Safety and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Meningococcal B Recombinant Vaccine When Administered Concomitantly With Routine Vaccines to Healthy Infants of 2 Months of Age and Older, in Taiwan.
Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT02173704
Collaborator
Novartis Vaccines (Industry)
225
2
2
21.2
112.5
5.3
Study Details
Study Description
Brief Summary
Assess the safety and immunogenicity of a 3-dose schedule (at 2, 4, 6 months) of GSK Biologicals' Meningococcal B recombinant vaccine followed by a booster at 12 months when concomitantly administered with routine vaccines in healthy infants in Taiwan.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
225 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
A Phase 3, Open Label, Randomized, Controlled, Multi-Center Study to Evaluate the Safety and Immunogenicity of GSK Biologicals' Meningococcal B Recombinant Vaccine When Administered Concomitantly With Routine Vaccines to Healthy Infants in Taiwan.
Actual Study Start Date
:
Sep 11, 2014
Actual Primary Completion Date
:
Dec 25, 2015
Actual Study Completion Date
:
Jun 17, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Bexsero + Routine Group Subjects received three doses of Bexsero® vaccine at 2, 4, 6 months followed by a booster dose at 12 months, concomitantly administered with routine vaccines (i.e. combined Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® at 6 months of age; Priorix® and Varilrix® at 12 months of age. |
Biological: Bexsero®
Four doses administered in the anterolateral area of the right or left thigh.
|
| Active Comparator: Routine Group Subjects received routine vaccines Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® vaccine at 6 months; Priorix® and Varilrix® vaccines at 12 months of age. |
Biological: Routine vaccines
Infanrix-IPV + Hib®, Prevenar-13®, Engerix-B®, Priorix® and Varilrix® administered in the anterolateral area of the right or left thigh.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Subjects With Human Serum Bactericidal Activity (hSBA) Titer ≥ 1:5 Against Neisseria Meningitidis Serogroup B Strains [At Day 1 and at one month after the third vaccination (Day 152)]
Percentage of subjects with hSBA titer ≥ 1:5 at 1 month following the third vaccination (at 7 months of age) against the indicator strains H44/76, 5/99, NZ98/254 and strain M10713 when Bexsero® was given concomitantly with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13® and Engerix-B®).
- Percentage of Subjects With Human Serum Bactericidal Assay (hSBA) Titer ≥ 1:4 Against Neisseria Meningitidis Serogroup B Strains [At Day 1 and at one month after third vaccination (Day 152)]
Percentage of subjects with hSBA titer ≥ 1:4 at 1 month after third vaccination (at 7 months of age) against the indicator strains H44/76, 5/99, NZ98/254 and strain M10713 when Bexsero® was given concomitantly with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13® and Engerix-B®).
Secondary Outcome Measures
- Percentage of Subjects With hSBA Titer ≥ 1:5 Against Neisseria Meningitidis Serogroup B, When Bexsero® Booster Was Given With Routine Vaccines (Priorix® + Varilrix® Vaccines) [At Day 305 and Day 335]
Percentage of subjects with hSBA titer ≥ 1:5 before booster vaccination and after booster vaccination when Bexsero® booster dose was given with routine vaccines (Priorix® + Varilrix® vaccine) as compared to when only routine vaccines were administered.
- hSBA Geometric Mean Titers (GMTs) Against Neisseria Meningitidis Serogroup B Indicator Strains, When Bexsero® Vaccine Was Given With Routine Vaccines [At Day 1, Day 152, Day 305 and Day 335]
hSBA GMTs against the indicator strains H44/76, 5/99, NZ98/254 and strain M10713 was evaluated at baseline (2 months of age, Day 1), 1 month after the third vaccination with Bexsero® with concomitant routine vaccines (Infanrix-IPV+Hib®, Prevenar-13®, Engerix®) (7 months of age, Day 152) or prior to the booster dose of Bexsero® with routine vaccines (Priorix®, Varilrix®) (12 months of age, Day 305) and 1 month after the booster dose (13 months of age, Day 335), as compared to when only routine vaccines were administered.
- hSBA Geometric Mean Ratios (GMRs) Against Neisseria Meningitidis Serogroup B Strains. [At Day 1, Day 152, Day 305 and Day 335]
GMRs of post-vaccination versus pre-vaccination of hSBA titer against the indicator strains H44/76, 5/99, NZ98/254 and strain M10713 were evaluated at one month after the third vaccination with Bexsero® vaccine and concomitant routine vaccines (Infanrix-IPV+Hib®, Prevenar-13® and Engerix®) (Day 152) compared to baseline (Day 1) or at one month after the booster dose of Bexsero® vaccine with routine vaccines (Priorix®, Varilrix®) (Day 335) compared to prior to the booster dose (Day 305).
- Percentages of Subjects With hSBA Titers ≥1:8 Against Neisseria Meningitidis Serogroup B, When Bexsero® Vaccine Was Given With Routine Vaccines [At Day 1,Day 152,Day 305, Day 335]
Percentages of subjects with hSBA titers ≥1:8 against N.meningitidis serogroup B strains, at one month after concomitant administration of third primary dose of Bexsero® with routine vaccines [Infanrix-IPV + Hib®, Prevenar-13® and Engerix-B®] and at one month after concomitant administration of Bexsero® booster dose with routine vaccines [Priorix® and Varilrix® vaccine],as compared to when only routine vaccines were administered.
- Number of Subjects Reporting Solicited Local Adverse Events (AEs) After Receiving Bexsero® Vaccine With Routine Vaccine or Routine Vaccines Alone, at 2, 4, 6 and 12 Months of Age. [From day 1 (6 hours) to day 7 after each vaccination (1st, 2nd, 3rd and 4th vaccination)]
Number of subjects reporting solicited local AEs following concomitant administration of Bexsero® vaccine with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13® and Engerix-B® at 2, 4 and 6 months of age and Priorix® and Varilrix® at 12 months of age)compared to when only routine vaccines were administered alone at 2,4,6 and 12 months. Solicited local symptoms assessed were Erythema, Induration, Swelling and Tenderness.
- Number of Subjects Reporting Solicited Systemic Adverse Events (AEs) After Receiving Bexsero® Vaccine With Routine Vaccine or Routine Vaccines Alone, at 2, 4, 6 and 12 Months of Age. [From day 1 (6 hours) to day 7 after each vaccination]
Number of subjects reporting solicited systemic AEs following concomitant administration of Bexsero® vaccine with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13® and Engerix-B® at 2, 4 and 6 months of age and Priorix® and Varilrix® at 12 months of age) compared to when only routine vaccines were alone, at 2, 4, 6 and 12 months. Systemic solicited symptoms assessed were Change in Eating Habits, Diarrhea, Irritability, Persistent Crying, Rash, Sleepiness, Vomiting and Fever (body temperature ≥ 38.0 °C)
- Number of Subjects Reporting Solicited Systemic AEs After Receiving Priorix® and Varilrix® Routine Vaccines (With and Without Bexsero® Vaccine) at 12 Months of Age. [From Day 1 to Day 28 after vaccination]
Number of subjects who reported solicited systemic AEs reported after the administration of Varilrix® and Priorix® vaccines (with and without Bexsero® vaccine) at 12 months of age. Solicited systemic AEs assessed were Rash, Lymphadenopathy and Fever. This analysis was conducted for a prolonged period of 28 Days following Varilrix® and Priorix® administration.
