Post-licensure Safety Study of IMOJEV® in Thailand

• Sponsor: Sanofi Pasteur, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01981967
• Collaborator: (none)
• Enrollment: 10,000
• Locations: 8
• Arms: 2
• Duration (Months): 23
• Patients Per Site: 1250
• Patients Per Site Per Month: 54.4

Study Details

Study Description

Brief Summary

The aim of this study is to further characterize the safety profile of IMOJEV®.

Primary Objective:

• To describe serious adverse events (SAEs, including adverse events of special interest [AESIs]) up to 60 days after administration of one dose of IMOJEV®.

Secondary Objective:

• To describe Grade 3 (severe) systemic Adverse Events (AEs) up to 30 minutes after administration of one dose of IMOJEV®.

Condition or Disease	Intervention/Treatment	Phase
Japanese Encephalitis	Biological: IMOJEV®: Live attenuated Japanese encephalitis chimeric virus vaccine; Biological: IMOJEV®: Live attenuated Japanese encephalitis chimeric virus vaccine	Phase 4

Detailed Description

Participants aged 1 year to less than 5 years will be randomized to receive one injection of IMOJEV® either as a primary vaccination or as a booster. Safety data will be collected for 60 days after IMOJEV® vaccination. The duration of each subject's participation in the trial will be 60 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10000 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Post-licensure, Phase IV, Safety Study of IMOJEV® in Thailand
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Primary Vaccination Group Participants who never received a JE vaccine, or who received a single dose of inactivated JE vaccine, or whose JE vaccination history is unknown or not documented.	Biological: IMOJEV®: Live attenuated Japanese encephalitis chimeric virus vaccine; 0.5 mL, Subcutaneous.; Other Names: IMOJEV®
Active Comparator: Booster Vaccination Group Participants who received at least 2 doses of inactivated JE vaccine (at least 1 year earlier for the last dose), or received a single dose of IMOJEV®, THAIJEV®, or IMOJEV® MD as part of the routine vaccination schedule (i.e., outside of Study JEC17) at least 1 year earlier	Biological: IMOJEV®: Live attenuated Japanese encephalitis chimeric virus vaccine; 0.5 mL, Subcutaneous.; Other Names: IMOJEV®

Outcome Measures

Primary Outcome Measures

1. Number of Participants Experiencing a Grade 3 Immediate Systemic Adverse Events and Serious Adverse Events Following Any Vaccination With IMOJEV® [30 minutes post-vaccination up to Day 60 post-vaccination]

2. Number of Participants Experiencing Serious Adverse Events By Age Following Any Vaccination With IMOJEV® [Day O up to Day 60 post-vaccination]

Secondary Outcome Measures

1. Number of Participants Experiencing Adverse Events of Special Interest Within 60 Days Following Vaccination With IMOJEV® [Day O up to Day 60 post-vaccination]

   Adverse Events of Special Interest (AESIs) included hypersensitivity/allergic reactions, neurological events (including febrile convulsions), and vaccine failure.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 9 Months to 4 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Children requiring vaccination against Japanese encephalitis

• Children aged 9 months to less than 5 years on the day of inclusion

• In good general health at the time of inclusion

• Informed consent form has been signed and dated by the parent(s)/legal guardian(s)

• Subject and parent(s)/legal guardian(s) are able to attend the scheduled visit and any additional visits that may need to be done in case of an SAE (including AESI), and are able to comply with all trial procedures

• The subject's parent(s)/legal guardian(s) have a telephone number at which they can be contacted throughout the study

Exclusion Criteria:

• Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the vaccination

• 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

• Planned participation in another clinical trial during the present trial period

• Children previously vaccinated with the live attenuated Japanese encephalitis vaccine CD-JEVAX® (SA14-14-2 LAV)

• Contraindications to vaccination according to the IMOJEV® Summary of Product Characteristics (SmPC)

• Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study

• Children who received IMOJEV® as primary vaccination in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Bangkok		Thailand	10330
2		Bangkok		Thailand	10400
3		Chiang Mai		Thailand	50200
4		Khon Kaen		Thailand	40002
5		Nakornnayok		Thailand	26120
6		Nonthaburi		Thailand	11120
7		Pathumthani		Thailand	12120
8		Songkla		Thailand	90110

Sponsors and Collaborators

• Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director, Sanofi Pasteur SA

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01981967
• Other Study ID Numbers: JEC17; U1111-1127-7052
• First Posted: Nov 13, 2013
• Last Update Posted: May 4, 2016
• Last Verified: Mar 1, 2016

• Keywords provided by Sanofi Pasteur, a Sanofi Company: Japanese encephalitis; IMOJEV®; Japanese encephalitis chimeric virus vaccine
• Additional relevant MeSH terms: Encephalitis, Japanese; Encephalitis; Vaccines

Study Results

Participant Flow

Recruitment Details	The study participants were enrolled from 03 November 2013 to 08 February 2015 in 10 trial centers in Thailand.
Pre-assignment Detail	A total of 10,000 participants who met all of the inclusion and none of the exclusion criteria were vaccinated in this study.

Arm/Group Title	Primary Vaccination Group	Booster Vaccination Group
Arm/Group Description	Children aged 9 months to less than 5 years who received one injection of IMOJEV® as a primary vaccination.	Children aged 9 months to less than 5 years who received one injection of IMOJEV® as a booster.
Period Title: Overall Study
STARTED	6851	3149
COMPLETED	6851	3149
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Primary Vaccination Group	Booster Vaccination Group	Total
Arm/Group Description	Children aged 9 months to less than 5 years who received one injection of IMOJEV® as a primary vaccination.	Children aged 9 months to less than 5 years who received one injection of IMOJEV® as a booster.	Total of all reporting groups
Overall Participants	6851	3149	10000
Age (Count of Participants)
<=18 years	6851 100%	3149 100%	10000 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	1.22 (0.486)	3.60 (0.892)	1.97 (1.28)
Sex: Female, Male (Count of Participants)
Female	3321 48.5%	1550 49.2%	4871 48.7%
Male	3530 51.5%	1599 50.8%	5129 51.3%
Region of Enrollment (Number) [Number]
Thailand	6851 100%	3149 100%	10000 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Experiencing a Grade 3 Immediate Systemic Adverse Events and Serious Adverse Events Following Any Vaccination With IMOJEV®
Time Frame	30 minutes post-vaccination up to Day 60 post-vaccination

Outcome Measure Data

Analysis Population Description

Safety outcome were assessed in subjects who had received the study vaccine, the Safety Analysis Set

Arm/Group Title	Primary Vaccination Group	Booster Vaccination Group
Arm/Group Description	Children aged 9 months to less than 5 years who received one injection of IMOJEV® as a primary vaccination.	Children aged 9 months to less than 5 years who received one injection of IMOJEV® as a booster.
Measure Participants	6851	3149
Grade 3 immediate systemic adverse event	0 0%	0 0%
Seriuos adverse events	204 3%	59 1.9%
Death	0 0%	1 0%

2. Primary Outcome

Title	Number of Participants Experiencing Serious Adverse Events By Age Following Any Vaccination With IMOJEV®
Time Frame	Day O up to Day 60 post-vaccination

Outcome Measure Data

Analysis Population Description

Safety outcome were assessed in subjects who had received the study vaccine, the Safety Analysis Set

Arm/Group Title	Primary Vaccination Group	Booster Vaccination Group
Arm/Group Description	Children aged 9 months to less than 5 years who received one injection of IMOJEV® as a primary vaccination.	Children aged 9 months to less than 5 years who received one injection of IMOJEV® as a booster.
Measure Participants	6851	3149
SAEs in Subjects 9 to <12 Months	43 0.6%	0 0%
SAEs in Subjects 1 to 2 Years	155 2.3%	0 0%
SAEs in Subjects 2 to <5 Years	6 0.1%	59 1.9%

3. Secondary Outcome

Title	Number of Participants Experiencing Adverse Events of Special Interest Within 60 Days Following Vaccination With IMOJEV®
Description	Adverse Events of Special Interest (AESIs) included hypersensitivity/allergic reactions, neurological events (including febrile convulsions), and vaccine failure.
Time Frame	Day O up to Day 60 post-vaccination

Outcome Measure Data

Analysis Population Description

Safety outcome were assessed in subjects who had received the study vaccine, the Safety Analysis Set

Arm/Group Title	Primary Vaccination Group	Booster Vaccination Group
Arm/Group Description	Children aged 9 months to less than 5 years who received one injection of IMOJEV® as a primary vaccination.	Children aged 9 months to less than 5 years who received one injection of IMOJEV® as a booster.
Measure Participants	6851	3149
Febrile convulsion	25 0.4%	2 0.1%
Convulsion	1 0%	0 0%
Epilepsy	1 0%	0 0%
Frontal lobe epilepsy	1 0%	0 0%
Urticaria	0 0%	2 0.1%

Adverse Events

Time Frame	Adverse event data were collected from Day 0 (post-vaccination) up to 60 post-vaccination
Arm/Group Title	Primary Vaccination Group		Booster Vaccination Group
Arm/Group Description	Children aged 9 months to less than 5 years who received one injection of IMOJEV® as a primary vaccination.		Children aged 9 months to less than 5 years who received one injection of IMOJEV® as a booster.
All Cause Mortality
	Primary Vaccination Group		Booster Vaccination Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Primary Vaccination Group		Booster Vaccination Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	204/6851 (3%)		59/3149 (1.9%)
Gastrointestinal disorders
Diarrhoea	8/6851 (0.1%)	8	0/3149 (0%)	0
Dyspepsia	0/6851 (0%)	0	1/3149 (0%)	1
Enteritis	1/6851 (0%)	1	0/3149 (0%)	0
Food poisoning	0/6851 (0%)	0	1/3149 (0%)	1
Gastritis	8/6851 (0.1%)	8	4/3149 (0.1%)	4
Mouth ulceration	1/6851 (0%)	1	0/3149 (0%)	0
General disorders
Influenza like illness	0/6851 (0%)	0	1/3149 (0%)	1
Pyrexia	0/6851 (0%)	0	1/3149 (0%)	1
Immune system disorders
Allergy to arthropod sting	1/6851 (0%)	1	0/3149 (0%)	0
Infections and infestations
Abscess limb	0/6851 (0%)	0	1/3149 (0%)	1
Acute tonsillitis	4/6851 (0.1%)	4	0/3149 (0%)	0
Anal abscess	1/6851 (0%)	1	0/3149 (0%)	0
Bronchiolitis	6/6851 (0.1%)	6	0/3149 (0%)	0
Bronchitis	17/6851 (0.2%)	17	10/3149 (0.3%)	10
Bronchitis viral	1/6851 (0%)	1	0/3149 (0%)	0
Burkholderia pseudomallei infection	1/6851 (0%)	1	0/3149 (0%)	0
Cellulitis	2/6851 (0%)	2	0/3149 (0%)	0
Croup infectious	2/6851 (0%)	2	0/3149 (0%)	0
Dengue fever	1/6851 (0%)	1	1/3149 (0%)	1
Diarrhoea infectious	5/6851 (0.1%)	5	0/3149 (0%)	0
