A Safety and Efficacy Study of Two Japanese Encephalitis Vaccines ChimeriVax™-JE and JE-VAX

• ClinicalTrials.gov Identifier: NCT00314145
• Recruitment Status: Completed
• First Posted: April 13, 2006
• Results First Posted: December 5, 2012
• Last Update Posted: December 6, 2012
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Japanese Encephalitis
• Interventions: Biological: ChimeriVax™-JE; Biological: JE-VAX®
• Enrollment: 820

Participant Flow

Recruitment Details	Participants were enrolled and treated from 07 November 2005 to 15 November 2006 at 5 clinical centers in Australia and 5 clinical centers in the US.
Pre-assignment Details	A total of 820 participants who met all of the inclusion criteria and none of the exclusion criteria were enrolled and vaccinated.

Arm/Group Title	JE-VAX®	ChimeriVax™-JE
Arm/Group Description	All participants received 1 subcutaneous dose each of JE-VAX® vaccine on Days 0, 7, and 30, and a subcutaneous dose of saline placebo into a different arm on Day 30.	All participants received 1 dose each of saline placebo on Days 0 and 7. On Day 30, participants received vaccinations of ChimeriVax™-JE vaccine 4 log10 Plaque-forming unit (PFU) and saline placebo into different arms.
Period Title: Overall Study
Started	410	410
Completed	389	381
Not Completed	21	29
Reason Not Completed
Withdrawal by Subject	8	10
Lost to Follow-up	5	12
Physician Decision	3	4
Adverse Event	0	3
Protocol Violation	3	0
Sponsor Decision	2	0

Baseline Characteristics

Arm/Group Title		JE-VAX®	ChimeriVax™-JE	Total
Arm/Group Description		All participants received 1 subcutaneous dose each of JE-VAX® vaccine on Days 0, 7, and 30, and a subcutaneous dose of saline placebo into a different arm on Day 30.	All participants received 1 dose each of saline placebo on Days 0 and 7. On Day 30, participants received vaccinations of ChimeriVax™-JE vaccine 4 log10 Plaque-forming unit (PFU) and saline placebo into different arms.	Total of all reporting groups
Overall Number of Baseline Participants		410	410	820
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	410 participants	410 participants	820 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	410 100.0%	410 100.0%	820 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	410 participants	410 participants	820 participants
		37.0 (14.81)	37.7 (15.11)	37.4 (14.96)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	410 participants	410 participants	820 participants
	Female	205 50.0%	217 52.9%	422 51.5%
	Male	205 50.0%	193 47.1%	398 48.5%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	410 participants	410 participants	820 participants
Australia		203	120	323
United States		207	290	497

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Japanese Encephalitis (Homologous Virus) Seroconversion Following Either ChimeriVax™-JE or JE-Vax® Vaccination
Description	Antibodies to Japanese encephalitis (JE) were measured by 50% plaque reduction neutralization test (PRNT50). Seroconversion was defined as a titer of ≥ 1:10.
Time Frame	Up to Day 60 post-first vaccination

Outcome Measure Data

Analysis Population Description

Seroconversion was assessed in all participants who were seronegative to JE (both Nakayama and ChimeriVax™-JE strains) at baseline and had no protocol violations that would have interfered with evaluation of primary outcomes (Efficacy Population).

Arm/Group Title	JE-VAX®	ChimeriVax™-JE
Arm/Group Description:	All participants received 1 subcutaneous dose each of JE-VAX® vaccine on Days 0, 7, and 30, and a subcutaneous dose of saline placebo into a different arm on Day 30.	All participants received 1 subcutaneous dose each of saline placebo on Days 0 and 7. On Day 30, participants received vaccinations of ChimeriVax™-JE vaccine 4 log10 PFU and saline placebo into different arms.
Overall Number of Participants Analyzed	365	346
Measure Type: Number; Unit of Measure: Participants
Day 44 (N = 0, 346)	NA [1]	324
Day 60 (N = 365, 346)	273	343

[1]

Seroconversion was not assessed at this time point for this group.

2. Primary Outcome

Title	Number of Participants Reporting Treatment Emergent Local Adverse Events and Treatment Emergent Systemic Reactions Post-Vaccination With Either ChimeriVax™-JE or JE-Vax®
Description	Treatment emergent local adverse events: Pain, Erythema, Pruritus, Swelling, Induration, and others as reported. Treatment emergent systemic reactions: Fatigue, Malaise, Chills, Pyrexia, Headache, Myalgia, Arthralgia, Diarrhea, Nausea, Vomiting, and Rash.
Time Frame	Day 0 (Pre-vaccination) up to 60 days post-first vaccination

Outcome Measure Data

Analysis Population Description

Treatment emergent local adverse events and systemic reactions were assessed in all subjects who had at least one injection (ChimeriVax™-JE, JE-Vax®, or placebo), according to the treatment actually received (Safety Population).

Arm/Group Title	JE-VAX®	ChimeriVax™-JE
Arm/Group Description:	All participants received 1 subcutaneous dose each of JE-VAX® vaccine on Days 0, 7, and 30, and a subcutaneous dose of saline placebo into a different arm on Day 30.	All participants received 1 dose each of saline placebo on Days 0 and 7. On Day 30, participants received vaccinations of ChimeriVax™-JE vaccine 4 log10 Plaque-forming unit (PFU) and saline placebo into different arms.
Overall Number of Participants Analyzed	410	410
Measure Type: Number; Unit of Measure: Participants
Injection Site Pain	262	105
Injection Site Erythema	123	27
Injection Site Pruritus	107	29
Injection Site Swelling	85	15
Injection Site Hemorrhage	20	14
Injection Site Rash	6	2
Injection Site Edema	2	0
Injection Site Joint Pain	1	1
Injection Site Reaction	1	1
Injection Site Discomfort	1	0
Injection Site Joint Movement Impairment	0	1
Injection Site Warmth	0	1
Venipuncture Site Bruise	1	0
Fatigue	131	152
Malaise	113	113
Chills	32	43
Pyrexia	18	14
Headache	190	193
Myalgia	107	105
Arthralgia	58	58
Diarrhea	56	57
Nausea	53	56
Vomiting	15	13
Rash	26	23

3. Secondary Outcome

Title	Neutralizing Antibody Geometric Mean Titers (GMTs) to Japanese Encephalitis (Homologous Virus) Following Either ChimeriVax™-JE or JE-Vax® Vaccination
Description	Antibodies to Japanese encephalitis (JE) were measured by 50% plaque reduction neutralization test (PRNT50).
Time Frame	Up to Day 60 post-first vaccination

Outcome Measure Data

Analysis Population Description

Geometric mean titers were assessed in all participants who were seronegative to JE (both Nakayama and ChimeriVax™-JE strains) at baseline and had no protocol violations that would have interfered with evaluation of primary outcomes (Efficacy Population).

Arm/Group Title	JE-VAX®	ChimeriVax™-JE
Arm/Group Description:	All participants received 1 subcutaneous dose each of JE-VAX® vaccine on Days 0, 7, and 30, and a subcutaneous dose of saline placebo into a different arm on Day 30.	All participants received 1 subcutaneous dose each of saline placebo on Days 0 and 7. On Day 30, participants received vaccinations of ChimeriVax™-JE vaccine 4 log10 PFU and saline placebo into different arms.
Overall Number of Participants Analyzed	365	346
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers
Day 44 (N = 0, 346)	NA [1]; (NA to NA)	312.3; (255.1 to 382.3)
Day 60 (N = 365, 346)	37.4; (32.5 to 42.9)	1391.7; (1156.6 to 1674.5)

[1]

Geometric mean titers were not assessed at this time point for this group.

4. Secondary Outcome

Title	Number of Participants in the Japanese Encephalitis (Homologous Virus) Neutralizing Antibody Titer Categories on Day 60 Following Either ChimeriVax™-JE or JE-Vax® Vaccination
Description	Antibodies to Japanese encephalitis (JE) were measured by 50% plaque reduction neutralization test (PRNT50).
Time Frame	Day 60 post-first vaccination

Outcome Measure Data

Analysis Population Description

Antibody titers were assessed in all participants who were seronegative to JE (both Nakayama and ChimeriVax™-JE strains) at baseline and had no protocol violations that would have interfered with evaluation of primary outcomes (Efficacy Population).