- Number of Subjects Reporting Unsolicited Adverse Events After Receiving Bexsero® Vaccination With Routine Vaccines [From day 1 to day 7 after each vaccination]
Number of subjects reporting any unsolicited AEs following concomitant administration of Bexsero® vaccine with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13®, Engerix-B® or Priorix® and Varilrix®) compared to when only routine vaccines were administered alone.
- Number of Subjects Reporting Serious Adverse Events (SAEs), Medically Attended AEs (MAEs) and AEs Leading to Premature Withdrawal and Death and AEs Leading to Hospitalization. [Throughout the study period (Day 1 to Day 335)]
Number of subjects reporting SAEs, medically attended AEs and AEs leading to premature withdrawal from the study and leading to death and AEs leading to hospitalization following concomitant administration of Bexsero® vaccine with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13®, Engerix-B®, Priorix® and Varilrix®) compared to when only routine vaccines were administered alone. SAEs assessed included medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Possibly or probably related SAE were SAEs assessed by the investigator as related to the vaccination. Medically attended AEs were events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason.
Eligibility Criteria
Criteria
Ages Eligible for Study:
55 Days
to 89 Days
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
healthy 2-month old infants (55-89 days, inclusive), who were born after full term pregnancy with an estimated gestational age ≥ 37 weeks and a birth weight ≥ 2.5 kg;
-
for whom a parent/legal guardian has given written informed consent after the nature of the study has been explained;
-
available for all the visits scheduled in the study;
-
in good health as determined by medical history, physical examination and clinical judgment of the investigator.
Exclusion Criteria:
-
History of any meningococcal vaccine administration;
-
Prior vaccination with any Diphtheria, Tetanus, Pertussis (acellular or whole cell), Polio (either Inactivated or Oral), Haemophilus influenzae type b (Hib), Pneumococcal, MMR or varicella antigens;
-
Previous ascertained or suspected disease caused by N. meningitidis;
-
Household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis;
-
History of severe allergic reaction after previous vaccinations or hypersensitivity to any vaccine component;
-
Significant acute or chronic infection within the previous 7 days or body temperature higher or equal to 38C degrees within the previous day;
-
Antibiotics within 6 days prior to enrollment;
-
Any serious chronic or progressive disease according to the judgment of the investigator (e.g., neoplasm, insulin dependent diabetes mellitus Type I, cardiac disease, hepatic disease, progressive neurological disease or seizure, either associated with fever or as part of an underlying neurological disorder or syndrome, autoimmune disease, HIV infection or AIDS, or blood dyscrasias or diathesis, signs of cardiac or renal failure or severe malnutrition);
-
Known or suspected impairment/alteration of the immune system, immunosuppressive therapy, use of systemic corticosteroids or chronic use of inhaled high-potency corticosteroids since birth;
-
Receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation;
-
Receipt of, or intent to immunize with any other vaccine(s) (with the exception of rotavirus vaccine, influenza vaccine and second HepB vaccine), within 28 days prior and throughout the study period. Furthermore, subjects must have received HepB vaccine preferably at 0, 1 month of age, with the second dose at least 14 days prior to study vaccination. Influenza vaccine should be administered at least 14 days before or 14 days after study vaccination; Rotavirus vaccine may be administered during the study as per local practice.
-
Participation in another clinical trial since birth or planned for during study;
-
Family members and household members of research staff;
-
Any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | Taipei | Taiwan | 10041 | |
| 2 | GSK Investigational Site | Taipei | Taiwan | 10449 |
Sponsors and Collaborators
- GlaxoSmithKline
- Novartis Vaccines
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02173704
Other Study ID Numbers:
- 205249
- V72_60
- 2014-005568-14
First Posted:
Jun 25, 2014
Last Update Posted:
Aug 25, 2020
Last Verified:
Aug 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by GlaxoSmithKline
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Subjects were recruited from 2 sites in Taiwan |
|---|---|
| Pre-assignment Detail | All subjects were enrolled |
| Arm/Group Title | Bexsero + Routine Group | Routine Group |
|---|---|---|
| Arm/Group Description | Subjects received three doses of Bexsero® vaccine at 2, 4, 6 months followed by a booster dose at 12 months, concomitantly administered with routine vaccines (i.e. combined Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® at 6 months of age; Priorix® and Varilrix® at 12 months of age. | Subjects received routine vaccines Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® vaccine at 6 months; Priorix® and Varilrix® vaccines at 12 months of age. |
| Period Title: Overall Study | ||
| STARTED | 150 | 75 |
| COMPLETED | 137 | 71 |
| NOT COMPLETED | 13 | 4 |
Baseline Characteristics
| Arm/Group Title | Bexsero + Routine Group | Routine Group | Total |
|---|---|---|---|
| Arm/Group Description | Subjects received three doses of Bexsero® vaccine at 2, 4, 6 months followed by a booster dose at 12 months, concomitantly administered with routine vaccines (i.e. combined Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® at 6 months of age; Priorix® and Varilrix® at 12 months of age. | Subjects received routine vaccines Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® vaccine at 6 months; Priorix® and Varilrix® vaccines at 12 months of age. | Total of all reporting groups |
| Overall Participants | 150 | 75 | 225 |
| Age (Days) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Days] |
67.9
(6.46)
|
68.9
(6.86)
|
68.3
(6.60)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
82
54.7%
|
27
36%
|
109
48.4%
|
| Male |
68
45.3%
|
48
64%
|
116
51.6%
|
Outcome Measures
| Title | Percentage of Subjects With Human Serum Bactericidal Activity (hSBA) Titer ≥ 1:5 Against Neisseria Meningitidis Serogroup B Strains |
|---|---|
| Description | Percentage of subjects with hSBA titer ≥ 1:5 at 1 month following the third vaccination (at 7 months of age) against the indicator strains H44/76, 5/99, NZ98/254 and strain M10713 when Bexsero® was given concomitantly with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13® and Engerix-B®). |
| Time Frame | At Day 1 and at one month after the third vaccination (Day 152) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on Full Analysis Population (FAS) population day 152, which included all subjects in the exposed set who received at least one dose of a study vaccination and provided immunogenicity data at relevant time points. |
| Arm/Group Title | Bexsero + Routine Group | Routine Group |
|---|---|---|
| Arm/Group Description | Subjects received three doses of Bexsero® vaccine at 2, 4, 6 months followed by a booster dose at 12 months, concomitantly administered with routine vaccines (i.e. combined Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® at 6 months of age; Priorix® and Varilrix® at 12 months of age. | Subjects received routine vaccines Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® vaccine at 6 months; Priorix® and Varilrix® vaccines at 12 months of age. |
| Measure Participants | 135 | 71 |
| H44/76 strain [Day 1] |
0
|
0
|
| H44/76 strain [Day 152] |
100
|
0
|
| 5/99 strain [Day 1] |
1
|
1
|
| 5/99 strain [Day 152] |
100
|
0
|
| M10713 strain [Day 1] |
10
|
19
|
| M10713 strain [Day 152] |
59
|
8
|
| NZ98/254 strain [Day 1] |
0
|
0
|
| NZ98/254 strain [Day 152] |
79
|
0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bexsero + Routine Group, Routine Group |
|---|---|---|
| Comments | Statistical analysis 5/99 strain: The power to reject the null hypothesis associated with the primary objective for strain 5/99 was 99%. | |
| Type of Statistical Test | Non-Inferiority or Equivalence (legacy) | |
| Comments | Sufficiency: The criterion for a sufficient immune response was that the lower limit of the two-sided 95% CI for the percentage of subjects with hSBA titer ≥1:5 should be ≥ 70%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Single binomial proportion |
| Estimated Value | 100 | |
| Confidence Interval |
(2-Sided) 95% 97.2 to 100 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Bexsero + Routine Group, Routine Group |
|---|---|---|
| Comments | Statistical analysis NZ98/254 strain: The power to reject the null hypothesis associated with the primary objective for strain NZ98/25 was 94%. | |
| Type of Statistical Test | Non-Inferiority or Equivalence (legacy) | |
| Comments | Sufficiency: The criterion for a sufficient immune response was that the lower limit of the two-sided 95% CI for the percentage of subjects with hSBA titer ≥ 1:5 should be ≥ 70%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | single binomial proportion |
| Estimated Value | 79 | |
| Confidence Interval |
(2-Sided) 95% 71.4 to 85.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Subjects With Human Serum Bactericidal Assay (hSBA) Titer ≥ 1:4 Against Neisseria Meningitidis Serogroup B Strains |
|---|---|
| Description | Percentage of subjects with hSBA titer ≥ 1:4 at 1 month after third vaccination (at 7 months of age) against the indicator strains H44/76, 5/99, NZ98/254 and strain M10713 when Bexsero® was given concomitantly with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13® and Engerix-B®). |
| Time Frame | At Day 1 and at one month after third vaccination (Day 152) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on Full Analysis Set (FAS) population day 152. The FAS population included all subjects in the exposed set who received at least one dose of a study vaccination and provided immunogenicity data at relevant time points. |
| Arm/Group Title | Bexsero + Routine Group | Routine Group |
|---|---|---|
| Arm/Group Description | Subjects received three doses of Bexsero® vaccine at 2, 4, 6 months followed by a booster dose at 12 months, concomitantly administered with routine vaccines (i.e. combined Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® at 6 months of age; Priorix® and Varilrix® at 12 months of age. | Subjects received routine vaccines Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® vaccine at 6 months; Priorix® and Varilrix® vaccines at 12 months of age. |
| Measure Participants | 136 | 71 |
| H44/76 strain [Day 1] |
0
|
0
|
| H44/76 strain [Day 152] |
100
|
0
|
| 5/99 strain [Day 1] |
1
|
1
|
| 5/99 strain [Day 152] |
100
|
0
|
| M10713 strain [Day 1] |
11
|
25
|
| M10713 strain [Day 152] |
71
|
8
|
| NZ98/254 strain [Day 1] |
0
|
0
|
| NZ98/254 strain [Day 152] |
87
|
0
|
| Title | Percentage of Subjects With hSBA Titer ≥ 1:5 Against Neisseria Meningitidis Serogroup B, When Bexsero® Booster Was Given With Routine Vaccines (Priorix® + Varilrix® Vaccines) |
|---|---|
| Description | Percentage of subjects with hSBA titer ≥ 1:5 before booster vaccination and after booster vaccination when Bexsero® booster dose was given with routine vaccines (Priorix® + Varilrix® vaccine) as compared to when only routine vaccines were administered. |
| Time Frame | At Day 305 and Day 335 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on FAS population Day 335. The FAS population included all subjects in the exposed set who received at least one dose of a study vaccination and provided immunogenicity data at relevant time points. |
| Arm/Group Title | Bexsero + Routine Group | Routine Group |
|---|---|---|
| Arm/Group Description | Subjects received three doses of Bexsero® vaccine at 2, 4, 6 months followed by a booster dose at 12 months, concomitantly administered with routine vaccines (i.e. combined Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® at 6 months of age; Priorix® and Varilrix® at 12 months of age. | Subjects received routine vaccines Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® vaccine at 6 months; Priorix® and Varilrix® vaccines at 12 months of age. |
| Measure Participants | 136 | 71 |
| H44/76 strain [Day 305] |
81
|
2
|
| H44/76 strain [Day 335] |
99
|
2
|
| 5/99 strain [Day 305] |
99
|
1
|
| 5/99 strain [Day 335] |
99
|
0
|
| M10713 strain [Day 305] |
22
|
11
|
| M10713 strain [Day 335] |
92
|
13
|
| NZ98/254 strain [Day 305] |
17
|
1
|
| NZ98/254 strain [Day 335] |
94
|
0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bexsero + Routine Group, Routine Group |
|---|---|---|
| Comments | Statistical analysis H44/76 strain: The null hypothesis associated with the primary objective is that the proportion of subjects with hSBA titers ≥ 1:5 one month after the third dose of the Bexsero® vaccine was ≤ 0.70. Assuming the results for the three strains are independent, the power to reject the null hypothesis associated with the primary objectives to demonstrate sufficiency of response (for all three strains was 92%. | |
| Type of Statistical Test | Non-Inferiority or Equivalence (legacy) | |
| Comments | Sufficiency: The criterion for a sufficient immune response was that the lower limit of the two-sided 95% CI for the percentage of subjects with hSBA titer ≥1:5 should be ≥ 70%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Single binomial proportion |
| Estimated Value | 99 | |
| Confidence Interval |
(2-Sided) 95% 95.7 to 99.98 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Bexsero + Routine Group, Routine Group |
|---|---|---|
| Comments | Statistical analysis 5/99 strain: The power to reject the null hypothesis associated with the secondary objective for strain 5/99 was 99%. | |
| Type of Statistical Test | Non-Inferiority or Equivalence (legacy) | |
| Comments | Sufficiency: The criterion for a sufficient immune response was that the lower limit of the two-sided 95% CI for the percentage of subjects with hSBA titer ≥1:5 should be ≥ 75%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Single binomial proportion |
| Estimated Value | 99 | |
| Confidence Interval |
(2-Sided) 95% 94.7 to 99.82 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Bexsero + Routine Group, Routine Group |
|---|---|---|
| Comments | Statistical analysis NZ98/254 strain: The power to reject the null hypothesis associated with the secondary objective for strain NZ98/254 was 99%. | |
| Type of Statistical Test | Non-Inferiority or Equivalence (legacy) | |
| Comments | Sufficiency: The criterion for a sufficient immune response was that the lower limit of the two-sided 95% CI for the percentage of subjects with hSBA titer ≥1:5 should be ≥ 75%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Single binomial proportion |
| Estimated Value | 94 | |
| Confidence Interval |
(2-Sided) 95% 88.7 to 97.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | hSBA Geometric Mean Titers (GMTs) Against Neisseria Meningitidis Serogroup B Indicator Strains, When Bexsero® Vaccine Was Given With Routine Vaccines |
|---|---|
| Description | hSBA GMTs against the indicator strains H44/76, 5/99, NZ98/254 and strain M10713 was evaluated at baseline (2 months of age, Day 1), 1 month after the third vaccination with Bexsero® with concomitant routine vaccines (Infanrix-IPV+Hib®, Prevenar-13®, Engerix®) (7 months of age, Day 152) or prior to the booster dose of Bexsero® with routine vaccines (Priorix®, Varilrix®) (12 months of age, Day 305) and 1 month after the booster dose (13 months of age, Day 335), as compared to when only routine vaccines were administered. |
| Time Frame | At Day 1, Day 152, Day 305 and Day 335 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on the FAS population, which included all subjects in the exposed set who received at least one dose of a study vaccination and provided immunogenicity data at relevant time points. |
| Arm/Group Title | Bexsero + Routine Group | Routine Group |
|---|---|---|
| Arm/Group Description | Subjects received three doses of Bexsero® vaccine at 2, 4, 6 months followed by a booster dose at 12 months, concomitantly administered with routine vaccines (i.e. combined Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® at 6 months of age; Priorix® and Varilrix® at 12 months of age. | Subjects received routine vaccines Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® vaccine at 6 months; Priorix® and Varilrix® vaccines at 12 months of age. |
| Measure Participants | 145 | 73 |
| H44/76 strain [Day 1] |
1.01
|
1.02
|
| H44/76 strain [Day 152] |
72
|
1.01
|
| H44/76 strain [Day 305] |
11
|
1.26
|
| H44/76 strain [Day 335] |
157
|
1.1
|
| 5/99 strain [Day 1] |
1.08
|
1.03
|
| 5/99 strain [Day 152] |
963
|
1
|
| 5/99 strain [Day 305] |
205
|
1.1
|
| 5/99 strain [Day 335] |
2315
|
1
|
| M10713 strain [Day 1] |
1.36
|
1.75
|
| M10713 strain [Day 152] |
8.41
|
1.25
|
| M10713 strain [Day 305] |
2.18
|
1.6
|
| M10713 strain [Day 335] |
17
|
1.58
|
| NZ98/254 strain [Day 1] |
1.01
|
1
|
| NZ98/254 strain [Day 152] |
9.2
|
1.02
|
| NZ98/254 strain [Day 305] |
1.91
|
1.04
|
| NZ98/254 strain [Day 335] |
26
|
1
|
| Title | hSBA Geometric Mean Ratios (GMRs) Against Neisseria Meningitidis Serogroup B Strains. |
|---|---|
| Description | GMRs of post-vaccination versus pre-vaccination of hSBA titer against the indicator strains H44/76, 5/99, NZ98/254 and strain M10713 were evaluated at one month after the third vaccination with Bexsero® vaccine and concomitant routine vaccines (Infanrix-IPV+Hib®, Prevenar-13® and Engerix®) (Day 152) compared to baseline (Day 1) or at one month after the booster dose of Bexsero® vaccine with routine vaccines (Priorix®, Varilrix®) (Day 335) compared to prior to the booster dose (Day 305). |
| Time Frame | At Day 1, Day 152, Day 305 and Day 335 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on the FAS population, which included all subjects in the exposed set who received at least one dose of a study vaccination and provided immunogenicity data at relevant time points. |
| Arm/Group Title | Bexsero + Routine Group | Routine Group |
|---|---|---|
| Arm/Group Description | Subjects received three doses of Bexsero® vaccine at 2, 4, 6 months followed by a booster dose at 12 months, concomitantly administered with routine vaccines (i.e. combined Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® at 6 months of age; Priorix® and Varilrix® at 12 months of age. | Subjects received routine vaccines Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® vaccine at 6 months; Priorix® and Varilrix® vaccines at 12 months of age. |
| Measure Participants | 135 | 71 |
| H44/76 strain [Day 152/Day 1] |
71
|
0.99
|
| H44/76 strain [Day 335/Day 305] |
155
|
1.07
|
| 5/99 strain [Day 152/Day 1] |
875
|
0.97
|
| 5/99 strain [Day 335/Day 305] |
2110
|
0.97
|
| M10713 strain [Day 152/Day 1] |
5.69
|
0.68
|
| M10713 strain [Day 335/Day 305] |
12
|
0.91
|
| NZ98/254 strain [Day 152/Day 1] |
9.18
|
1.02
|
| NZ98/254 strain [Day 335/Day 305] |
25
|
1
|
| Title | Percentages of Subjects With hSBA Titers ≥1:8 Against Neisseria Meningitidis Serogroup B, When Bexsero® Vaccine Was Given With Routine Vaccines |
|---|---|
| Description | Percentages of subjects with hSBA titers ≥1:8 against N.meningitidis serogroup B strains, at one month after concomitant administration of third primary dose of Bexsero® with routine vaccines [Infanrix-IPV + Hib®, Prevenar-13® and Engerix-B®] and at one month after concomitant administration of Bexsero® booster dose with routine vaccines [Priorix® and Varilrix® vaccine],as compared to when only routine vaccines were administered. |
| Time Frame | At Day 1,Day 152,Day 305, Day 335 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on FAS population, which included all subjects in the exposed set who received at least one dose of a study vaccination and provided immunogenicity data at relevant time points. |
| Arm/Group Title | Bexsero + Routine Group | Routine Group |
|---|---|---|
| Arm/Group Description | Subjects received three doses of Bexsero® vaccine at 2, 4, 6 months followed by a booster dose at 12 months, concomitantly administered with routine vaccines (i.e. combined Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® at 6 months of age; Priorix® and Varilrix® at 12 months of age. | Subjects received routine vaccines Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® vaccine at 6 months; Priorix® and Varilrix® vaccines at 12 months of age. |
| Measure Participants | 145 | 73 |
| H44/76 strain (Day 1) |
0
|
0
|
| H44/76 strain (Day 152) |
100
|
0
|
| H44/76 strain (Day 305) |
66
|
2
|
| H44/76 strain (Day 335) |
99
|
0
|
| 5/99 strain (Day 1) |
1
|
0
|
| 5/99 strain (Day 152) |
100
|
0
|
| 5/99 strain (Day 305) |
99
|
1
|
| 5/99 strain (Day 335) |
99
|
0
|
| M10713 strain (Day 1) |
3
|
8
|
| M10713 strain (Day 152) |
49
|
5
|
| M10713 strain (Day 305) |
15
|
3
|
| M10713 strain (Day 335) |
77
|
6
|
| NZ98/254 strain (Day 1) |
0
|
0
|
| NZ98/254 strain (Day 152) |
59
|
0
|
| NZ98/254 strain (Day 305) |
9
|
0
|
| NZ98/254 strain (Day 335) |
86
|
0
|
| Title | Number of Subjects Reporting Solicited Local Adverse Events (AEs) After Receiving Bexsero® Vaccine With Routine Vaccine or Routine Vaccines Alone, at 2, 4, 6 and 12 Months of Age. |
|---|---|
| Description | Number of subjects reporting solicited local AEs following concomitant administration of Bexsero® vaccine with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13® and Engerix-B® at 2, 4 and 6 months of age and Priorix® and Varilrix® at 12 months of age)compared to when only routine vaccines were administered alone at 2,4,6 and 12 months. Solicited local symptoms assessed were Erythema, Induration, Swelling and Tenderness. |
| Time Frame | From day 1 (6 hours) to day 7 after each vaccination (1st, 2nd, 3rd and 4th vaccination) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on Safety set population (solicited AEs).The safety set population (solicited AEs) included all subjects in the Exposed Population who provided postvaccination reactogenicity data. |
| Arm/Group Title | Bexsero + Routine Group | Routine Group |
|---|---|---|
| Arm/Group Description | Subjects received three doses of Bexsero® vaccine at 2, 4, 6 months followed by a booster dose at 12 months, concomitantly administered with routine vaccines (i.e. combined Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® at 6 months of age; Priorix® and Varilrix® at 12 months of age. | Subjects received routine vaccines Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® vaccine at 6 months; Priorix® and Varilrix® vaccines at 12 months of age. |
| Measure Participants | 148 | 73 |
| Any Erythema (1st Bexsero®) |
54
36%
|
|
| Grade 3 Erythema (1st Bexsero®) |
0
0%
|
|
| Any Swelling (1st Bexsero®) |
34
22.7%
|
|
| Grade 3 Swelling (1st Bexsero®) |
0
0%
|
|
| Any Induration (1st Bexsero®) |
63
42%
|
|
| Grade 3 Induration (1st Bexsero®) |
0
0%
|
|
| Any Tenderness (1st Bexsero®) |
75
50%
|
|
| Grade 3 Tenderness (1st Bexsero®) |
8
5.3%
|
|
| Any Erythema (1st Infanrix-IPV + Hib®) |
26
17.3%
|
3
4%
|
| Grade 3 Erythema(1st Infanrix-IPV+Hib®) |
0
0%
|
0
0%
|
| Any Swelling (1st Infanrix-IPV + Hib®) |
15
10%
|
3
4%
|
| Grade 3 Swelling(1st Infanrix-IPV+Hib®) |
0
0%
|
0
0%
|
| Any Tenderness (1st Infanrix-IPV + Hib®) |
45
30%
|
12
16%
|
| Grade 3Tenderness(1st Infanrix-IPV+Hib®) |
2
1.3%
|
0
0%
|
| Any Induration(1st Infanrix-IPV + Hib®) |
23
15.3%
|
11
14.7%
|
| Grade 3Induration(1st Infanrix-IPV+Hib®) |
0
0%
|
0
0%
|
| Any Erythema (1st Prevenar-13®) |
26
17.3%
|
9
12%
|
| Grade 3 Erythema (1st Prevenar-13®) |
0
0%
|
0
0%
|
| Any Induration (1st Prevenar-13®) |
29
19.3%
|
15
20%
|
| Grade 3 Induration (1st Prevenar-13®) |
0
0%
|
0
0%
|
| Any Swelling (1st Prevenar-13®) |
11
7.3%
|
4
5.3%
|
| Grade 3 Swelling (1st Prevenar-13®) |
0
0%
|
0
0%
|
| Any Tenderness (1st Prevenar-13®) |
50
33.3%
|
12
16%
|
| Grade 3 Tenderness (1st Prevenar-13®) |
3
2%
|
0
0%
|
| Any Erythema (2nd Bexsero®) |
59
39.3%
|
|
| Grade 3 Erythema (2nd Bexsero®) |
0
0%
|
|
| Any Swelling (2nd Bexsero®) |
35
23.3%
|
|
| Grade 3 Swelling (2nd Bexsero®) |
0
0%
|
|
| Any Induration (2nd Bexsero®) |
51
34%
|
|
| Grade 3 Induration (2nd Bexsero®) |
0
0%
|
|
| Any Tenderness (2nd Bexsero®) |
67
44.7%
|
|
| Grade 3 Tenderness (2nd Bexsero®) |
5
3.3%
|
|
| Any Erythema (2nd Infanrix-IPV + Hib®) |
39
26%
|
12
16%
|
| Grade 3 Erythema(2nd Infanrix-IPV+Hib®) |
0
0%
|
0
0%
|
| Any Swelling (2nd Infanrix-IPV + Hib®) |
18
12%
|
6
8%
|
| Grade 3 Swelling(2nd Infanrix-IPV+Hib®) |
0
0%
|
0
0%
|
| Any Induration (2nd Infanrix-IPV + Hib®) |
23
15.3%
|
16
21.3%
|
| Grade 3Induration(2nd Infanrix-IPV+Hib®) |
0
0%
|
0
0%
|
| Any Tenderness (2nd Infanrix-IPV + Hib®) |
45
30%
|
10
13.3%
|
| Grade 3Tenderness(2nd Infanrix-IPV+Hib®) |
3
2%
|
0
0%
|
| Any Erythema (2nd Prevenar-13®) |
35
23.3%
|
12
16%
|
| Grade 3 Erythema (2nd Prevenar-13®) |
0
0%
|
0
0%
|
| Any Induration (2nd Prevenar-13®) |
18
12%
|
8
10.7%
|
| Grade 3 Induration (2nd Prevenar-13®) |
0
0%
|
0
0%
|
| Any Swelling (2nd Prevenar-13®) |
12
8%
|
6
8%
|
| Grade 3 Swelling (2nd Prevenar-13®) |
0
0%
|
0
0%
|
| Any Tenderness (2nd Prevenar-13®) |
44
29.3%
|
9
12%
|
| Grade 3 Tenderness (2nd Prevenar-13®) |
3
2%
|
0
0%
|
| Any Erythema (3rd Engerix-B®) |
33
22%
|
12
16%
|
| Grade 3 Erythema (3rd Engerix-B®) |
0
0%
|
0
0%
|
| Any Induration (3rd Engerix-B®) |
33
22%
|
17
22.7%
|
| Grade 3 Induration (3rd Engerix-B®) |
0
0%
|
0
0%
|
| Any Swelling (3rd Engerix-B®) |
25
16.7%
|
6
8%
|
| Grade 3 Swelling (3rd Engerix-B®) |
0
0%
|
0
0%
|
| Any Tenderness (3rd Engerix-B®) |
45
30%
|
7
9.3%
|
| Grade 3 Tenderness (3rd Engerix-B®) |
3
2%
|
0
0%
|
| Any Erythema (3rd Bexsero®) |
55
36.7%
|
|
| Grade 3 Erythema (3rd Bexsero®) |
0
0%
|
|
| Any Induration (3rd Bexsero®) |
57
38%
|
|
| Grade 3 Induration (3rd Bexsero®) |
0
0%
|
|
| Any Swelling (3rd Bexsero®) |
49
32.7%
|
|
| Grade 3 Swelling (3rd Bexsero®) |
0
0%
|
|
| Any Tenderness (3rd Bexsero®) |
68
45.3%
|
|
| Grade 3 Tenderness (3rd Bexsero®) |
6
4%
|
|
| Any Swelling (3rd Infanrix-IPV+Hib®) |
20
13.3%
|
10
13.3%
|
| Grade 3 Swelling (3rd Infanrix-IPV+Hib®) |
0
0%
|
0
0%
|
| Any Erythema (3rd Infanrix-IPV+Hib®) |
28
18.7%
|
15
20%
|
| Grade 3 Erythema (3rd Infanrix-IPV+Hib®) |
0
0%
|
0
0%
|
| Any Induration(3rd Infanrix-IPV+Hib®) |
25
16.7%
|
16
21.3%
|
| Grade 3Induration(3rd Infanrix-IPV+Hib®) |
0
0%
|
0
0%
|
| Any Tenderness (3rd Infanrix-IPV+ Hib®) |
42
28%
|
8
10.7%
|
| Grade 3Tenderness(3rd Infanrix-IPV+Hib®) |
2
1.3%
|
0
0%
|
| Any Erythema (3rd Prevenar-13®) |
27
18%
|
12
16%
|
| Grade 3 Erythema (3rd Prevenar-13®) |
0
0%
|
0
0%
|
| Any Induration (3rd Prevenar-13®) |
21
14%
|
11
14.7%
|
| Grade 3 Induration (3rd Prevenar-13®) |
0
0%
|
0
0%
|
| Any Swelling (3rd Prevenar-13®) |
17
11.3%
|
4
5.3%
|
| Grade 3 Swelling (3rd Prevenar-13®) |
0
0%
|
0
0%
|
| Any Tenderness (3rd Prevenar-13®) |
45
30%
|
9
12%
|
| Grade 3 Tenderness (3rd Prevenar-13®) |
3
2%
|
0
0%
|
| Any Erythema (4th Bexsero®) |
53
35.3%
|
|
| Grade 3 Erythema (4th Bexsero®) |
0
0%
|
|
| Any Swelling (4th Bexsero®) |
44
29.3%
|
|
| Grade 3 Swelling (4th Bexsero®) |
0
0%
|
|
| Any Induration (4th Bexsero®) |
56
37.3%
|
|
| Grade 3 Induration(4th Bexsero®) |
0
0%
|
|
| Any Tenderness (4th Bexsero®) |
66
44%
|
|
| Grade 3 Tenderness (4th Bexsero®) |
6
4%
|
|
| Any Erythema (4th Priorix®) |
24
16%
|
13
17.3%
|
| Grade 3 Erythema (4th Priorix®) |
0
0%
|
0
0%
|
| Any Induration (4th Priorix®) |
15
10%
|
6
8%
|
| Grade 3 Induration (4th Priorix®) |
0
0%
|
0
0%
|
| Any Swelling (4th Priorix®) |
19
12.7%
|
4
5.3%
|
| Grade 3 Swelling (4th Priorix®) |
0
0%
|
0
0%
|
| Any Tenderness (4th Priorix®) |
37
24.7%
|
6
8%
|
| Grade 3 Tenderness (4th Priorix®) |
3
2%
|
0
0%
|
| Any Erythema (4th Varilrix®) |
32
21.3%
|
14
18.7%
|
| Grade 3 Erythema (4th Varilrix®) |
0
0%
|
0
0%
|
| Any Induration (4th Varilrix®) |
14
9.3%
|
7
9.3%
|
| Grade 3 Induration (4th Varilrix®) |
0
0%
|
0
0%
|
| Any Swelling (4th Varilrix®) |
21
14%
|
6
8%
|
| Grade 3 Swelling (4th Varilrix®) |
0
0%
|
0
0%
|
| Any Tenderness (4th Varilrix®) |
41
27.3%
|
5
6.7%
|
| Grade 3 Tenderness (4th Varilrix®) |
3
2%
|
0
0%
|
| Title | Number of Subjects Reporting Solicited Systemic Adverse Events (AEs) After Receiving Bexsero® Vaccine With Routine Vaccine or Routine Vaccines Alone, at 2, 4, 6 and 12 Months of Age. |
|---|---|
| Description | Number of subjects reporting solicited systemic AEs following concomitant administration of Bexsero® vaccine with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13® and Engerix-B® at 2, 4 and 6 months of age and Priorix® and Varilrix® at 12 months of age) compared to when only routine vaccines were alone, at 2, 4, 6 and 12 months. Systemic solicited symptoms assessed were Change in Eating Habits, Diarrhea, Irritability, Persistent Crying, Rash, Sleepiness, Vomiting and Fever (body temperature ≥ 38.0 °C) |
| Time Frame | From day 1 (6 hours) to day 7 after each vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on Safety set population (solicited AEs).The safety set population (solicited AEs) included all subjects in the Exposed Population who provided postvaccination reactogenicity data. |
| Arm/Group Title | Bexsero + Routine Group | Routine Group |
|---|---|---|
| Arm/Group Description | Subjects received three doses of Bexsero® vaccine at 2, 4, 6 months followed by a booster dose at 12 months, concomitantly administered with routine vaccines (i.e. combined Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® at 6 months of age; Priorix® and Varilrix® at 12 months of age. | Subjects received routine vaccines Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® vaccine at 6 months; Priorix® and Varilrix® vaccines at 12 months of age. |
| Measure Participants | 148 | 73 |
| Any Change in Eating Habits (1st vacc) |
92
61.3%
|
26
34.7%
|
| Grade3 Change in Eating Habits(1st vacc) |
0
0%
|
0
0%
|
| Any Change in Eating Habits (2nd vacc) |
72
48%
|
21
28%
|
| Grade3 Change in Eating Habits(2nd vacc) |
2
1.3%
|
0
0%
|
| Any Change in Eating Habits (3rd vacc) |
72
48%
|
17
22.7%
|
| Grade3 Change in Eating Habits(3rd vacc) |
1
0.7%
|
0
0%
|
| Any Diarrhea (1st vacc) |
28
18.7%
|
8
10.7%
|
| Grade 3 Diarrhea (1st vacc) |
2
1.3%
|
1
1.3%
|
| Any Diarrhea (2nd vacc) |
30
20%
|
9
12%
|
| Grade 3 Diarrhea (2nd vacc) |
1
0.7%
|
0
0%
|
| Any Diarrhea (3rd vacc) |
19
12.7%
|
4
5.3%
|
| Grade 3 Diarrhea (3rd vacc) |
0
0%
|
0
0%
|
| Any Irritability (1st vacc) |
111
74%
|
32
42.7%
|
| Grade 3 Irritability (1st vacc) |
3
2%
|
0
0%
|
| Any Irritability (2nd vacc) |
90
60%
|
31
41.3%
|
| Grade 3 Irritability (2nd vacc) |
5
3.3%
|
0
0%
|
| Any Irritability (3rd vacc) |
94
62.7%
|
28
37.3%
|
| Grade 3 Irritability (3rd vacc) |
3
2%
|
1
1.3%
|
| Any Persistent Crying (1st vacc) |
96
64%
|
30
40%
|
| Grade 3 Persistent Crying (1st vacc) |
5
3.3%
|
0
0%
|
| Any Persistent Crying (2nd vacc) |
82
54.7%
|
23
30.7%
|
| Grade 3 Persistent Crying (2nd vacc) |
5
3.3%
|
0
0%
|
| Any Persistent Crying (3rd vacc) |
72
48%
|
28
37.3%
|
| Grade 3 Persistent Crying (3rd vacc) |
3
2%
|
0
0%
|
| Any Rash (1st vacc) |
18
12%
|
4
5.3%
|
| Grade 3 Rash (1st vacc) |
0
0%
|
0
0%
|
| Any Rash (2nd vacc) |
18
12%
|
8
10.7%
|
| Grade 3 Rash (2nd vacc) |
0
0%
|
1
1.3%
|
| Any Rash (3rd vacc) |
16
10.7%
|
4
5.3%
|
| Grade 3 Rash (3rd vacc) |
1
0.7%
|
0
0%
|
| Any Sleepiness (1st vacc) |
79
52.7%
|
33
44%
|
| Grade 3 Sleepiness (1st vacc) |
0
0%
|
1
1.3%
|
| Any Sleepiness (2nd vacc) |
66
44%
|
21
28%
|
| Grade 3 Sleepiness (2nd vacc) |
0
0%
|
0
0%
|
| Any Sleepiness (3rd vacc) |
49
32.7%
|
13
17.3%
|
| Grade 3 Sleepiness (3rd vacc) |
0
0%
|
0
0%
|
| Any Vomiting (1st vacc) |
21
14%
|
6
8%
|
| Grade 3 Vomiting (1st vacc) |
0
0%
|
0
0%
|
| Any Vomiting (2nd vacc) |
16
10.7%
|
9
12%
|
| Grade 3 Vomiting (2nd vacc) |
0
0%
|
0
0%
|
| Any Vomiting (3rd vacc) |
15
10%
|
7
9.3%
|
| Grade 3 Vomiting (3rd vacc) |
0
0%
|
0
0%
|
| Fever (1st vacc) |
71
47.3%
|
11
14.7%
|
| Fever (2nd vacc) |
72
48%
|
11
14.7%
|
| Fever (3rd vacc) |
68
45.3%
|
12
16%
|
| Any Change in Eating Habits (4th vacc) |
58
38.7%
|
19
25.3%
|
| Grade3 Change in Eating Habits(4th vacc) |
2
1.3%
|
1
1.3%
|
| Any Diarrhea (4th vacc) |
27
18%
|
10
13.3%
|
| Grade 3 Diarrhea (4th vacc) |
1
0.7%
|
0
0%
|
| Any Irritability (4th vacc) |
71
47.3%
|
16
21.3%
|
| Grade 3 Irritability (4th vacc) |
2
1.3%
|
0
0%
|
| Any Persistent Crying (4th vacc) |
58
38.7%
|
15
20%
|
| Grade 3 Persistent Crying (4th vacc) |
0
0%
|
1
1.3%
|
| Any Rash (4th vacc) |
25
16.7%
|
9
12%
|
| Grade 3 Rash (4th vacc) |
1
0.7%
|
0
0%
|
| Any Sleepiness (4th vacc) |
36
24%
|
9
12%
|
| Grade 3 Sleepiness (4th vacc) |
0
0%
|
0
0%
|
| Any Vomiting (4th vacc) |
10
6.7%
|
6
8%
|
| Grade 3 Vomiting (4th vacc) |
0
0%
|
0
0%
|
| Fever (4th vacc) |
60
40%
|
6
8%
|
| Lymphadenopathy (4th vacc) |
1
0.7%
|
1
1.3%
|
| Title | Number of Subjects Reporting Solicited Systemic AEs After Receiving Priorix® and Varilrix® Routine Vaccines (With and Without Bexsero® Vaccine) at 12 Months of Age. |
|---|---|
| Description | Number of subjects who reported solicited systemic AEs reported after the administration of Varilrix® and Priorix® vaccines (with and without Bexsero® vaccine) at 12 months of age. Solicited systemic AEs assessed were Rash, Lymphadenopathy and Fever. This analysis was conducted for a prolonged period of 28 Days following Varilrix® and Priorix® administration. |
| Time Frame | From Day 1 to Day 28 after vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on Safety set population (solicited AEs).The safety set population (solicited AEs) included all subjects in the Exposed Population who provided postvaccination reactogenicity data. |
| Arm/Group Title | Bexsero + Routine Group | Routine Group |
|---|---|---|
| Arm/Group Description | Subjects received three doses of Bexsero® vaccine at 2, 4, 6 months followed by a booster dose at 12 months, concomitantly administered with routine vaccines (i.e. combined Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® at 6 months of age; Priorix® and Varilrix® at 12 months of age. | Subjects received routine vaccines Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® vaccine at 6 months; Priorix® and Varilrix® vaccines at 12 months of age. |
| Measure Participants | 137 | 72 |
| Any Rash (4th vacc) |
50
33.3%
|
24
32%
|
| Grade 3 rash (4th vacc) |
5
3.3%
|
5
6.7%
|
| Lymphadenopathy (4th vacc) |
34
22.7%
|
21
28%
|
| Fever (temperature ≥ 38.0°C) |
91
60.7%
|
33
44%
|
| Grade 3 fever (temperature ≥ 40.0°C) |
2
1.3%
|
5
6.7%
|
| Title | Number of Subjects Reporting Unsolicited Adverse Events After Receiving Bexsero® Vaccination With Routine Vaccines |
|---|---|
| Description | Number of subjects reporting any unsolicited AEs following concomitant administration of Bexsero® vaccine with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13®, Engerix-B® or Priorix® and Varilrix®) compared to when only routine vaccines were administered alone. |
| Time Frame | From day 1 to day 7 after each vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on Safety set population (unsolicited AEs). The safety set population (unsolicited AEs) included all subjects in the Exposed Population who had postvaccination unsolicited AE records. |
| Arm/Group Title | Bexsero + Routine Group | Routine Group |
|---|---|---|
| Arm/Group Description | Subjects received three doses of Bexsero® vaccine at 2, 4, 6 months followed by a booster dose at 12 months, concomitantly administered with routine vaccines (i.e. combined Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® at 6 months of age; Priorix® and Varilrix® at 12 months of age. | Subjects received routine vaccines Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® vaccine at 6 months; Priorix® and Varilrix® vaccines at 12 months of age. |
| Measure Participants | 145 | 72 |
| Any AEs (1st vacc) |
46
|
8
|
| At least possible related AEs (1st vacc) |
35
|
6
|
| Any AEs (2nd vacc) |
30
|
7
|
| At least possible related AEs (2nd vacc) |
22
|
5
|
| Any AEs (3rd vacc) |
51
|
18
|
| At least possible related AEs (3rd vacc) |
45
|
7
|
| Any AEs (booster) |
43
|
9
|
| At least possible related AEs (booster) |
37
|
4
|
| Title | Number of Subjects Reporting Serious Adverse Events (SAEs), Medically Attended AEs (MAEs) and AEs Leading to Premature Withdrawal and Death and AEs Leading to Hospitalization. |
|---|---|
| Description | Number of subjects reporting SAEs, medically attended AEs and AEs leading to premature withdrawal from the study and leading to death and AEs leading to hospitalization following concomitant administration of Bexsero® vaccine with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13®, Engerix-B®, Priorix® and Varilrix®) compared to when only routine vaccines were administered alone. SAEs assessed included medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Possibly or probably related SAE were SAEs assessed by the investigator as related to the vaccination. Medically attended AEs were events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason. |
| Time Frame | Throughout the study period (Day 1 to Day 335) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on Safety set population (unsolicited AEs). The safety set population (unsolicited AEs) included all subjects in the Exposed Population who had postvaccination unsolicited AE records. |
| Arm/Group Title | Bexsero + Routine Group | Routine Group |
|---|---|---|
| Arm/Group Description | Subjects received three doses of Bexsero® vaccine at 2, 4, 6 months followed by a booster dose at 12 months, concomitantly administered with routine vaccines (i.e. combined Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® at 6 months of age; Priorix® and Varilrix® at 12 months of age. | Subjects received routine vaccines Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® vaccine at 6 months; Priorix® and Varilrix® vaccines at 12 months of age. |
| Measure Participants | 145 | 72 |
| Any SAEs |
13
8.7%
|
8
10.7%
|
| At least possible related SAEs |
0
0%
|
0
0%
|
| AEs resulting in premature withdrawal |
4
2.7%
|
0
0%
|
| AEs leading to hospitalization |
13
8.7%
|
8
10.7%
|
| Medically attended AEs |
131
87.3%
|
66
88%
|
| AEs leading to death |
0
0%
|
0
0%
|
Adverse Events
| Time Frame | Solicited local AEs and systemic symptoms: from Day 1 to Day 7 after each vaccination; Unsolicited AEs and SAEs: throughout the study period (from Day 1 to Day 335). | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Serious adverse events were analysed based on the unsolicited safety set and other adverse events were analysed based on the overall safety set. Therefore, the number of participants at risk in the serious adverse events are lesser compared to the number of participants at risk in the other adverse events. | |||
| Arm/Group Title | Bexsero + Routine Group | Routine Group | ||
| Arm/Group Description | Subjects received three doses of Bexsero® vaccine at 2, 4, 6 months followed by a booster dose at 12 months, concomitantly administered with routine vaccines (i.e. combined Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® at 6 months of age; Priorix® and Varilrix® at 12 months of age. | Subjects received routine vaccines Infanrix-IPV + Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® vaccine at 6 months; Priorix® and Varilrix® vaccines at 12 months of age. | ||
All Cause Mortality |
||||
| Bexsero + Routine Group | Routine Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/148 (0%) | 0/73 (0%) | ||
Serious Adverse Events |
||||
| Bexsero + Routine Group | Routine Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/145 (9%) | 8/72 (11.1%) | ||
| Gastrointestinal disorders | ||||
| Colitis | 0/145 (0%) | 1/72 (1.4%) | ||
| General disorders | ||||
| Pyrexia | 1/145 (0.7%) | 1/72 (1.4%) | ||
| Infections and infestations | ||||
| Bronchiolitis | 3/145 (2.1%) | 1/72 (1.4%) | ||
| Urinary tract infection | 4/145 (2.8%) | 0/72 (0%) | ||
| Gastroenteritis | 1/145 (0.7%) | 1/72 (1.4%) | ||
| Hand-foot-and-mouth disease | 2/145 (1.4%) | 0/72 (0%) | ||
| Otitis media acute | 1/145 (0.7%) | 1/72 (1.4%) | ||
| Pneumonia | 1/145 (0.7%) | 1/72 (1.4%) | ||
| Respiratory syncytial virus infection | 1/145 (0.7%) | 1/72 (1.4%) | ||
| Cellulitis | 1/145 (0.7%) | 0/72 (0%) | ||
| Croup infectious | 0/145 (0%) | 1/72 (1.4%) | ||
| Exanthema subitum | 1/145 (0.7%) | 0/72 (0%) | ||
| Gastroenteritis salmonella | 1/145 (0.7%) | 0/72 (0%) | ||
| Oral herpes | 1/145 (0.7%) | 0/72 (0%) | ||
| Osteomyelitis | 0/145 (0%) | 1/72 (1.4%) | ||
| Pneumonia pneumococcal | 1/145 (0.7%) | 0/72 (0%) | ||
| Pyelonephritis acute | 1/145 (0.7%) | 0/72 (0%) | ||
| Pyuria | 1/145 (0.7%) | 0/72 (0%) | ||
| Respiratory syncytial virus bronchiolitis | 0/145 (0%) | 1/72 (1.4%) | ||
| Salmonella bacteraemia | 1/145 (0.7%) | 0/72 (0%) | ||
| Upper respiratory tract infection | 1/145 (0.7%) | 0/72 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Head injury | 1/145 (0.7%) | 0/72 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 2/145 (1.4%) | 0/72 (0%) | ||
| Nervous system disorders | ||||
| Seizure | 0/145 (0%) | 1/72 (1.4%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash | 0/145 (0%) | 1/72 (1.4%) | ||
| Vascular disorders | ||||
| Kawasaki's disease | 0/145 (0%) | 1/72 (1.4%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Bexsero + Routine Group | Routine Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 148/148 (100%) | 72/73 (98.6%) | ||
| Blood and lymphatic system disorders | ||||
| LYMPHADENOPATHY | 34/148 (23%) | 21/73 (28.8%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 72/148 (48.6%) | 29/73 (39.7%) | ||
| Vomiting | 45/148 (30.4%) | 16/73 (21.9%) | ||
| General disorders | ||||
| Pyrexia | 134/148 (90.5%) | 51/73 (69.9%) | ||
| Crying | 124/148 (83.8%) | 50/73 (68.5%) | ||
| Injection site erythema | 113/148 (76.4%) | 35/73 (47.9%) | ||
| Injection site pain | 121/148 (81.8%) | 27/73 (37%) | ||
| Injection site induration | 105/148 (70.9%) | 39/73 (53.4%) | ||
| Injection site swelling | 89/148 (60.1%) | 24/73 (32.9%) | ||
| Infections and infestations | ||||
| Nasopharyngitis | 86/148 (58.1%) | 45/73 (61.6%) | ||
| Upper respiratory tract infection | 42/148 (28.4%) | 16/73 (21.9%) | ||
| Bronchiolitis | 9/148 (6.1%) | 4/73 (5.5%) | ||
| Exanthema subitum | 9/148 (6.1%) | 6/73 (8.2%) | ||
| Conjunctivitis | 5/148 (3.4%) | 4/73 (5.5%) | ||
| Pharyngitis | 5/148 (3.4%) | 4/73 (5.5%) | ||
| Tonsillitis | 4/148 (2.7%) | 4/73 (5.5%) | ||
| Gastroenteritis | 14/148 (9.5%) | 12/73 (16.4%) | ||
| Nervous system disorders | ||||
| Somnolence | 111/148 (75%) | 45/73 (61.6%) | ||
| Psychiatric disorders | ||||
| Irritability | 127/148 (85.8%) | 50/73 (68.5%) | ||
| Eating disorder | 125/148 (84.5%) | 43/73 (58.9%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 10/148 (6.8%) | 3/73 (4.1%) | ||
| Rhinorrhoea | 5/148 (3.4%) | 8/73 (11%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash | 72/148 (48.6%) | 30/73 (41.1%) | ||
| Eczema | 17/148 (11.5%) | 5/73 (6.8%) | ||
| Dermatitis | 15/148 (10.1%) | 4/73 (5.5%) | ||
| Dermatitis atopic | 8/148 (5.4%) | 5/73 (6.8%) | ||
| Dermatitis diaper | 7/148 (4.7%) | 6/73 (8.2%) | ||
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 |
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02173704
Other Study ID Numbers:
- 205249
- V72_60
- 2014-005568-14
First Posted:
Jun 25, 2014
Last Update Posted:
Aug 25, 2020
Last Verified:
Aug 1, 2020