Series Cohort 2: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers |
37.7; 29.0; 38.9 | — |
| SECONDARY Primary Series Cohort 1: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization |
0.2; 0.6; 1.3; 99.8; 99.4; 98.7 | — |
| SECONDARY Primary Series Cohort 2: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization |
0.9; 4.2; 0; 99.1; 95.8; 100 | — |
| SECONDARY Booster Phase: Rabies Virus Neutralizing Antibody (RVNA) Geometric Mean Titers (GMTs) Against Rabies Virus |
0.679; 0.540; 0.487; 56.5; 57.1; 33.7 | — |
| SECONDARY Booster Phase: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL |
53.8; 53.8; 35.7; 100; 100; 100 | — |
| SECONDARY Booster Phase: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (LLOQ) |
86.3; 76.9; 85.7; 100; 100; 100 | — |
| SECONDARY Booster Phase: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers |
6.79; 5.40; 4.78; 565; 571; 331 | — |
| SECONDARY Booster Phase: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization |
96.1; 84.0; 95.7; 3.9; 16.0; 4.3 | — |
| SECONDARY Booster Phase Cohort 2: Rabies Virus Neutralizing Antibody (RVNA) Geometric Mean Titers (GMTs) Against Rabies Virus |
0.761; 0.536; 0.903; 95.4; 89.4; 64.7 | — |
| SECONDARY Booster Phase Cohort 2: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL |
62.0; 51.5; 64.9; 100; 100; 100 | — |
| SECONDARY Booster Phase Cohort 2: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (Lower Limit of Quantification [LLOQ]) |
89.8; 87.9; 89.2; 100; 100; 100 | — |
| SECONDARY Booster Phase Cohort 2: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers |
7.58; 5.30; 9.03; 951; 885; 647 | — |
| SECONDARY Booster Phase Cohort 2: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization |
94.1; 93.8; 91.9; 5.9; 6.3; 8.1 | — |
| SECONDARY Number of Participants With Immediate Unsolicited Adverse Events (AEs) |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Booster Phase Cohort 2: Number of Participants With Immediate Unsolicited Adverse Events (AEs) |
0; 0; 0 | — |
| SECONDARY Number of Participants With Systemic Reactions |
50; 11; 4; 2; 0; 0 | — |
| SECONDARY Booster Phase Cohort 2: Number of Participants With Systemic Reactions |
0; 0; 0; 3; 0; 0 | — |
| SECONDARY Number of Participants With Solicited Injection Site Reactions |
344; 95; 106; 111; 30; 43 | — |
| SECONDARY Booster Phase Cohort 2: Number of Participants With Solicited Injection Site Reactions |
20; 2; 6; 0; 0; 0 | — |
| SECONDARY Number of Participants With Unsolicited Adverse Events |
137; 45; 40; 44; 18; 12 | — |
| SECONDARY Booster Phase Cohort 2: Number of Participants With Unsolicited Adverse Events |
15; 1; 3 | — |
| SECONDARY Number of Participants With Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) |
10; 3; 5; 2; 0; 1 | — |
| SECONDARY Booster Phase Cohort 2: Number of Participants With Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) |
3; 0; 1; 0; 0; 0 | — |
Summary
The primary objective of this study is:
To demonstrate the VRVg-2 is non-inferior to Verorab and Imovax Rabies vaccines in each age group (pediatric and adult populations) when administered as a 3-dose PrEP regimen, in terms of proportion of participants achieving a rabies virus neutralizing antibody (RVNA) titer ≥ 0.5 IU/mL at Day 42, ie. 14 days after the 3rd injection (for Primary Series Cohort 1).
The secondary objectives of this study are: First 1-5 with hypotheses testing will be evaluated sequentially - only if the previous objective is achieved, will the next objective be tested
To demonstrate that:
* the observed proportion of participants in the VRVg2(VRVg) group at D42 is at least 99% with a lower limit of the 95% confidence interval (CI) of at least 97%
* VRVg is non inferior (NI) to Verorab and Imovax Rabies vaccines (Imovax) in each age group at D28
* 2-dose VRVg at D28 is NI to 3-dose Imovax at D42 in each age group
* the observed proportion of participants in the VRVg group at D28 is at least 99% with a lower limit of the 95% CI of at least 97%
* 2-dose Imovax at D28 is NI to 3-dose Imovax at D42 in overall participants (Cohort1)
To describe:
* the immune response induced by VRVg versus Verorab and Imovax at D28 and at D42 in all age groups
* the immune response induced by VRVg at D14 after a booster dose of VRVg administered at M12 (Cohort1) and between M24 up to M36 (Cohort2)
* the persistence of immune response at M6,12,18, and pre-booster between M24 up to M36 post-primary series vaccination (Cohort2)
* safety profile of VRVg versus Verorab and Imovax in primary series and after a booster dose of VRVg
Eligibility Criteria
Inclusion Criteria
- Aged ≥1 year on the day of inclusion
- Cohort 1 - pediatrics (>1 to 17 years old) and adult (≥18 years old)
- Cohort 2 - all adults (≥18 years old)
- Informed consent form has been signed and dated by the participant and /or and parent(s) or legally acceptable representative (LAR) and by an independent witness (if required by local regulations), as necessary; and assent form has been signed and dated by the participant, as required
- Participant (adult ≥18 years) or participant and parent/LAR (1 year to <18 years) are able to attend all scheduled visits and to comply with all study procedures.
Exclusion Criteria
- Participant is 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 1 month after each vaccination. To be considered of non-childbearing potential, a female must be pre-menarche or post-menopausal for at least 1 year, or surgically sterile.
- Participation at the time of study enrollment or, planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure.
- Receipt of any vaccine in the 4 weeks (28 days) preceding the first study vaccination or planned receipt of any vaccine prior to Visit 5 for pediatric participants and adult participants in Cohort 1, and prior to Visit 4 for adult participants in Cohort 2.
- Previous vaccination against rabies (in pre- or post-exposure regimen) with either the study vaccines or another vaccine.
- Bite by, or exposure to a potentially rabid animal in the previous 6 months with or without post-exposure prophylaxis.
- 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 study.
- Known systemic hypersensitivity to any of the study/control vaccine components, or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances.
- Self-reported thrombocytopenia, contraindicating intramuscular vaccination.
- Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination.
- Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
- Current alcohol or substance abuse that, in the opinion of the investigator, might interfere with the study conduct or completion.
- Chronic illness(1) that, in the opinion of the Investigator, is at a stage where it might interfere with study conduct or completion.
- Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C). A prospective participant should not be included in the study until the condition has resolved or the febrile event has 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.
- Chronic illness may include, but is not limited to, neurological, cardiopulmonary, gastrointestinal, renal, genitourinary, metabolic, hematologic, auto-immune, or psychiatric disorders or infection
Data sourced from ClinicalTrials.gov (NCT04127786). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.