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.

NCT02545517 | Completed Phase 3 Results

• 3 other identifiers: 2052142015-000382-31V49_23E1
• Study Type: interventional
• Target: 459
• Locations: 3 countries
• Sites: 7

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 GSK Clinical Study Register is no longer maintained for this study.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

Conditions

Virus Diseases; Rabies

Keywords

Rabies disease; Pre-exposure (PrEP) or post exposure prophylaxis (PEP); Long-term Immunogenicity

Outcome Measures

Primary Outcomes (20)

• 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 Outcomes (2)

• 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

Study Arms (3)

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.

Biological: Rabipur; Procedure: Blood sampling; Biological: Purified Chick-Embryo Cell Rabies Vaccine

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.

Biological: Rabipur; Procedure: Blood sampling

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.

Biological: Rabipur; Procedure: Blood sampling

Interventions

Rabipur BIOLOGICAL

Participants in all the groups received Rabipur vaccine booster dose, administered intramuscularly in the deltoid region of the non-dominant arm.

Acc-R/JE Group; Conv-R Group; Conv-R/JE Group

Blood sampling PROCEDURE

Blood samples were drawn from all participants at Day 1 and then at subsequent year intervals from extension study Day 1 onwards.

Acc-R/JE Group; Conv-R Group; Conv-R/JE Group

Purified Chick-Embryo Cell Rabies Vaccine BIOLOGICAL

1 booster dose of 1.0 mL of Purified Chick-Embryo Cell Rabies Vaccine intramuscular (IM).

Conv-R/JE Group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (7)

GSK Investigational Site

Vienna, 1090, Austria

Location

GSK Investigational Site

Munich, Bavaria, 80802, Germany

Location

GSK Investigational Site

Rostock, Mecklenburg-Vorpommern, 18057, Germany

Location

GSK Investigational Site

Berlin, 10117, Germany

Location

GSK Investigational Site

Berlin, 13353, Germany

Location

GSK Investigational Site

Hamburg, 20359, Germany

Location

GSK Investigational Site

Zurich, 8001, Switzerland

Location

MeSH Terms

Conditions

Virus Diseases; Rabies

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Infections; Rhabdoviridae Infections; Mononegavirales Infections; RNA Virus Infections

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2015
• First Posted: September 10, 2015
• Study Start: October 5, 2015
• Primary Completion: December 23, 2022
• Study Completion: December 23, 2022
• Last Updated: July 18, 2024
• Results First Posted: July 18, 2024

Record last verified: 2024-07

Locations

AU (1); DE (5); CH (1)