E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rabies is a viral infection that affects the central nervous system. It causes encephalitis which is almost invariably fatal. Preventive vaccination alone implies no complete protection, but simplifies the post-exposure procedure considerably, as the immunological response comes much more rapid in case of a booster vaccination post-exposure. This lowers the risk of morbidity and mortality. |
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E.1.1.1 | Medical condition in easily understood language |
Vaccination to prevent rabies infection. |
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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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the clinical non-inferiority of an accelerated rabies vaccination schedule (of 2 two-sided intradermal injections on day 0 and 2 intradermal injections on day 7) to the standard schedule (of 3 one-side intradermal injections for pre-exposure immunization on day 0, day 7 and day 21 or 28) as assessed by "boostability" (% of subjects that have boostable rabies antibodies) after 1 to 3 years. Clinical non-inferiority is defined as a loss of no more than 10% of subjects that have boostable rabies antibody levels compared to standard treatment. |
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives
- To investigate the serological response after the primary vaccination in both treatment groups. A titer ≥ 0,5 IU/ml is considered to be protective.
- To assess long lasting protection after primary vaccination and booster vaccination in both treatment groups. A titer > 10 IU/ml is considered to give long-lasting immunity.
Tertiary Objective
- To investigate the serological response of booster vaccinations for non- or hypo-responders in both groups. If titer is < 0,5 IU/ml, a second booster will be given and antibody levels will be checked after 7 days.
Safety objective
- To compare adverse events occurring during the primary vaccination schedule and in a 28-day period after finalization of the primary vaccination or booster vaccination in the 2 groups. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
» Willingness to provide written consent
» Age between 18 and 47 years
» Seronegative for rabies
» Belgian soldiers who are deployable and visit the Travel clinic in Brussels during their preparation phase before deployment OR military students at the schools of Belgian Defense are eligible in preparation of an overseas exercise or during the scheduled vaccination program at the end of their studies
» Prepared to follow the study schedule
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E.4 | Principal exclusion criteria |
» Subjects who have had rabies vaccination (complete or incomplete) in the past due to post-exposure prophylaxis.
» Subjects with a known allergy to one of the components of the vaccine.
» Immune depressed persons or intake of immunodepressant medication.
» Subjects who take mefloquine
» Planned deployment to overseas areas within 35 days.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the boostability of the rabies antibodies on day 7 after booster vaccination at years 1 to 3 after initial vaccination.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
between 1 and 3 years after the finalisation of the initial vaccination schedule |
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E.5.2 | Secondary end point(s) |
Boostability of the rabies antibodies on day 7 after booster vaccination at years 1 to 3 after initial vaccination.
- Rabies serology more than 0,5 IU/ml on day 7 after primary vaccination.
- Rabies serology more than 10 IU/ml on day 7 after primary vaccination, and after booster vaccination.
- Serological response of booster vaccinations for non- or hypo-responders in both arms.
- Adverse events within one week after initial and booster vaccinations and serious adverse event within 28 days after initial and booster vaccinations |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- 7 days after primary vaccination
- 7 days after booster vaccination
- safety endpoint; 7 and 28 days after primary and booster 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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
other vaccination schedule with same IMP |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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
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End of the trial is defined as the last visit of the last patient. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 15 |