A Study of Japanese Encephalitis Chimeric Virus Vaccine Compared With SA14-14-2 Vaccine in Infants and Toddlers

• ClinicalTrials.gov Identifier: NCT01092507
• Recruitment Status: Completed
• First Posted: March 25, 2010
• Results First Posted: December 2, 2013
• Last Update Posted: December 25, 2013
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Conditions: Encephalitis; Japanese Encephalitis
• Interventions: Biological: Japanese encephalitis chimeric virus vaccine (JE-CV); Biological: Japanese encephalitis live vaccine (SA14-14-2 vaccine) (CD.JEVAX®)
• Enrollment: 300

Participant Flow

Recruitment Details	Participants were enrolled from 07 March 2010 to 27 April 2011 at 3 clinical centers in Thailand.
Pre-assignment Details	A total of 300 participants who met all of the inclusion criteria and none of the exclusion criteria were enrolled; 299 were vaccinated.

Arm/Group Title	Japanese Encephalitis Chimeric Vaccine (JE-CV)	Japanese Encephalitis Live Vaccine (SA14-14-2)
Arm/Group Description	Participants received a single dose of Japanese encephalitis chimeric vaccine (JE-CV) on Day 0.	Participants received a single dose of Japanese encephalitis live vaccine (SA14-14-2; CD.JEVAX®) on Day 0.
Period Title: Overall Study
Started	149	150
Completed	147	150
Not Completed	2	0
Reason Not Completed
Withdrawal by Subject	2	0

Baseline Characteristics

Arm/Group Title		Japanese Encephalitis Chimeric Vaccine (JE-CV)	Japanese Encephalitis Live Vaccine (SA14-14-2)	Total
Arm/Group Description		Participants received a single dose of Japanese encephalitis chimeric vaccine (JE-CV) on Day 0.	Participants received a single dose of Japanese encephalitis live vaccine (SA14-14-2; CD.JEVAX®) on Day 0.	Total of all reporting groups
Overall Number of Baseline Participants		149	150	299
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	149 participants	150 participants	299 participants
	<=18 years	149 100.0%	150 100.0%	299 100.0%
	Between 18 and 65 years	0 0.0%	0 0.0%	0 0.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	149 participants	150 participants	299 participants
		13.1 (2.11)	13.2 (1.89)	13.2 (2.00)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	149 participants	150 participants	299 participants
	Female	69 46.3%	75 50.0%	144 48.2%
	Male	80 53.7%	75 50.0%	155 51.8%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Thailand	Number Analyzed	149 participants	150 participants	299 participants
		149	150	299

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Japanese Encephalitis Seroconversion After Vaccination With One Dose of Either Japanese Encephalitis Chimeric Vaccine (JE-CV) or Japanese Encephalitis Live Vaccine (SA14-14-2) (CD.JEVAX®)
Description	Immunogenicity was assessed by the JE-CV virus and the SA14-14-2 virus 50% plaque reduction neutralization test (PRNT50). Japanese Encephalitis seroconversion was defined as a pre-vaccination titer <10 1/dil and post-vaccination titer ≥ 10 1/dil; or a pre-vaccination titer ≥ 10 1/dil and a 4-fold increase from pre- to post-vaccination.
Time Frame	Day 0 through Day 28 after vaccination

Outcome Measure Data

Analysis Population Description

Japanese encephalitis antibody titers were assessed in all participants with immunogenicity data and who did not have any protocol violations that might have interfered with primary criteria evaluation (Per-Protocol Population)

Arm/Group Title	Japanese Encephalitis Chimeric Vaccine (JE-CV)	Japanese Encephalitis Live Vaccine (SA14-14-2)
Arm/Group Description:	Participants received a single dose of Japanese encephalitis chimeric vaccine (JE-CV) on Day 0.	Participants received a single dose of Japanese encephalitis live vaccine (SA14-14-2; CD.JEVAX®) on Day 0.
Overall Number of Participants Analyzed	126	128
Measure Type: Number; Unit of Measure: Participants
	125	127

2. Secondary Outcome

Title	Number of Participants With Japanese Encephalitis Seroprotection 28 Days After Vaccination With One Dose of Either Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) or Japanese Encephalitis Live Vaccine (SA14-14-2, CD.JEVAX®)
Description	Immunogenicity was assessed by JE-CV virus 50% plaque reduction neutralization test (PRNT50) or SA14-14-2 virus PRNT50. Japanese encephalitis seroprotection defined as participant with antibody titer ≥ 1:10 at baseline (D0) and on Day 28, Month 6, and Month 12.
Time Frame	Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

Japanese encephalitis antibody titers were assessed in all participants with any immunogenicity data who did not have any protocol violations that might have interfered with primary criteria evaluation (Per-Protocol Population)

Arm/Group Title	Japanese Encephalitis Chimeric Vaccine (JE-CV)	Japanese Encephalitis Live Vaccine (SA14-14-2)
Arm/Group Description:	Participants received a single dose of Japanese encephalitis chimeric vaccine (JE-CV) on Day 0.	Participants received a single dose of Japanese encephalitis live vaccine (SA14-14-2; CD.JEVAX®) on Day 0.
Overall Number of Participants Analyzed	127	129
Measure Type: Number; Unit of Measure: Participants
Day 0, JE-CV PRNT50 (N = 127, 129)	0	0
Day 28, JE-CV PRNT50 (N = 125, 128)	125	127
Day 0, SA14-14-2 PRNT50 (N = 125, 128)	0	0
Day 28, SA14-14-2 PRNT50 (N = 125, 126)	122	123

3. Secondary Outcome

Title	Number of Participants With Seroconversion After Vaccination With Either Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) or Japanese Encephalitis Live Vaccine (SA14-14-2) (CD.JEVAX®)
Description	Immunogenicity was assessed by JE-CV virus 50% plaque reduction neutralization test (PRNT50) or SA14-14-2 virus PRNT50. Seroconversion was defined as a pre-vaccination titer < 10 1/dil and post vaccination titer ≥ 10 1/dil, or a pre-vaccination titer ≥ 10 and a 4-fold increase from pre- to post-vaccination.
Time Frame	Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

Antibody titers were assessed in all participants with any immunogenicity data who did not have any protocol violations that might have interfered with primary criteria evaluation (Per-Protocol Population)

Arm/Group Title	Japanese Encephalitis Chimeric Vaccine (JE-CV)	Japanese Encephalitis Live Vaccine (SA14-14-2)
Arm/Group Description:	Participants received a single dose of Japanese encephalitis chimeric vaccine (JE-CV) on Day 0.	Participants received a single dose of Japanese encephalitis live vaccine (SA14-14-2; CD.JEVAX®) on Day 0.
Overall Number of Participants Analyzed	127	129
Measure Type: Number; Unit of Measure: Participants
JE-CV PRNT50 (N = 126, 128)	125	127
SA14-14-2 PRNT50 (N = 124, 125)	121	122

4. Secondary Outcome

Title	Summary of Geometric Mean Titers of Vaccine Antibodies Before and Following One Dose of Vaccination With Either Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) or Japanese Encephalitis Live Vaccine (SA14-14-2; CD.JEVAX®)
Description	Immunogenicity was assessed by JE-CV virus 50% plaque reduction neutralization test (PRNT50) or SA14-14-2 virus PRNT50.
Time Frame	Day 0 (pre-vaccination) and Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

Antibody titers were assessed in all participants with any immunogenicity data who did not have any protocol violations that might have interfered with primary criteria evaluation (Per-Protocol Population)

Arm/Group Title	Japanese Encephalitis Chimeric Vaccine (JE-CV)	Japanese Encephalitis Live Vaccine (SA14-14-2)
Arm/Group Description:	Participants received a single dose of Japanese encephalitis chimeric vaccine (JE-CV) on Day 0.	Participants received a single dose of Japanese encephalitis live vaccine (SA14-14-2; CD.JEVAX®) on Day 0.
Overall Number of Participants Analyzed	127	129
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers
Day 0, JE-CV PRNT50 (N = 127, 129)	5.0; (5.0 to 5.0)	5.0; (5.0 to 5.0)
Day 28, JE-CV PRNT50 (N = 126, 128)	491; (378 to 638)	395; (304 to 514)
Day 0, SA14-14-2 PRNT50 (N = 125, 128)	5.00; (5.00 to 5.00)	5.0; (5.0 to 5.0)
Day 28, SA14-14-2 PRNT50 (N = 125, 126)	205; (162 to 259)	190; (152 to 239)

5. Secondary Outcome

Title	Summary of Participants With Japanese Encephalitis Seroprotection After Vaccination With One Dose of Either Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) or Japanese Encephalitis Live Vaccine (SA14-14-2, CD.JEVAX®)
Description	Immunogenicity was assessed by JE-CV virus 50% plaque reduction neutralization test (PRNT50) or SA14-14-2 virus PRNT50. Japanese encephalitis seroprotection defined as participant with antibody titer ≥ 1:10 at baseline (D0) and on Day 28, Month 6, and Month 12.
Time Frame	Day 28 up to 12 months post-vaccination

Outcome Measure Data

Analysis Population Description

Japanese encephalitis antibody titers were assessed in all vaccinated participants with available immunogenicity data (Full Analysis Set)

Arm/Group Title	Japanese Encephalitis Chimeric Vaccine (JE-CV)	Japanese Encephalitis Live Vaccine (SA14-14-2)
Arm/Group Description:	Participants received a single dose of Japanese encephalitis chimeric vaccine (JE-CV) on Day 0.	Participants received a single dose of Japanese encephalitis live vaccine (SA14-14-2; CD.JEVAX®) on Day 0.
Overall Number of Participants Analyzed	149	150
Measure Type: Number; Unit of Measure: Participants
Day 0, JE-CV PRNT50 (N = 149, 150)	6	5
Day 28, JE-CV PRNT50 (N = 146, 148)	145	147
Month 6, JE-CV PRNT50 (N = 145, 145)	137	141
Month 12, JE-CV PRNT50 (N = 143, 146)	126	142
Day 0, SA14-14-2 PRNT50 (N = 147, 149)	0	0
Day 28, SA14-14-2 PRNT50 (N = 145, 146)	141	142
Month 6, SA14-14-2 PRNT50 (N = 145, 145)	122	129
Month 12, SA14-14-2 PRNT50 (N = 142, 144)	109	126

6. Secondary Outcome

Title	Summary of Geometric Mean Titers of Vaccine Antibodies Before and Following One Dose of Vaccination With Either Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) or Japanese Encephalitis Live Vaccine (SA14-14-2; CD.JEVAX®)
Description	Immunogenicity was assessed by JE-CV virus 50% plaque reduction neutralization test (PRNT50) or SA14-14-2 virus PRNT50.
Time Frame	Day 0 (pre-vaccination) and up to 12 months post-vaccination

Outcome Measure Data

Analysis Population Description

Japanese encephalitis antibody titers were assessed in all participants that received a vaccine and with available immunogenicity data (Full Analysis Set)

Arm/Group Title	Japanese Encephalitis Chimeric Vaccine (JE-CV)	Japanese Encephalitis Live Vaccine (SA14-14-2)
Arm/Group Description:	Participants received a single dose of Japanese encephalitis chimeric vaccine (JE-CV) on Day 0.	Participants received a single dose of Japanese encephalitis live vaccine (SA14-14-2; CD.JEVAX®) on Day 0.
Overall Number of Participants Analyzed	149	150
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers
Day 0, JE-CV PRNT50 (N = 149, 150)	5.39; (5.05 to 5.74)	5.29; (4.98 to 5.61)
Day 28, JE-CV PRNT50 (N = 146, 148)	507; (395 to 651)	370; (291 to 470)
Month 6, JE-CV PRNT50 (N = 145, 145)	119; (91.7 to 154)	103; (85.6 to 124)
Month 12, JE-CV PRNT50 (N = 143, 146)	97.6; (74.0 to 129)	121; (96.7 to 151)
Day 0, SA14-14-2 PRNT50 (N = 147, 149)	5.00; (5.00 to 5.00)	5.00; (5.00 to 5.00)
Day 28, SA14-14-2 PRNT50 (N = 145, 146)	198; (158 to 247)	171; (138 to 212)
Month 6, SA14-14-2 PRNT50 (N = 145, 145)	52.7; (41.2 to 67.4)	51.4; (41.6 to 63.6)
Month 12, SA14-14-2 PRNT50 (N = 142, 144)	46.5; (35.8 to 60.4)	54.8; (43.9 to 68.4)

7. Secondary Outcome

Title	Number of Participants Reporting a Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) or Japanese Encephalitis Live Vaccine (SA14-14-2 Vaccine) (CD.JEVAX®)
Description	Solicited Injection Site Reactions: Tenderness, Erythema, Swelling. Solicited Systemic Reactions: Fever (Temperature), Vomiting, Crying Abnormal, Drowsiness, Appetite Loss, Irritability. Grade 3 Reactions defined as: Tenderness - crying when injected limb was moved, or movement of the injected limb was reduced; Erythema and Swelling - ≥ 5 cm; Fever - temperature > 39.5ºC; Vomiting - ≥ 6 episodes per 24 hours or requiring parenteral hydration; Crying Abnormal - > 3 hours; Drowsiness - Sleeping most of the time or difficult to wake up; Appetite loss - refused ≥ 3 feeds or refused most feeds; and Irritability - inconsolable.
Time Frame	Day 0 through Day 14 post-vaccination

Outcome Measure Data

Analysis Population Description

Solicited injection site and systemic reactions were assessed in all participants who received a study vaccination and for whom safety data were available, according to the vaccine actually received (Safety Population).

Arm/Group Title	Japanese Encephalitis Chimeric Vaccine (JE-CV)	Japanese Encephalitis Live Vaccine (SA14-14-2)
Arm/Group Description:	Participants received a single dose of Japanese encephalitis chimeric vaccine (JE-CV) on Day 0.	Participants received a single dose of Japanese encephalitis live vaccine (SA14-14-2; CD.JEVAX®) on Day 0.
Overall Number of Participants Analyzed	147	152
Measure Type: Number; Unit of Measure: Participants
Any injection site Tenderness	44	57
Grade 3 injection site Tenderness	0	1
Any injection site Erythema	26	35
Grade 3 injection site Erythema	0	0
Any injection site Swelling	9	12
Grade 3 injection site Swelling	0	0
Any Fever	24	33
Grade 3 Fever	0	1
Any Vomiting	21	40
Grade 3 Vomiting	1	2
Any Crying Abnormal	28	39
Grade 3 Crying Abnormal	1	2
Any Drowsiness	25	38
Grade 3 Drowsiness	0	0
Any Appetite Loss	32	54
Grade 3 Appetite Loss	0	3
Any Irritability	41	58
Grade 3 Irritability	0	5

