Study of a Single Primary Dose Live Attenuated Japanese Encephalitis Chimeric Virus Vaccine (IMOJEV®) in Healthy Subjects

• ClinicalTrials.gov Identifier: NCT02492165
• Recruitment Status: Completed
• First Posted: July 8, 2015
• Results First Posted: November 29, 2016
• Last Update Posted: November 29, 2016
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Collaborator: National Institute of Hygiene and Epidemiology, Vietnam
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Description

Brief Summary:

The purpose of this study is to describe the immunogenicity and safety of IMOJEV® in adult and pediatric populations in Vietnam and serve a bridging study to compare immunogenicity, reactogenicity, and safety data obtained with IMOJEV® in the Vietnamese population with data from other Asian pediatric populations.

Primary objective:

- To describe the safety profile of a single dose of IMOJEV®.

Secondary objectives:

• To evaluate the immune response to JE 28 days after the administration of a single dose of IMOJEV® in healthy Vietnamese subjects aged from 9 months to 60 years.

Condition or disease	Intervention/treatment	Phase
Japanese Encephalitis	Biological: Live attenuated Japanese encephalitis chimeric virus vaccine (IMOJEV®)	Phase 3

Detailed Description:

Study participants will be enrolled by age group and will each receive one injection of IMOJEV® on Day 0 given as primary vaccination. They will be assessed for immunogenicity and safety, post-vaccination.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 250 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety of a Single Primary Dose of a Live Attenuated Japanese Encephalitis Chimeric Virus Vaccine (IMOJEV®) Given to Healthy Subjects in Vietnam
• Study Start Date: June 2015
• Actual Primary Completion Date: March 2016
• Actual Study Completion Date: June 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Age 9 Months through 4 Years Group; Participants age 9 Months through 4 Years old at enrollment	Biological: Live attenuated Japanese encephalitis chimeric virus vaccine (IMOJEV®); 0.5 mL, Subcutaneous; Other Name: IMOJEV®
Experimental: Age 5 Years through 11 Years Group; Participants age 5 Years through 11 Years old at enrollment	Biological: Live attenuated Japanese encephalitis chimeric virus vaccine (IMOJEV®); 0.5 mL, Subcutaneous; Other Name: IMOJEV®
Experimental: Age 12 Years through 17 Years Group; Participants age 12 Years through 17 Years old at enrollment	Biological: Live attenuated Japanese encephalitis chimeric virus vaccine (IMOJEV®); 0.5 mL, Subcutaneous; Other Name: IMOJEV®
Experimental: Age 18 Years through 60 Years Group; Participants age 18 Years through 60 Years old at enrollment	Biological: Live attenuated Japanese encephalitis chimeric virus vaccine (IMOJEV®); 0.5 mL, Subcutaneous; Other Name: IMOJEV®

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Solicited Injection Site Reactions and Systemic Events Following a Single Primary Dose of a Live Attenuated Japanese Encephalitis Chimeric Virus Vaccine (IMOJEV®) [ Time Frame: Day 0 up to Day 14 post-vaccination ]

   Solicited injection-site: ≤ 23 months age: Tenderness, Erythema, and Swelling. For ≥ 2 years age: Pain, Erythema, and Swelling. Solicited systemic reactions: ≤ 23 months age, Fever (temperature) Vomiting, Crying abnormal, Drowsiness, Appetite loss, Irritability, For ≥ 2 years age, Fever (temperature) Headache, Malaise, and Myalgia.

   Grade 3: Tenderness, Cries when injected limb is moved; Pain, Incapacitating, unable to perform usual activities or Significant; prevents daily activity (≥ 12 years); Erythema and Swelling (≤23 months to 11 years), ≥50 mm or >100 mm (≥ 12 years).

   Grade 3 Fever, > 39.5°C (≤ 23 months) or ≥39.0°C (≥ 2 years); Vomiting, ≥ 6 episodes per 24 hours; Crying abnormal, > 3 hours; Drowsiness, Sleeping most of the time; Appetite loss, Refuses ≥ 3 feeds / meals; Irritability, Inconsolable. Headache, Malaise, and Myalgia, Significant; prevents daily activity.

2. Percentage of Participants With Japanese Encephalitis Seroprotection Following a Single Primary Dose of a Live Attenuated Japanese Encephalitis Chimeric Virus Vaccine (IMOJEV®) [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ]
   Neutralizing antibodies were measured using a Japanese encephalitis chimeric virus (JE CV) 50% plaque reduction neutralization test (PRNT50). Seroprotection was defined as antibody titer levels ≥10 (1/dil).
3. Percentage of Participants With Japanese Encephalitis Seroconversion Following a Single Primary Dose of a Live Attenuated Japanese Encephalitis Chimeric Virus Vaccine (IMOJEV®) [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ]
   Neutralizing antibodies were measured using a Japanese encephalitis chimeric virus (JE CV) 50% plaque reduction neutralization test (PRNT50). Seroconversion was defined as participants with a pre-vaccination titer <10 (1/dil) and post-vaccination titer ≥10 (1/dil) or participants with pre vaccination titer ≥10 (1/dil) and a ≥4-fold increase from pre- to post-vaccination.
4. Summary of Geometric Mean Titers of Japanese Encephalitis Antibodies Following a Single Primary Dose of a Live Attenuated Japanese Encephalitis Chimeric Virus Vaccine (IMOJEV®) [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ]
   Neutralizing antibodies were measured using a Japanese encephalitis chimeric virus (JE CV) 50% plaque reduction neutralization test (PRNT50).

Eligibility Criteria

• Ages Eligible for Study: 9 Months to 60 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Aged 9 months through 60 years on the day of inclusion.
• For adults: Informed consent form has been signed and dated by the subject. For minors: Informed consent form has been signed and dated by the parent or legally acceptable representative. In addition, in accordance with the Institution Ethics Committee / Institution Review Board requirements and as appropriate for the age of the subject, the subject may be required to sign and date the informed consent form if aged 12 to 17 years or assent form if aged 8 to 11 years.
• Subject and parent(s)/legally acceptable representative(s) are able to attend all scheduled visits and comply with all study procedures.

Exclusion Criteria:

• Subject is pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be pre-menarche, or post-menopausal for at least 1 year, or surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after vaccination).
• Participation at the time of study enrollment (or in the 4 weeks preceding the study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or a medical procedure.
• Receipt of any vaccine in the 4 weeks preceding the study vaccination or planned receipt of any vaccine in the 4 weeks following the study vaccination, except for inactivated influenza vaccination, which may be received at least 2 weeks before the study vaccine
• Previous vaccination against flavivirus disease, including Japanese Encephalitis (JE), dengue, and yellow fever.
• Receipt of immune globulins, blood, or blood-derived products in the past 3 months that might interfere with the assessment of the immune response.
• Known or suspected congenital or acquired immunodeficiency, or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term systemic corticosteroids therapy (for more than 2 consecutive weeks within the 4 weeks preceding vaccination).
• History of flavivirus infection (confirmed either clinically, serologically, or virologically).
• History of central nervous system disorder or disease, including seizures.
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the study or to a vaccine containing any of the same substances.
• Known thrombocytopenia, contraindicating vaccination.
• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating vaccination.
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
• Current alcohol abuse or drug addiction.
• Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion.
• Febrile illness (temperature ≥ 38.0°C) or moderate or severe acute illness/infection on the day of vaccination, according to Investigator judgment. A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided.
• Receipt of any chronic anti-viral in the 2 months preceding the study vaccination or planned receipt of any anti-viral in the 4 weeks following the study vaccination. Short-term antiviral drugs for flu or herpes can be administered provided there is a wash-out period of 1 week before the administration of the vaccine.
• Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.

Contacts and Locations

Locations

Vietnam

Preventive Medicine Centre of Hoa Binh Province

Hoa Binh, Vietnam

Sponsors and Collaborators

Sanofi Pasteur, a Sanofi Company

National Institute of Hygiene and Epidemiology, Vietnam

Investigators

• Study Director: Medical Director; Sanofi Pasteur SA

More Information

Additional Information:

Related Info 

Related Info 

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

Vu TD, Nguyen QD, Tran HTA, Bosch-Castells V, Zocchetti C, Houillon G. Immunogenicity and safety of a single dose of a live attenuated Japanese encephalitis chimeric virus vaccine in Vietnam: A single-arm, single-center study. Int J Infect Dis. 2018 Jan;66:137-142. doi: 10.1016/j.ijid.2017.10.010. Epub 2017 Nov 27.

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT02492165
• Obsolete Identifiers: NCT02821221
• Other Study ID Numbers: JEC13; U1111-1143-8142 ( Other Identifier: WHO )
• First Posted: July 8, 2015
• Results First Posted: November 29, 2016
• Last Update Posted: November 29, 2016
• Last Verified: October 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Individual participant data (IPD) and supporting clinical documents are available for request at www.clinicalstudydatarequest.com. While making information available we continue to protect the privacy of the participants in our clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: Clinicalstudydatarequest.com/Sanofi".

Keywords provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):

Japanese Encephalitis; Japanese encephalitis chimeric virus vaccine; IMOJEV®; Live attenuated vaccine

Additional relevant MeSH terms:

Encephalitis, Japanese; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Encephalitis, Arbovirus; Arbovirus Infections; Virus Diseases; Encephalitis, Viral; Central Nervous System Viral Diseases; RNA Virus Infections; Flavivirus Infections; Flaviviridae Infections; Infectious Encephalitis; Central Nervous System Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs