- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02545517
A Clinical Study to Evaluate Immune Responses to Rabies Vaccine in Adults Who Received Different Primary Rabies Vaccination Regimens
A Phase 3, Open-label, Multicenter Study to Evaluate Long-term Immunogenicity and Boostability of Immune Responses in Adults Who Received Different Primary Vaccination Regimens of Pre-exposure Prophylaxis With Purified Chick-Embryo Cell Rabies Vaccine Administered Concomitantly or Separately From a Japanese Encephalitis Vaccine.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The protocol was amended to clarify:
- Timeframe between each yearly scheduled visit,
- Number of additional booster doses a subject may receive depending on the RVNA level reached,
- Premature withdrawal from the study
- Exclusion criteria on scheduled visits
- That only SAEs experienced by subjects who received the booster must be reported
- Rewording of the protocol.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Wien, Austria, 1090
- GSK Investigational Site
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Berlin, Germany, 10117
- GSK Investigational Site
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Berlin, Germany, 13353
- GSK Investigational Site
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Hamburg, Germany, 20359
- GSK Investigational Site
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Bayern
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Muenchen, Bayern, Germany, 80802
- GSK Investigational Site
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Mecklenburg-Vorpommern
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Rostock, Mecklenburg-Vorpommern, Germany, 18057
- GSK Investigational Site
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Zuerich, Switzerland, 8001
- GSK Investigational Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
In order to participate in this study, all subjects must meet ALL of the inclusion criteria described.
- 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.
- 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.
- Individuals who can comply with study procedures
- 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.
Exclusion Criteria:
Prior to extension study entry, each subject must not have:
- Completed the parent study V49_23 without receiving the full 3 rabies vaccine doses following the assigned pre-exposure prophylaxis regimen.
- History of exposure to suspected or confirmed rabid animal.
- Receipt of rabies immunoglobulins, rabies post exposure prophylaxis following completion of V49_23 study.
- Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study.
- Clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
- 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.
- 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.
- Received immunoglobulins or any blood products within 180 days prior to informed consent or planning to receive them during the participation to the study.
- Study personnel as well as their immediate family or household member.
- 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:
- History of exposure to suspected or confirmed rabid animal.
- Receipt of rabies immunoglobulins, non-study rabies vaccine following completion of V49_23 study.
- Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study.
- Clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
- 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.
- 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.
- Received immunoglobulins or any blood products within 180 days prior to informed consent or planning to receive them during the participation to the study.
- Study personnel as well as their immediate family or household member.
- 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:
- Progressive, unstable or uncontrolled clinical conditions.
Abnormal function of the immune system resulting from:
- Clinical conditions.
- 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.
- 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.
- Receipt of non-study rabies vaccine.
- 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.
- Receipt of any investigational or non-registered medicinal product within 14 days before booster dose till next Scheduled Clinic Visit after booster dose administration.
- Receipt of anti-malarial medications 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: N/A
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Conv-R/JE Group
Subjects who completed the Rabies PrEP regimen on days 1,8 and 29 and JE primary series regimen on days 1 and 29 in the parent study V49_23 were enrolled in the Conv-R/JE Group and received a single booster dose of the PCEC rabies vaccine in this extension study.
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Subjects in all the groups received Rabipur vaccine booster dose, administered intramuscularly in the deltoid region of the non-dominant arm
Blood samples were drawn from all subjects at day 1 and then at subsequent year intervals from extension study day 1 onwards.
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Experimental: Acc-R/JE Group
Subjects who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study V49_23 were enrolled in the Acc-R/JE Group and received a single booster dose of the PCEC rabies vaccine in this extension study.
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Subjects in all the groups received Rabipur vaccine booster dose, administered intramuscularly in the deltoid region of the non-dominant arm
Blood samples were drawn from all subjects at day 1 and then at subsequent year intervals from extension study day 1 onwards.
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Experimental: Conv-R Group
Subjects who completed the Rabies PrEP regimen on days 1,8 and 29 in the parent study V49_23 were enrolled into the Conv-R Group and received a single booster dose of the PCEC rabies vaccine in this extension study.
