E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•To demonstrate that PEP using the new "one-week, 4-site" (4-4-4-0-0) intradermal (ID) vaccination regimen is non-inferior to PEP using the updated TRC (2-2-2-0-2) ID vaccination regimen. |
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E.2.2 | Secondary objectives of the trial |
•Primary immunization: To describe the immune response in each group at Day 0, Day 14 and Day 90.
•Antibody persistence: To describe rabies virus-neutralizing antibody persistence during the 5 years after completion of PEP in each group.
•Booster vaccination: To describe the immune response induced by a single-visit 4-site intradermal booster vaccination in each group at Year 5.
•Safety: To describe the safety profile of each group after the primary and booster vaccinations.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For all patients:
•Patient aged ≤50 years, with WHO category II or III contacts happened within 48 hours before appearance at site.
For adults:
•Informed consent form has been signed and dated.
•Able to attend all scheduled visits and to comply with all trial procedures.
For children:
•For children under 18 years of age, informed consent form has been signed and dated by the parent(s) or another legally acceptable representative.
•For children under 18 years, assent form or informed consent form has been signed and dated by the appropriate age-range patient, according to country specific institution requirement as detailed in each country specific assent form or informed consent form.
•Patient and parent/guardian are able to attend all scheduled visits and to comply with all trial procedures.
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E.4 | Principal exclusion criteria |
For all patients:
•Receipt of chloroquine or other medications used for malaria chemoprophylaxis, with or without other anti-malarial treatment, for more than 4 weeks (duration of anti-malarial course) and part of the treatment received within the 2 weeks before vaccination.
•Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the first trial immunization
•Planned participation in another clinical trial during the present trial period
•Receipt of any vaccine in the 4 weeks preceding the first trial vaccination, except for influenza vaccination and tetanus immunization (related only to current animal bite exposure
•Planned receipt of any vaccine in the 4 weeks following the trial primary and booster vaccination
•Previous immunization against rabies at any time in the past with either the trial vaccine and immunoglobulin or another rabies immunobiological product (in pre-or post-exposure regimen)
•Receipt of blood or blood-derived products in the past 3 months, which might interfere with assessment of the immune response
•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)
•Self-reported seropositivity for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus
•Patient with clinical signs of encephalitis
•Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances
•Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
•Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures
•Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion
•Identified as employees of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members (i.e., immediate, husband, wife and their children, adopted or natural) of the employees or the Investigator
•Febrile illness (temperature ≥38.0°C) or moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination
•Prior history of mammal animal bite within the past 5 years.
For infants or toddlers :
•Known personal or maternal seropositivity for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus, as reported by the parent/guardian
•Prior history of seizures |
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E.5 End points |
E.5.1 | Primary end point(s) |
1.Percentage of participants with seroconversion on Day 14
Seroconversion is defined as rabies virus neutralizing antibody titers ≥ 0.5 IU/mL |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
[ Time Frame: Day 14 post vaccination ] |
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E.5.2 | Secondary end point(s) |
1.Percentage of participants with seroconversion before and after primary vaccination
Seroconversion is defined as rabies virus neutralizing antibody titers ≥ 0.5 IU/mL
2.Percentage of participants with seroconversion after primary vaccination (antibody persistence)
Seroconversion is defined as rabies virus neutralizing antibody titers ≥ 0.5 IU/mL
3.Percentage of participants with seroconversion after booster vaccination
Seroconversion is defined as rabies virus neutralizing antibody titers ≥ 0.5 IU/mL
4.Geometric mean titers (GMTs) before and after primary vaccination
Titers of rabies virus-neutralizing antibodies were assessed by the rapid fluorescent focus inhibition test
5.GMTs after primary vaccination (antibody persistence)
Titers of rabies virus-neutralizing antibodies were assessed by the rapid fluorescent focus inhibition test
6.GMTs after booster vaccination
Titers of rabies virus-neutralizing antibodies were assessed by the rapid fluorescent focus inhibition test
7.Number of participants reporting solicited injection site reactions following primary and booster vaccination
Solicited injection site reactions are tenderness (for participants aged ≤ 23 months), pain (for participants aged ≥ 2 years), redness and swelling (for all participants)
8.Number of participants reporting solicited systemic reactions following primary and booster vaccination
Solicited systemic reactions are Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, and Irritability for participants aged ≤ 23 months and Fever (Temperature), Headache, Malaise, and Myalgia for participants aged ≥ 2 years
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.[ Time Frame: Day 0, Day 14, Day 90 ]
2.[ Time Frame: Year 1 to Year 5 ]
3.[ Time Frame: Year 5 + 11 days ]
4.[ Time Frame: Day 0, Day 14, Day 90 ]
5.[ Time Frame: Year 1 to Year 5 ]
6.[ Time Frame: Year 5 + 11 days ]
7.[ Time Frame: 7 days after each and any injection ]
8.[ Time Frame: From Day 0 up to 7 days after injection 3, and 7 days after subsequent injections ]
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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 | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | 3 |
E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 2 |