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.

Phase 3

Completed

• Conditions: Virus Diseases; Rabies
• Interventions: Biological: Rabipur; Procedure: Blood sampling; Biological: Purified Chick-Embryo Cell Rabies Vaccine

• Registration Number: NCT02545517
• Lead Sponsor: GlaxoSmithKline

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 GSK Clinical Study Register is no longer maintained for this study.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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-08-31
• Study First Submitted QC: 2015-09-07
• Study First Posted: 2015-09-10
• Study Start: 2015-10-05
• Primary Completion: 2022-12-23
• Study Completion: 2022-12-23
• Results First Submitted: 2023-12-21
• Status Verified: 2024-07
• Results First Submitted QC: 2024-07-15
• Last Update Submitted: 2024-07-15
• Results First Posted: 2024-07-18
• Last Update Posted: 2024-07-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 459

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Conv-R/JE Group	Purified Chick-Embryo Cell Rabies Vaccine	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.
Acc-R/JE Group	Rabipur	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.
Conv-R/JE Group	Blood sampling	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.
Conv-R Group	Rabipur	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.
Conv-R/JE Group	Rabipur	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.
Acc-R/JE Group	Blood sampling	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.
Conv-R Group	Blood sampling	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.

Primary Outcome Measures

Name	Time	Method
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 7 and Year 8	Year 7 to Year 8 (after primary series of vaccination)
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 8	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	Year 8 to Year 9 (after primary series of vaccination)
RVNA Antibody Concentrations 7 Days After the Booster Dose	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	At Year 4 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 9	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	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 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)
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 7	At Year 7 after primary series of vaccine administration
Number of Participants Reporting Serious Adverse Events (SAEs) After a Booster Dose of Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine	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 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 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 9 and Year 10	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	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	At Year 5 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

Name	Time	Method
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	Antibody concentrations were measured in terms of GMCs and expressed in IU/mL.
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	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.

Trial Locations

Locations (1)

GSK Investigational Site; 🇨🇭 Zuerich, Switzerland