Long-term Immunogenicity After Receipt of JE Vaccine and Antibody Response and Safety to a Booster Dose

• ClinicalTrials.gov Identifier: NCT02514746
• Recruitment Status: Completed
• First Posted: August 4, 2015
• Results First Posted: October 19, 2020
• Last Update Posted: October 19, 2020
• Sponsor: PATH
• Collaborator: International Centre for Diarrhoeal Disease Research, Bangladesh
• Information provided by (Responsible Party): PATH

Study Description

Brief Summary:

This study aims to understand the persistence of the Japanese encephalitis (JE) antibody response in previously vaccinated children. The proposed study will enrol Bangladeshi children who had previously participated in a lot to lot consistency study (JEV05; NCT01567865) of JE live attenuated SA 14-14-2 vaccine (CD-JEV).

Condition or disease	Intervention/treatment	Phase
Encephalitis, Japanese	Biological: Live Attenuated Japanese Encephalitis SA-14-14-2 Vaccine	Phase 4

Detailed Description:

Study participants previously immunized with CD-JEV (Clinical Trials identifier: NCT01567865, JEV05) will have serum collected three and four years after initial vaccination to assess long-term immunogenicity. Four years after receiving the initial dose of CD-JEV, eligible participants will be vaccinated with a second subcutaneous dose of CD-JEV to assess the antibody response.

Participants will be monitored for safety for 28 days following receipt of the booster dose.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 561 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Assessment of Long Term Immunogenicity of Japanese Encephalitis Live Attenuated SA-14-14-2 Vaccine in Previously Vaccinated Bangladeshi Children and Antibody Response and Safety to a Booster Dose
• Actual Study Start Date: July 30, 2015
• Actual Primary Completion Date: December 15, 2016
• Actual Study Completion Date: January 12, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Live Attenuated JE SA-14-14-2 Vaccine (CD-JEV); Participants previously vaccinated with CD-JEV will receive a booster dose of live, attenuated Japanese encephalitis SA-14-14-2 vaccine four years after initial vaccination.	Biological: Live Attenuated Japanese Encephalitis SA-14-14-2 Vaccine; 0.5 mL subcutaneous injection; Other Names: CD-JEV; CD.JEVAX®; RS.JEV®

Outcome Measures

Primary Outcome Measures :

1. Seroprotection Rate Three and Four Years After Initial Vaccination With CD-JEV [ Time Frame: 3 years after initial vaccination (Study Day 1) and 4 years after initial vaccination (Study Day 365) ]
   Seroprotection rate is defined as the percentage of participants with an anti-Japanese encephalitis (JE) neutralizing antibody titer ≥ 1:10 as measured using a 50% plaque reduction neutralization test (PRNT-50). Seroprotection was assessed at 3 and 4 years after the initial vaccination in Study JEV05, prior to participants receiving a booster vaccination in the current study.
2. Geometric Mean Titer of Anti-JE Neutralizing Antibodies Three and Four Years After Initial Vaccination With CD-JEV [ Time Frame: 3 years after initial vaccination (Study Day 1) and 4 years after initial vaccination (Study Day 365) ]
   The geometric mean titer (GMT) of anti-JE neutralizing antibodies 3 and 4 years after initial vaccination with CD-JEV in Study JEV05 and prior to receiving the booster vaccination in the current study, measured using PRNT-50.

Secondary Outcome Measures :

1. Seroprotection Rate 7 Days and 28 Days After Booster Dose [ Time Frame: 7 days and 28 days following booster vaccination (Study Days 372 and 393) ]
   Seroprotection rate is defined as the percentage of study participants with an anti-JE neutralizing antibody titer ≥1:10 assessed using PRNT-50.
2. GMT of Anti-JE Neutralizing Antibodies 7 Days and 28 Days After Booster Dose [ Time Frame: 7 days and 28 days following booster vaccination (Study Days 372 and 393) ]
   Geometric mean titer of anti-JE neutralizing antibodies measured using PRNT-50.
3. Seroconversion Rate 7 Days and 28 Days After Booster Dose [ Time Frame: 7 days and 28 days following booster vaccination (Study Days 372 and 393) ]

   Seroconversion rate is defined as the percentage of study participants with either:

   • For participants who were seronegative at Baseline (defined as anti-JE neutralizing antibody titer of < 1:10 assessed using PRNT-50 at Year 4, prior to booster vaccination): A change in serostatus from seronegative (anti-JE neutralizing antibody titer of < 1:10) to positive (anti-JE neutralizing antibody titer ≥ 1:10)
   • For participants who were seropositive at Baseline (defined as an anti-JE neutralizing antibody titer ≥1:10 assessed using PRNT-50 at Year 4, prior to booster vaccination): a 4-fold increase in anti-JE neutralizing antibody titer relative to Baseline anti-JE neutralizing antibody titer
4. GMT Ratio of Anti-JE Neutralizing Antibody Titers Between Post-Booster and Pre-Booster Vaccination [ Time Frame: 4 years after the initial vaccination (Study Day 365, pre-booster vaccination) and 7 and 28 days following booster vaccination (Study Days 372 and 393) ]

   To evaluate the magnitude of the increase in GMTs, the GMT ratio of anti-JE neutralizing antibody titers between post-booster vaccination and pre-booster vaccination was calculated for the following:

   • GMT of anti-JE neutralizing antibodies at 7 days after booster vaccination to the Year 4, pre-booster GMT of anti-JE neutralizing antibodies
   • GMT of anti-JE neutralizing antibodies at 28 days after booster vaccination to the Year 4, pre-booster GMT of anti-JE neutralizing antibodies
5. Number of Participants With Immediate Reactions 30 Minutes Following Booster Vaccination [ Time Frame: 30 minutes following booster vaccination (Study Day 365) ]
   The number of participants with at least one occurrence of an immediate reaction, including local, systemic, or unsolicited adverse event that occurred within 30 minutes of the booster vaccination.
6. Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination [ Time Frame: From 30 minutes to 7 days following booster vaccination (Study Day 365 to 372) ]

   Participants were monitored for local reactions from 30 minutes through 7 days post booster vaccination. Local reactions (at the injection site) included the following:

   • Ecchymosis (bruising)
   • Erythema (redness)
   • Edema (swelling)
   • Induration (hardness)
   • Pain/tenderness

   Local ecchymosis, erythema, edema, and induration were graded as follows:

   • Grade 1: ≤ 2.5 cm in diameter
   • Grade 2: > 2.5 cm in diameter with < 50% surface area of extremity involved
   • Grade 3: ≥ 50% surface area of extremity involved OR ulceration OR secondary infection OR phlebitis OR sterile abscess OR drainage
   • Grade 4: potentially life-threatening consequences

   Injection site pain/tenderness were graded as follows:

   • Grade 1: causing no or minimal limitation in use of limb
   • Grade 2: causing greater than minimal limitation of use of limb
   • Grade 3: causing inability to perform usual social or functional activities
   • Grade 4: inability to perform basic self-care OR hospitalization indicated.
7. Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination [ Time Frame: From 30 minutes to 7 days following booster vaccination (Study Day 365 to 372) ]

   Participants were monitored for systemic reactions from 30 minutes through 7 days post booster vaccination. Systemic reactions (general signs / symptoms) included the following:

   • Fever
   • Change in eating habits
   • Diarrhea
   • Sleepiness
   • Irritability
   • Unusual crying
   • Vomiting

   Fever was graded as follows:

   • Grade 1: 37.5 ℃ to 37.9 ℃
   • Grade 2: 38.0 ℃ to 38.4 ℃
   • Grade 3: 38.5 ℃ to 40.0 ℃
   • Grade 4: > 40.0 ℃

   Change in eating habits, diarrhea, sleepiness, irritability, unusual crying, vomiting were graded as follows:

