Trial Outcomes & Findings for Immunogenicity & Safety of Hepatitis A Vaccine Co-admin With a Measles/Mumps/Rubella & a Varicella Vaccine in Children (NCT NCT00197015)

NCT ID: NCT00197015

Last Updated: 2018-07-31

Results Overview

Concentrations are given as geometric mean concentrations (GMCs) expressed as milli-international units per milliliter (mIU/mL).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1474 participants

Primary outcome timeframe

31 days following the second dose of Havrix®

Results posted on

2018-07-31

Participant Flow

While the total numbers of subjects enrolled in the study was 1474, the total number of subjects that entered the study was 1241. The remaining subjects received a subject number but no vaccine dose and were therefore excluded from the analysis and group assignment.

Participant milestones

Participant milestones
Measure	HAV Group Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
Overall Study STARTED	324	455	462
Overall Study COMPLETED	274	366	385
Overall Study NOT COMPLETED	50	89	77

Reasons for withdrawal

Reasons for withdrawal
Measure	HAV Group Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
Overall Study Adverse Event	3	0	1
Overall Study Protocol Violation	0	3	3
Overall Study Withdrawal by Subject	17	37	34
Overall Study Lost to Follow-up	28	46	37
Overall Study Other	2	3	2

Baseline Characteristics

Immunogenicity & Safety of Hepatitis A Vaccine Co-admin With a Measles/Mumps/Rubella & a Varicella Vaccine in Children

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HAV Group n=324 Participants Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group n=455 Participants Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group n=462 Participants Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9	Total n=1241 Participants Total of all reporting groups
Age, Continuous	15.0 months STANDARD_DEVIATION 0.27 • n=5 Participants	15.0 months STANDARD_DEVIATION 0.22 • n=7 Participants	15.0 months STANDARD_DEVIATION 0.25 • n=5 Participants	15.0 months STANDARD_DEVIATION 0.25 • n=4 Participants
Sex: Female, Male Female	154 Participants n=5 Participants	208 Participants n=7 Participants	232 Participants n=5 Participants	594 Participants n=4 Participants
Sex: Female, Male Male	170 Participants n=5 Participants	247 Participants n=7 Participants	230 Participants n=5 Participants	647 Participants n=4 Participants

PRIMARY outcome

Timeframe: 31 days following the second dose of Havrix®

Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, on subjects with available results from HAV and HAV+MMR+V Groups.

Concentrations are given as geometric mean concentrations (GMCs) expressed as milli-international units per milliliter (mIU/mL).

Outcome measures

Outcome measures
Measure	HAV Group n=206 Participants Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group n=286 Participants Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
Anti-hepatitis A Virus (HAV) Antibody Concentrations in HAV and HAV+MMR+V Groups.	1390.4 mIU/mL Interval 1186.3 to 1629.6	—	1895.2 mIU/mL Interval 1682.7 to 2134.5

PRIMARY outcome

Timeframe: 31 days following the second dose of Havrix®

Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, on subjects with available results from HAV and HAV+MMR+V groups.

Anti-HAV antibody cut-off value assessed include 15 milli-international units per milliliter (mIU/mL).

Outcome measures

Outcome measures
Measure	HAV Group n=206 Participants Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group n=286 Participants Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentration Equal or Above the Cut-off Value in HAV and HAV+MMR+V Groups	204 Participants	—	285 Participants

PRIMARY outcome

Timeframe: 42 days following the administration of M-M-R®II and VARIVAX®

Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, on subjects with available results from HAV+MMR+V and MMR+V→HAV groups.

Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off values assessed include 150 milli-international units per milliliter (mIU/mL) for anti-measles antibodies, 28 Effective Dose 50 (ED50) for anti-mumps antibodies and 1:5 for anti-varicella antibodies.

Outcome measures

Outcome measures
Measure	HAV Group Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group n=250 Participants Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group n=268 Participants Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
Number of Subjects Seroconverted for Anti-measle, Anti-mumps and Anti-varicella Antibodies in HAV+MMR+V and MMR+V→HAV Groups Anti-mumps	—	193 Participants	207 Participants
Number of Subjects Seroconverted for Anti-measle, Anti-mumps and Anti-varicella Antibodies in HAV+MMR+V and MMR+V→HAV Groups Anti-varicella	—	168 Participants	187 Participants
Number of Subjects Seroconverted for Anti-measle, Anti-mumps and Anti-varicella Antibodies in HAV+MMR+V and MMR+V→HAV Groups Anti-measles	—	247 Participants	267 Participants

PRIMARY outcome

Timeframe: 42 days following administration of M-M-R®II and VARIVAX®

Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, on subjects with available results from HAV+MMR+V and MMR+V→HAV groups.

Vaccine response is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off value assessed include 10 milli-international units per milliliter (mIU/mL).

Outcome measures

Outcome measures
Measure	HAV Group Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group n=247 Participants Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group n=271 Participants Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
Number of Subjects With Vaccine Response for Anti-rubella Antibodies in HAV+MMR+V and MMR+V→HAV Groups	—	246 Participants	270 Participants

SECONDARY outcome

Timeframe: 42 days following the administration of M-M-R®II and VARIVAX®

Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, on subjects with available results from HAV+MMR+V and MMR+V→HAV groups.

Titers are given as geometric mean titers (GMTs).

Outcome measures

Outcome measures
Measure	HAV Group Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group n=269 Participants Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group n=304 Participants Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
Anti-measles, Anti-mumps, Anti-rubella and Anti-varicella Antibody Titers in HAV+MMR+V and MMR+V→HAV Groups Anti-measles	—	3218.3 titers Interval 2940.9 to 3521.8	3136.3 titers Interval 2922.0 to 3366.3
Anti-measles, Anti-mumps, Anti-rubella and Anti-varicella Antibody Titers in HAV+MMR+V and MMR+V→HAV Groups Anti-rubella	—	88.3 titers Interval 81.9 to 95.3	76.0 titers Interval 70.7 to 81.7
Anti-measles, Anti-mumps, Anti-rubella and Anti-varicella Antibody Titers in HAV+MMR+V and MMR+V→HAV Groups Anti-varicella	—	281.7 titers Interval 246.7 to 321.8	286.9 titers Interval 252.1 to 326.5
Anti-measles, Anti-mumps, Anti-rubella and Anti-varicella Antibody Titers in HAV+MMR+V and MMR+V→HAV Groups Anti-mumps	—	215.7 titers Interval 190.9 to 243.7	170.3 titers Interval 152.2 to 190.5

SECONDARY outcome

Timeframe: 42 days following the first dose of Havrix®

Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, on subjects with available results from HAV and HAV+MMR+V groups.

Concentrations are given as geometric mean concentrations (GMCs).

Outcome measures

Outcome measures
Measure	HAV Group n=228 Participants Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group n=306 Participants Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
Anti-hepatitis A Virus (HAV) Antibody Concentrations in HAV and HAV+MMR+V Groups	43.1 milli-international units per milliliter Interval 37.9 to 49.1	—	43.5 milli-international units per milliliter Interval 39.3 to 48.2

SECONDARY outcome

Timeframe: 42 days following the first dose of Havrix®

Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, on subjects with available results from HAV and HAV+MMR+V groups.

Anti-HAV antibody cut-off value assessed include 15 milli-international units per millilitre (mIU/mL).

Outcome measures

Outcome measures
Measure	HAV Group n=228 Participants Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group n=306 Participants Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentration Equal or Above the Cut-off Value in HAV and HAV+MMR+V Groups	194 Participants	—	276 Participants

SECONDARY outcome

Timeframe: 31 days following the second dose of Havrix®

Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, on subjects with available results from MMR+V→HAV Group.

Concentrations are given as geometric mean concentrations (GMCs).

Outcome measures

Outcome measures
Measure	HAV Group Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group n=237 Participants Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
Anti-hepatitis A Virus (HAV) Antibody Concentrations in MMR+V→HAV Group	—	1770.3 milli-international units per milliliter Interval 1569.9 to 1996.4	—

SECONDARY outcome

Timeframe: 31 days following the second dose of Havrix®

Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, on subjects with available results from MMR+V→HAV Group.

Anti-HAV antibody cut-off value assessed include 15 milli-international units per millilitre (mIU/mL).

Outcome measures

Outcome measures
Measure	HAV Group Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group n=237 Participants Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentrations Above the Cut-off Value in MMR+V→HAV Group	—	237 Participants	—

SECONDARY outcome

Timeframe: 31 days following the second dose of Havrix®

Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, on subjects with available results.

Vaccine response was defined as: 1) a detectable anti-hepatitis A virus (HAV) antibody concentration 31 days following the second dose in subjects who were initially seronegative; and 2) a 2-fold increase in anti-HAV antibody concentrations above the pre-study concentration 31 days following the second dose in subjects who were initially seropositive.

Outcome measures

Outcome measures
Measure	HAV Group n=194 Participants Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group n=224 Participants Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group n=259 Participants Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
Number of Subjects With Vaccine Response to Havrix®	192 Participants	224 Participants	257 Participants

SECONDARY outcome

Timeframe: During the 4-day period following each dose of vaccine

Population: Analysis was performed on the Total Vaccinated cohort, on subjects with available data.

Solicited local symptoms assessed include pain, rash (local), redness and swelling.

Outcome measures

Outcome measures
Measure	HAV Group n=304 Participants Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group n=411 Participants Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group n=419 Participants Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
Number of Subjects Reporting Solicited Local Symptoms Redness	97 Participants	149 Participants	151 Participants
Number of Subjects Reporting Solicited Local Symptoms Pain	103 Participants	162 Participants	187 Participants
Number of Subjects Reporting Solicited Local Symptoms Rash (local)	0 Participants	3 Participants	4 Participants
Number of Subjects Reporting Solicited Local Symptoms Swelling	45 Participants	70 Participants	82 Participants

SECONDARY outcome

Timeframe: During the 4-day period following each dose of vaccine

Population: Analysis was performed on the Total Vaccinated cohort, on subjects with available data.

Solicited general symptoms assessed include drowsiness, fever, irritability, loss of appetite and rash (general).

Outcome measures

Outcome measures
Measure	HAV Group n=304 Participants Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group n=424 Participants Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group n=411 Participants Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
Number of Subjects Reporting Solicited General Symptoms Drowsiness	95 Participants	179 Participants	178 Participants
Number of Subjects Reporting Solicited General Symptoms Fever	54 Participants	110 Participants	80 Participants
Number of Subjects Reporting Solicited General Symptoms Irritability	144 Participants	238 Participants	216 Participants
Number of Subjects Reporting Solicited General Symptoms Loss of appetite	94 Participants	170 Participants	154 Participants
Number of Subjects Reporting Solicited General Symptoms Rash (general)	5 Participants	7 Participants	10 Participants

SECONDARY outcome

Timeframe: During the 43-day period following each dose of vaccine

Population: Analysis was performed on the Total Vaccinated cohort, on subjects from MMR+V→HAV and HAV+MMR+V groups.

Specific adverse events assessed include papules, vesicles, crusts, parotid/salivary gland swelling and suspected signs of meningitis/febrile seizures.

Outcome measures

Outcome measures
Measure	HAV Group Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group n=455 Participants Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group n=462 Participants Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
Number of Subjects Reporting Measles, Mumps, Rubella and Varicella Specific Solicited General Adverse Events Suspected signs of meningitidis/febrile seizures	—	1 Participants	2 Participants
Number of Subjects Reporting Measles, Mumps, Rubella and Varicella Specific Solicited General Adverse Events Papules	—	23 Participants	23 Participants
Number of Subjects Reporting Measles, Mumps, Rubella and Varicella Specific Solicited General Adverse Events Vesicles	—	17 Participants	17 Participants
Number of Subjects Reporting Measles, Mumps, Rubella and Varicella Specific Solicited General Adverse Events Crusts	—	12 Participants	12 Participants
Number of Subjects Reporting Measles, Mumps, Rubella and Varicella Specific Solicited General Adverse Events Parotid/salivary gland swelling	—	0 Participants	1 Participants

SECONDARY outcome

Timeframe: During the 31-day period following each dose of vaccine

Population: Analysis was performed on the Total Vaccinated cohort.

Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms

Outcome measures

Outcome measures
Measure	HAV Group n=324 Participants Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group n=455 Participants Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group n=462 Participants Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
Number of Subjects Reporting Unsolicited Adverse Events (AEs)	186 Participants	286 Participants	249 Participants

SECONDARY outcome

Timeframe: During the Active Phase (from Day 0 up to Day 31 after the second dose) and the Extended Safety Follow-up Phase of the study (from Day 31 after the second dose up to study end)

Population: Analysis was performed on the Total Vaccinated cohort.

SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.

Outcome measures

Outcome measures
Measure	HAV Group n=324 Participants Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group n=455 Participants Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group n=462 Participants Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
Number of Subjects Reporting Serious Adverse Events (SAEs) Active Phase	1 Participants	6 Participants	5 Participants
Number of Subjects Reporting Serious Adverse Events (SAEs) Extended Safety Follow-up Phase	6 Participants	6 Participants	11 Participants

SECONDARY outcome

Timeframe: During the Active Phase (from Day 0 up to Day 31 after the second dose) and the Extended Safety Follow-up Phase of the study (from Day 31 after the second dose up to study end)

Population: Analysis was performed on the Total Vaccinated cohort (for the Active Phase) and the Extended Safety Follow-up cohort (for the Extended Safety Follow-up Phase).

New Chronic illnesses include autoimmune disorders, asthma, type I diabetes, allergies.

Outcome measures

Outcome measures
Measure	HAV Group n=324 Participants Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group n=455 Participants Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group n=462 Participants Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
Number of Subjects Reporting New Chronic Illnesses Active Phase	0 Participants	0 Participants	0 Participants
Number of Subjects Reporting New Chronic Illnesses Extended Safety Follow-Up Phase	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: During the Active Phase (from Day 0 up to Day 31 after the second dose) and the Extended Safety Follow-up Phase of the study (from Day 31 after the second dose up to study end)

Population: Analysis was performed on the Total Vaccinated cohort (for the Active Phase) and the Extended Safety Follow-up cohort (for the Extended Safety Follow-up Phase).

Medically significant events include, but are not limited to, diabetes, autoimmune disease, asthma, allergies and/or conditions prompting emergency room or physician office visits that are not related to well-child care, vaccination or common acute illnesses (e.g., upper respiratory infection, otitis media, pharyngitis, gastroenteritis, injury and visits for routine physical examination).

Outcome measures

Outcome measures
Measure	HAV Group n=324 Participants Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group n=455 Participants Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group n=462 Participants Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
Number of Subjects Reporting Medically Significant Events Active Phase	0 Participants	0 Participants	0 Participants
Number of Subjects Reporting Medically Significant Events Extended Safety Follow-Up Phase	0 Participants	0 Participants	0 Participants

Adverse Events

HAV Group

Serious events: 7 serious events

Other events: 251 other events

Deaths: 0 deaths

MMR+V→HAV Group

Serious events: 12 serious events

Other events: 366 other events

Deaths: 0 deaths

HAV+MMR+V Group

Serious events: 16 serious events

Other events: 363 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	HAV Group n=324 participants at risk Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	MMR+V→HAV Group n=455 participants at risk Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	HAV+MMR+V Group n=462 participants at risk Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
Infections and infestations Otitis media	10.8% 35/324 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	17.4% 79/455 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	14.1% 65/462 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort
General disorders Pyrexia	10.5% 34/324 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	14.9% 68/455 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	12.1% 56/462 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort
Infections and infestations Upper respiratory tract infection	9.6% 31/324 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	14.1% 64/455 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	12.6% 58/462 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort
Gastrointestinal disorders Diarrhoea	4.9% 16/324 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	8.6% 39/455 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	4.8% 22/462 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort
Gastrointestinal disorders Teething	7.7% 25/324 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	5.3% 24/455 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	4.1% 19/462 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort
Respiratory, thoracic and mediastinal disorders Cough	6.5% 21/324 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	4.4% 20/455 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	5.0% 23/462 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	6.2% 20/324 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	4.8% 22/455 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	3.7% 17/462 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort
Infections and infestations Nasopharyngitis	5.9% 19/324 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	4.2% 19/455 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	4.1% 19/462 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort
Gastrointestinal disorders Vomiting	4.3% 14/324 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	6.6% 30/455 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	2.6% 12/462 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort
General disorders Papules	— 0/0 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	5.1% 23/455 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	5.0% 23/462 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort
General disorders Drowsiness	31.2% 95/304 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	43.6% 179/411 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	42.0% 178/424 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort
General disorders Fever	17.8% 54/304 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	26.8% 110/411 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	18.9% 80/424 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort
General disorders Irritability	47.4% 144/304 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	57.9% 238/411 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	50.9% 216/424 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort
General disorders Loss of appetite	30.9% 94/304 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	41.4% 170/411 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	36.3% 154/424 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort
General disorders Pain	33.9% 103/304 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	39.4% 162/411 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	44.6% 187/419 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort
General disorders Redness	31.9% 97/304 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	36.3% 149/411 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	36.0% 151/419 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort
General disorders Swelling	14.8% 45/304 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	17.0% 70/411 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort	19.6% 82/419 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by non-systematic method are reported for the Total Vaccinated Cohort