Exanthema subitum	1/6851 (0%)	1	0/3149 (0%)	0
Gastritis bacterial	1/6851 (0%)	1	0/3149 (0%)	0
Gastroenteritis	28/6851 (0.4%)	29	8/3149 (0.3%)	8
Gastroenteritis rotavirus	2/6851 (0%)	2	0/3149 (0%)	0
Gastroenteritis viral	4/6851 (0.1%)	4	0/3149 (0%)	0
Hand-foot-mouth disease	6/6851 (0.1%)	6	2/3149 (0.1%)	2
Herpangina	1/6851 (0%)	1	0/3149 (0%)	0
Infectious mononucleosis	1/6851 (0%)	1	2/3149 (0.1%)	2
Influenza	4/6851 (0.1%)	4	5/3149 (0.2%)	5
Laryngitis	1/6851 (0%)	1	0/3149 (0%)	0
Nasopharyngitis	2/6851 (0%)	2	3/3149 (0.1%)	3
Oral herpes	0/6851 (0%)	0	1/3149 (0%)	1
Otitis media acute	3/6851 (0%)	3	0/3149 (0%)	0
Pharyngitis	10/6851 (0.1%)	10	0/3149 (0%)	0
Pharyngitis bacterial	2/6851 (0%)	2	0/3149 (0%)	0
Pharyngotonsillitis	1/6851 (0%)	1	0/3149 (0%)	0
Pneumonia	24/6851 (0.4%)	24	7/3149 (0.2%)	7
Pneumonia bacterial	4/6851 (0.1%)	4	0/3149 (0%)	0
Pneumonia respiratory syncytial viral	4/6851 (0.1%)	4	0/3149 (0%)	0
Pneumonia viral	10/6851 (0.1%)	11	1/3149 (0%)	1
Pyelonephritis	1/6851 (0%)	1	0/3149 (0%)	0
Respiratory syncytial virus bronchiolitis	1/6851 (0%)	1	1/3149 (0%)	1
Respiratory syncytial virus bronchitis	1/6851 (0%)	1	0/3149 (0%)	0
Respiratory syncytial virus infection	1/6851 (0%)	1	0/3149 (0%)	0
Respiratory tract infection	0/6851 (0%)	0	2/3149 (0.1%)	2
Scarlet fever	1/6851 (0%)	1	0/3149 (0%)	0
Scrotal abcess	1/6851 (0%)	1	0/3149 (0%)	0
Sinusitis	2/6851 (0%)	2	0/3149 (0%)	0
Tonsillitis	0/6851 (0%)	0	1/3149 (0%)	1
Upper respiratory tract infection	4/6851 (0.1%)	4	1/3149 (0%)	1
Urinary track infection	6/6851 (0.1%)	6	0/3149 (0%)	0
Viral diarrhoea	1/6851 (0%)	1	0/3149 (0%)	0
Viral infection	2/6851 (0%)	2	0/3149 (0%)	0
Viral rash	2/6851 (0%)	2	0/3149 (0%)	0
Injury, poisoning and procedural complications
Femur fracture	1/6851 (0%)	1	0/3149 (0%)	0
Metabolism and nutrition disorders
Hypoglycaemia	0/6851 (0%)	0	1/3149 (0%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	0/6851 (0%)	0	1/3149 (0%)	1
Nervous system disorders
Convulsion	1/6851 (0%)	1	0/3149 (0%)	0
Epilepsy	1/6851 (0%)	1	0/3149 (0%)	0
Febrile convulsion	25/6851 (0.4%)	28	2/3149 (0.1%)	2
Frontal lobe epilepsy	1/6851 (0%)	1	0/3149 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	2/6851 (0%)	2	1/3149 (0%)	1
Pneumonitis	0/6851 (0%)	0	1/3149 (0%)	1
Skin and subcutaneous tissue disorders
Urticaria	2/6851 (0%)	2	2/3149 (0.1%)	2
Vascular disorders
Kawasaki's disease	1/6851 (0%)	1	0/3149 (0%)	0
Other (Not Including Serious) Adverse Events
	Primary Vaccination Group		Booster Vaccination Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6851 (0%)		0/3149 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications