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 determine if a 2 x 0,1 ml priming dose results in an acceptable boostability (% of subjects that have boostable rabies antibodies) after 1 year. - To determine the lowest booster dose (4 x 0,1 ml, or 2 x 0,1 ml) after a 2 x 0,1 ml priming dose needed to induce an acceptable boostability after 1 year. - A vaccination regimen is considered to have an acceptable boostability if at least 90% of vaccinated subjects would reach a rabies titre of > 0.5 IU/mL 7 days after booster vaccination. This will be assessed by comparing the one-sided 95% confidence interval for the % of boostable subjects with the target value of 90%. If the one-sided 95% confidence interval excludes 90%, an acceptable boostability is considered to be established.
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E.2.2 | Secondary objectives of the trial |
- To assess good protection after primary vaccination and booster vaccination in both treatment groups (day 372). A titer > 3 IU/ml is considered to give good protection. - To assess long lasting protection after primary vaccination and booster vaccination in both treatment groups (day 372). A titer > 10 IU/ml is considered to give long-lasting immunity. - To investigate the serological response after the primary vaccination (on day 7) in both treatment groups. A titer ≥ 0,5 IU/ml is considered to be boostable.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
» Willingness to provide written consent » Seronegative for rabies » Belgian soldiers or military students who are deployable but not for an high rabies risk area (as land deployment to Africa or Asia) » 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 28 days. » Planned deployment to high rabies risk areas within 2 years; for example (as land deployment to Africa or Asia).
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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 1 year after initial vaccination. A rabies serology value of more than 3 IU/ml on day 7 after booster vaccination is considered to be protective. Subjects showing this serology value at day 7 are considered to be boostable.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
day 7 after booster vaccination at 1 year after initial vaccination |
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E.5.2 | Secondary end point(s) |
- Rabies serology more than 3 IU/ml on day 7 after simulated booster vaccination. - Rabies serology more than 10 IU/ml on day 7 after simulated booster vaccination. - The initial long lasting protection (= rabies serology more than 10 IU/ml on day 7 after primary vaccination) after primary vaccination will be determined. - Rabies serology more than 0,5 IU/ml on day 7 after primary vaccination in both arms. - Serological response of booster vaccination for non-responders in both arms. - Adverse events within one week after initial and booster vaccinations and serious adverse event within 14 days after initial and booster vaccinations (as described in section 7).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
day 7 after simulated booster vaccination 14 days after initial and booster vaccinations |
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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 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 | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |