Evaluation of Immunogenicity and Safety of Two Formulations of GSK Biologicals' Human Rotavirus (HRV) Vaccine (444563), in Healthy Infants Starting at Age 6-12 Weeks
Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT02914184
Collaborator
(none)
1,612
66
4
25
24.4
1
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the clinical consistency of three production lots of the Porcine circovirus (PCV)-free liquid formulation of oral live attenuated human rotavirus (HRV) vaccine and to evaluate the PCV-free liquid formulation of HRV vaccine as compared to the currently licensed lyophilised formulation of the HRV vaccine in terms of immunogenicity, reactogenicity and safety when administered as a two-dose vaccination in healthy infants starting at age 6-12 weeks. No new subjects will be enrolled in the extension phase of the study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
-
Experimental design: Phase IIIA, observer-blind, randomised (1:1:1:1), controlled, multi-centric, with four parallel groups and a staggered enrolment (Part A and Part B).
-
Duration of the study: The intended duration of the study, per subject, will be approximately 7-8 months including the 6 months of extended safety follow-up period after the last dose of HRV vaccine.
-
Epoch 001: Primary starting at Visit 1 (Day 0) and ending at the safety follow-up contact (Month 7-8).
-
Primary completion Date (PCD): Visit 3 (Month 2-4).
-
End of Study (EoS): Last testing results released of samples collected at Visit 3 or Last Subject Last Visit (LSLV) (Follow up contact at month 7-8).
-
Study Groups:
-
PCV-free HRV liquid formulation lot A (also referred to as Liq_A Group)
-
PCV-free HRV liquid formulation lot B (also referred to as Liq_B Group)
-
PCV-free HRV liquid formulation lot C (also referred to as Liq_C Group)
-
GSK Biologicals' currently licensed lyophilised HRV formulation (also referred to as Lyo Group)
-
Control:active control-GSK Biologicals' currently licensed lyophilised HRV vaccine
-
Vaccination schedule: Two doses of HRV vaccine to be administered according to a 0, 1-2 month schedule according to the immunisation schedule for RV vaccine.
Note that as a result of internal change in data standards terminology, the study data collected was converted to cDISC and the statistical analysis plan was amended accordingly. "Day 0" in the study design was replaced by "Day 1"; consequently, "Day n" was replaced by "Day n+1". Thus, the time frames (Day 0, Day n) of Outcome Measures described in this study record are different to that denoted in the full protocol document posted.
Study Design
Study Type:
Interventional
Actual Enrollment
:
1612 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
Immunogenicity and Safety Study of Two Formulations of GlaxoSmithKline (GSK) Biologicals' Human Rotavirus (HRV) Vaccine (444563), in Healthy Infants Starting at Age 6-12 Weeks
Actual Study Start Date
:
Oct 27, 2016
Actual Primary Completion Date
:
Jun 27, 2018
Actual Study Completion Date
:
Nov 26, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Liq_A Group All subjects will receive two doses of PCV-free HRV liquid formulation lot A, at 6 and 12 weeks of age |
Biological: HRV PCV-free liquid vaccine
Subjects will receive two doses of PCV-free HRV vaccine at 6 and 12 weeks of age. The vaccine will be administered orally
|
| Experimental: Liq_B Group All subjects will receive two doses of PCV-free HRV liquid formulation lot B, at 6 and 12 weeks of age |
Biological: HRV PCV-free liquid vaccine
Subjects will receive two doses of PCV-free HRV vaccine at 6 and 12 weeks of age. The vaccine will be administered orally
|
| Experimental: Liq_C Group All subjects will receive two doses of PCV-free HRV liquid formulation lot C, at 6 and 12 weeks of age |
Biological: HRV PCV-free liquid vaccine
Subjects will receive two doses of PCV-free HRV vaccine at 6 and 12 weeks of age. The vaccine will be administered orally
|
| Active Comparator: Lyo Group All subjects will receive two doses of currently licensed lyophilised HRV vaccine, at 6 and 12 weeks of age |
Biological: Rotarix
Subjects will receive two doses of currently licensed lyophilised HRV vaccine at 6 and 12 weeks of age. The vaccine will be administered orally
|
Outcome Measures
Primary Outcome Measures
- Anti-Rota Virus (Anti-RV) Immunoglobulin A (IgA) Antibody Concentrations in the Human Rotavirus (HRV) Liquid Formulation Groups (Liq_A, Liq_B and Liq_C) [At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)]
Antibody concentrations against Rota Virus (RV) were determined as Geometric Mean Antibody Concentration (GMC) and expressed as Units per milliliter (U/mL).
- Percentage of Seroconverted Subjects With RV Antibody Concentrations Above or Equal to Cut-off Value in Porcine Circovirus (PCV) -Free Liquid HRV Vaccine (Pooled HRV Liquid Group) and Control Group [At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)]
Seroconversion rate (SCR) was defined as the percentage of subjects who were initially seronegative (i.e., with anti-RV IgA antibody concentration less than (<) 20 U/mL before the first dose of HRV vaccine) and developed anti-RV IgA antibody concentration greater than or equal to (≥) 20 U/mL at Month 2-4 (1-2 months after dose 2). SCR was analysed using Enzyme Linked Immunosorbent Assay (ELISA). For this outcome measure, the three groups (Liq_A, Liq_B & Liq_C) were pooled into a single group (Liq_Pool group) as they all received PCV free-liquid HRV vaccine, and as pre-specified in the protocol, the immunological non-inferiority of the Liq_Pool group was compared to the currently licensed lyophilized HRV vaccine (Lyo_Control group) in terms of seroconversion rates of 1-2 months after Dose 2.
- Percentage of Seroconverted Subjects With RV Antibody Concentrations Above or Equal to 20 U/mL in Porcine Circovirus (PCV)-Free Liquid HRV Vaccine (Individual HRV Liquid Groups) and Lyophilised Control Group [At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)]
Seroconversion rate (SCR) was defined as the percentage of subjects who were initially seronegative (i.e., with anti-RV IgA antibody concentration less than (<) 20 U/mL before the first dose of HRV vaccine) and developed anti-RV IgA antibody concentration greater than or equal to (≥) 20 U/mL at Month 2-4 (1-2 months after dose 2). SCR was analysed using Enzyme Linked Immunosorbent Assay (ELISA). The analysis was assessed to demonstrate the immunogenicity of PCV-free liquid HRV vaccine as compared to the currently licensed lyophilised HRV vaccine (individual HRV liquid groups) in terms of seroconversion rates 1-2 months after Dose 2.
- Anti-RV IgA Antibody Concentrations in the PCV-free Liquid HRV Vaccine (Pooled HRV Liquid Group) and Lyophilised Control Group [At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)]
Antibody concentrations against RV were determined as GMCs and expressed as U/mL. For this outcome measure, the three groups (Liq_A, Liq_B & Liq_C) were pooled into a single group (Liq_Pool group) as they all received PCV free-liquid HRV vaccine, and as pre-specified in the protocol, the immunological non-inferiority of the Liq_Pool group was compared to the currently licensed lyophilized HRV vaccine (Lyo_Control group) in terms of antibody concentrations at 1-2 months after Dose 2.
- Anti-RV IgA Antibody Concentrations in the PCV-free Liquid HRV Vaccine (Individual HRV Liquid Groups) and Lyophilised Control Group [At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)]
Antibody concentrations against RV were determined as GMCs and expressed as U/mL. The analysis was assessed to demonstrate the immunogenicity of the PCV-free liquid HRV vaccine (individual HRV liquid groups) to that of the currently licensed lyophilised HRV vaccine in terms of serum anti-RV IgA antibody concentrations 1-2 months after Dose 2.
Secondary Outcome Measures
- Percentage of Subjects With Anti-RV IgA Concentrations (Pooled HRV Liquid Group) [At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)]
Antibody concentrations ≥90 U/mL were determined and expressed as GMCs, assessed for the pooled HRV liquid groups and Control Group. The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations. For this outcome measure, the three groups (Liq_A, Liq_B & Liq_C) were pooled into a single group (Liq_Pool group) as they all received PCV free-liquid HRV vaccine, and as pre-specified in the protocol, the immunogenicity of the Liq_Pool group was compared to the currently licensed lyophilized HRV vaccine (Lyo_Control group) in terms of percentage of subjects with anti-RV IgA antibody concentrations ≥ 90 U/mL, 1-2 months after Dose 2
- Percentage of Subjects With Anti-RV IgA Concentrations (Individual HRV Liquid Groups) [At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)]
Antibody concentrations ≥90 U/mL were determined and expressed as GMCs, assessed for the individual HRV liquid groups and Control Group. The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations. The analysis was performed to assess the immunogenicity of the PCV-free liquid HRV vaccine (pooled HRV liquid groups) and the currently licensed lyophilised HRV vaccine, in terms of percentage of subjects with anti-RV IgA antibody concentrations ≥ 90 U/mL 1-2 months after Dose 2.
- Number of Subjects With Any Solicited General Adverse Events (AEs). [During the 8 days (Day 1 to Day 8) follow-up period after each dose of HRV vaccine]
Assessed solicited general AEs were cough/runny nose, diarrhea, fever (defined as temperature ≥ 38.0°C), irritability/fussiness, loss of appetite and vomiting. Any solicited general AE is defined as any occurrence of the specified symptom, irrespective of intensity grade and relationship to vaccination.
- Number of Subjects With Any Unsolicited AEs. [During the 31 day (Day 1 to Day 31) follow-up period after HRV vaccination across doses]
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any is defined as the occurrence of any unsolicited AE irrespective of its intensity grade and relationship to vaccination.
- Number of Subjects With Any Serious Adverse Events (SAEs) [During the entire study period (Day 1 to Month 7-8)]
SAEs assessed include any untoward medical occurrence that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization or resulted in disability/incapacity.
Eligibility Criteria
Criteria
Ages Eligible for Study:
6 Weeks
to 12 Weeks
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
Subjects' parent(s)/LAR(s) who, in the opinion of the investigator can and will comply with the requirements of the protocol.
-
Written informed consent obtained from the parent(s)/LAR(s) (Legally acceptable representatives) of the subject prior to performing any study specific procedure.
-
A male or female infant between, and including, 6 and 12 weeks (42-90 days) of age at the time of the first study vaccination.
-
Born full-term (i.e., between a gestation period of 37 weeks 0 days and 41 weeks 6 days).
-
Healthy subjects as established by medical history and clinical examination before entering into the study.
Exclusion Criteria:
-
Child in care
-
Use of any investigational or non-registered product other than the study vaccines during the period starting 30 days before the first dose of study vaccines (Day-29 to Day 0), or planned use during the study period.
-
Chronic administration of immunosuppressants or other immune-modifying drugs since birth. For corticosteroids, this will mean prednisone (0.5 mg/kg/day, or equivalent). Inhaled and topical steroids are allowed.
-
Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
-
Administration of long-acting immune-modifying drugs at any time during the study period.
-
Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose of vaccine administration and ending at Visit 3, with the exception of the inactivated influenza vaccine, which is allowed at any time during the study and other licensed routine childhood vaccinations.
-
Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product.
-
Uncorrected congenital malformation of the gastrointestinal tract that would predispose for Intussusception (IS).
-
History of IS.
-
Family history of congenital or hereditary immunodeficiency.
-
Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
-
Major congenital defects or serious chronic illness.
-
Previous vaccination against RV.
-
Previous confirmed occurrence of RVGE.
-
GE within 7 days preceding the study vaccine administration.
-
History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
-
Hypersensitivity to latex.
-
Acute disease and/or fever at the time of enrolment.
-
Fever is defined as temperature ≥38.0°C/100.4°F. The preferred location for measuring temperature in this study will be the oral cavity, the axilla and the rectum.
-
Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | Birmingham | Alabama | United States | 35235 |
| 2 | GSK Investigational Site | Anaheim | California | United States | 92804 |
| 3 | GSK Investigational Site | Paramount | California | United States | 90723 |
| 4 | GSK Investigational Site | Sacramento | California | United States | 95815 |
| 5 | GSK Investigational Site | San Jose | California | United States | 95119 |
| 6 | GSK Investigational Site | Nampa | Idaho | United States | 83686 |
| 7 | GSK Investigational Site | Newton | Kansas | United States | 67114 |
| 8 | GSK Investigational Site | Topeka | Kansas | United States | 66604 |
| 9 | GSK Investigational Site | Kansas City | Missouri | United States | 64108 |
| 10 | GSK Investigational Site | Cleveland | Ohio | United States | 44121 |
| 11 | GSK Investigational Site | Erie | Pennsylvania | United States | 16506 |
| 12 | GSK Investigational Site | Cheraw | South Carolina | United States | 29520 |
| 13 | GSK Investigational Site | North Charleston | South Carolina | United States | 29456-9170 |
| 14 | GSK Investigational Site | Layton | Utah | United States | 84041 |
| 15 | GSK Investigational Site | Murray | Utah | United States | 84107 |
| 16 | GSK Investigational Site | Orem | Utah | United States | 84057 |
| 17 | GSK Investigational Site | Provo | Utah | United States | 84604 |
| 18 | GSK Investigational Site | Syracuse | Utah | United States | 84075 |
| 19 | GSK Investigational Site | Marshfield | Wisconsin | United States | 54449 |
| 20 | GSK Investigational Site | San Jose | San José | Costa Rica | |
| 21 | GSK Investigational Site | San José | Costa Rica | ||
| 22 | GSK Investigational Site | Espoo | Finland | 02230 | |
| 23 | GSK Investigational Site | Helsinki | Finland | 00100 | |
| 24 | GSK Investigational Site | Helsinki | Finland | 00930 | |
| 25 | GSK Investigational Site | Jarvenpaa | Finland | 04400 | |
| 26 | GSK Investigational Site | Kokkola | Finland | 67100 | |
| 27 | GSK Investigational Site | Oulu | Finland | 90220 | |
| 28 | GSK Investigational Site | Pori | Finland | 28100 | |
| 29 | GSK Investigational Site | Seinajoki | Finland | 60100 | |
| 30 | GSK Investigational Site | Tampere | Finland | 33100 | |
| 31 | GSK Investigational Site | Turku | Finland | 20520 | |
| 32 | GSK Investigational Site | Mannheim | Baden-Wuerttemberg | Germany | 68161 |
| 33 | GSK Investigational Site | Tauberbischofsheim | Baden-Wuerttemberg | Germany | 97941 |
| 34 | GSK Investigational Site | Schoenau Am Koenigssee | Bayern | Germany | 83471 |
| 35 | GSK Investigational Site | Goch | Nordrhein-Westfalen | Germany | 47574 |
| 36 | GSK Investigational Site | Frankenthal | Rheinland-Pfalz | Germany | 67227 |
| 37 | GSK Investigational Site | Bramsche | Germany | 49565 | |
| 38 | GSK Investigational Site | Chiba | Japan | 274-0063 | |
| 39 | GSK Investigational Site | Chiba | Japan | 299-4503 | |
| 40 | GSK Investigational Site | Saitama | Japan | 350-0001 | |
| 41 | GSK Investigational Site | Saitama | Japan | 360-0846 | |
| 42 | GSK Investigational Site | Tokyo | Japan | 146-0095 | |
| 43 | GSK Investigational Site | Tokyo | Japan | 167-0052 | |
| 44 | GSK Investigational Site | Tokyo | Japan | 190-0002 | |
| 45 | GSK Investigational Site | Gangwon-do | Korea, Republic of | 26426 | |
| 46 | GSK Investigational Site | Gyeonggido | Korea, Republic of | 442723 | |
| 47 | GSK Investigational Site | Incheon | Korea, Republic of | 21431 | |
| 48 | GSK Investigational Site | Seoul | Korea, Republic of | 01450 | |
| 49 | GSK Investigational Site | Seoul | Korea, Republic of | 02447 | |
| 50 | GSK Investigational Site | Seoul | Korea, Republic of | 04619 | |
| 51 | GSK Investigational Site | Malaga | Andalucia | Spain | 29004 |
| 52 | GSK Investigational Site | Antequera/Málaga | Spain | 29200 | |
| 53 | GSK Investigational Site | Castellón | Spain | 12004 | |
| 54 | GSK Investigational Site | Castellón | Spain | 12530 | |
| 55 | GSK Investigational Site | Madrid | Spain | 28050 | |
| 56 | GSK Investigational Site | Marbella | Spain | 29600 | |
| 57 | GSK Investigational Site | Sevilla | Spain | 41013 | |
| 58 | GSK Investigational Site | Valencia | Spain | 46020 | |
| 59 | GSK Investigational Site | Valencia | Spain | 46023 | |
| 60 | GSK Investigational Site | Valencia | Spain | 46200 | |
| 61 | GSK Investigational Site | Hsinchu | Taiwan | 300 | |
| 62 | GSK Investigational Site | Taichung | Taiwan | 404 | |
| 63 | GSK Investigational Site | Taichung | Taiwan | 407 | |
| 64 | GSK Investigational Site | Taipei | Taiwan | 100 | |
| 65 | GSK Investigational Site | Taipei | Taiwan | 104 | |
| 66 | GSK Investigational Site | Taoyuan | Taiwan | 333 |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
More Information
Publications
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02914184
Other Study ID Numbers:
- 115461
- 2016-000598-19
First Posted:
Sep 26, 2016
Last Update Posted:
Jul 21, 2020
Last Verified:
Jul 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by GlaxoSmithKline
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study was conducted at 66 centers in 8 countries: 2 in Costa Rica, 10 in Finland, 6 in Germany, 7 in Japan, 6 in Republic of Korea, 9 in Spain, 6 in Taiwan and 20 in the United States (US). |
|---|---|
| Pre-assignment Detail | Among 1612 subjects enrolled in the study, 1600 were vaccinated and 1545 completed the study. |
| Arm/Group Title | Liq_A Group | Liq_B Group | Liq_C Group | Lyo Control Group |
|---|---|---|---|---|
| Arm/Group Description | Subjects who received two doses of PCV-free HRV liquid formulation of lot A at 6 and 12 weeks of age. | Subjects who received two doses of PCV-free HRV liquid formulation of lot B at 6 and 12 weeks of age. | Subjects who received two doses of PCV-free HRV liquid formulation of lot C at 6 and 12 weeks of age. | Subjects who received two doses of currently licensed lyophilised HRV vaccine, at 6 and 12 weeks of age. |
| Period Title: Overall Study | ||||
| STARTED | 400 | 396 | 402 | 402 |
| COMPLETED | 386 | 383 | 385 | 391 |
| NOT COMPLETED | 14 | 13 | 17 | 11 |
Baseline Characteristics
| Arm/Group Title | Liq_A Group | Liq_B Group | Liq_C Group | Lyo Control Group | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Subjects who received two doses of PCV-free HRV liquid formulation of lot A at 6 and 12 weeks of age. | Subjects who received two doses of PCV-free HRV liquid formulation of lot B at 6 and 12 weeks of age. | Subjects who received two doses of PCV-free HRV liquid formulation of lot C at 6 and 12 weeks of age. | Subjects who received two doses of currently licensed lyophilised HRV vaccine, at 6 and 12 weeks of age. | Total of all reporting groups |
| Overall Participants | 400 | 396 | 402 | 402 | 1600 |
| Age (Weeks) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Weeks] |
8.5
(1.5)
|
8.3
(1.5)
|
8.4
(1.6)
|
8.5
(1.5)
|
8.4
(1.5)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
208
52%
|
198
50%
|
205
51%
|
203
50.5%
|
814
50.9%
|
| Male |
192
48%
|
198
50%
|
197
49%
|
199
49.5%
|
786
49.1%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||
| American Indian Or Alaska Native |
6
1.5%
|
2
0.5%
|
3
0.7%
|
5
1.2%
|
16
1%
|
| Asian |
95
23.8%
|
96
24.2%
|
98
24.4%
|
95
23.6%
|
384
24%
|
| Black Or African American |
6
1.5%
|
9
2.3%
|
13
3.2%
|
13
3.2%
|
41
2.6%
|
| Native Hawaiian Or Other Pacific Islander |
1
0.3%
|
0
0%
|
0
0%
|
0
0%
|
1
0.1%
|
| Other |
29
7.3%
|
31
7.8%
|
26
6.5%
|
27
6.7%
|
113
7.1%
|
| White |
263
65.8%
|
258
65.2%
|
262
65.2%
|
262
65.2%
|
1045
65.3%
|
Outcome Measures
| Title | Anti-Rota Virus (Anti-RV) Immunoglobulin A (IgA) Antibody Concentrations in the Human Rotavirus (HRV) Liquid Formulation Groups (Liq_A, Liq_B and Liq_C) |
|---|---|
| Description | Antibody concentrations against Rota Virus (RV) were determined as Geometric Mean Antibody Concentration (GMC) and expressed as Units per milliliter (U/mL). |
| Time Frame | At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the Per-protocol analysis set (PPS) for immunogenicity that included all subjects who received both doses of study vaccine and for whom the liquid HRV vaccine or control vaccine was administered according to protocol and for whom immunogenicity data were available at the post-vaccination sampling time point. |
| Arm/Group Title | Liq_A Group | Liq_B Group | Liq_C Group |
|---|---|---|---|
| Arm/Group Description | Subjects who received two doses of PCV-free HRV liquid formulation of lot A at 6 and 12 weeks of age. | Subjects who received two doses of PCV-free HRV liquid formulation of lot B at 6 and 12 weeks of age. | Subjects who received two doses of PCV-free HRV liquid formulation of lot C at 6 and 12 weeks of age. |
| Measure Participants | 332 | 326 | 326 |
| Geometric Mean (95% Confidence Interval) [U/mL] |
155.7
|
147.3
|
175.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Liq_A Group, Liq_B Group |
|---|---|---|
| Comments | GMC Ratio of Anti-RV IgA antibody for Liq_A and Liq_B groups was calculated using ANOVA model with vaccine groups and country as fixed effects. | |
| Type of Statistical Test | Other | |
| Comments | The two-sided 95% CIs for the ratio of anti RV IgA antibody GMCs should be within the [0.5; 2] clinical limit interval. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GMC Ratio at At Month 2-4 |
| Estimated Value | 1.07 | |
| Confidence Interval |
(2-Sided) 95% 0.79 to 1.44 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Liq_A Group, Liq_C Group |
|---|---|---|
| Comments | GMC Ratio of Anti-RV IgA antibody for Liq_A and Liq_C groups was calculated using ANOVA model with vaccine groups and country as fixed effects. | |
| Type of Statistical Test | Other | |
| Comments | The two-sided 95% CIs for the ratio of anti RV IgA antibody GMCs should be within the [0.5; 2] clinical limit interval. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GMC Ratio at At Month 2-4 |
| Estimated Value | 0.88 | |
| Confidence Interval |
(2-Sided) 95% 0.65 to 1.19 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Liq_B Group, Liq_C Group |
|---|---|---|
| Comments | GMC Ratio of Anti-RV IgA antibody for Liq_B and Liq_C groups was calculated using ANOVA model with vaccine groups and country as fixed effects. | |
| Type of Statistical Test | Other | |
| Comments | The two-sided 95% CIs for the ratio of anti RV IgA antibody GMCs should be within the [0.5; 2] clinical limit interval. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GMC Ratio at At Month 2-4 |
| Estimated Value | 0.82 | |
| Confidence Interval |
(2-Sided) 95% 0.61 to 1.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Seroconverted Subjects With RV Antibody Concentrations Above or Equal to Cut-off Value in Porcine Circovirus (PCV) -Free Liquid HRV Vaccine (Pooled HRV Liquid Group) and Control Group |
|---|---|
| Description | Seroconversion rate (SCR) was defined as the percentage of subjects who were initially seronegative (i.e., with anti-RV IgA antibody concentration less than (<) 20 U/mL before the first dose of HRV vaccine) and developed anti-RV IgA antibody concentration greater than or equal to (≥) 20 U/mL at Month 2-4 (1-2 months after dose 2). SCR was analysed using Enzyme Linked Immunosorbent Assay (ELISA). For this outcome measure, the three groups (Liq_A, Liq_B & Liq_C) were pooled into a single group (Liq_Pool group) as they all received PCV free-liquid HRV vaccine, and as pre-specified in the protocol, the immunological non-inferiority of the Liq_Pool group was compared to the currently licensed lyophilized HRV vaccine (Lyo_Control group) in terms of seroconversion rates of 1-2 months after Dose 2. |
| Time Frame | At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the PPS for immunogenicity that included all subjects who received both doses of study vaccine and for whom the liquid HRV vaccine or control vaccine was administered according to protocol and for whom immunogenicity data were available at the post-vaccination sampling time point. |
| Arm/Group Title | Liq_Pool Group | Lyo Control Group |
|---|---|---|
| Arm/Group Description | Subjects who received two doses of PCV-free HRV liquid formulation of pooled lot A, B and C at 6 and 12 weeks of age. | Subjects who received two doses of currently licensed lyophilised HRV vaccine, at 6 and 12 weeks of age. |
| Measure Participants | 984 | 329 |
| Number (95% Confidence Interval) [Percentage of subjects] |
79.3
|
81.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Liq_A Group, Liq_B Group |
|---|---|---|
| Comments | Non-inferiority of Liq_Pool group compared to Lyo Control group in terms of difference in % of subjects with anti-RV IgA titer ≥ specified cut off with its 2-sided 95% CI in initially seronegative subjects | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Lower limit (LL) of the two-sided asymptotic standardized 95% CI for the difference in SCR for antibodies to rota virus at month 2-4 between the Liq_Pool group and Lyo Control group should be ≥ -10%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | SCR difference at Month 2-4 |
| Estimated Value | -2.49 | |
| Confidence Interval |
(2-Sided) 95% -7.15 to 2.63 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Seroconverted Subjects With RV Antibody Concentrations Above or Equal to 20 U/mL in Porcine Circovirus (PCV)-Free Liquid HRV Vaccine (Individual HRV Liquid Groups) and Lyophilised Control Group |
|---|---|
| Description | Seroconversion rate (SCR) was defined as the percentage of subjects who were initially seronegative (i.e., with anti-RV IgA antibody concentration less than (<) 20 U/mL before the first dose of HRV vaccine) and developed anti-RV IgA antibody concentration greater than or equal to (≥) 20 U/mL at Month 2-4 (1-2 months after dose 2). SCR was analysed using Enzyme Linked Immunosorbent Assay (ELISA). The analysis was assessed to demonstrate the immunogenicity of PCV-free liquid HRV vaccine as compared to the currently licensed lyophilised HRV vaccine (individual HRV liquid groups) in terms of seroconversion rates 1-2 months after Dose 2. |
| Time Frame | At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the PPS for immunogenicity that included all subjects who received both doses of study vaccine and for whom the liquid HRV vaccine or control vaccine was administered according to protocol and for whom immunogenicity data were available at the post-vaccination sampling time point. |
| Arm/Group Title | Liq_A Group | Liq_B Group | Liq_C Group | Lyo Control Group |
|---|---|---|---|---|
| Arm/Group Description | Subjects who received two doses of PCV-free HRV liquid formulation of lot A at 6 and 12 weeks of age. | Subjects who received two doses of PCV-free HRV liquid formulation of lot B at 6 and 12 weeks of age. | Subjects who received two doses of PCV-free HRV liquid formulation of lot C at 6 and 12 weeks of age. | Subjects who received two doses of currently licensed lyophilised HRV vaccine, at 6 and 12 weeks of age. |
| Measure Participants | 332 | 326 | 326 | 329 |
| Number (95% Confidence Interval) [Percentage of subjects] |
77.7
|
77.6
|
82.5
|
81.8
|
| Title | Anti-RV IgA Antibody Concentrations in the PCV-free Liquid HRV Vaccine (Pooled HRV Liquid Group) and Lyophilised Control Group |
|---|---|
| Description | Antibody concentrations against RV were determined as GMCs and expressed as U/mL. For this outcome measure, the three groups (Liq_A, Liq_B & Liq_C) were pooled into a single group (Liq_Pool group) as they all received PCV free-liquid HRV vaccine, and as pre-specified in the protocol, the immunological non-inferiority of the Liq_Pool group was compared to the currently licensed lyophilized HRV vaccine (Lyo_Control group) in terms of antibody concentrations at 1-2 months after Dose 2. |
| Time Frame | At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the PPS for immunogenicity that included all subjects who received both doses of study vaccine and for whom the liquid HRV vaccine or control vaccine was administered according to protocol and for whom immunogenicity data were available at the post-vaccination sampling time point. |
| Arm/Group Title | Liq_Pool Group | Lyo Control Group |
|---|---|---|
| Arm/Group Description | Subjects who received two doses of PCV-free HRV liquid formulation of pooled lot A, B and C at 6 and 12 weeks of age. | Subjects who received two doses of currently licensed lyophilised HRV vaccine, at 6 and 12 weeks of age. |
| Measure Participants | 984 | 329 |
| Geometric Mean (95% Confidence Interval) [U/mL] |
159.2
|
153.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Liq_A Group, Liq_B Group |
|---|---|---|
| Comments | Non-inferiority of Liq_Pool Group as compared to Lyo Control group in terms of the GMC ratio calculated using ANOVA model with vaccine groups and country as fixed effects | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | LL of the two-sided 95% CI for the ratio of anti-RV IgA antibody GMCs between the Liq_Pool Group and Control group should be ≥ 0.67. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GMC Ratio at At Month 2-4 |
| Estimated Value | 1.04 | |
| Confidence Interval |
(2-Sided) 95% 0.82 to 1.33 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Anti-RV IgA Antibody Concentrations in the PCV-free Liquid HRV Vaccine (Individual HRV Liquid Groups) and Lyophilised Control Group |
|---|---|
| Description | Antibody concentrations against RV were determined as GMCs and expressed as U/mL. The analysis was assessed to demonstrate the immunogenicity of the PCV-free liquid HRV vaccine (individual HRV liquid groups) to that of the currently licensed lyophilised HRV vaccine in terms of serum anti-RV IgA antibody concentrations 1-2 months after Dose 2. |
| Time Frame | At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the PPS for immunogenicity that included all subjects who received both doses of study vaccine and for whom the liquid HRV vaccine or control vaccine was administered according to protocol and for whom immunogenicity data were available at the post-vaccination sampling time point. |
| Arm/Group Title | Liq_A Group | Liq_B Group | Liq_C Group | Lyo Control Group |
|---|---|---|---|---|
| Arm/Group Description | Subjects who received two doses of PCV-free HRV liquid formulation of lot A at 6 and 12 weeks of age. | Subjects who received two doses of PCV-free HRV liquid formulation of lot B at 6 and 12 weeks of age. | Subjects who received two doses of PCV-free HRV liquid formulation of lot C at 6 and 12 weeks of age. | Subjects who received two doses of currently licensed lyophilised HRV vaccine, at 6 and 12 weeks of age. |
| Measure Participants | 332 | 326 | 326 | 329 |
| Geometric Mean (95% Confidence Interval) [U/mL] |
155.7
|
147.3
|
175.9
|
153.8
|
| Title | Percentage of Subjects With Anti-RV IgA Concentrations (Pooled HRV Liquid Group) |
|---|---|
| Description | Antibody concentrations ≥90 U/mL were determined and expressed as GMCs, assessed for the pooled HRV liquid groups and Control Group. The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations. For this outcome measure, the three groups (Liq_A, Liq_B & Liq_C) were pooled into a single group (Liq_Pool group) as they all received PCV free-liquid HRV vaccine, and as pre-specified in the protocol, the immunogenicity of the Liq_Pool group was compared to the currently licensed lyophilized HRV vaccine (Lyo_Control group) in terms of percentage of subjects with anti-RV IgA antibody concentrations ≥ 90 U/mL, 1-2 months after Dose 2 |
| Time Frame | At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the PPS for immunogenicity that included all subjects who received both doses of study vaccine and for whom the liquid HRV vaccine or control vaccine was administered according to protocol and for whom immunogenicity data were available at the post-vaccination sampling time point. |
| Arm/Group Title | Liq_Pool Group | Lyo Control Group |
|---|---|---|
| Arm/Group Description | Subjects who received two doses of PCV-free HRV liquid formulation of pooled lot A, B and C at 6 and 12 weeks of age. | Subjects who received two doses of currently licensed lyophilised HRV vaccine, at 6 and 12 weeks of age. |
| Measure Participants | 984 | 329 |
| Number (95% Confidence Interval) [Percentage of subjects] |
63.0
|
62.3
|
| Title | Percentage of Subjects With Anti-RV IgA Concentrations (Individual HRV Liquid Groups) |
|---|---|
| Description | Antibody concentrations ≥90 U/mL were determined and expressed as GMCs, assessed for the individual HRV liquid groups and Control Group. The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations. The analysis was performed to assess the immunogenicity of the PCV-free liquid HRV vaccine (pooled HRV liquid groups) and the currently licensed lyophilised HRV vaccine, in terms of percentage of subjects with anti-RV IgA antibody concentrations ≥ 90 U/mL 1-2 months after Dose 2. |
| Time Frame | At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the PPS for immunogenicity that included all subjects who received both doses of study vaccine and for whom the liquid HRV vaccine or control vaccine was administered according to protocol and for whom immunogenicity data were available at the post-vaccination sampling time point. |
| Arm/Group Title | Liq_A Group | Liq_B Group | Liq_C Group | Lyo Control Group |
|---|---|---|---|---|
| Arm/Group Description | Subjects who received two doses of PCV-free HRV liquid formulation of lot A at 6 and 12 weeks of age. | Subjects who received two doses of PCV-free HRV liquid formulation of lot B at 6 and 12 weeks of age. | Subjects who received two doses of PCV-free HRV liquid formulation of lot C at 6 and 12 weeks of age. | Subjects who received two doses of currently licensed lyophilised HRV vaccine, at 6 and 12 weeks of age. |
| Measure Participants | 322 | 326 | 326 | 329 |
| Number (95% Confidence Interval) [Percentage of subjects] |
62.7
|
61.0
|
65.3
|
62.3
|
| Title | Number of Subjects With Any Solicited General Adverse Events (AEs). |
|---|---|
| Description | Assessed solicited general AEs were cough/runny nose, diarrhea, fever (defined as temperature ≥ 38.0°C), irritability/fussiness, loss of appetite and vomiting. Any solicited general AE is defined as any occurrence of the specified symptom, irrespective of intensity grade and relationship to vaccination. |
| Time Frame | During the 8 days (Day 1 to Day 8) follow-up period after each dose of HRV vaccine |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on the Exposed Set (ES). The ES included all subjects with at least one study vaccine administration documented. A safety analysis based on the ES included all vaccinated subjects. |
| Arm/Group Title | Liq_A Group | Liq_B Group | Liq_C Group | Lyo Control Group |
|---|---|---|---|---|
| Arm/Group Description | Subjects who received two doses of PCV-free HRV liquid formulation of lot A at 6 and 12 weeks of age. | Subjects who received two doses of PCV-free HRV liquid formulation of lot B at 6 and 12 weeks of age. | Subjects who received two doses of PCV-free HRV liquid formulation of lot C at 6 and 12 weeks of age. | Subjects who received two doses of currently licensed lyophilised HRV vaccine, at 6 and 12 weeks of age. |
| Measure Participants | 400 | 396 | 402 | 402 |
| Any - Cough / Runny Nose - Dose 1 |
93
23.3%
|
91
23%
|
94
23.4%
|
102
25.4%
|
| Any - Cough / Runny Nose - Dose 2 |
114
28.5%
|
100
25.3%
|
94
23.4%
|
109
27.1%
|
| Any - Diarrhea - Dose 1 |
14
3.5%
|
13
3.3%
|
8
2%
|
10
2.5%
|
| Any - Diarrhea - Dose 2 |
7
1.8%
|
12
3%
|
8
2%
|
11
2.7%
|
| Any - Fever (≥ 38.0°C) - Dose 1 |
24
6%
|
22
5.6%
|
20
5%
|
23
5.7%
|
| Any - Fever (≥ 38.0°C) - Dose 2 |
36
9%
|
36
9.1%
|
34
8.5%
|
32
8%
|
| Any - Irritability / Fussiness - Dose 1 |
226
56.5%
|
214
54%
|
209
52%
|
216
53.7%
|
| Any - Irritability / Fussiness - Dose 2 |
191
47.8%
|
189
47.7%
|
194
48.3%
|
194
48.3%
|
| Any - Loss of appetite - Dose 1 |
97
24.3%
|
93
23.5%
|
99
24.6%
|
96
23.9%
|
| Any - Loss of appetite - Dose 2 |
92
23%
|
84
21.2%
|
78
19.4%
|
94
23.4%
|
| Any - Vomiting - Dose 1 |
39
9.8%
|
51
12.9%
|
38
9.5%
|
42
10.4%
|
| Any - Vomiting - Dose 2 |
25
6.3%
|
28
7.1%
|
31
7.7%
|
34
8.5%
|
| Title | Number of Subjects With Any Unsolicited AEs. |
|---|---|
| Description | An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any is defined as the occurrence of any unsolicited AE irrespective of its intensity grade and relationship to vaccination. |
| Time Frame | During the 31 day (Day 1 to Day 31) follow-up period after HRV vaccination across doses |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on the Exposed set (ES). The ES included all subjects with at least one study vaccine administration documented. A safety analysis based on the ES included all vaccinated subjects. |
| Arm/Group Title | Liq_A Group | Liq_B Group | Liq_C Group | Lyo Control Group |
|---|---|---|---|---|
| Arm/Group Description | Subjects who received two doses of PCV-free HRV liquid formulation of lot A at 6 and 12 weeks of age. | Subjects who received two doses of PCV-free HRV liquid formulation of lot B at 6 and 12 weeks of age. | Subjects who received two doses of PCV-free HRV liquid formulation of lot C at 6 and 12 weeks of age. | Subjects who received two doses of currently licensed lyophilised HRV vaccine, at 6 and 12 weeks of age. |
| Measure Participants | 400 | 396 | 402 | 402 |
| Count of Participants [Participants] |
183
45.8%
|
189
47.7%
|
200
49.8%
|
184
45.8%
|
| Title | Number of Subjects With Any Serious Adverse Events (SAEs) |
|---|---|
| Description | SAEs assessed include any untoward medical occurrence that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization or resulted in disability/incapacity. |
| Time Frame | During the entire study period (Day 1 to Month 7-8) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on the Exposed set (ES). The ES included all subjects with at least one study vaccine administration documented. A safety analysis based on the ES included all vaccinated subjects. |
| Arm/Group Title | Liq_A Group | Liq_B Group | Liq_C Group | Lyo Control Group |
|---|---|---|---|---|
| Arm/Group Description | Subjects who received two doses of PCV-free HRV liquid formulation of lot A at 6 and 12 weeks of age. | Subjects who received two doses of PCV-free HRV liquid formulation of lot B at 6 and 12 weeks of age. | Subjects who received two doses of PCV-free HRV liquid formulation of lot C at 6 and 12 weeks of age. | Subjects who received two doses of currently licensed lyophilised HRV vaccine, at 6 and 12 weeks of age. |
| Measure Participants | 400 | 396 | 402 | 402 |
| Count of Participants [Participants] |
21
5.3%
|
18
4.5%
|
21
5.2%
|
18
4.5%
|
Adverse Events
| Time Frame | Solicited AEs: During the 8 days (Day 1 to Day 8) follow-up period after each vaccination. Unsolicited AEs: During the 31 days (Day 1 to Day 31) follow-up period after vaccination. SAEs: Throughout the study period (Day 1 to Month 7-8). | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Liq_A Group | Liq_B Group | Liq_C Group | Lyo Control Group | ||||
| Arm/Group Description | Subjects who received two doses of PCV-free HRV liquid formulation of lot A at 6 and 12 weeks of age. | Subjects who received two doses of PCV-free HRV liquid formulation of lot B at 6 and 12 weeks of age. | Subjects who received two doses of PCV-free HRV liquid formulation of lot C at 6 and 12 weeks of age. | Subjects who received two doses of currently licensed lyophilised HRV vaccine, at 6 and 12 weeks of age. | ||||
All Cause Mortality |
||||||||
| Liq_A Group | Liq_B Group | Liq_C Group | Lyo Control Group | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/400 (0%) | 0/396 (0%) | 0/402 (0%) | 0/402 (0%) | ||||
Serious Adverse Events |
||||||||
| Liq_A Group | Liq_B Group | Liq_C Group | Lyo Control Group | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 21/400 (5.3%) | 18/396 (4.5%) | 21/402 (5.2%) | 18/402 (4.5%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Leukocytosis | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Lymphadenitis | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Allergic gastroenteritis | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Gastrooesophageal reflux disease | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Infantile colic | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Intussusception | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Vomiting | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| General disorders | ||||||||
| Pyrexia | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Immune system disorders | ||||||||
| Milk allergy | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Infections and infestations | ||||||||
| Abscess jaw | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Acute sinusitis | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Bronchiolitis | 4/400 (1%) | 4 | 3/396 (0.8%) | 3 | 3/402 (0.7%) | 4 | 3/402 (0.7%) | 3 |
| Bronchitis | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 2/402 (0.5%) | 2 | 2/402 (0.5%) | 2 |
| Conjunctivitis | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Encephalitis enteroviral | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Gastroenteritis | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 1/402 (0.2%) | 1 |
| Gastroenteritis viral | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Influenza | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Meningitis haemophilus | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Metapneumovirus infection | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Myelitis | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Otitis media | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Otitis media acute | 1/400 (0.3%) | 1 | 3/396 (0.8%) | 3 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Otitis media chronic | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Pharyngitis | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Pneumococcal sepsis | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Pneumonia | 1/400 (0.3%) | 1 | 1/396 (0.3%) | 1 | 1/402 (0.2%) | 1 | 1/402 (0.2%) | 1 |
| Pneumonia pneumococcal | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Pneumonia respiratory syncytial viral | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Pyelonephritis acute | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Respiratory syncytial virus bronchiolitis | 6/400 (1.5%) | 6 | 6/396 (1.5%) | 6 | 3/402 (0.7%) | 3 | 2/402 (0.5%) | 2 |
| Respiratory syncytial virus bronchitis | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Respiratory syncytial virus infection | 1/400 (0.3%) | 1 | 2/396 (0.5%) | 2 | 1/402 (0.2%) | 1 | 2/402 (0.5%) | 2 |
| Staphylococcal abscess | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Urinary tract infection | 1/400 (0.3%) | 2 | 0/396 (0%) | 0 | 3/402 (0.7%) | 3 | 2/402 (0.5%) | 2 |
| Viral infection | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Vulval abscess | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Concussion | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 2/402 (0.5%) | 2 | 0/402 (0%) | 0 |
| Hyponatraemia | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Haemangioma | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Metastases to liver | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Neuroblastoma | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Nervous system disorders | ||||||||
| Infantile spasms | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Seizure | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Subdural hygroma | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Bronchospasm | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Hypoxia | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Respiratory distress | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Eczema | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 3 | 0/402 (0%) | 0 |
| Seborrhoeic dermatitis | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| Liq_A Group | Liq_B Group | Liq_C Group | Lyo Control Group | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 333/400 (83.3%) | 242/396 (61.1%) | 338/402 (84.1%) | 338/402 (84.1%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Lymphadenopathy | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Cardiac disorders | ||||||||
| Arrhythmia | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||||||
| Ankyloglossia congenital | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Brachycephaly | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Craniosynostosis | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Developmental hip dysplasia | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 2/402 (0.5%) | 2 |
| Gray matter heterotopia | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Hydrocele | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Plagiocephaly | 2/400 (0.5%) | 2 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Trisomy 21 | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||
| Cerumen impaction | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Eye disorders | ||||||||
| Blepharitis | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Conjunctival haemorrhage | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Dacryostenosis acquired | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Eye allergy | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Eye discharge | 1/400 (0.3%) | 1 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Lacrimation increased | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Ocular hyperaemia | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Abdominal discomfort | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Abdominal pain | 6/400 (1.5%) | 7 | 3/396 (0.8%) | 3 | 5/402 (1.2%) | 5 | 7/402 (1.7%) | 7 |
| Abdominal pain upper | 3/400 (0.8%) | 4 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Abnormal faeces | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Aerophagia | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Anal fissure | 1/400 (0.3%) | 1 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Constipation | 6/400 (1.5%) | 8 | 10/396 (2.5%) | 10 | 4/402 (1%) | 5 | 8/402 (2%) | 9 |
| Diarrhoea | 38/400 (9.5%) | 57 | 25/396 (6.3%) | 25 | 31/402 (7.7%) | 45 | 44/402 (10.9%) | 59 |
| Enteritis | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Epigastric discomfort | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Eructation | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Flatulence | 5/400 (1.3%) | 7 | 3/396 (0.8%) | 3 | 4/402 (1%) | 5 | 8/402 (2%) | 9 |
| Gastrooesophageal reflux disease | 10/400 (2.5%) | 10 | 9/396 (2.3%) | 9 | 4/402 (1%) | 4 | 11/402 (2.7%) | 11 |
| Haematochezia | 2/400 (0.5%) | 2 | 0/396 (0%) | 0 | 3/402 (0.7%) | 3 | 3/402 (0.7%) | 3 |
| Infantile colic | 2/400 (0.5%) | 2 | 2/396 (0.5%) | 2 | 2/402 (0.5%) | 2 | 0/402 (0%) | 0 |
| Mucous stools | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Perianal erythema | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Post-tussive vomiting | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Regurgitation | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 2/402 (0.5%) | 2 | 3/402 (0.7%) | 3 |
| Salivary hypersecretion | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Teething | 1/400 (0.3%) | 1 | 4/396 (1%) | 4 | 3/402 (0.7%) | 3 | 2/402 (0.5%) | 2 |
| Vomiting | 7/400 (1.8%) | 7 | 6/396 (1.5%) | 6 | 3/402 (0.7%) | 3 | 2/402 (0.5%) | 2 |
| General disorders | ||||||||
| Crying | 0/400 (0%) | 0 | 2/396 (0.5%) | 2 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Discomfort | 0/400 (0%) | 0 | 2/396 (0.5%) | 2 | 1/402 (0.2%) | 1 | 2/402 (0.5%) | 2 |
| Fatigue | 1/400 (0.3%) | 1 | 2/396 (0.5%) | 2 | 1/402 (0.2%) | 1 | 2/402 (0.5%) | 2 |
| Injection site induration | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Injection site mass | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Injection site pain | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 2/402 (0.5%) | 2 | 1/402 (0.2%) | 1 |
| Injection site swelling | 1/400 (0.3%) | 1 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Pain | 1/400 (0.3%) | 1 | 3/396 (0.8%) | 3 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Pyrexia | 10/400 (2.5%) | 10 | 8/396 (2%) | 8 | 13/402 (3.2%) | 13 | 6/402 (1.5%) | 6 |
| Vaccination site discomfort | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Vaccination site pain | 3/400 (0.8%) | 3 | 1/396 (0.3%) | 1 | 1/402 (0.2%) | 2 | 4/402 (1%) | 4 |
| Immune system disorders | ||||||||
| Anaphylactic reaction | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Hypersensitivity | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 1/402 (0.2%) | 1 |
| Immunisation reaction | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 2/402 (0.5%) | 2 | 0/402 (0%) | 0 |
| Milk allergy | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 2/402 (0.5%) | 2 | 0/402 (0%) | 0 |
| Infections and infestations | ||||||||
| Acarodermatitis | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Acute sinusitis | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Anal abscess | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Anal candidiasis | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Bronchiolitis | 10/400 (2.5%) | 10 | 10/396 (2.5%) | 10 | 7/402 (1.7%) | 7 | 9/402 (2.2%) | 9 |
| Bronchitis | 5/400 (1.3%) | 5 | 4/396 (1%) | 4 | 6/402 (1.5%) | 6 | 4/402 (1%) | 4 |
| Bronchitis bacterial | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Candida infection | 1/400 (0.3%) | 1 | 3/396 (0.8%) | 3 | 1/402 (0.2%) | 1 | 1/402 (0.2%) | 1 |
| Conjunctivitis | 7/400 (1.8%) | 7 | 5/396 (1.3%) | 5 | 11/402 (2.7%) | 11 | 11/402 (2.7%) | 12 |
| Conjunctivitis bacterial | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Conjunctivitis viral | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Croup infectious | 2/400 (0.5%) | 2 | 2/396 (0.5%) | 2 | 1/402 (0.2%) | 1 | 1/402 (0.2%) | 1 |
| Ear infection | 1/400 (0.3%) | 1 | 3/396 (0.8%) | 3 | 3/402 (0.7%) | 3 | 1/402 (0.2%) | 1 |
| Fungal infection | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Fungal skin infection | 0/400 (0%) | 0 | 2/396 (0.5%) | 2 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Gastroenteritis | 9/400 (2.3%) | 9 | 6/396 (1.5%) | 6 | 3/402 (0.7%) | 5 | 3/402 (0.7%) | 5 |
| Hand-foot-and-mouth disease | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 2/402 (0.5%) | 2 |
| Herpangina | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Impetigo | 2/400 (0.5%) | 2 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 3/402 (0.7%) | 3 |
| Influenza | 4/400 (1%) | 4 | 4/396 (1%) | 4 | 2/402 (0.5%) | 2 | 6/402 (1.5%) | 6 |
| Laryngitis | 2/400 (0.5%) | 2 | 1/396 (0.3%) | 1 | 2/402 (0.5%) | 2 | 1/402 (0.2%) | 1 |
| Lower respiratory tract infection | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Nasopharyngitis | 24/400 (6%) | 25 | 25/396 (6.3%) | 25 | 36/402 (9%) | 40 | 29/402 (7.2%) | 37 |
| Oral candidiasis | 3/400 (0.8%) | 3 | 2/396 (0.5%) | 2 | 3/402 (0.7%) | 3 | 8/402 (2%) | 8 |
| Oral fungal infection | 3/400 (0.8%) | 3 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 1/402 (0.2%) | 1 |
| Oral herpes | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Otitis media | 2/400 (0.5%) | 2 | 5/396 (1.3%) | 5 | 4/402 (1%) | 4 | 2/402 (0.5%) | 2 |
| Otitis media acute | 2/400 (0.5%) | 2 | 3/396 (0.8%) | 3 | 1/402 (0.2%) | 1 | 5/402 (1.2%) | 5 |
| Paronychia | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Pharyngitis | 1/400 (0.3%) | 1 | 2/396 (0.5%) | 2 | 3/402 (0.7%) | 3 | 1/402 (0.2%) | 1 |
| Pneumonia | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 1/402 (0.2%) | 1 | 1/402 (0.2%) | 1 |
| Respiratory syncytial virus bronchiolitis | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Respiratory syncytial virus infection | 0/400 (0%) | 0 | 2/396 (0.5%) | 2 | 1/402 (0.2%) | 1 | 2/402 (0.5%) | 2 |
| Respiratory tract infection | 2/400 (0.5%) | 3 | 8/396 (2%) | 8 | 4/402 (1%) | 4 | 8/402 (2%) | 9 |
| Respiratory tract infection viral | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Rhinitis | 3/400 (0.8%) | 5 | 7/396 (1.8%) | 7 | 6/402 (1.5%) | 6 | 6/402 (1.5%) | 6 |
| Skin bacterial infection | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Streptococcal infection | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Subglottic laryngitis | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Tonsillitis | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 2/402 (0.5%) | 2 | 0/402 (0%) | 0 |
| Tracheobronchitis | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Upper respiratory tract infection | 31/400 (7.8%) | 33 | 34/396 (8.6%) | 34 | 31/402 (7.7%) | 36 | 30/402 (7.5%) | 32 |
| Urinary tract infection | 0/400 (0%) | 0 | 2/396 (0.5%) | 2 | 2/402 (0.5%) | 2 | 2/402 (0.5%) | 2 |
| Viral infection | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 1/402 (0.2%) | 1 | 1/402 (0.2%) | 1 |
| Viral rash | 2/400 (0.5%) | 2 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Viral upper respiratory tract infection | 3/400 (0.8%) | 3 | 3/396 (0.8%) | 3 | 2/402 (0.5%) | 2 | 1/402 (0.2%) | 1 |
| Vulvovaginal candidiasis | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Injury, poisoning and procedural complications | ||||||||
| Arthropod bite | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Arthropod sting | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Contusion | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 2/402 (0.5%) | 2 | 1/402 (0.2%) | 1 |
| Fall | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Head injury | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Sunburn | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Vaccination complication | 4/400 (1%) | 4 | 3/396 (0.8%) | 3 | 3/402 (0.7%) | 4 | 6/402 (1.5%) | 6 |
| Investigations | ||||||||
| Body temperature increased | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 1/402 (0.2%) | 1 |
| Metabolism and nutrition disorders | ||||||||
| Abnormal weight gain | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Appetite disorder | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Decreased appetite | 145/400 (36.3%) | 192 | 0/396 (0%) | 0 | 139/402 (34.6%) | 177 | 141/402 (35.1%) | 191 |
| Feeding disorder | 2/400 (0.5%) | 2 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 2/402 (0.5%) | 2 |
| Lactose intolerance | 0/400 (0%) | 0 | 2/396 (0.5%) | 2 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Malnutrition | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Poor feeding infant | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Underweight | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Weight gain poor | 2/400 (0.5%) | 2 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Acquired plagiocephaly | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Head deformity | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Musculoskeletal stiffness | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Pain in extremity | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Torticollis | 2/400 (0.5%) | 2 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Nervous system disorders | ||||||||
| Depressed level of consciousness | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Drooling | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Febrile convulsion | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Seizure | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Somnolence | 2/400 (0.5%) | 2 | 0/396 (0%) | 0 | 2/402 (0.5%) | 2 | 1/402 (0.2%) | 1 |
| Psychiatric disorders | ||||||||
| Agitation | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Insomnia | 2/400 (0.5%) | 2 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Irritability | 276/400 (69%) | 426 | 5/396 (1.3%) | 5 | 264/402 (65.7%) | 408 | 261/402 (64.9%) | 419 |
| Merycism | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Selective eating disorder | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Crystalluria | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||
| Balanoposthitis | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Penile adhesion | 2/400 (0.5%) | 2 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Asthma | 2/400 (0.5%) | 2 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Catarrh | 0/400 (0%) | 0 | 2/396 (0.5%) | 2 | 1/402 (0.2%) | 1 | 2/402 (0.5%) | 3 |
| Cough | 165/400 (41.3%) | 213 | 6/396 (1.5%) | 6 | 152/402 (37.8%) | 198 | 163/402 (40.5%) | 214 |
| Dysphonia | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Nasal congestion | 2/400 (0.5%) | 2 | 6/396 (1.5%) | 6 | 2/402 (0.5%) | 2 | 5/402 (1.2%) | 5 |
| Nasal obstruction | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Oropharyngeal pain | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 1/402 (0.2%) | 1 |
| Respiratory disorder | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Respiratory tract congestion | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Rhinitis allergic | 1/400 (0.3%) | 1 | 1/396 (0.3%) | 1 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Rhinorrhoea | 2/400 (0.5%) | 2 | 2/396 (0.5%) | 2 | 6/402 (1.5%) | 6 | 2/402 (0.5%) | 3 |
| Upper respiratory tract inflammation | 1/400 (0.3%) | 2 | 3/396 (0.8%) | 3 | 1/402 (0.2%) | 1 | 3/402 (0.7%) | 3 |
| Wheezing | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 1/402 (0.2%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||
| Acne infantile | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Asteatosis | 1/400 (0.3%) | 1 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Blister | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Dermatitis | 6/400 (1.5%) | 6 | 3/396 (0.8%) | 3 | 3/402 (0.7%) | 3 | 4/402 (1%) | 4 |
| Dermatitis atopic | 2/400 (0.5%) | 2 | 2/396 (0.5%) | 2 | 9/402 (2.2%) | 9 | 4/402 (1%) | 4 |
| Dermatitis contact | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Dermatitis diaper | 4/400 (1%) | 4 | 6/396 (1.5%) | 6 | 8/402 (2%) | 10 | 6/402 (1.5%) | 6 |
| Eczema | 9/400 (2.3%) | 10 | 3/396 (0.8%) | 3 | 8/402 (2%) | 8 | 7/402 (1.7%) | 8 |
| Eczema asteatotic | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Eczema infantile | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 1/402 (0.2%) | 1 | 2/402 (0.5%) | 2 |
| Erythema | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Hyperhidrosis | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Ingrowing nail | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Intertrigo | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Mechanical urticaria | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Miliaria | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
| Perioral dermatitis | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 2 | 0/402 (0%) | 0 |
| Petechiae | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Rash | 3/400 (0.8%) | 3 | 2/396 (0.5%) | 2 | 1/402 (0.2%) | 1 | 4/402 (1%) | 4 |
| Rash generalised | 0/400 (0%) | 0 | 0/396 (0%) | 0 | 1/402 (0.2%) | 1 | 0/402 (0%) | 0 |
| Rash maculo-papular | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Seborrhoea | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 2/402 (0.5%) | 2 | 1/402 (0.2%) | 1 |
| Seborrhoeic dermatitis | 3/400 (0.8%) | 3 | 3/396 (0.8%) | 3 | 1/402 (0.2%) | 1 | 1/402 (0.2%) | 1 |
| Skin lesion | 0/400 (0%) | 0 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 0/402 (0%) | 0 |
| Urticaria | 1/400 (0.3%) | 1 | 1/396 (0.3%) | 1 | 0/402 (0%) | 0 | 1/402 (0.2%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | GSK Response Center |
|---|---|
| Organization | GlaxoSmithKline |
| Phone | 866-435-7343 |
| GSKClinicalSupportHD@gsk.com |
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02914184
Other Study ID Numbers:
- 115461
- 2016-000598-19
First Posted:
Sep 26, 2016
Last Update Posted:
Jul 21, 2020
Last Verified:
Jul 1, 2020