Immunogenicity and Safety of Japanese Encephalitis Vaccine When Given With Measles-Mumps-Rubella (MMR) Vaccine

• Sponsor: PATH (Other)
• Overall Status: Completed
• CT.gov ID: NCT02880865
• Collaborator: Research Institute for Tropical Medicine, (Other), Syneos Health (Other), DF/Net Research, Inc. (Other)
• Enrollment: 628
• Location: 1
• Arms: 2
• Actual Duration (Months): 8.9
• Patients Per Site Per Month: 70.5

Study Details

Study Description

Brief Summary

This study aims to provide evidence that co-administration of measles-mumps-rubella vaccine (MMR) and live attenuated SA 14-14-2 Japanese encephalitis vaccine (CD-JEV) does not adversely affect immunogenicity or safety.

Condition or Disease	Intervention/Treatment	Phase
Encephalitis, Japanese; Measles; Mumps; Rubella	Biological: Live attenuated SA 14-14-2 Japanese Encephalitis vaccine; Biological: Measles, mumps, rubella vaccine	Phase 4

Detailed Description

When incorporating a new vaccine in the Expanded Programme on Immunization (EPI), it is important to provide evidence that it can be introduced concurrently with other routine pediatric vaccines without significantly impairing the immune response to any vaccine while maximizing coverage and minimizing cost. This non-inferiority study aims to compare CD-JEV and MMR responses in a population of children in a country where MMR introduction is ongoing or planned. This information will help the ministries of health evaluate the addition of CD-JEV into routine EPI.

Study Design

• Study Type: Interventional
• Actual Enrollment: 628 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety of Concurrent Administration of Live, Attenuated SA 14-14-2 Japanese Encephalitis Vaccine and Measles-Mumps-Rubella Vaccine in Infants 9-12 Months of Age in the Philippines
• Actual Study Start Date: Oct 13, 2016
• Actual Primary Completion Date: May 19, 2017
• Actual Study Completion Date: Jul 11, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 - MMR and CD-JEV Participants receiving one dose of CD-JEV vaccine and one dose of MMR vaccine concurrently at Day 0; Group 1 will also receive a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).	Biological: Live attenuated SA 14-14-2 Japanese Encephalitis vaccine; Single 0.5 mL dose of World Health Organization prequalified live, attenuated SA 14-14-2 JE vaccine manufactured by Chengdu Institute of Biological Products, Chengdu, China, administered by subcutaneous injection; Other Names: CD-JEV CD.JEVAX® RS.JEV® ; Biological: Measles, mumps, rubella vaccine; Single 0.5 mL dose of live, attenuated measles-mumps-rubella vaccine (Schwarz measles virus, RIT 4385 mumps strain, and Wistar RA 27/3 rubella virus) manufactured by GlaxoSmithKline, Inc., administered by subcutaneous injection.; Other Names: MMR Priorix®
Experimental: Group 2 - MMR then CD-JEV Participants receiving one dose of MMR vaccine at Day 0 and one dose of CD-JEV 56 days later. Group 2 will receive a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).	Biological: Live attenuated SA 14-14-2 Japanese Encephalitis vaccine; Single 0.5 mL dose of World Health Organization prequalified live, attenuated SA 14-14-2 JE vaccine manufactured by Chengdu Institute of Biological Products, Chengdu, China, administered by subcutaneous injection; Other Names: CD-JEV CD.JEVAX® RS.JEV® ; Biological: Measles, mumps, rubella vaccine; Single 0.5 mL dose of live, attenuated measles-mumps-rubella vaccine (Schwarz measles virus, RIT 4385 mumps strain, and Wistar RA 27/3 rubella virus) manufactured by GlaxoSmithKline, Inc., administered by subcutaneous injection.; Other Names: MMR Priorix®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Measles Seropositivity 56 Days Post-vaccination [56 days after MMR dose 1 vaccination (Day 56)]

   Measles immunogenicity was assessed by the percentage of participants with demonstrated seropositivity for measles at 56 days post-vaccination. Seropositivity was defined by a concentration of ≥ 120 mIU/mL of anti-measles neutralizing antibody titer, as measured by the plaque reduction neutralization test (PRNT) (dilution converted to concentration using the 3rd International Standard Reference serum).

2. Percentage of Participants With Rubella Seropositivity 56 Days Post-vaccination [56 days after MMR dose 1 vaccination (Day 56)]

   Rubella immunogenicity was assessed by the percentage of participants with demonstrated seropositivity for rubella at 56 days post-vaccination. Seropositivity was defined as antirubella immunoglobulin G (IgG) concentration of ≥ 10 IU/mL (corresponding to an optical density ratio ≥ 1.10) using a commercial IgG enzyme-linked immunosorbent assay (ELISA).

Secondary Outcome Measures

1. Percentage of Participants With Mumps Seropositivity 56 Days Post-vaccination [56 days after MMR dose 1 vaccination (Day 56)]

   Mumps immunogenicity was assessed by the percentage of participants with demonstrated seropositivity for mumps at 56 days post-vaccination. Seropositivity was defined as an optical density ratio ≥ 1.10 using a commercial ELISA.

2. Geometric Mean Concentration (GMC) for Anti-measles Neutralizing Antibody Concentration at 56 Days Post-vaccination [56 days after MMR dose 1 vaccination (Day 56)]

   Anti-measles neutralizing antibody concentration was measured by the plaque reduction neutralization test (PRNT).

3. GMC for Anti-rubella IgG Antibody Concentration at 56 Days Post-vaccination [56 days after MMR dose 1 vaccination (Day 56)]

   Anti-rubella immunoglobulin G (IgG) concentration was measured using a commercial IgG enzyme-linked immunosorbent assay (ELISA).

4. Seroconversion Rate for Measles 56 Days Post-vaccination [56 days after MMR dose 1 vaccination (Day 56)]

   The seroconversion rate for measles at 56 days post-vaccination was defined as the percentage of participants with a change in serostatus from negative to positive 56 days after vaccination or a four-fold rise in concentration 56 days after vaccination if seropositive for measles at baseline. Seropositivity was defined by a concentration of ≥ 120 mIU/mL of anti-measles neutralizing antibody titer, as measured by the plaque reduction neutralization test (PRNT).

5. Seroconversion Rate for Mumps 56 Days Post-vaccination [56 days after MMR dose 1 vaccination (Day 56)]

   The seroconversion rate for mumps at 56 days post-vaccination was defined as the percentage of participants with a change in serostatus from negative to positive 56 days after vaccination. Seropositivity was defined as an optical density ratio ≥ 1.10, measured using a commercial ELISA. Participants with equivocal serostatus at baseline are counted as non-responders.

6. Seroconversion Rate for Rubella 56 Days Post-vaccination [56 days after MMR dose 1 vaccination (Day 56)]

   The seroconversion rate for rubella at 56 days post-vaccination was defined as the percentage of participants with a change in serostatus from negative to positive 56 days after vaccination or a four-fold rise in concentration 56 days after vaccination if seropositive for rubella at baseline. Seropositivity is defined as a post-vaccination concentration of ≥ 10 IU/mL measured using a commercial ELISA.

7. Percentage of Participants With Japanese Encephalitis Seropositivity 28 Days Post-vaccination [28 days after CD-JEV vaccination (Day 28 for Group 1 and Day 84 for Group 2)]

   Japanese encephalitis (JE) immunogenicity was assessed by the percentage of participants with demonstrated seropositivity 28 days after CD-JEV vaccination. Seropositivity was defined as an anti-JE serum neutralizing antibody titer of ≥ 1:10, as measured by JE PRNT-50.

8. Geometric Mean Titer (GMT) for Serum Neutralizing Antibody Titer to JE Virus at 28 Days Post-vaccination [28 days after CD-JEV vaccination (Day 28 for Group 1 and Day 84 for Group 2)]

   Anti-JE serum neutralizing antibody titer was measured using JE PRNT-50.

9. Number of Participants With Immediate Reactions Within 30 Minutes of Each Vaccination [30 minutes following each study vaccination]

   Participants were observed for 30 minutes after each vaccination for immediate reactions. Immediate reactions included both local (injection site) and systemic reactions. MMR vaccine was injected on left upper thigh and CD-JEV was injected on right upper thigh. Serious reactions were those meeting one of the following conditions: Death. Life threatening Required inpatient hospitalization or prolongation of existing hospitalization. Resulted in a persistent or significant disability or incapacity. Important medical events that, based upon appropriate medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed above.

10. Number of Participants With Solicited Local and Systemic Reactions Within 14 Days of Each Vaccination [30 minutes through 14 days following each vaccination]

    Reactogenicity post-vaccination was assessed from 30 minutes through 14 days following vaccination. Parents used a structured reactogenicity diary card to record the following solicited (pre-listed) local and system reactions. Local reactions (at injection site): Ecchymosis (bruising) Erythema (redness) Edema (swelling) Induration (hardness) Pain/tenderness Systemic reactions: Fever Rash Cough Runny nose Change in eating habits Diarrhea Sleepiness Irritability Unusual crying Vomiting

11. Number of Participants With Solicited Local Reactions Within 14 Days of Each Vaccination by Maximum Severity [30 minutes through 14 days following each vaccination]

    Parents recorded local reactions on a diary card. 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% of surface area of extremity segment involved. Grade 3: ≥50% surface area of extremity segment involved OR ulceration OR secondary infection OR phlebitis OR sterile abscess OR drainage. Grade 4: potentially life-threatening (e.g., abscess, exfoliative dermatitis, necrosis involving dermis or deeper tissue). Injection site pain/tenderness (pain without touching or tenderness when the area is touched) were graded as follows: Grade 1: pain/tenderness causing no or minimal limitation of use of limb. Grade 2: pain/tenderness causing greater than minimal limitation of use of limb. Grade 3: pain/tenderness causing inability to perform usual social and functional activities. Grade 4: pain/tenderness causing inability to perform basic self-care OR hospitalization indicated.

12. Number of Participants With Systemic Reactions Within 14 Days of Each Vaccination by Maximum Severity [30 minutes through 14 days following each vaccination]

    Parents recorded systemic reactions on a diary card. Fever was recorded and graded as follows (axillary temperature): Grade 1: 37.5°C to 37.9°C Grade 2: 38.0°C to 38.4°C Grade 3: 38.5°C to 40.0°C Grade 4: >40.0°C Rash, cough, runny nose, change in eating habits, diarrhea, sleepiness, irritability, unusual crying, vomiting, and any other unsolicited reaction occurring from 30 minutes through 14 days post vaccination were graded as follows: Grade 1: symptoms causing no or minimal interference with usual social and functional activities. Grade 2: symptoms causing greater than minimal interference with usual social and functional activities. Grade 3: symptoms causing inability to perform usual social and functional activities with intervention or hospitalization indicated. Grade 4: symptoms causing inability to perform basic self-care functions OR medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death.

13. Number of Participants With Unsolicited Adverse Events Within 28 Days of Each Vaccination [28 days following each vaccination]

    Each adverse event (AE) was assessed for relationship to vaccine by the study clinician according to the following: Definitely Related: An adverse event or unanticipated problem clearly related to the research procedures. Possibly Related: There is a reasonable possibility that the adverse event or unanticipated problem, incident, experience, or outcome may have been caused by the procedures involved in the research. Not Related: Any adverse event or unanticipated problem clearly not related to study procedures. Related adverse events includes events that were assessed as definitely or possibly related.

14. Number of Participants With Serious Adverse Events Throughout the Study [Up to 112 days]

    A serious adverse event (SAE) was defined as an AE that met one of the following: Death Life threatening Required inpatient hospitalization or prolongation of existing hospitalization Resulted in persistent or significant disability or incapacity Important medical events that, based upon appropriate medical judgment, jeopardized the participant and required medical or surgical intervention to prevent an outcomes listed above AEs were assessed for relationship to vaccine by the study clinician according to the following: Definitely Related: An AE or unanticipated problem clearly related to the research procedures. Possibly Related: There is a reasonable possibility that the AE or unanticipated problem, incident, experience, or outcome may have been caused by the procedures involved in the research. Not Related: Any AE or unanticipated problem clearly not related to study procedures. Related SAEs includes events that were assessed as definitely or possibly related.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age 9 months to < 10 months at the time of enrollment.

• Residence in the study area.

• At least one parent or guardian willing to provide written informed consent.

• Generally healthy and free of obvious health problems as established by medical history, physical examination, and clinical judgment.

• A parent or guardian is willing to attend all planned study visits and allow home visits and phone contacts, as required by the protocol.

Exclusion Criteria:

• Previous receipt of any measles-mumps-rubella containing vaccine.

• Previous receipt of any Japanese encephalitis vaccine.

• History of measles, mumps, rubella, or Japanese encephalitis infection.

• Administration of any other vaccine within 28 days prior to administration of a study vaccine or planned vaccination of any vaccine other than catch-up doses of routine EPI vaccines or oral polio vaccine during the 28 days after study vaccination.

• History of allergic disease or known hypersensitivity to any component of the study vaccines and/or following administration of vaccines included in the local program of immunization.

• Use of any investigational or non-registered drug within 90 days prior to the administration of study vaccines or planned administration during the study period.

• Administration of immunoglobulins and/or any blood products within 90 days prior to the administration of study vaccines or planned administration during the study period.

• Chronic administration (defined as > 7 days) of immunosuppressing or other immune-modifying agents within 14 days before or after vaccination (including systemic corticosteroids equivalent to prednisone ≥ 0.5 mg/kg/day; topical and inhaled steroids are allowed).

• Primary or acquired immunodeficiency, including human immunodeficiency virus (HIV) infection, or a family history of congenital or hereditary immunodeficiency as reported by parent.

• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by medical history or physical examination, which might interfere with the study objectives.

• Severely malnourished infants as measured by World Health Organization weight-for-height tables (Z-score < -3).

• Any condition or criterion that, in the opinion of the study physician, might compromise the well-being of the participant, compliance with study procedures, or interpretation of the outcomes of the study.

• Acute illness at the time of enrollment defined as the presence of a moderate or severe illness with fever (axillary temperature ≥ 38.0°C) or without fever (severity determined at the discretion of the study physician). Acute illness is a temporary exclusion. Vaccination should be postponed at least 7 days after recovery. A visit for reassessment may be scheduled 7 days or more after temporary exclusion illness is resolved. Eligibility for study participation must be reassessed again at the next visit.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Institute for Tropical Medicine	Manila		Philippines

Sponsors and Collaborators

• PATH
• Research Institute for Tropical Medicine,
• Syneos Health
• DF/Net Research, Inc.

Investigators

• Principal Investigator: Maria Rosario Capeding, MD, Research Institute for Tropical Medicine,

Study Documents (Full-Text)

• Study Protocol - Jan 18, 2017
• Statistical Analysis Plan - Jun 6, 2017

More Information

Publications

None provided.

• Responsible Party: PATH
• ClinicalTrials.gov Identifier: NCT02880865
• Other Study ID Numbers: JEV06; PHRR160822-001339
• First Posted: Aug 26, 2016
• Last Update Posted: Oct 14, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by PATH: vaccine
• Additional relevant MeSH terms: Measles; Rubella; Mumps; Encephalitis, Japanese; Encephalitis; Vaccines

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at 2 health centers in the Philippines.
Pre-assignment Detail	Filipino children aged 9 to < 10 months were randomized in a 1:1 ratio to receive measles, mumps, and rubella vaccine (MMR) and prequalified live, attenuated SA-14-4-2 Japanese encephalitis vaccine (CD-JEV) together (Group 1) or 56 days apart (Group 2). All participants received a second dose of MMR at 12 months of age.

Arm/Group Title	Group 1: MMR and CD-JEV	Group 2: MMR Then CD-JEV
Arm/Group Description	Participants received one dose of CD-JEV vaccine and one dose of MMR vaccine concurrently at Day 0. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).	Participants received one dose of MMR vaccine at Day 0 and one dose of CD-JEV 56 days later. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).
Period Title: Overall Study
STARTED	314	314
Received MMR Dose 1	314	314
Received CD-JEV	314	309
Received MMR Dose 2	313	311
COMPLETED	313	311
NOT COMPLETED	1	3

Baseline Characteristics

Arm/Group Title	Group 1: MMR and CD-JEV	Group 2: MMR Then CD-JEV	Total
Arm/Group Description	Participants received one dose of CD-JEV vaccine and one dose of MMR vaccine concurrently at Day 0. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).	Participants received one dose of MMR vaccine at Day 0 and one dose of CD-JEV 56 days later. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).	Total of all reporting groups
Overall Participants	314	314	628
Age (months) [Median (Full Range) ]
Median (Full Range) [months]	9.2	9.2	9.2
Sex: Female, Male (Count of Participants)
Female	144 45.9%	157 50%	301 47.9%
Male	170 54.1%	157 50%	327 52.1%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Philippines	314 100%	314 100%	628 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Measles Seropositivity 56 Days Post-vaccination
Description	Measles immunogenicity was assessed by the percentage of participants with demonstrated seropositivity for measles at 56 days post-vaccination. Seropositivity was defined by a concentration of ≥ 120 mIU/mL of anti-measles neutralizing antibody titer, as measured by the plaque reduction neutralization test (PRNT) (dilution converted to concentration using the 3rd International Standard Reference serum).
Time Frame	56 days after MMR dose 1 vaccination (Day 56)

Outcome Measure Data

Analysis Population Description

The measles per-protocol population included participants who fulfilled the eligibility criteria, received all study vaccines as assigned, provided valid measles serology results at baseline and Day 56, did not take any prohibited concomitant medications within 28 days post-vaccination, and did not show measles seropositivity at baseline.

Arm/Group Title	Group 1: MMR and CD-JEV	Group 2: MMR Then CD-JEV
Arm/Group Description	Participants received one dose of CD-JEV vaccine and one dose of MMR vaccine concurrently at Day 0. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).	Participants received one dose of MMR vaccine at Day 0 and one dose of CD-JEV 56 days later. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).
Measure Participants	311	306
Number (95% Confidence Interval) [percentage of participants]	98.1 31.2%	98.0 31.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: MMR and CD-JEV, Group 2: MMR Then CD-JEV
	Comments	The primary hypotheses evaluated the non-inferiority of the concomitant administration of MMR and CD-JEV vaccines (Group 1) to MMR and CD-JEV vaccines given 2 months apart (Group 2) in children 9 months of age at 56 days in terms of percentage of participants achieving seropositivity to measles and rubella assuming a non-inferiority margin of 10%.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority was achieved if the lower limit of the two-sided 95% confidence interval (CI) for the difference in percentages of participants with seropositivity between the two groups (concurrent administration minus separate administration) at 56 days post-vaccination was > -10% for both measles and rubella results.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -2.1 to 2.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants With Rubella Seropositivity 56 Days Post-vaccination
Description	Rubella immunogenicity was assessed by the percentage of participants with demonstrated seropositivity for rubella at 56 days post-vaccination. Seropositivity was defined as antirubella immunoglobulin G (IgG) concentration of ≥ 10 IU/mL (corresponding to an optical density ratio ≥ 1.10) using a commercial IgG enzyme-linked immunosorbent assay (ELISA).
Time Frame	56 days after MMR dose 1 vaccination (Day 56)

Outcome Measure Data

Analysis Population Description

The rubella per-protocol population included participants who fulfilled the eligibility criteria, received all study vaccines as assigned, provided valid rubella serology results at baseline and Day 56, did not take any prohibited concomitant medications within 28 days post-vaccination, and did not show rubella seropositivity at baseline.

Arm/Group Title	Group 1: MMR and CD-JEV	Group 2: MMR Then CD-JEV
Arm/Group Description	Participants received one dose of CD-JEV vaccine and one dose of MMR vaccine concurrently at Day 0. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).	Participants received one dose of MMR vaccine at Day 0 and one dose of CD-JEV 56 days later. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).
Measure Participants	285	295
Number (95% Confidence Interval) [percentage of participants]	100.0 31.8%	99.7 31.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: MMR and CD-JEV, Group 2: MMR Then CD-JEV
	Comments	The primary hypotheses evaluated the non-inferiority of the concomitant administration of MMR and CD-JEV vaccines (Group 1) to MMR and CD-JEV vaccines given 2 months apart (Group 2) in children 9 months of age at 56 days in terms of percentage of participants achieving seropositivity to measles and rubella assuming a non-inferiority margin of 10%.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority was achieved if the lower limit of the two-sided 95% CI for the difference in percentages of participants with seropositivity between the two groups (concurrent administration minus separate administration) at 56 days post-vaccination was > -10% for both measles and rubella results.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.3 to 1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Mumps Seropositivity 56 Days Post-vaccination
Description	Mumps immunogenicity was assessed by the percentage of participants with demonstrated seropositivity for mumps at 56 days post-vaccination. Seropositivity was defined as an optical density ratio ≥ 1.10 using a commercial ELISA.
Time Frame	56 days after MMR dose 1 vaccination (Day 56)

Outcome Measure Data

Analysis Population Description

The mumps per-protocol population included participants who fulfilled eligibility criteria, received all study vaccines as assigned, provided valid mumps serology results at baseline and Day 56, did not take any prohibited concomitant medications within within 28 days post-vaccination, and did not show mumps seropositivity at baseline.

Arm/Group Title	Group 1: MMR and CD-JEV	Group 2: MMR Then CD-JEV
Arm/Group Description	Participants received one dose of CD-JEV vaccine and one dose of MMR vaccine concurrently at Day 0. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).	Participants received one dose of MMR vaccine at Day 0 and one dose of CD-JEV 56 days later. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).
Measure Participants	270	265
Number (95% Confidence Interval) [percentage of participants]	98.5 31.4%	98.5 31.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: MMR and CD-JEV, Group 2: MMR Then CD-JEV
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	The percentage of participants with seropositivity for mumps at 56 days post-vaccination between Group 1 and Group 2 were compared using a non-inferiority test. Non-inferiority of Group 1 to Group 2 in terms of seropositivity for mumps was demonstrated if the lower limit of the two-sided 95% CI for the difference of seropositivity rates between the two groups (concurrent administration minus separate administration) at 56 days post-vaccination was > -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -2.0 to 2.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Geometric Mean Concentration (GMC) for Anti-measles Neutralizing Antibody Concentration at 56 Days Post-vaccination
Description	Anti-measles neutralizing antibody concentration was measured by the plaque reduction neutralization test (PRNT).
Time Frame	56 days after MMR dose 1 vaccination (Day 56)

Outcome Measure Data

Analysis Population Description

The measles per-protocol population included participants who fulfilled the eligibility criteria, received all study vaccines as assigned, provided valid measles serology results at baseline and Day 56, did not take any prohibited concomitant medications within 28 days post-vaccination, and did not show measles seropositivity at baseline.

Arm/Group Title	Group 1: MMR and CD-JEV	Group 2: MMR Then CD-JEV
Arm/Group Description	Participants received one dose of CD-JEV vaccine and one dose of MMR vaccine concurrently at Day 0. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).	Participants received one dose of MMR vaccine at Day 0 and one dose of CD-JEV 56 days later. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).
Measure Participants	311	306
Geometric Mean (95% Confidence Interval) [mIU/mL]	1964.4	1866.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: MMR and CD-JEV, Group 2: MMR Then CD-JEV
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC Ratio
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; 0.9 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Group 1/Group 2 ratio obtained using analysis of covariance (ANCOVA) with log10-transformed antibody concentration as dependent variable and treatment group as the explanatory variable adjusted for log10-transformed baseline antibody concentration.

5. Secondary Outcome

Title	GMC for Anti-rubella IgG Antibody Concentration at 56 Days Post-vaccination
Description	Anti-rubella immunoglobulin G (IgG) concentration was measured using a commercial IgG enzyme-linked immunosorbent assay (ELISA).
Time Frame	56 days after MMR dose 1 vaccination (Day 56)

Outcome Measure Data

Analysis Population Description

The rubella per-protocol population included participants who fulfilled the eligibility criteria, received all study vaccines as assigned, provided valid rubella serology results at baseline and Day 56, did not take any prohibited concomitant medications within 28 days post-vaccination, and did not show rubella seropositivity at baseline.

Arm/Group Title	Group 1: MMR and CD-JEV	Group 2: MMR Then CD-JEV
Arm/Group Description	Participants received one dose of CD-JEV vaccine and one dose of MMR vaccine concurrently at Day 0. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).	Participants received one dose of MMR vaccine at Day 0 and one dose of CD-JEV 56 days later. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).
Measure Participants	285	295
Geometric Mean (95% Confidence Interval) [IU/mL]	230.8	229.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: MMR and CD-JEV, Group 2: MMR Then CD-JEV
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC Ratio
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; 0.9 to 1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Group 1/Group 2 ratio obtained using an ANCOVA method with log 10-transformed antibody concentration as dependent variable and treatment group as explanatory variable adjusted for log 10-transformed baseline antibody concentration.

6. Secondary Outcome

Title	Seroconversion Rate for Measles 56 Days Post-vaccination
Description	The seroconversion rate for measles at 56 days post-vaccination was defined as the percentage of participants with a change in serostatus from negative to positive 56 days after vaccination or a four-fold rise in concentration 56 days after vaccination if seropositive for measles at baseline. Seropositivity was defined by a concentration of ≥ 120 mIU/mL of anti-measles neutralizing antibody titer, as measured by the plaque reduction neutralization test (PRNT).
Time Frame	56 days after MMR dose 1 vaccination (Day 56)

Outcome Measure Data

Analysis Population Description

The measles per-protocol population included participants who fulfilled the eligibility criteria, received all study vaccines as assigned, provided valid measles serology results at baseline and Day 56, did not take any prohibited concomitant medications within 28 days post-vaccination, and did not show measles seropositivity at baseline.

Arm/Group Title	Group 1: MMR and CD-JEV	Group 2: MMR Then CD-JEV
Arm/Group Description	Participants received one dose of CD-JEV vaccine and one dose of MMR vaccine concurrently at Day 0. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).	Participants received one dose of MMR vaccine at Day 0 and one dose of CD-JEV 56 days later. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).
Measure Participants	311	306
Number (95% Confidence Interval) [percentage of participants]	98.1 31.2%	98.0 31.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: MMR and CD-JEV, Group 2: MMR Then CD-JEV
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -2.1 to 2.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Group 1 - Group 2

7. Secondary Outcome

Title	Seroconversion Rate for Mumps 56 Days Post-vaccination
Description	The seroconversion rate for mumps at 56 days post-vaccination was defined as the percentage of participants with a change in serostatus from negative to positive 56 days after vaccination. Seropositivity was defined as an optical density ratio ≥ 1.10, measured using a commercial ELISA. Participants with equivocal serostatus at baseline are counted as non-responders.
Time Frame	56 days after MMR dose 1 vaccination (Day 56)

Outcome Measure Data

Analysis Population Description

The mumps per-protocol population included participants who fulfilled eligibility criteria, received all study vaccines as assigned, provided valid mumps serology results at baseline and Day 56, did not take any prohibited concomitant medications within within 28 days post-vaccination, and did not show mumps seropositivity at baseline.

Arm/Group Title	Group 1: MMR and CD-JEV	Group 2: MMR Then CD-JEV
Arm/Group Description	Participants received one dose of CD-JEV vaccine and one dose of MMR vaccine concurrently at Day 0. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).	Participants received one dose of MMR vaccine at Day 0 and one dose of CD-JEV 56 days later. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).
Measure Participants	270	265
Number (95% Confidence Interval) [percentage of participants]	96.7 30.8%	95.1 30.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: MMR and CD-JEV, Group 2: MMR Then CD-JEV
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95%; -1.8 to 4.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Group 1 - Group 2

8. Secondary Outcome

Title	Seroconversion Rate for Rubella 56 Days Post-vaccination
Description	The seroconversion rate for rubella at 56 days post-vaccination was defined as the percentage of participants with a change in serostatus from negative to positive 56 days after vaccination or a four-fold rise in concentration 56 days after vaccination if seropositive for rubella at baseline. Seropositivity is defined as a post-vaccination concentration of ≥ 10 IU/mL measured using a commercial ELISA.
Time Frame	56 days after MMR dose 1 vaccination (Day 56)

Outcome Measure Data

Analysis Population Description

The rubella per-protocol population included participants who fulfilled the eligibility criteria, received all study vaccines as assigned, provided valid rubella serology results at baseline and Day 56, did not take any prohibited concomitant medications within 28 days post-vaccination, and did not show rubella seropositivity at baseline.

Arm/Group Title	Group 1: MMR and CD-JEV	Group 2: MMR Then CD-JEV
Arm/Group Description	Participants received one dose of CD-JEV vaccine and one dose of MMR vaccine concurrently at Day 0. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).	Participants received one dose of MMR vaccine at Day 0 and one dose of CD-JEV 56 days later. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).
Measure Participants	285	295
Number (95% Confidence Interval) [percentage of participants]	100.0 31.8%	99.7 31.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: MMR and CD-JEV, Group 2: MMR Then CD-JEV
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.3 to 1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Group 1 - Group 2

9. Secondary Outcome

Title	Percentage of Participants With Japanese Encephalitis Seropositivity 28 Days Post-vaccination
Description	Japanese encephalitis (JE) immunogenicity was assessed by the percentage of participants with demonstrated seropositivity 28 days after CD-JEV vaccination. Seropositivity was defined as an anti-JE serum neutralizing antibody titer of ≥ 1:10, as measured by JE PRNT-50.
Time Frame	28 days after CD-JEV vaccination (Day 28 for Group 1 and Day 84 for Group 2)

Outcome Measure Data

Analysis Population Description

The JE per-protocol population included participants who fulfilled eligibility criteria, received all study vaccines as assigned, provided valid JE serology results at baseline and 28 days post-vaccination with CD-JEV, did not take any prohibited concomitant medications within 28 days post-vaccination, and did not show JE seropositivity at baseline

Arm/Group Title	Group 1: MMR and CD-JEV	Group 2: MMR Then CD-JEV
Arm/Group Description	Participants received one dose of CD-JEV vaccine and one dose of MMR vaccine concurrently at Day 0. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).	Participants received one dose of MMR vaccine at Day 0 and one dose of CD-JEV 56 days later. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).
Measure Participants	314	305
Number (95% Confidence Interval) [percentage of participants]	72.3 23%	68.2 21.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: MMR and CD-JEV, Group 2: MMR Then CD-JEV
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	4.1
	Confidence Interval	(2-Sided) 95%; -3.1 to 11.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Geometric Mean Titer (GMT) for Serum Neutralizing Antibody Titer to JE Virus at 28 Days Post-vaccination
Description	Anti-JE serum neutralizing antibody titer was measured using JE PRNT-50.
Time Frame	28 days after CD-JEV vaccination (Day 28 for Group 1 and Day 84 for Group 2)

Outcome Measure Data

Analysis Population Description

The JE per-protocol population included participants who fulfilled eligibility criteria, received all study vaccines as assigned, provided valid JE serology results at baseline and 28 days post-vaccination with CD-JEV, did not take any prohibited concomitant medications within 28 days post-vaccination, and did not show JE seropositivity at baseline

Arm/Group Title	Group 1 - MMR and CD-JEV	Group 2 - MMR Then CD-JEV
Arm/Group Description	Participants received one dose of CD-JEV vaccine and one dose of MMR vaccine concurrently at Day 0; Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).	Participants received one dose of MMR vaccine at Day 0 and one dose of CD-JEV 56 days later. Participants received a second dose of MMR per the routine immunization schedule at Day 84 (12 months of age).
Measure Participants	314	305
Geometric Mean (95% Confidence Interval) [titer]	24.0	20.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: MMR and CD-JEV, Group 2: MMR Then CD-JEV
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; 1.0 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Group 1 / Group 2 ratio obtained using an analysis of covariance (ANCOVA) method with log 10-transformed antibody concentration as dependent variable and treatment group as explanatory variable adjusted for log 10-transformed baseline antibody titer.

11. Secondary Outcome

Title	Number of Participants With Immediate Reactions Within 30 Minutes of Each Vaccination
Description	Participants were observed for 30 minutes after each vaccination for immediate reactions. Immediate reactions included both local (injection site) and systemic reactions. MMR vaccine was injected on left upper thigh and CD-JEV was injected on right upper thigh. Serious reactions were those meeting one of the following conditions: Death. Life threatening Required inpatient hospitalization or prolongation of existing hospitalization. Resulted in a persistent or significant disability or incapacity. Important medical events that, based upon appropriate medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed above.
Time Frame	30 minutes following each study vaccination

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received a study vaccine and had at least one safety measure post-vaccination.

Arm/Group Title	Group 1: MMR Dose 1 + CD-JEV	Group 2: MMR Dose 1	Group 2: CD-JEV	Group 1: MMR Dose 2	Group 2: MMR Dose 2
Arm/Group Description	Participants in Group 1 received one dose of CD-JEV vaccine and one dose of MMR vaccine concurrently on Day 0.	Participants in Group 2 received one dose of MMR vaccine on Day 0.	Participants in Group 2 received one dose of CD-JEV on Day 56.	Participants in Group 1 received a second dose of MMR vaccine on Day 84.	Participants in Group 2 received a second dose of MMR vaccine on Day 84.
Measure Participants	314	314	309	313	311
Any immediate reaction	6 1.9%	3 1%	5 0.8%	5 NaN	3 NaN
MMR local reaction	3 1%	2 0.6%	3 0.5%	1 NaN
CD-JEV local reaction	3 1%	4 1.3%
Systemic	1 0.3%	1 0.3%	1 0.2%	1 NaN	2 NaN
Serious reactions	0 0%	0 0%	0 0%	0 NaN	0 NaN

12. Secondary Outcome

Title	Number of Participants With Solicited Local and Systemic Reactions Within 14 Days of Each Vaccination
Description	Reactogenicity post-vaccination was assessed from 30 minutes through 14 days following vaccination. Parents used a structured reactogenicity diary card to record the following solicited (pre-listed) local and system reactions. Local reactions (at injection site): Ecchymosis (bruising) Erythema (redness) Edema (swelling) Induration (hardness) Pain/tenderness Systemic reactions: Fever Rash Cough Runny nose Change in eating habits Diarrhea Sleepiness Irritability Unusual crying Vomiting
Time Frame	30 minutes through 14 days following each vaccination

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Group 1: MMR Dose 1 + CD-JEV	Group 2: MMR Dose 1	Group 2: CD-JEV	Group 1: MMR Dose 2	Group 2: MMR Dose 2
Arm/Group Description	Participants in Group 1 received one dose of CD-JEV vaccine and one dose of MMR vaccine concurrently on Day 0.	Participants in Group 2 received one dose of MMR vaccine on Day 0.	Participants in Group 2 received one dose of CD-JEV on Day 56.	Participants in Group 1 received a second dose of MMR vaccine on Day 84.	Participants in Group 2 received a second dose of MMR vaccine on Day 84.
Measure Participants	314	314	309	313	311
Any local reactions at MMR injection site	35 11.1%	31 9.9%	12 1.9%	9 NaN
Any local reactions at CD-JEV injection site	34 10.8%	13 4.1%
Any systemic reactions	224 71.3%	222 70.7%	190 30.3%	168 NaN	174 NaN

13. Secondary Outcome

Title	Number of Participants With Solicited Local Reactions Within 14 Days of Each Vaccination by Maximum Severity
Description	Parents recorded local reactions on a diary card. 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% of surface area of extremity segment involved. Grade 3: ≥50% surface area of extremity segment involved OR ulceration OR secondary infection OR phlebitis OR sterile abscess OR drainage. Grade 4: potentially life-threatening (e.g., abscess, exfoliative dermatitis, necrosis involving dermis or deeper tissue). Injection site pain/tenderness (pain without touching or tenderness when the area is touched) were graded as follows: Grade 1: pain/tenderness causing no or minimal limitation of use of limb. Grade 2: pain/tenderness causing greater than minimal limitation of use of limb. Grade 3: pain/tenderness causing inability to perform usual social and functional activities. Grade 4: pain/tenderness causing inability to perform basic self-care OR hospitalization indicated.
Time Frame	30 minutes through 14 days following each vaccination

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Group 1: MMR Dose 1	Group 1: CD-JEV	Group 2: MMR Dose 1	Group 2: CD-JEV	Group 1: MMR Dose 2	Group 2: MMR Dose 2
Arm/Group Description	Participants in Group 1 received one dose of MMR vaccine injected on the left upper thigh on Day 0.	Participants in Group 1 received one dose of CD-JEV vaccine injected on the right upper thigh on Day 0.	Participants in Group 2 received one dose of MMR vaccine injected on the left upper thigh on Day 0.	Participants in Group 2 received one dose of CD-JEV vaccine injected on the left upper thigh on Day 56.	Participants in Group 1 received a 2nd dose of MMR vaccine injected on the left upper thigh on Day 84.	Participants in Group 2 received a 2nd dose of MMR vaccine injected on the left upper thigh on Day 84.
Measure Participants	314	314	314	309	313	311
Ecchymosis: Any	6 1.9%	6 1.9%	10 1.6%	3 NaN	0 NaN	5 NaN
Ecchymosis: Grade 1	6 1.9%	6 1.9%	10 1.6%	3 NaN	0 NaN	5 NaN
Ecchymosis: Grade 2	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN
Ecchymosis: Grade 3	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN
Ecchymosis: Grade 4	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN
Erythema: Any	15 4.8%	13 4.1%	14 2.2%	8 NaN	5 NaN	7 NaN
Erythema: Grade 1	15 4.8%	12 3.8%	14 2.2%	8 NaN	5 NaN	7 NaN
Erythema: Grade 2	0 0%	1 0.3%	0 0%	0 NaN	0 NaN	0 NaN
Erythema: Grade 3	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN
Erythema: Grade 4	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN
Edema: Any	6 1.9%	3 1%	7 1.1%	5 NaN	0 NaN	4 NaN
Edema: Grade 1	5 1.6%	3 1%	7 1.1%	5 NaN	0 NaN	4 NaN
Edema: Grade 2	1 0.3%	0 0%	0 0%	0 NaN	0 NaN	0 NaN
Edema: Grade 3	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN
Edema: Grade 4	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN
Induration: Any	4 1.3%	7 2.2%	7 1.1%	4 NaN	0 NaN	3 NaN
Induration: Grade 1	4 1.3%	6 1.9%	7 1.1%	4 NaN	0 NaN	3 NaN
Induration: Grade 2	0 0%	1 0.3%	0 0%	0 NaN	0 NaN	0 NaN
Induration: Grade 3	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN
Induration: Grade 4	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN
Pain/Tenderness: Any	18 5.7%	18 5.7%	19 3%	6 NaN	8 NaN	5 NaN
Pain/Tenderness: Grade 1	17 5.4%	17 5.4%	17 2.7%	5 NaN	8 NaN	4 NaN
Pain/Tenderness: Grade 2	1 0.3%	1 0.3%	2 0.3%	1 NaN	0 NaN	1 NaN
Pain/Tenderness: Grade 3	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN
Pain/Tenderness: Grade 4	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN

14. Secondary Outcome

Title	Number of Participants With Systemic Reactions Within 14 Days of Each Vaccination by Maximum Severity
Description	Parents recorded systemic reactions on a diary card. Fever was recorded and graded as follows (axillary temperature): Grade 1: 37.5°C to 37.9°C Grade 2: 38.0°C to 38.4°C Grade 3: 38.5°C to 40.0°C Grade 4: >40.0°C Rash, cough, runny nose, change in eating habits, diarrhea, sleepiness, irritability, unusual crying, vomiting, and any other unsolicited reaction occurring from 30 minutes through 14 days post vaccination were graded as follows: Grade 1: symptoms causing no or minimal interference with usual social and functional activities. Grade 2: symptoms causing greater than minimal interference with usual social and functional activities. Grade 3: symptoms causing inability to perform usual social and functional activities with intervention or hospitalization indicated. Grade 4: symptoms causing inability to perform basic self-care functions OR medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death.
Time Frame	30 minutes through 14 days following each vaccination

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Group 1: MMR Dose 1 + CD-JEV	Group 2: MMR Dose 1	Group 2: CD-JEV	Group 1: MMR Dose 2	Group 2: MMR Dose 2
Arm/Group Description	Participants in Group 1 received one dose of MMR vaccine and one dose of CD-JEV concurrently on Day 0.	Participants in Group 2 received one dose of MMR vaccine on Day 0.	Participants in Group 2 received one dose of CD-JEV vaccine on Day 56.	Participants in Group 1 received a second dose of MMR vaccine on Day 84.	Participants in Group 2 received a second dose of MMR vaccine on Day 84.
Measure Participants	314	314	309	313	311
Fever: Any	135 43%	119 37.9%	87 13.9%	79 NaN	84 NaN
Fever: Grade 1	52 16.6%	35 11.1%	39 6.2%	31 NaN	25 NaN
Fever: Grade 2	38 12.1%	43 13.7%	21 3.3%	23 NaN	26 NaN
Fever: Grade 3	44 14%	40 12.7%	26 4.1%	25 NaN	32 NaN
Fever: Grade 4	1 0.3%	1 0.3%	1 0.2%	0 NaN	1 NaN
Rash: Any	27 8.6%	33 10.5%	13 2.1%	19 NaN	18 NaN
Rash: Grade 1	23 7.3%	28 8.9%	12 1.9%	16 NaN	16 NaN
Rash: Grade 2	3 1%	4 1.3%	1 0.2%	2 NaN	2 NaN
Rash: Grade 3	0 0%	1 0.3%	0 0%	0 NaN	0 NaN
Rash: Grade 4	1 0.3%	0 0%	0 0%	1 NaN	0 NaN
Cough: Any	127 40.4%	116 36.9%	118 18.8%	111 NaN	103 NaN
Cough: Grade 1	103 32.8%	92 29.3%	98 15.6%	95 NaN	90 NaN
Cough: Grade 2	20 6.4%	22 7%	18 2.9%	16 NaN	13 NaN
Cough: Grade 3	4 1.3%	2 0.6%	2 0.3%	0 NaN	0 NaN
Cough: Grade 4	0 0%	0 0%	0 0%	0 NaN	0 NaN
Runny nose: Any	167 53.2%	163 51.9%	143 22.8%	133 NaN	135 NaN
Runny nose: Grade 1	139 44.3%	138 43.9%	128 20.4%	117 NaN	119 NaN
Runny nose: Grade 2	26 8.3%	23 7.3%	14 2.2%	14 NaN	16 NaN
Runny nose: Grade 3	2 0.6%	2 0.6%	1 0.2%	2 NaN	0 NaN
Runny nose: Grade 4	0 0%	0 0%	0 0%	0 NaN	0 NaN
Change in eating habits: Any	49 15.6%	32 10.2%	27 4.3%	36 NaN	27 NaN
Change in eating habits: Grade 1	40 12.7%	25 8%	23 3.7%	29 NaN	21 NaN
Change in eating habits: Grade 2	9 2.9%	6 1.9%	4 0.6%	6 NaN	5 NaN
Change in eating habits: Grade 3	0 0%	1 0.3%	0 0%	1 NaN	1 NaN
Change in eating habits: Grade 4	0 0%	0 0%	0 0%	0 NaN	0 NaN
Diarrhea: Any	58 18.5%	49 15.6%	29 4.6%	34 NaN	36 NaN
Diarrhea: Grade 1	49 15.6%	45 14.3%	23 3.7%	30 NaN	25 NaN
Diarrhea: Grade 2	7 2.2%	2 0.6%	5 0.8%	1 NaN	9 NaN
Diarrhea: Grade 3	1 0.3%	0 0%	1 0.2%	2 NaN	1 NaN
Diarrhea: Grade 4	1 0.3%	2 0.6%	0 0%	1 NaN	1 NaN
Sleepiness: Any	43 13.7%	32 10.2%	12 1.9%	15 NaN	16 NaN
Sleepiness: Grade 1	39 12.4%	29 9.2%	12 1.9%	15 NaN	15 NaN
Sleepiness: Grade 2	4 1.3%	3 1%	0 0%	0 NaN	1 NaN
Sleepiness: Grade 3	0 0%	0 0%	0 0%	0 NaN	0 NaN
Sleepiness: Grade 4	0 0%	0 0%	0 0%	0 NaN	0 NaN
Irritability: Any	80 25.5%	63 20.1%	36 5.7%	46 NaN	33 NaN
Irritability: Grade 1	63 20.1%	51 16.2%	32 5.1%	40 NaN	30 NaN
Irritability: Grade 2	14 4.5%	10 3.2%	4 0.6%	4 NaN	2 NaN
Irritability: Grade 3	3 1%	2 0.6%	0 0%	2 NaN	1 NaN
Irritability: Grade 4	0 0%	0 0%	0 0%	0 NaN	0 NaN
Unusual crying: Any	54 17.2%	29 9.2%	20 3.2%	29 NaN	20 NaN
Unusual crying: Grade 1	45 14.3%	23 7.3%	17 2.7%	24 NaN	16 NaN
Unusual crying: Grade 2	8 2.5%	5 1.6%	3 0.5%	5 NaN	3 NaN
Unusual crying: Grade 3	1 0.3%	1 0.3%	0 0%	0 NaN	1 NaN
Unusual crying: Grade 4	0 0%	0 0%	0 0%	0 NaN	0 NaN
Vomiting: Any grade	29 9.2%	26 8.3%	21 3.3%	22 NaN	31 NaN
Vomiting: Grade 1	25 8%	18 5.7%	17 2.7%	16 NaN	20 NaN
Vomiting: Grade 2	4 1.3%	8 2.5%	4 0.6%	3 NaN	9 NaN
Vomiting Grade 3	0 0%	0 0%	0 0%	2 NaN	1 NaN
Vomiting: Grade 4	0 0%	0 0%	0 0%	1 NaN	1 NaN

15. Secondary Outcome

Title	Number of Participants With Unsolicited Adverse Events Within 28 Days of Each Vaccination
Description	Each adverse event (AE) was assessed for relationship to vaccine by the study clinician according to the following: Definitely Related: An adverse event or unanticipated problem clearly related to the research procedures. Possibly Related: There is a reasonable possibility that the adverse event or unanticipated problem, incident, experience, or outcome may have been caused by the procedures involved in the research. Not Related: Any adverse event or unanticipated problem clearly not related to study procedures. Related adverse events includes events that were assessed as definitely or possibly related.
Time Frame	28 days following each vaccination

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Group 1: MMR Dose 1 + CD-JEV	Group 2: MMR Dose 1	Group 2: CD-JEV	Group 1: MMR Dose 2	Group 2: MMR Dose 2
Arm/Group Description	Participants in Group 1 received one dose of CD-JEV vaccine and one dose of MMR vaccine concurrently on Day 0.	Participants in Group 2 received one dose of MMR vaccine at Day 0.	Participants in Group 2 received one dose of CD-JEV on Day 56.	Participants in Group 1 received a second dose of MMR vaccine on Day 84.	Participants in Group 2 received a second dose of MMR vaccine on Day 84.
Measure Participants	314	314	309	313	311
Any adverse event	207 65.9%	211 67.2%	164 26.1%	110 NaN	148 NaN
Related adverse events	35 11.1%	22 7%	20 3.2%	22 NaN	30 NaN

16. Secondary Outcome

Title	Number of Participants With Serious Adverse Events Throughout the Study
Description	A serious adverse event (SAE) was defined as an AE that met one of the following: Death Life threatening Required inpatient hospitalization or prolongation of existing hospitalization Resulted in persistent or significant disability or incapacity Important medical events that, based upon appropriate medical judgment, jeopardized the participant and required medical or surgical intervention to prevent an outcomes listed above AEs were assessed for relationship to vaccine by the study clinician according to the following: Definitely Related: An AE or unanticipated problem clearly related to the research procedures. Possibly Related: There is a reasonable possibility that the AE or unanticipated problem, incident, experience, or outcome may have been caused by the procedures involved in the research. Not Related: Any AE or unanticipated problem clearly not related to study procedures. Related SAEs includes events that were assessed as definitely or possibly related.
Time Frame	Up to 112 days

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Group 1: MMR and CD-JEV	Group 2: MMR Then CD-JEV
Arm/Group Description	Participants received one dose of CD-JEV vaccine and one dose of MMR vaccine concurrently on Day 0. Participants received a second dose of MMR per the routine immunization schedule on Day 84 (12 months of age).	Participants received one dose of MMR vaccine on Day 0 and one dose of CD-JEV 56 days later. Participants received a second dose of MMR per the routine immunization schedule on Day 84 (12 months of age).
Measure Participants	314	314
Any serious adverse event	8 2.5%	15 4.8%
Related serious adverse event	0 0%	0 0%

Adverse Events

Time Frame	Mortality and serious adverse events were collected through the end of study, up to 112 days. Non-serious adverse events were collected through 28 days after each vaccination.
Arm/Group Title	Group 1: MMR Dose 1 + CD-JEV		Group 2: MMR Dose 1		Group 2: CD-JEV		Group 1: MMR Dose 2		Group 2: MMR Dose 2
Arm/Group Description	Participants in Group 1 received one dose of CD-JEV vaccine and one dose of MMR vaccine concurrently on Day 0.		Participants in Group 2 received one dose of MMR vaccine at Day 0.		Participants in Group 2 received one dose of CD-JEV on Day 56.		Participants in Group 1 received a second dose of MMR vaccine on Day 84.		Participants in Group 2 received a second dose of MMR vaccine on Day 84.
All Cause Mortality
	Group 1: MMR Dose 1 + CD-JEV		Group 2: MMR Dose 1		Group 2: CD-JEV		Group 1: MMR Dose 2		Group 2: MMR Dose 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/314 (0%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Serious Adverse Events
	Group 1: MMR Dose 1 + CD-JEV		Group 2: MMR Dose 1		Group 2: CD-JEV		Group 1: MMR Dose 2		Group 2: MMR Dose 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/314 (1.9%)		12/314 (3.8%)		3/309 (1%)		2/313 (0.6%)		1/311 (0.3%)
Infections and infestations
Amoebiasis	0/314 (0%)		3/314 (1%)		0/309 (0%)	0	0/313 (0%)	0	0/311 (0%)	0
Bronchitis	0/314 (0%)		1/314 (0.3%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Gastroenteritis	5/314 (1.6%)		3/314 (1%)		1/309 (0.3%)		2/313 (0.6%)		0/311 (0%)
Urinary tract infection	0/314 (0%)		1/314 (0.3%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Pneumonia	0/314 (0%)		3/314 (1%)		2/309 (0.6%)		0/313 (0%)		1/311 (0.3%)
Metabolism and nutrition disorders
Food intolerance	0/314 (0%)		1/314 (0.3%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Nervous system disorders
Febrile convulsion	1/314 (0.3%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Other (Not Including Serious) Adverse Events
	Group 1: MMR Dose 1 + CD-JEV		Group 2: MMR Dose 1		Group 2: CD-JEV		Group 1: MMR Dose 2		Group 2: MMR Dose 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	207/314 (65.9%)		211/314 (67.2%)		164/309 (53.1%)		110/313 (35.1%)		147/311 (47.3%)
Blood and lymphatic system disorders
Lymphadenopathy	0/314 (0%)		1/314 (0.3%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Iron deficiency anaemia	0/314 (0%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		1/311 (0.3%)
Eye disorders
Blepharitis	1/314 (0.3%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Gastrointestinal disorders
Aphthous ulcer	1/314 (0.3%)		1/314 (0.3%)		1/309 (0.3%)		0/313 (0%)		1/311 (0.3%)
Abdominal pain	1/314 (0.3%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Constipation	0/314 (0%)		0/314 (0%)		1/309 (0.3%)		0/313 (0%)		0/311 (0%)
Dyspepsia	0/314 (0%)		1/314 (0.3%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Stomatitis	2/314 (0.6%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Teething	1/314 (0.3%)		2/314 (0.6%)		2/309 (0.6%)		0/313 (0%)		0/311 (0%)
Vomiting	1/314 (0.3%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
General disorders
Pyrexia	4/314 (1.3%)		2/314 (0.6%)		5/309 (1.6%)		8/313 (2.6%)		5/311 (1.6%)
Injection site induration	1/314 (0.3%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Immune system disorders
Allergy to arthropod sting	0/314 (0%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		1/311 (0.3%)
Hypersensitivity	4/314 (1.3%)		2/314 (0.6%)		1/309 (0.3%)		2/313 (0.6%)		0/311 (0%)
Food allergy	0/314 (0%)		1/314 (0.3%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Infections and infestations
Abscess	0/314 (0%)		0/314 (0%)		2/309 (0.6%)		0/313 (0%)		0/311 (0%)
Body tinea	1/314 (0.3%)		0/314 (0%)		0/309 (0%)		1/313 (0.3%)		0/311 (0%)
Bronchiolitis	1/314 (0.3%)		5/314 (1.6%)		0/309 (0%)		2/313 (0.6%)		2/311 (0.6%)
Bronchitis	16/314 (5.1%)		24/314 (7.6%)		20/309 (6.5%)		13/313 (4.2%)		15/311 (4.8%)
Bullous impetigo	0/314 (0%)		1/314 (0.3%)		1/309 (0.3%)		0/313 (0%)		0/311 (0%)
Carbuncle	0/314 (0%)		1/314 (0.3%)		2/309 (0.6%)		2/313 (0.6%)		1/311 (0.3%)
Conjunctivitis	0/314 (0%)		4/314 (1.3%)		1/309 (0.3%)		3/313 (1%)		1/311 (0.3%)
Cellulitis orbital	1/314 (0.3%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Conjunctivitis bacterial	0/314 (0%)		0/314 (0%)		0/309 (0%)		1/313 (0.3%)		0/311 (0%)
Conjunctivitis viral	0/314 (0%)		0/314 (0%)		0/309 (0%)		1/313 (0.3%)		0/311 (0%)
Dermatitis infected	2/314 (0.6%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Exanthema subitum	5/314 (1.6%)		6/314 (1.9%)		1/309 (0.3%)		2/313 (0.6%)		2/311 (0.6%)
Erythema infectiosum	0/314 (0%)		1/314 (0.3%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Folliculitis	2/314 (0.6%)		1/314 (0.3%)		0/309 (0%)		1/313 (0.3%)		0/311 (0%)
Gastroenteritis	31/314 (9.9%)		22/314 (7%)		19/309 (6.1%)		10/313 (3.2%)		24/311 (7.7%)
Gastroenteritis viral	2/314 (0.6%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Hand-foot-and-mouth disease	2/314 (0.6%)		6/314 (1.9%)		8/309 (2.6%)		5/313 (1.6%)		1/311 (0.3%)
Herpangina	1/314 (0.3%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Hordeolum	1/314 (0.3%)		0/314 (0%)		1/309 (0.3%)		0/313 (0%)		1/311 (0.3%)
Impetigo	6/314 (1.9%)		1/314 (0.3%)		4/309 (1.3%)		1/313 (0.3%)		1/311 (0.3%)
Ludwig angina	0/314 (0%)		0/314 (0%)		1/309 (0.3%)		1/313 (0.3%)		0/311 (0%)
Nasopharyngitis	21/314 (6.7%)		19/314 (6.1%)		16/309 (5.2%)		5/313 (1.6%)		13/311 (4.2%)
Oral candidiasis	0/314 (0%)		1/314 (0.3%)		2/309 (0.6%)		0/313 (0%)		2/311 (0.6%)
Otitis media	1/314 (0.3%)		0/314 (0%)		0/309 (0%)		1/313 (0.3%)		1/311 (0.3%)
Otitis externa	0/314 (0%)		1/314 (0.3%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Otitis media acute	2/314 (0.6%)		1/314 (0.3%)		3/309 (1%)		1/313 (0.3%)		0/311 (0%)
Parasitic gastroenteritis	0/314 (0%)		2/314 (0.6%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Pharyngotonsillitis	2/314 (0.6%)		3/314 (1%)		1/309 (0.3%)		2/313 (0.6%)		2/311 (0.6%)
Pneumonia	11/314 (3.5%)		9/314 (2.9%)		6/309 (1.9%)		9/313 (2.9%)		5/311 (1.6%)
Respiratory tract infection	1/314 (0.3%)		1/314 (0.3%)		1/309 (0.3%)		1/313 (0.3%)		0/311 (0%)
Rhinitis	31/314 (9.9%)		39/314 (12.4%)		34/309 (11%)		17/313 (5.4%)		21/311 (6.8%)
Roseola	0/314 (0%)		1/314 (0.3%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Subcutaneous abscess	0/314 (0%)		0/314 (0%)		0/309 (0%)		1/313 (0.3%)		0/311 (0%)
Tinea cruris	1/314 (0.3%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Tinea versicolour	1/314 (0.3%)		1/314 (0.3%)		2/309 (0.6%)		0/313 (0%)		0/311 (0%)
Upper respiratory tract infection	76/314 (24.2%)		77/314 (24.5%)		54/309 (17.5%)		40/313 (12.8%)		62/311 (19.9%)
Upper respiratory tract infection bacterial	6/314 (1.9%)		4/314 (1.3%)		2/309 (0.6%)		0/313 (0%)		0/311 (0%)
Urinary tract infection	2/314 (0.6%)		0/314 (0%)		2/309 (0.6%)		1/313 (0.3%)		3/311 (1%)
Varicella	2/314 (0.6%)		4/314 (1.3%)		3/309 (1%)		1/313 (0.3%)		0/311 (0%)
Viral infection	24/314 (7.6%)		21/314 (6.7%)		12/309 (3.9%)		8/313 (2.6%)		6/311 (1.9%)
Viral rash	5/314 (1.6%)		5/314 (1.6%)		0/309 (0%)		0/313 (0%)		4/311 (1.3%)
Viral upper respiratory tract infection	8/314 (2.5%)		9/314 (2.9%)		1/309 (0.3%)		0/313 (0%)		0/311 (0%)
Wound infection	6/314 (1.9%)		3/314 (1%)		3/309 (1%)		3/313 (1%)		1/311 (0.3%)
Injury, poisoning and procedural complications
Anal injury	0/314 (0%)		1/314 (0.3%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Animal bite	0/314 (0%)		1/314 (0.3%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Arthropod bite	0/314 (0%)		0/314 (0%)		2/309 (0.6%)		0/313 (0%)		0/311 (0%)
Burns second degree	1/314 (0.3%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Contusion	3/314 (1%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Head injury	1/314 (0.3%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Skin abrasion	2/314 (0.6%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Thermal burn	1/314 (0.3%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Wound	0/314 (0%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		1/311 (0.3%)
Metabolism and nutrition disorders
Food intolerance	0/314 (0%)		1/314 (0.3%)		1/309 (0.3%)		0/313 (0%)		0/311 (0%)
Hypokalaemia	0/314 (0%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		1/311 (0.3%)
Irritability	1/314 (0.3%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Nervous system disorders
Febrile convulsion	0/314 (0%)		0/314 (0%)		0/309 (0%)		1/313 (0.3%)		0/311 (0%)
Psychiatric disorders
Breath holding	0/314 (0%)		0/314 (0%)		0/309 (0%)		1/313 (0.3%)		0/311 (0%)
Respiratory, thoracic and mediastinal disorders
Allergic cough	0/314 (0%)		0/314 (0%)		2/309 (0.6%)		2/313 (0.6%)		1/311 (0.3%)
Bronchial hyperreactivity	0/314 (0%)		1/314 (0.3%)		1/309 (0.3%)		1/313 (0.3%)		2/311 (0.6%)
Epistaxis	0/314 (0%)		0/314 (0%)		0/309 (0%)		1/313 (0.3%)		0/311 (0%)
Rhinitis allergic	2/314 (0.6%)		2/314 (0.6%)		2/309 (0.6%)		1/313 (0.3%)		4/311 (1.3%)
Skin and subcutaneous tissue disorders
Dermatitis	0/314 (0%)		0/314 (0%)		0/309 (0%)		0/313 (0%)		1/311 (0.3%)
Dermatitis allergic	0/314 (0%)		1/314 (0.3%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Dermatitis atopic	0/314 (0%)		0/314 (0%)		1/309 (0.3%)		0/313 (0%)		0/311 (0%)
Dermatitis contact	1/314 (0.3%)		1/314 (0.3%)		1/309 (0.3%)		2/313 (0.6%)		0/311 (0%)
Dermatitis diaper	1/314 (0.3%)		3/314 (1%)		3/309 (1%)		2/313 (0.6%)		2/311 (0.6%)
Miliaria	1/314 (0.3%)		1/314 (0.3%)		1/309 (0.3%)		1/313 (0.3%)		3/311 (1%)
Seborrhoeic dermatitis	0/314 (0%)		2/314 (0.6%)		0/309 (0%)		0/313 (0%)		0/311 (0%)
Skin hyperpigmentation	0/314 (0%)		0/314 (0%)		0/309 (0%)		1/313 (0.3%)		0/311 (0%)
Urticaria	0/314 (0%)		0/314 (0%)		0/309 (0%)		1/313 (0.3%)		0/311 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.