A Clinical Study to Evaluate Immune Responses to Rabies Vaccine in Adults Who Received Different Primary Rabies Vaccination Regimens

January 3, 2022 updated by: GlaxoSmithKline

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.

GlaxoSmithKline (GSK) Biologicals' Rabipur vaccine is indicated for active immunization against rabies in individuals of all ages. This includes pre-exposure prophylaxis (PrEP), in both primary series and booster dose, and post exposure prophylaxis.The aim of this extension study is to evaluate the long-term (up to approx.10 years) persistence and to assess the boostability of immune responses in subjects who received a primary series of accelerated or conventional rabies PrEP IM regimen No new subjects were enrolled in this study.

Study Overview

Status

Active, not recruiting

Conditions

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

Interventional

Enrollment (Actual)

459

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Wien, Austria, 1090
        • GSK Investigational Site
      • Berlin, Germany, 10117
        • GSK Investigational Site
      • Berlin, Germany, 13353
        • GSK Investigational Site
      • Hamburg, Germany, 20359
        • GSK Investigational Site
    • Bayern
      • Muenchen, Bayern, Germany, 80802
        • GSK Investigational Site
    • Mecklenburg-Vorpommern
      • Rostock, Mecklenburg-Vorpommern, Germany, 18057
        • GSK Investigational Site
      • Zuerich, Switzerland, 8001
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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:

    1. Clinical conditions.
    2. 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.
    3. 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 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
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.
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.
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.
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.
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)

An SAE is defined as any untoward medical occurrence that at any dose results in one or more of the following:

  • Death
  • Is life-threatening
  • Requires or prolonged hospitalization.
  • Persistent or significant disability/incapacity
  • Congenital anomaly/or birth defect.
  • An important and significant medical event that may not be immediately life threatening or resulting in death or hospitalization but, based upon appropriate medical judgment, may jeopardize the subject or may require intervention to prevent one of the other outcomes listed above.

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)
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).
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
Throughout the study duration (From 1 year after primary dose schedule in parent study V49_23 to year 10).
RVNA concentrations in terms of Geometric Mean Concentrations (GMCs) 7 days after the booster dose.
Time Frame: At 7 days after booster dose
Antibody concentrations at 7 days after booster dose are measured in terms of GMCs.
At 7 days after booster dose
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).
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.
At 7 days after booster dose versus before booster dose administration (baseline- 6 months before booster dose).
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
The percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL are measured at 7 days after booster dose
At 7 days after booster dose
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.
The percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL are measured at year 3 after primary series of vaccination.
At year 3 after primary series of vaccine administration.
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.
The percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL are measured at year 4 after primary series of vaccination.
At year 4 after primary series of vaccine administration.
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.
The percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL are measured at year 5 after primary series of vaccination.
At year 5 after primary series of vaccine administration.
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.
The percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL are measured at year 6 after primary series of vaccination.
At year 6 after primary series of vaccine administration.
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.
The percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL are measured at year 7 after primary series of vaccination.
At year 7 after primary series of vaccine administration.
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.
The percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL are measured at year 8 after primary series of vaccination.
At year 8 after primary series of vaccine administration.
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.
The percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL are measured at year 9 after primary series of vaccination.
At year 9 after primary series of vaccine administration.
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.
The percentages of subjects with RVNA concentrations ≥ 0.5 IU/mL are measured at year 10 after primary series of vaccination.
At year 10 after primary series of vaccine administration.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
RVNA Geometric Mean Concentrations (GMCs)
Time Frame: At year 3 after primary series of vaccine administration.
The RVNA GMCs with the 95% CI are calculated at Year 3 after primary series of vaccination
At year 3 after primary series of vaccine administration.
RVNA Geometric Mean Concentrations (GMCs)
Time Frame: At year 4 after primary series of vaccine administration.
The RVNA GMCs with the 95% CI are calculated at Year 4 after primary series of vaccination
At year 4 after primary series of vaccine administration.
RVNA Geometric Mean Concentrations (GMCs)
Time Frame: At year 5 after primary series of vaccine administration.
The RVNA GMCs with the 95% CI are calculated at Year 5 after primary series of vaccination
At year 5 after primary series of vaccine administration.
RVNA Geometric Mean Concentrations (GMCs)
Time Frame: At year 6 after primary series of vaccine administration.
The RVNA GMCs with the 95% CI are calculated at Year 6 after primary series of vaccination
At year 6 after primary series of vaccine administration.
RVNA Geometric Mean Concentrations (GMCs)
Time Frame: At year 7 after primary series of vaccine administration.
The RVNA GMCs with the 95% CI are calculated at Year 7 after primary series of vaccination
At year 7 after primary series of vaccine administration.
RVNA Geometric Mean Concentrations (GMCs)
Time Frame: At year 8 after primary series of vaccine administration.
The RVNA GMCs with the 95% CI are calculated at Year 8 after primary series of vaccination
At year 8 after primary series of vaccine administration.
RVNA Geometric Mean Concentrations (GMCs)
Time Frame: At year 9 after primary series of vaccine administration.
The RVNA GMCs with the 95% CI are calculated at Year 9 after primary series of vaccination
At year 9 after primary series of vaccine administration.
RVNA Geometric Mean Concentrations (GMCs)
Time Frame: At year 10 after primary series of vaccine administration.
The RVNA GMCs with the 95% CI are calculated at Year 10 after primary series of vaccination
At year 10 after primary series of vaccine administration.
Reverse Cumulative Distribution Plots (RCDPs) for subjects with RVNA concentrations ≥0.5 IU/mL.
Time Frame: At year 3
The RCDPs are provided by treatment group, at year 3
At year 3
RCDPs for subjects with RVNA concentrations ≥0.5 IU/mL.
Time Frame: At year 4
The RCDPs are provided by treatment group, at year 4
At year 4
RCDPs for subjects with RVNA concentrations ≥0.5 IU/mL.
Time Frame: At year 5
The RCDPs are provided by treatment group, at year 5
At year 5
RCDPs for subjects with RVNA concentrations ≥0.5 IU/mL.
Time Frame: At year 6
The RCDPs are provided by treatment group, at year 6
At year 6
RCDPs for subjects with RVNA concentrations ≥0.5 IU/mL.
Time Frame: At year 7
The RCDPs are provided by treatment group, at year 7
At year 7
RCDPs for subjects with RVNA concentrations ≥0.5 IU/mL.
Time Frame: At year 8
The RCDPs are provided by treatment group, at year 8
At year 8
RCDPs for subjects with RVNA concentrations ≥0.5 IU/mL.
Time Frame: At year 9
The RCDPs are provided by treatment group, at year 9
At year 9
RCDPs for subjects with RVNA concentrations ≥0.5 IU/mL.
Time Frame: At year 10
The RCDPs are provided by treatment group, at year 10
At year 10

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 5, 2015

Primary Completion (Anticipated)

November 18, 2022

Study Completion (Anticipated)

November 18, 2022

Study Registration Dates

First Submitted

August 31, 2015

First Submitted That Met QC Criteria

September 7, 2015

First Posted (Estimate)

September 10, 2015

Study Record Updates

Last Update Posted (Actual)

January 4, 2022

Last Update Submitted That Met QC Criteria

January 3, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

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)?

Yes

IPD Plan Description

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

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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