| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | |
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10037742 |
| E.1.2 | Term | Rabies |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To demonstrate that Vero Rabies Vaccine generation 2 (VRVg-2) is non-inferior to Verorab and Imovax Rabies vaccines when co-administered with Human Rabies Immunoglobulins (HRIG), in terms of proportion of subjects achieving a RVNA titer ≥ 0.5 IU/mL at D28, ie, 14 days after the fourth vaccine injection. |
|
| E.2.2 | Secondary objectives of the trial |
- 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 subjects in the VRVg-2 + HRIG group achieving an RVNA titer ≥ 0.5 IU/mL at D28 is at least 95%.
- 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 D14 (7 days after the third injection), at D28 (14 days after the fourth injection) and at D42 (14 days after the last injection).
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 Kg/m2 ≤ BMI ≤ 30 Kg/m2.
|
|
| E.4 | Principal exclusion criteria |
- Subject 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 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 is 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 intramuscular 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, is 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°C). A prospective subject 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.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Rabies Virus Neutralizing Antibodies (RVNA) Titers >=0.5 IU/mL : Percentage of participants achieving RVNA Titer >=0.5 IU/mL as measured by the rapid fluorescent focus inhibition test (RFFIT) assay |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1- Occurrence of solicited injection site and systemic reactions: Percentage of paritcipants reporting solicited injection site reactions (pain, erythema, and swelling) and systemic reactions (fever, headache, malaise, myalgia)
2- RVNA Titers: Geometric Mean Titers (GMTs) of RVNA
3- RVNA Titers >=0.5 IU/mL: Percentage of participants achieving RVNA Titer >=0.5 IU/mL as measured by the RFFIT assay
4- RVNA titer ≥ Lower Limit Of Quantitation (LLOQ) IU/mL:Percentage of participants with an RVNA titer ≥ LLOQ
5- RVNA titer ratio:Individual Geometric Mean Titer Ratio (GMTR): (post-/pre-vaccination)
6- Virus neutralization: Percentage of participants with complete or incomplete neutralization at the starting dilution (1/5) of the RFFIT assay |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1- Within 7 days post-vaccination
2- Day 0, Day 14, Day 28 and Day 42
3- Day 0, Day 14, Day 28 and Day 42
4- Day 0, Day 14, Day 28 and Day 42
5- Day 0, Day 14, Day 28 and Day 42
6- Day 0, Day 14, Day 28 and Day 42 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Modified double-blind (groups 1 to 3), Open-label (group 4) |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 2 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| End of the safety follow-up period, that is the last subject last contact through a phone call 6 months after the last vaccine injection. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | |
Print