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Subjects in all the groups received Rabipur vaccine booster dose, administered intramuscularly in the deltoid region of the non-dominant arm
Blood samples were drawn from all subjects at day 1 and then at subsequent year intervals from extension study day 1 onwards.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of subjects reporting serious adverse events (SAEs) after a booster dose of PCEC (purified chick embryo cell culture) rabies vaccine
Time Frame: From the time of booster dose administration(Day 1 in extension study)until completion of safety follow-up period(day of next Scheduled Clinic Visit after booster dose/on date of Early Termination Visit, whichever is earlier,assessed up to year 10)
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An SAE is defined as any untoward medical occurrence that at any dose results in one or more of the following:
Safety is assessed as the number of subjects reporting SAEs after a booster dose of PCEC rabies vaccine following a primary series of accelerated or conventional rabies PrEP (pre-exposure) IM (intramuscular) regimen in the parent study V49_23. |
From the time of booster dose administration(Day 1 in extension study)until completion of safety follow-up period(day of next Scheduled Clinic Visit after booster dose/on date of Early Termination Visit, whichever is earlier,assessed up to year 10)
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Time to first RVNA (Rabies Virus Neutralizing Antibodies) concentrations <0.5 IU/mL.
Time Frame: Throughout the study duration (From 1 year after primary dose schedule in parent study V49_23 to year 10).
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The time until RVNA concentrations drop below 0.5 IU/mL is calculated to compare the long-term persistence of antibody responses in subjects who received a primary series of accelerated or conventional rabies PrEP IM regimen in the parent study V49_23
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Throughout the study duration (From 1 year after primary dose schedule in parent study V49_23 to year 10).
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RVNA concentrations in terms of Geometric Mean Concentrations (GMCs) 7 days after the booster dose.
Time Frame: At 7 days after booster dose
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Antibody concentrations at 7 days after booster dose are measured in terms of GMCs.
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At 7 days after booster dose
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RVNA Geometric Mean Ratios (GMRs) at 7 days after the booster dose vs. antibody concentration before the booster dose.
Time Frame: At 7 days after booster dose versus before booster dose administration (baseline- 6 months before booster dose).
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For subjects receiving a booster dose, analysis of boostability is conducted 7 days after administration of the booster dose by providing GMRs and associated CIs, considering the antibody value at the time of booster dose administration as baseline.
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At 7 days after booster dose versus before booster dose administration (baseline- 6 months before booster dose).
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Percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL as measured by RFFIT (Rapid Fluorescent Focus Inhibition Test) analysis at 7 days after booster dose.
Time Frame: At 7 days after booster dose
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The percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL are measured at 7 days after booster dose
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At 7 days after booster dose
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Percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL as measured by RFFIT (Rapid Fluorescent Focus Inhibition Test) analysis.
Time Frame: At year 3 after primary series of vaccine administration.
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The percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL are measured at year 3 after primary series of vaccination.
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At year 3 after primary series of vaccine administration.
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Percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL as measured by RFFIT (Rapid Fluorescent Focus Inhibition Test) analysis.
Time Frame: At year 4 after primary series of vaccine administration.
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The percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL are measured at year 4 after primary series of vaccination.
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At year 4 after primary series of vaccine administration.
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Percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL as measured by RFFIT (Rapid Fluorescent Focus Inhibition Test) analysis.
Time Frame: At year 5 after primary series of vaccine administration.
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The percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL are measured at year 5 after primary series of vaccination.
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At year 5 after primary series of vaccine administration.
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Percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL as measured by RFFIT (Rapid Fluorescent Focus Inhibition Test) analysis.
Time Frame: At year 6 after primary series of vaccine administration.
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The percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL are measured at year 6 after primary series of vaccination.
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At year 6 after primary series of vaccine administration.
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Percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL as measured by RFFIT (Rapid Fluorescent Focus Inhibition Test) analysis.
Time Frame: At year 7 after primary series of vaccine administration.
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The percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL are measured at year 7 after primary series of vaccination.
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At year 7 after primary series of vaccine administration.
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Percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL as measured by RFFIT (Rapid Fluorescent Focus Inhibition Test) analysis.
Time Frame: At year 8 after primary series of vaccine administration.
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The percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL are measured at year 8 after primary series of vaccination.
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At year 8 after primary series of vaccine administration.
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Percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL as measured by RFFIT (Rapid Fluorescent Focus Inhibition Test) analysis.
Time Frame: At year 9 after primary series of vaccine administration.
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The percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL are measured at year 9 after primary series of vaccination.
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At year 9 after primary series of vaccine administration.
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Percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL as measured by RFFIT (Rapid Fluorescent Focus Inhibition Test) analysis.
Time Frame: At year 10 after primary series of vaccine administration.
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The percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL are measured at year 10 after primary series of vaccination.
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At year 10 after primary series of vaccine administration.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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RVNA Geometric Mean Concentrations (GMCs)
Time Frame: At year 3 after primary series of vaccine administration.
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The RVNA GMCs with the 95% CI are calculated at Year 3 after primary series of vaccination
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At year 3 after primary series of vaccine administration.
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RVNA Geometric Mean Concentrations (GMCs)
Time Frame: At year 4 after primary series of vaccine administration.
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The RVNA GMCs with the 95% CI are calculated at Year 4 after primary series of vaccination
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At year 4 after primary series of vaccine administration.
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RVNA Geometric Mean Concentrations (GMCs)
Time Frame: At year 5 after primary series of vaccine administration.
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The RVNA GMCs with the 95% CI are calculated at Year 5 after primary series of vaccination
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At year 5 after primary series of vaccine administration.
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RVNA Geometric Mean Concentrations (GMCs)
Time Frame: At year 6 after primary series of vaccine administration.
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The RVNA GMCs with the 95% CI are calculated at Year 6 after primary series of vaccination
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At year 6 after primary series of vaccine administration.
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RVNA Geometric Mean Concentrations (GMCs)
Time Frame: At year 7 after primary series of vaccine administration.
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The RVNA GMCs with the 95% CI are calculated at Year 7 after primary series of vaccination
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At year 7 after primary series of vaccine administration.
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RVNA Geometric Mean Concentrations (GMCs)
Time Frame: At year 8 after primary series of vaccine administration.
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The RVNA GMCs with the 95% CI are calculated at Year 8 after primary series of vaccination
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At year 8 after primary series of vaccine administration.
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RVNA Geometric Mean Concentrations (GMCs)
Time Frame: At year 9 after primary series of vaccine administration.
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The RVNA GMCs with the 95% CI are calculated at Year 9 after primary series of vaccination
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At year 9 after primary series of vaccine administration.
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RVNA Geometric Mean Concentrations (GMCs)
Time Frame: At year 10 after primary series of vaccine administration.
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The RVNA GMCs with the 95% CI are calculated at Year 10 after primary series of vaccination
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At year 10 after primary series of vaccine administration.
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Reverse Cumulative Distribution Plots (RCDPs) for subjects with RVNA concentrations ≥0.5 IU/mL.
Time Frame: At year 3
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The RCDPs are provided by treatment group, at year 3
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At year 3
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RCDPs for subjects with RVNA concentrations ≥0.5 IU/mL.
Time Frame: At year 4
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The RCDPs are provided by treatment group, at year 4
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At year 4
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RCDPs for subjects with RVNA concentrations ≥0.5 IU/mL.
Time Frame: At year 5
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The RCDPs are provided by treatment group, at year 5
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At year 5
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RCDPs for subjects with RVNA concentrations ≥0.5 IU/mL.
Time Frame: At year 6
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The RCDPs are provided by treatment group, at year 6
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At year 6
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RCDPs for subjects with RVNA concentrations ≥0.5 IU/mL.
Time Frame: At year 7
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The RCDPs are provided by treatment group, at year 7
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At year 7
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RCDPs for subjects with RVNA concentrations ≥0.5 IU/mL.
Time Frame: At year 8
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The RCDPs are provided by treatment group, at year 8
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At year 8
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RCDPs for subjects with RVNA concentrations ≥0.5 IU/mL.
Time Frame: At year 9
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The RCDPs are provided by treatment group, at year 9
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At year 9
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RCDPs for subjects with RVNA concentrations ≥0.5 IU/mL.
Time Frame: At year 10
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The RCDPs are provided by treatment group, at year 10
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At year 10
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 205214
- 2015-000382-31 (EudraCT Number)
- V49_23E1 (Other Identifier: Novartis)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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