Adverse Events

Time Frame	Adverse events were assessed from Day 0 (post-vaccination) through 12 months post-vaccination.
Adverse Event Reporting Description	Two participants randomized to receive JE-CV received SA14-14-2 vaccine instead. They were analyzed in the Full Analysis Set according to the group to which they were randomized (JE-CV) and in the Safety Analysis Set according to the vaccine actually received (SA14-14-2 vaccine)
Arm/Group Title	Japanese Encephalitis Chimeric Vaccine (JE-CV)		Japanese Encephalitis Live Vaccine (SA14-14-2)
Arm/Group Description	Participants received a single dose of Japanese encephalitis chimeric vaccine (JE-CV) on Day 0.		Participants received a single dose of Japanese encephalitis live vaccine (SA14-14-2; CD.JEVAX®) on Day 0.
All-Cause Mortality
	Japanese Encephalitis Chimeric Vaccine (JE-CV)		Japanese Encephalitis Live Vaccine (SA14-14-2)
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Japanese Encephalitis Chimeric Vaccine (JE-CV)		Japanese Encephalitis Live Vaccine (SA14-14-2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/147 (9.52%)		18/152 (11.84%)
Gastrointestinal disorders
Oesophageal Obstruction * 1	0/147 (0.00%)	0	1/152 (0.66%)	1
Infections and infestations
Anal Abscess * 1	1/147 (0.68%)	1	0/152 (0.00%)	0
Bronchitis * 2	1/147 (0.68%)	1	2/152 (1.32%)	2
Dengue Fever * 2	1/147 (0.68%)	1	1/152 (0.66%)	1
Diarrhoea Infectious * 2	0/147 (0.00%)	0	1/152 (0.66%)	1
Gastroenteritis * 2	6/147 (4.08%)	6	1/152 (0.66%)	1
Gastroenteritis Rotavirus * 2	0/147 (0.00%)	0	3/152 (1.97%)	3
Gastroenteritis Viral * 2	0/147 (0.00%)	0	1/152 (0.66%)	1
Nasopharyngitis * 2	0/147 (0.00%)	0	1/152 (0.66%)	1
Pharyngitis * 2	1/147 (0.68%)	1	0/152 (0.00%)	0
Pneumonia * 2	1/147 (0.68%)	1	0/152 (0.00%)	0
Pneumonia Bacterial * 2	0/147 (0.00%)	0	1/152 (0.66%)	1
Pneumonia Respiratory Syncytial Viral * 2	1/147 (0.68%)	1	1/152 (0.66%)	1
Urinary Tract Infection Enterococcal * 2	1/147 (0.68%)	1	0/152 (0.00%)	0
Viral Infection * 2	2/147 (1.36%)	2	1/152 (0.66%)	1
Nervous system disorders
Febrile Convulsion * 2	0/147 (0.00%)	0	4/152 (2.63%)	4
Reproductive system and breast disorders
Balanitis * 2	1/147 (0.68%)	1	0/152 (0.00%)	0
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedRA 12.0; 2 Term from vocabulary, MedDRA 12.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5.00%
	Japanese Encephalitis Chimeric Vaccine (JE-CV)		Japanese Encephalitis Live Vaccine (SA14-14-2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/147 (44.90%)		88/152 (57.89%)
Gastrointestinal disorders
Vomiting † 1	21/146 (14.38%)	21	40/152 (26.32%)	40
General disorders
Crying Abnormal † 1	28/146 (19.18%)	28	39/152 (25.66%)	39
Injection Site Erythema † 1	26/146 (17.81%)	26	35/152 (23.03%)	35
Injection Site Swelling † 1	9/146 (6.16%)	9	12/152 (7.89%)	12
Injection Site Tenderness † 1	44/146 (30.14%)	44	57/152 (37.50%)	57
Irritability † 1	41/146 (28.08%)	41	58/152 (38.16%)	58
Fever † 2	24/147 (16.33%)	24	33/152 (21.71%)	33
Infections and infestations
Nasopharyngitis * 1	14/147 (9.52%)	14	10/152 (6.58%)	12
Pharyngitis * 1	4/147 (2.72%)	4	9/152 (5.92%)	9
Upper Respiratory Tract Infection * 1	11/147 (7.48%)	12	31/152 (20.39%)	35
Metabolism and nutrition disorders
Appetite Loss † 1	32/146 (21.92%)	32	54/152 (35.53%)	54
Nervous system disorders
Drowsiness † 1	25/146 (17.12%)	25	38/152 (25.00%)	38
† Indicates events were collected by systematic assessment; * Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA12.0; 2 Term from vocabulary, MedDRA 12.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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

Results Point of Contact

• Name/Title: Medical Director
• Organization: Sanofi Pasteur Inc.
• EMail: RegistryContactUs@sanofipasteur.com

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

Feroldi E, Pancharoen C, Kosalaraksa P, Chokephaibulkit K, Boaz M, Meric C, Hutagalung Y, Bouckenooghe A. Primary immunization of infants and toddlers in Thailand with Japanese encephalitis chimeric virus vaccine in comparison with SA14-14-2: a randomized study of immunogenicity and safety. Pediatr Infect Dis J. 2014 Jun;33(6):643-9. doi: 10.1097/INF.0000000000000276.

• Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
• ClinicalTrials.gov Identifier: NCT01092507
• Other Study ID Numbers: JEC07; UTN: U1111-1112-2269 ( Other Identifier: WHO )
• First Submitted: March 23, 2010
• First Posted: March 25, 2010
• Results First Submitted: September 30, 2013
• Results First Posted: December 2, 2013
• Last Update Posted: December 25, 2013