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Clinical Trials/NCT02545517
NCT02545517CompletedPhase 3

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.

GlaxoSmithKline7 sites in 3 countries459 target enrollmentStarted: October 5, 2015Last updated:
Conditions
Interventions

Trial Snapshot

Phase
Phase 3
Status
Completed
Enrollment
459
Locations
7
Primary Endpoint
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

Study Overview

Brief Summary

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 GSK Clinical Study Register is no longer maintained for this study.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 Design

Study Type
Interventional
Allocation
Non Randomized
Intervention Model
Single Group
Primary Purpose
Prevention
Masking
None

Eligibility Criteria

Sex
All
Accepts Healthy Volunteers
Yes

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

Arms & Interventions

Conv-R/JE Group

Experimental

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.

Intervention: Blood sampling (Procedure)

Conv-R/JE Group

Experimental

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.

Intervention: Purified Chick-Embryo Cell Rabies Vaccine (Biological)

Acc-R/JE Group

Experimental

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.

Intervention: Blood sampling (Procedure)

Conv-R Group

Experimental

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.

Intervention: Blood sampling (Procedure)

Conv-R Group

Experimental

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.

Intervention: Rabipur (Biological)

Acc-R/JE Group

Experimental

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.

Intervention: Rabipur (Biological)

Conv-R/JE Group

Experimental

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.

Intervention: Rabipur (Biological)

Outcomes

Primary Outcomes

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

Time Frame: 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

Time Frame: 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

Time Frame: Year 4 to Year 5 (after primary series of vaccination)

Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 3

Time Frame: At Year 3 after primary series of vaccine administration

Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 7

Time Frame: At Year 7 after primary series of vaccine administration

Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 5 and Year 6

Time Frame: 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 7 and Year 8

Time Frame: Year 7 to Year 8 (after primary series of vaccination)

Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 8

Time Frame: At Year 8 after primary series of vaccine administration

Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 8 and Year 9

Time Frame: Year 8 to Year 9 (after primary series of vaccination)

RVNA Antibody Concentrations 7 Days After the Booster Dose

Time Frame: At Day 7 after 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.

Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 4

Time Frame: At Year 4 after primary series of vaccine administration

Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 6

Time Frame: At Year 6 after primary series of vaccine administration

Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 9

Time Frame: At Year 9 after primary series of vaccine administration

RVNA Geometric Mean Ratios (GMRs) 7 Days After the Booster Dose Versus Antibody Concentrations Before the Booster Dose

Time Frame: Day 7 after booster dose compared to baseline (7 days before 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.

Number of Participants Reporting Serious Adverse Events (SAEs) After a Booster Dose of Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine

Time Frame: 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)

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.

Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 6 and Year 7

Time Frame: 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 9 and Year 10

Time Frame: Year 9 to Year 10 (after primary series of vaccination)

Percentage of Participants With RVNA Concentrations Greater Than or Equal to (>=) 0.5 IU/mL, 7 Days After Booster Dose

Time Frame: At Day 7 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.

Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 5

Time Frame: At Year 5 after primary series of vaccine administration

Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 10

Time Frame: At Year 10 after primary series of vaccine administration

Secondary Outcomes

  • Rabies Virus Neutralizing Antibody Concentrations(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(At Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and Year 10 after primary series of vaccine administration)

Investigators

Sponsor Class
Industry
Responsible Party
Sponsor

Study Sites (7)

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