A Phase 3 Clinical Trial to Evaluate Long-term Immunogenicity and Boostability of Purified Chick-Embryo Cell Rabies Vaccine in Adults Following Primary Series of Pre/Exposure Prophylaxis.

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.

The aim of this study is to evaluate the long-term (up to approx.10 years) persistence and to assess the boostability of immune responses in participants who received a primary series of accelerated or conventional rabies PrEP IM regimen.

This product has been transferred to BN. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on www.clinicaltrials.gov.

Study Overview

• Status: Completed
• Conditions: Virus Diseases; Rabies
• Intervention / Treatment: Biological: Rabipur; Procedure: Blood sampling; Biological: Purified Chick-Embryo Cell Rabies Vaccine

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

Study Locations

• Austria
  • Wien, Austria, 1090
    • GSK Investigational Site
• Germany
  • 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
• Switzerland
  • Zuerich, Switzerland, 8001
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• All individuals who were randomized to a Rabies primary series vaccination for pre-exposure prophylaxis (PrEP), received the full PrEP regimen and completed the parent trial following study protocol.

Exclusion Criteria:

• Completed the parent study 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 the parent study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Conv-R/JE Group; Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (<)0.5 IU/mL at scheduled visits.	Biological: Rabipur; Participants in all the groups received Rabipur vaccine booster dose, administered intramuscularly in the deltoid region of the non-dominant arm.; Procedure: Blood sampling; Blood samples were drawn from all participants at Day 1 and then at subsequent year intervals from extension study Day 1 onwards.; Biological: Purified Chick-Embryo Cell Rabies Vaccine; 1 booster dose of 1.0 mL of Purified Chick-Embryo Cell Rabies Vaccine intramuscular (IM).
Experimental: Acc-R/JE Group; Participants 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) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were <0.5 IU/mL at scheduled visits.	Biological: Rabipur; Participants in all the groups received Rabipur vaccine booster dose, administered intramuscularly in the deltoid region of the non-dominant arm.; Procedure: Blood sampling; Blood samples were drawn from all participants at Day 1 and then at subsequent year intervals from extension study Day 1 onwards.
Experimental: Conv-R Group; Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were <0.5 IU/mL at scheduled visits.	Biological: Rabipur; Participants in all the groups received Rabipur vaccine booster dose, administered intramuscularly in the deltoid region of the non-dominant arm.; Procedure: Blood sampling; Blood samples were drawn from all participants 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 Participants Reporting Serious Adverse Events (SAEs) After a Booster Dose of Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine	A SAE is defined as any untoward medical occurrence that at any dose results in one or more of the following: death, is life-threatening, required/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 participants or may require intervention to prevent one of the other outcomes listed. Safety is assessed as the number of participants reporting SAEs after a booster dose of PCEC rabies vaccine administered in this extension study, if RNVA concentrations were <0.5 IU/mL, following a primary series of accelerated or conventional rabies pre-exposure (PrEP) intramuscular (IM) regimen in the parent study.	From booster vaccination [6 to 9 months after Year 3 (3 years after primary series of vaccination)] up until completion of the safety follow-up period (10 years after primary series of vaccination)
Number of Participants Who Had Their Rabies Virus Neutralizing Antibody (RNVA) Concentrations Drop Below 0.5 International Units (IU) Per Milliliter (mL) Between Day 366 and Year 3		Day 366 to Year 3 (after primary series of vaccination)
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 3 and Year 4		Year 3 to Year 4 (after primary series of vaccination)
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 4 and Year 5		Year 4 to Year 5 (after primary series of vaccination)
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 5 and Year 6		Year 5 to Year 6 (after primary series of vaccination)
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 6 and Year 7		Year 6 to Year 7 (after primary series of vaccination)
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 7 and Year 8		Year 7 to Year 8 (after primary series of vaccination)
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 8 and Year 9		Year 8 to Year 9 (after primary series of vaccination)
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 9 and Year 10		Year 9 to Year 10 (after primary series of vaccination)
RVNA Antibody Concentrations 7 Days After the Booster Dose	RVNA antibody concentrations were measured in terms of Geometric Mean Concentrations (GMCs) and expressed in IU/mL. The booster dose was administered in this Extension study (conducted from Year 3 to Year 9 after the primary schedule study) only when participants had RVNA concentrations <0.5 IU/mL at the yearly immunogenicity check (i.e., at "Scheduled Clinic Visit"). Booster dose administration occurred at an approximate timepoint between 6 and 9 months from the previous "Scheduled Clinic Visit" during the Years 3 to 9.	At Day 7 after booster dose
RVNA Geometric Mean Ratios (GMRs) 7 Days After the Booster Dose Versus Antibody Concentrations Before the Booster Dose	GMR was calculated as ratio of post booster dose RVNA GMCs (7-day post booster dose) to the baseline RVNA GMCs (7 days before booster dose). The booster dose was administered in this Extension study (conducted from Year 3 to Year 9 after the primary schedule study) only when participants had RVNA concentrations <0.5 IU/mL at the yearly immunogenicity check (i.e., at "Scheduled Clinic Visit"). Booster dose administration occurred at an approximate timepoint between 6 and 9 months from the previous "Scheduled Clinic Visit" during the Years 3 to 9.	Day 7 after booster dose compared to baseline (7 days before booster dose)
Percentage of Participants With RVNA Concentrations Greater Than or Equal to (>=) 0.5 IU/mL, 7 Days After Booster Dose	The booster dose was administered in this Extension study (conducted from Year 3 to Year 9 after the primary schedule study) only when participants had RVNA concentrations <0.5 IU/mL at the yearly immunogenicity check (i.e., at "Scheduled Clinic Visit"). Booster dose administration occurred at an approximate timepoint between 6 and 9 months from the previous "Scheduled Clinic Visit" during the Years 3 to 9.	At Day 7 after booster dose
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 3		At Year 3 after primary series of vaccine administration
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 4		At Year 4 after primary series of vaccine administration
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 5		At Year 5 after primary series of vaccine administration
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 6		At Year 6 after primary series of vaccine administration
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 7		At Year 7 after primary series of vaccine administration
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 8		At Year 8 after primary series of vaccine administration
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 9		At Year 9 after primary series of vaccine administration
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 10		At Year 10 after primary series of vaccine administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rabies Virus Neutralizing Antibody Concentrations	Antibody concentrations were measured in terms of GMCs and expressed in IU/mL.	At Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and Year 10 after primary series of vaccine administration
Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL	As specified in the statistical analysis plan, a graphical presentation of the Reverse Cumulative Distribution Plots for participants with RVNA concentrations >=0.5 IU/mL was analyzed for this outcome measure. Due to system constrains, only the reverse cumulative percentage values were reported, to depict the Reverse Cumulative Distribution Plots.	At Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and Year 10 after primary series of vaccine administration

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2015
• Primary Completion (Actual): December 23, 2022
• Study Completion (Actual): December 23, 2022

Study Registration Dates

• First Submitted: August 31, 2015
• First Submitted That Met QC Criteria: September 7, 2015
• First Posted (Estimated): September 10, 2015

Study Record Updates

• Last Update Posted (Actual): July 18, 2024
• Last Update Submitted That Met QC Criteria: July 15, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Long-term Immunogenicity; Rabies disease; Pre-exposure (PrEP) or post exposure prophylaxis (PEP)
• Additional Relevant MeSH Terms: RNA Virus Infections; Infections; Mononegavirales Infections; Rhabdoviridae Infections; Virus Diseases; Rabies
• Other Study ID Numbers: 205214; 2015-000382-31 (EudraCT Number); V49_23E1 (Other Identifier: Novartis)

Plan for Individual participant data (IPD)

• 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.