Arm/Group Title	JE-VAX®	ChimeriVax™-JE
Arm/Group Description:	All participants received 1 subcutaneous dose each of JE-VAX® vaccine on Days 0, 7, and 30, and a subcutaneous dose of saline placebo into a different arm on Day 30.	All participants received 1 subcutaneous dose each of saline placebo on Days 0 and 7. On Day 30, participants received vaccinations of ChimeriVax™-JE vaccine 4 log10 PFU and saline placebo into different arms.
Overall Number of Participants Analyzed	365	346
Measure Type: Number; Unit of Measure: Participants
Titer < 10	63	3
Titer 10 to < 20	29	0
Titer 20 to < 40	51	4
Titer 40 to < 160	151	18
Titer 160 to < 640	63	76
Titer 640 to < 2560	6	75
Titer ≥ 2560	2	170

Adverse Events

Time Frame	Adverse events data were collected from Day 0 (post-vaccination) through Day 60 post first vaccination.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	JE-VAX®		ChimeriVax™-JE
Arm/Group Description	All participants received 1 subcutaneous dose each of JE-VAX® vaccine on Days 0, 7, and 30, and a subcutaneous dose of saline placebo into a different arm on Day 30.		All participants received 1 dose each of saline placebo on Days 0 and 7. On Day 30, participants received vaccinations of ChimeriVax™-JE vaccine 4 log10 Plaque-forming unit (PFU) and saline placebo into different arms.
All-Cause Mortality
	JE-VAX®		ChimeriVax™-JE
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	JE-VAX®		ChimeriVax™-JE
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/410 (0.73%)		2/410 (0.49%)
General disorders
Non Cardiac Chest Pain † 1	0/410 (0.00%)	0	1/410 (0.24%)	1
Hepatobiliary disorders
Cholecystitis † 1	1/410 (0.24%)	1	0/410 (0.00%)	0
Immune system disorders
Drug Hypersensitivity † 1	1/410 (0.24%)	1	0/410 (0.00%)	0
Injury, poisoning and procedural complications
Head Injury † 1	0/410 (0.00%)	0	1/410 (0.24%)	1
Nervous system disorders
Multiple Sclerosis † 1	0/410 (0.00%)	0	1/410 (0.24%)	1
Parkinson's Disease † 1	0/410 (0.00%)	0	1/410 (0.24%)	1
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Airways Disease Exacerbated † 1	1/410 (0.24%)	1	0/410 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 7.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5.00%
	JE-VAX®		ChimeriVax™-JE
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	262/410 (63.90%)		193/410 (47.07%)
Gastrointestinal disorders
Diarrhea † 1	56/410 (13.66%)	80	57/410 (13.90%)	99
Nausea † 1	53/410 (12.93%)	96	56/410 (13.66%)	75
General disorders
Chills † 1	32/410 (7.80%)	48	43/410 (10.49%)	68
Fatigue † 1	131/410 (31.95%)	399	152/410 (37.07%)	366
Injection Site Pain † 1	262/410 (63.90%)	804	105/410 (25.61%)	207
Injection Site Erythema † 1	123/410 (30.00%)	256	27/410 (6.59%)	35
Injection Site Pruritus † 1	107/410 (26.10%)	187	29/410 (7.07%)	46
Injection Site Swelling † 1	85/410 (20.73%)	149	15/410 (3.66%)	16
Malaise † 1	113/410 (27.56%)	248	113/410 (27.56%)	224
Musculoskeletal and connective tissue disorders
Myalgia † 1	107/410 (26.10%)	228	105/410 (25.61%)	192
Arthralgia † 1	58/410 (14.15%)	99	58/410 (14.15%)	122
Nervous system disorders
Headache † 1	190/410 (46.34%)	546	193/410 (47.07%)	465
Skin and subcutaneous tissue disorders
Rash † 1	26/410 (6.34%)	36	23/410 (5.61%)	33
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 7.1

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):

Torresi J, McCarthy K, Feroldi E, Meric C. Immunogenicity, safety and tolerability in adults of a new single-dose, live-attenuated vaccine against Japanese encephalitis: Randomised controlled phase 3 trials. Vaccine. 2010 Nov 23;28(50):7993-8000. doi: 10.1016/j.vaccine.2010.09.035. Epub 2010 Oct 8.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT00314145
• Other Study ID Numbers: H-040-009
• First Submitted: April 11, 2006
• First Posted: April 13, 2006
• Results First Submitted: November 6, 2012
• Results First Posted: December 5, 2012
• Last Update Posted: December 6, 2012