   • Grade 1: causing no or minimal interference with usual social or functional activities
   • Grade 2: causing greater than minimal interference with usual social or functional activities
   • Grade 3: causing inability to perform usual social or functional activities OR hospitalization indicated
   • Grade 4: inability to perform basic self-care OR medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death.
8. Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination [ Time Frame: 28 days following booster vaccination (Study Days 365 to 393) ]

   AEs were graded for severity according to the following:

   Grade 1 (Mild): Symptoms causing no or minimal interference with usual social and functional activities

   Grade 2 (Moderate): Symptoms causing greater than minimal interference with usual social and functional activities

   Grade 3 (Severe): Symptoms causing inability to perform usual social and functional activities with intervention or hospitalization indicated

   Grade 4 (Potentially life-threatening): Symptoms causing inability to perform basic self-care functions OR medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death.

   Relationship to study vaccine was based on the Clinician's assessment.

   A serious adverse event is defined as an AE that meets 1 of the following criteria:

   • Death
   • Life-threatening
   • Requires hospitalization or prolongation of existing hospitalization
   • Results in persistent disability
   • Important medical event based on medical judgement

Eligibility Criteria

• Ages Eligible for Study: 43 Months to 51 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Participant in JEV05 study (NCT01567865) and received one dose of CD-JEV.
• Resides in the Matlab or Mirpur study area.
• At least one parent or guardian willing to provide written informed consent.

Exclusion Criteria:

• Received a second dose of Japanese encephalitis vaccine within the past three years.
• Received immunoglobulins and/or any blood products within 90 days prior to enrollment.
• Been diagnosed with a primary or acquired immunodeficiency, including human immunodeficiency virus (HIV) infection within the past three years.

Contacts and Locations

Sponsors and Collaborators

PATH

International Centre for Diarrhoeal Disease Research, Bangladesh

Investigators

• Principal Investigator: K Zaman, PhD, MPH, MBBS; International Centre for Diarrhoeal Disease Research, Bangladesh

  Study Documents (Full-Text)

Documents provided by PATH:

Study Protocol  [PDF] March 4, 2018

Statistical Analysis Plan  [PDF] July 12, 2018

More Information

Publications of Results:

Zaman K, Naser AM, Power M, Yaich M, Zhang L, Ginsburg AS, Luby SP, Rahman M, Hills S, Bhardwaj M, Flores J. Lot-to-lot consistency of live attenuated SA 14-14-2 Japanese encephalitis vaccine manufactured in a good manufacturing practice facility and non-inferiority with respect to an earlier product. Vaccine. 2014 Oct 21;32(46):6061-6. doi: 10.1016/j.vaccine.2014.09.012. Epub 2014 Sep 18.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Zaman K, Yunus M, Aziz AB, Feser J, Mooney J, Tang Y, Ellison DW, Thaisomboonsuk B, Zhang L, Neuzil KM, Marfin AA, Letson GW. Antibody persistence and immune memory response following primary vaccination and boosting with live attenuated SA 14-14-2 Japanese encephalitis vaccine (CD-JEV) in Bangladesh: A phase 4 open-label clinical trial. Vaccine X. 2022 Feb 5;10:100143. doi: 10.1016/j.jvacx.2022.100143. eCollection 2022 Apr.

• Responsible Party: PATH
• ClinicalTrials.gov Identifier: NCT02514746
• Other Study ID Numbers: JEV07; PR-15036 ( Other Identifier: International Centre for Diarrhoeal Disease Research, Bangladesh )
• First Posted: August 4, 2015
• Results First Posted: October 19, 2020
• Last Update Posted: October 19, 2020
• Last Verified: August 2020

Keywords provided by PATH:

Japanese Encephalitis Vaccines; Flavivirus Infections

Additional relevant MeSH terms:

Encephalitis, Japanese; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases; Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infections; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Virus Diseases; RNA Virus Infections; Flavivirus Infections; Flaviviridae Infections