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 |
Healthy volunteers (rabies immunization) |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10069573 |
E.1.2 | Term | Rabies immunisation |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 a short intramuscular (IM) pre-exposure prophylaxis (PrEP) regimen is non-inferior to the reference IM PrEP regimen in terms of seroconversion rate |
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E.2.2 | Secondary objectives of the trial |
- To describe the immunogenicity of the PrEP regimen in each group - To describe the antibody persistence in each group 6 months and 1 year after the last PrEP vaccination - To describe the immunogenicity of the simulated post-exposure prophylaxis (PEP) regimen in each group - To describe the safety profile of study vaccines administered as PrEP regimen and as a simulated PEP regimen in each group |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Aged ≥ 2 years on the day of inclusion - Participant aged < 18 years: Assent form has been signed and dated by the subject (as appropriate, according to country-specific institution requirements), and informed consent form (ICF) signed and dated by the parent or another legally acceptable representative - Participant aged ≥ 18 years: ICF signed and dated by the subject - The participant (and parent/legally acceptable representative, if applicable) is able to attend all scheduled visits and to comply with all trial procedures |
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E.4 | Principal 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 at least 4 weeks after the last 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 in the 4 weeks preceding the first trial vaccination) 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 preceding the first trial vaccination or planned receipt of any vaccine in the 4 weeks following any trial vaccination except for influenza vaccination, which may be received at least 2 weeks before study vaccines. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines. - Previous vaccination at any time against rabies with either the trial vaccine 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) - Known systemic hypersensitivity to any of the vaccine 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 - Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily - Current alcohol abuse or drug addiction - 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 - 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 (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study - History of Guillain-Barré syndrome - 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, contraindicating intradermal vaccination |
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E.5 End points |
E.5.1 | Primary end point(s) |
Seroconversion of participant : Rabies virus neutralizing antibodies (RVNA) titer ≥ 0.5 IU/mL |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
14 days after the last PrEP vaccination |
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E.5.2 | Secondary end point(s) |
1 - Participant RVNA titer 2 - Persistence of RVNA titer 3 - Participant RVNA titer after simulated PEP vaccination 4 - Seroconversion of participant : RVNA titer ≥ 0.5 IU/mL 5 - Persistence of seroconversion : RVNA titer ≥ 0.5 IU/mL 6 - Seroconversion of participant after simulated PEP vaccination : RVNA titer ≥ 0.5 IU/mL 7 - Seropositivity of participant : RVNA titer ≥ the lower limit of quantitation (LLOQ) 8 - Persistence of seropositivity : RVNA titer ≥ the LLOQ 9 - Seropositivity of participant after simulated PEP vaccination : RVNA titer ≥ the LLOQ 10 - Participant RVNA titer ratios : Titer 14 days after the last PrEP vaccination / titer at D0 11 - Participant RVNA titer ratios (persistence assessment) : RVNA titer ratios are assessed 6 months / 14 days after the last PrEP vaccination, and 1 year / 14 days after the last PrEP vaccination 12 - Participant RVNA titer after simulated PEP vaccination : Ratio of titers measured 7 and 14 days after the first simulated PEP vaccination / 1 year after the last PrEP vaccination 13 - Solicited injection site and systemic reactions after PrEP vaccination : Injection site reactions: injection site pain, erythema, and swelling. Systemic reactions: fever, headache, malaise and myalgia. 14 - Solicited injection site and systemic reactions after simulated PEP vaccination : Injection site reactions: injection site pain, erythema, and swelling. Systemic reactions: fever, headache, malaise and myalgia. Solicited systemic reactions are collected between the first and second PEP injection and within 7 days after the second PEP injection. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
[1] , [4] , [7] : Day (D) 0 and 14 days after the last PrEP vaccination [2] , [5] , [8] , [11] : 6 months and 1 years after the last PrEP vaccination [3] , [6] , [9] : 7 and 14 days after the first simulated PEP vaccination [10] : 14 days after last PrEP vaccination [12] : 1 year after the last PrEP vaccination [13] : 7 days after PrEP vaccination [14] : 7 days after simulated PEP vaccination |
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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 | No |
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 |
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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 | Yes |
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 | 5 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |