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 |
Rabies is caused by a virus that can be transfered via a bite from an infected animal. The virus can generate inflammation of the brain, leading to death within 2 weeks if no intensive care is set up. |
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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 | 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 |
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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 |
Immunogenicity Objectives:
1. To compare the long-term (up to approx.10 years) persistence of antibody responses (i.e. time until antibody concentrations drop below 0.5 IU/mL) in subjects who received a primary series of accelerated or conventional rabies PrEP intramuscular (IM) regimen in the parent study V49_23.
2. To evaluate the antibody responses to a booster dose of Purified Chick Embryo Cell-Culture (PCEC) rabies vaccine administered to subjects with Rabies Virus Neutralizing Antibody (RVNA) concentrations < 0.5 IU/mL following a primary
series of accelerated or conventional rabies PrEP IM regimen in the parent study V49_23.
Safety Objective:
To evaluate the safety of a booster dose of PCEC rabies vaccine following a primary series of accelerated or conventional rabies PrEP IM regimen in the parent study V49_23. |
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E.2.2 | Secondary objectives of the trial |
Immunogenicity Objective:
To evaluate the long-term (up to approx.10 years) immunogenicity in subjects who received a primary series of accelerated or conventional rabies PrEP intramuscular (IM) regimen in the parent study V49_23. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to participate in this study, all subjects must meet ALL of the inclusion criteria described.
1. All individuals who were randomized to Conventional Rabies and JE vaccination or to Accelerated Rabies and JE vaccination or to Conventional Rabies groups during the parent study, who received the full PrEP regimen and completed the trial following V49_23 study protocol.
2. Individuals who have voluntarily given written informed consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry.
3. Individuals who can comply with study procedures.
4. Males
Or
Females of non-childbearing potential
Or
Females of childbearing potential who are using an effective birth control method which they intend to use for at least 6 months after the booster vaccination. This
criterion is applicable only for those subjects who receive a booster dose.
Prior to receipt of booster vaccination during Ad hoc Clinic Visit, subjects must be evaluated to confirm that they are eligible. If subjects do not meet any of the original inclusion criteria listed above, they should not receive booster dose of rabies vaccine. |
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E.4 | Principal exclusion criteria |
Prior to extension study entry, each subject must not have:
1. Completed the parent study V49_23 without receiving the full 3 rabies vaccine doses following the assigned pre-exposure prophylaxis regimen.
2. History of exposure to suspected or confirmed rabid animal.
3. Receipt of rabies immunoglobulins, rabies post exposure prophylaxis following completion of V49_23 study.
4. Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study.
5. Clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
6. Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days within 90 days prior to informed consent or planning to receive them during the participation to the study.
7. Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to informed consent or planning to receive them during the participation to the study.
8. Received immunoglobulins or any blood products within 180 days prior to informed consent or planning to receive them during the participation to the study.
9. Study personnel as well as their immediate family or household member.
10. Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study.
Prior to Scheduled Visit, each subject must not have:
1. History of exposure to suspected or confirmed rabid animal.
2. Receipt of rabies immunoglobulins, non-study rabies vaccine following
completion of V49_23 study.
3. Hypersensitivity, including allergy, to any component of vaccines,
medicinal products or medical equipment whose use is foreseen in this
study.
4. Clinical conditions representing a contraindication to intramuscular
vaccination and blood draws.
5. Systemic administration of corticosteroids (PO/IV/IM) for more than
14 consecutive days within 90 days prior to informed consent or
planning to receive them during the participation to the study.
6. Administration of antineoplastic and immunomodulating agents or
radiotherapy within 90 days prior to informed consent or planning to
receive them during the participation to the study.
7. Received immunoglobulins or any blood products within 180 days
prior to informed consent or planning to receive them during the
participation to the study.
8. Study personnel as well as their immediate family or household
member.
9. Any other clinical condition that, in the opinion of the investigator,
might pose additional risk to the subject due to participation in the
study.
Prior to booster vaccination, each subject eligible for booster vaccination (i.e., subjects with RVNA concentrations <0.5 IU/mL at the first visit of this extension study [Day 1, Year 3] or at the following year visits [Year 4 to Year 9]) should be in good health status and must not have none of the following:
1. Progressive, unstable or uncontrolled clinical conditions.
2. Abnormal function of the immune system resulting from:
a. Clinical conditions.
b. Systemic administration of corticosteroids (PO/IV/IM) for more than
14 consecutive days within 90 days prior to the Ad hoc visit or receipt or
planning to receive them during the participation to the study.
c. Administration of antineoplastic and immunomodulating agents or
radiotherapy within 90 days prior to the Ad hoc visit or receipt or
planning to receive them during the participation to the study.
3. Receipt of non-study rabies vaccine.
4. Receipt of any other vaccines within 28 days prior to the booster dose or planning to receive any vaccine within 28 days from the booster dose.
5. Receipt of any investigational or non-registered medicinal product within 14 days before booster dose till next Scheduled Clinic Visit after booster dose administration.
6. Receipt of anti-malarial medications (e.g. Mefloquine) within 14 days before booster dose till next Scheduled Clinic Visit after booster dose administration.
Prior to receipt of booster study vaccination, subjects must be evaluated to confirm that they are in good health and they are eligible for subsequent vaccination. If subjects meet any of the original exclusion criteria listed above, they should not receive additional
vaccinations. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Immunogenicity Endpoints:
The primary immunogenicity endpoints will be based on the RVNA concentrations at Year 3, 4, 5, 6, 7, 8, 9 and 10 following a primary series of accelerated or conventional rabies PrEP IM regimen during the parent study V49_23, as measured by rapid
fluorescent focus inhibition test (RFFIT). RFFIT assays will be performed at a delegate, qualified laboratory, as specified by GSK.
Measures of immunogenicity will be summarized by the vaccination regimen received in the parent study V49_23, as follows:
-Time to first RVNA concentrations < 0.5 IU/mL.
- Geometric Mean Concentrations (GMCs) and Geometric Mean Ratios (GMRs) for subjects receiving the booster dose, as measured by antibody concentration at 7 days after the booster dose vs. antibody concentration before the booster dose.
Percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL, as measured by RFFIT assay at 7 days after the booster dose and at subsequent Scheduled Clinic Visits.
Safety Endpoint:
For subjects receiving PCEC rabies booster vaccination, Serious Adverse Events (SAEs) and the associated concomitant medications will be collected starting from the booster administration and until the day of next Scheduled Clinic Visit.
Number and percentages of SAEs will be summarized only for subjects receiving a booster dose by the vaccination regimen received in the parent study V49_23 and overall. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Year 3, 4, 5, 6, 7, 8, 9 and 10 |
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E.5.2 | Secondary end point(s) |
Immunogenicity Endpoints:
- Geometric Mean Antibody Concentrations (GMCs) at Year 3, 4, 5, 6, 7, 8, 9 and 10;
- Reverse Cumulative Distribution Plots (RCDPs) at Year 3, 4, 5, 6, 7, 8, 9 and 10;
- Percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL, as measured by RFFIT assay at Year 3, 4, 5, 6, 7, 8, 9 and 10. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Year 3, 4, 5, 6, 7, 8, 9 and 10;
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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 | No |
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 |
Immunogeneicity and boostability of immune responses |
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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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Germany |
Switzerland |
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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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The date of termination is the date of the last contact (clinic visit) in which the subject’s health status was assessed or, in cases where the subject does not agree to any further safety follow-up or blood draw; it is the date consent is withdrawn. |
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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 | 7 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |