The study listed may include approved and non-approved uses, formulations or treatment regimens. The results
reported in any single study may not reflect the overall results obtained on studies of a product. Before prescribing any
product mentioned in this Register, healthcare professionals should consult prescribing information for the product
approved in their country.
GSK Medicine: Combined Diphtheria, Tetanus, Acellular Pertussis, Hepatitis B, Poliovirus and Haemophilus influenzae type
b Vaccine
Study Number: 117119 (DTPA-HBV-IPV-135)
Title: Immunogenicity and safety study of GSK Biologicals’ Infanrix hexa™ at 2, 4 and 6 months of age in healthy infants.
Infanrix hexa™ (DTPa-HBV-IPV/Hib): GlaxoSmithKline (GSK) Biologicals’ combined diphtheria-tetanus-acellular pertussishepatitis B-Poliovirus and Haemophilus influenzae type b vaccine.
Rationale: The purpose of this study was to generate pivotal immunogenicity and safety data demonstrating non-inferiority of
the immune responses against pertussis antigens of DTPa-HBV-IPV/Hib compared to Pediarix. This study also provided
descriptive information regarding the immune response to the components of DTPa-HBV-IPV/Hib and Pentacel following a 3
dose primary series and the safety profile of DTPa-HBV-IPV/Hib in US subjects. The intended duration of the study per
subject was approximately 14-17 months: Primary Phase, starting at Visit 1 (Day 0) and ending at safety follow up contact (i.e.
six months following the third dose, Month 10) and Booster Phase, starting at Visit 5 (Month 13-16) and ending at Visit 6
(Month 14-17). The safety data presented includes all data up to the Data Lock Point 19-June-2015, which was prior to the to
the end of the safety follow up contact (i.e. six months following the third dose, Month 10).
Pediarix® (DTPa-HBV-IPV): GSK Biologicals’ Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B
(Recombinant) and Inactivated Poliovirus vaccine.
Pentacel® (DTaP-IPV/HIB): Sanofi Pasteur SA’s Diphtheria and tetanus toxoids and acellular pertussis adsorbed, inactivated
poliovirus and Haemophilus b conjugate (tetanus toxoid conjugate) vaccine
Prevnar13® (13Pn): Pfizer’s Pneumoccocal 13-valent conjugate vaccine (diphtheria CRM197 protein) vaccine
Rotarix® (HRV): GSK Biologicals’ Rotavirus Vaccine, Live, Oral
ActHIB® (ActHIB): Sanofi Pasteur SA’s Haemophilus type b conjugate vaccine (tetanus toxoid conjugate)
Engerix® (HBV): GSK Biologicals’ Hepatitis B vaccine (recombinant)
Hiberix™ (Hib): GSK Biologicals’ Haemophilus b conjugate vaccine (tetanus toxoid conjugate)
Infanrix® (DTPa) : GSK Biologicals’ Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed
Phase: III
Study Period: 16-Apr-2014 to 19-Jun-2015 Data Lock Point (prior to end of six-month follow up after the third dose)
Study Design: Open-label, randomized, controlled, multi-centric, single-country study with five parallel groups.
Centres: 44 centers in the United States.
Indication: Diphtheria-Tetanus-Pertussis-Hepatitis B-Poliomyelitis-Haemophilus influenzae type b
Treatment: The study groups were as follows:
Primary Phase:
DTPa-HBV/Hib Group: Subjects in this group received 3 doses of DTPa-HBV-IPV/Hib (lot A, lot B or lot C as per
the group allocation) co-administered with 13Pn at 2, 4 and 6 months of age and HRV at 2 and 4 months of age.
DTPa-HBV Group: Subjects in this group received 3 doses of DTPa-HBV-IPV and ActHIB co-administered with
13Pn at 2, 4 and 6 months of age and HRV at 2 and 4 months of age.
DTaP/Hib Group: Subjects in this group received 3 doses of DTaP-IPV/Hib and HBV co-administered with 13Pn at
2, 4 and 6 months of age and HRV at 2 and 4 months of age.
* Subjects in the DTaP/Hib Group who had received a dose of hepatitis B vaccine from birth up to 30 days prior to study
vaccination did not receive HBV at 4 months of age.
The injectable vaccines were administered by intramuscular injection in the anterolateral thigh (DTPa-HBV-IPV/Hib vaccine:
right thigh; 13Pn vaccine: lower left thigh; DTPa-HBV-IPV vaccine: right thigh; ActHIB vaccine: upper left thigh; DTaP-IPV/HIB
vaccine: right thigh; HBV: upper left thigh). HRV was administered orally
Booster Phase:
DTPa-HBV/Hib Group: Subjects in this group received a booster dose of DTPa and Hib vaccines at 15-18 months
of age.
DTPa-HBV Group: Subjects in this group received a booster dose of DTPa and ActHIB vaccines at 15-18 months
of age.
DTaP/Hib Group: Subjects in this group received a booster dose of DTaP-IPV/HIB at 15-18 months of age.
The injectable vaccines were administered by intramuscular injection in the anterolateral thigh (DTPa vaccine: right thigh; Hib
vaccine: left thigh; ActHIB vaccine: left thigh; DTaP-IPV/HIB vaccine: right thigh).
Objectives:
Primary Phase:
To demonstrate the non-inferiority of DTPa-HBV-IPV/Hib to DTPa-HBV-IPV co-administered with ActHIB, in terms of antibody
geometric mean concentrations (GMCs) for pertussis antigens [pertussis toxoid (PT), filamentous hemagglutinin (FHA) and
pertactin (PRN)] 1 month after the third dose of the primary vaccination.
Criteria for non-inferiority:
Non-inferiority in terms of immune response to pertussis antigens will be demonstrated if, for each of the three antigens, the
upper limit of the 95% confidence interval (CI) on the GMC ratio [DTPa Group divided by DTPa/Hib Group] is ≤ 1.5.
Primary Outcome Variable(s):
Primary Phase:

Immunogenicity with respect to pertussis components of the study vaccines DTPa-HBV-IPV/Hib and DTPa-HBV-IPV*.

Anti-PT, anti-FHA, anti-PRN antibody concentrations, 1 month after the third dose of the primary vaccination.
* Immunogenicity results were not available at the time this summary was written. Missing data will be added when results
become available.
Secondary Outcome Variable(s):
Primary Phase:

Immunogenicity (other parameters) with respect to the pertussis component of the study vaccines DTPa-HBV-IPV/Hib,
DTaP-IPV/HIB and DTPa-HBV-IPV*.

Anti-PT, anti-FHA, anti-PRN seropositivity status, 1 month after the third dose of the primary vaccination.

Anti-PT, anti-FHA, anti-PRN antibody concentrations, 1 month after the third dose of the primary vaccination (for
DTaP-IPV/HIB only).

Immunogenicity with respect to the other components of the study vaccines DTPa-HBV-IPV/Hib, DTPa-HBV-IPV,
ActHIB, DTaP-IPV/HIB and HBV*

Anti-diphtheria (anti-D), anti-tetanus (anti-T), anti-hepatitis B (anti-HBs), anti-poliovirus types 1, 2 and 3 and antipolyribosyl ribitol phosphate (anti-PRP) seroprotection status, anti-PRP antibody concentrations ≥1.0 µg/mL and
antibody concentrations/titers, 1 month after the third dose of the primary vaccination.

Solicited local and general symptoms.

Occurrence of each solicited local symptom (any, ≥Grade 2, Grade 3 and symptoms requiring medical attention)
within 4 days (Day 0 – Day 3) after each vaccination (DTPa-HBV-IPV/Hib, DTPa-HBV-IPV, ActHIB, DTaP-IPV/HIB
and HBV).

Occurrence of each solicited general symptom (any, ≥Grade 2, Grade 3, symptoms requiring medical attention,
related and Grade 3 related) within 4 days (Day 0 – Day 3) after each vaccination.

Unsolicited adverse events (AEs).

Occurrence of unsolicited AEs within 31 days (Day 0 – Day 30) after each vaccination, according to the Medical
Dictionary for Regulatory Activities (MedDRA) classification.

Specific AEs.

Occurrence of specific AEs, i.e., new onset chronic diseases (NOCD) (e.g. autoimmune disorders, asthma, type I
diabetes and allergies) from Day 0 up to 6 months post primary vaccination.

Serious adverse events (SAEs).

Occurrence of SAEs from Day 0 up to 6 months post primary vaccination.
Booster Phase#:

Immunogenicity with respect to all study vaccines

Anti-D, anti-T, anti- PT, anti-FHA and anti-PRN, anti-HBs, anti-PRP and anti-poliovirus 1, 2, 3 seroprotection/
seropositivity status, anti-PRP antibody concentrations ≥1 µg/mL and antibody concentrations/ titers before the
booster dose.

Immunogenicity with respect to the study vaccine DTaP-IPV/HIB.

Anti-D, anti-T, anti- PT, anti-FHA and anti-PRN, anti-PRP seroprotection/ seropositivity status and antibody
concentrations, one month after the booster dose.

Anti-PT, anti-FHA and anti-PRN booster response one month after the booster dose.

Anti-PRP antibody concentrations ≥1 µg/mL one month after the booster dose.

Anti-D and anti-T antibody concentrations ≥1 IU/mL one month after the booster dose.

Immunogenicity with respect to the study vaccine DTPa.

Anti-D, anti-T, anti- PT, anti-FHA and anti-PRN seroprotection/ seropositivity status and antibody concentrations,





one month after the booster dose.

Anti-PT, anti-FHA and anti-PRN booster response one month after the booster dose.

Anti-D and anti-T antibody concentrations ≥1 IU/mL one month after the booster dose.
Immunogenicity with respect to the study vaccines ActHIB and HBV.

Anti-PRP seroprotection status and antibody concentrations, one month after the booster dose.

Anti-PRP antibody concentrations ≥1 µg/mL one month after the booster dose.
Solicited local and general symptoms.

Occurrence of each solicited local symptom (any, ≥Grade 2, Grade 3 and symptoms requiring medical attention)
within 4 days (Day 0 – Day 3) after booster vaccination (DTPa, ActHIB, Hib and DTaP-IPV/HIB)

Occurrence of each solicited general symptom (any, ≥Grade 2, Grade 3, symptoms requiring medical attention,
related and Grade 3 related) within 4 days (Day 0 – Day 3) after booster vaccination.
Unsolicited AEs.

Occurrence of unsolicited AEs within 31 days (Day 0 – Day 30) after booster vaccination, according to the
MedDRA classification.
Specific AEs.

Occurrence of specific AEs, i.e., new onset chronic diseases (e.g. autoimmune disorders, asthma, type I diabetes
and allergies) from the booster dose up to one month after the booster vaccination.
SAEs.

Occurrence of SAEs from the booster dose up to one month after the booster vaccination.
* Immunogenicity results were not available at the time this Summary was written. Missing data will be added when results
become available.
# Results for the Booster Phase (safety and immunogenicity) were not available at the time this Summary was written. Missing
data will be added when results become available.
Statistical Methods:
The analyses were performed on the Primary Total Vaccinated cohort.
The Primary Total Vaccinated cohort included all subjects with documented administration of the study vaccines.
Analysis of safety
The analysis of safety was performed on the Primary Total Vaccinated cohort
The percentages of subjects reporting each individual solicited local symptom and general symptom during the 4-days (Days
0-3) after each study vaccination dose and across dose were tabulated with exact 95% CI. The same tabulation was
performed for grade 3 symptoms and for solicited general symptoms assessed by the investigators as related to the study
vaccination. The percentage of subjects with at least one report of unsolicited symptoms classified by the MedDRA preferred
terms within the 31-days (Days 0-30) after each study vaccination dose was tabulated. SAEs and NOCDs reported till Data
Base Freeze (DBF) date were tabulated.
Study Population: Healthy male or female subjects between, and including, 6 and 12 weeks of age at the time of the
vaccination were included in the study. Subjects were excluded from the study if they received any investigational or nonregistered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccines, or planned
receiving during the study period or vaccines to any of the antigens offered in the study, with the exception of a single dose of
HBV at least 30 days prior to dose 1. Written informed consent obtained from the parent(s)/legally authorized
representative(s) of the subjects.
Number of subjects
DTPa-HBV/Hib Group
DTPa-HBV Group
DTaP /HIB Group
Planned, N
195
195
195
Randomised, N (Total Vaccinated cohort)
195
194
196
Completed, n (%)
178 (91.3)
182 (93.8)
178 (90.8)
Total Number Subjects Withdrawn, n (%)
17 (8.7)
12
18 (9.2)
Withdrawn due to AEs, n (%)
1 (0.5)
0 (0.0)
1 (0.5)
Withdrawn due to Lack of Efficacy, n (%)
Not applicable
Not applicable
Not applicable
Withdrawn for other reasons, n (%)
16 (8.2)
0 (0.0)
17 (8.7)
Demographics
DTPa-HBV/Hib Group
DTPa-HBV Group
DTaP/HIB Group
N (Total Vaccinated cohort)
195
194
196
Females: Males
101:94
80:114
95:101
Mean Age, weeks (SD)
8.5 (1.0)
8.6 (1.1)
8.6 (1.1)
White - Caucasian / European Heritage, n
118 (60.5)
128 (66.0)
115 (58.7)
(%)
Mixed Origin, n (%)
29 (14.9)
27 (13.9)
32 (16.3)
American Indian or Alaskan Native, n (%)
15 (7.7)
15 (7.7)
17 (8.7)
Number of subjects vaccinated, completed and withdrawn with reasons of withdrawal up to Month 5 (Primary Total
Vaccinated cohort)
DTPaDTPa-HBV Group
DTaP/HIB Group
HBV/Hib
Group
Number of subjects vaccinated
195
194
196
Number of subjects completed
178
182
178
Number of subjects withdrawn
17
12
18
Reasons for withdrawal :
Subject died
0
0
0
Serious Adverse Event
1
0
0
Non-Serious Adverse Event
0
0
1
Eligibility criteria not fulfilled (inclusion and exclusion criteria)
0
0
0
Protocol violation
1
0
4
Consent withdrawal (not due to an adverse event)
3
6
5
Migrated/moved from study area
2
3
0
Lost to follow-up (subjects with incomplete vaccination course)
2
0
2
Lost to follow-up (subjects with complete vaccination course)
4
0
0
Sponsor study termination
0
0
1
Other - loss of kaiser insurance
0
0
1
Other - lost health plan
1
2
0
Other - lost health plan at kaiser
0
1
0
Other - lost kaiser insurance
1
0
0
Other - lost kaiser permanente health insurance
0
0
1
Other - parent no show x3
1
0
0
Other - refuses blood draws
0
0
1
Other - subject was discontiued due to non-compliance
0
0
1
Other - terminated by pi due to non-compliance with
1
0
0
appointment schedules
Other - traveling out of country and unable to meet visit window
0
0
1
Primary Outcome Results: Primary results were not available at the time of writing. The Summary will be updated when
these results become available.
Secondary Outcome Results: Number (%) of subjects reporting solicited local symptoms during the 4-day (Days 0-3) postvaccination period following each dose and across doses (Primary Total Vaccinated cohort)
DTPa-HBV/Hib Group
DTPa-HBV Group
DTaP/HIB Group
95 % CI
95 % CI
95 % CI
Symptom Product
Intensity N n % LL UL N n % LL UL N n
%
LL UL
Dose 1
Pain
Total
Any
185 94 50.8 43.4 58.2 189 128 67.7 60.6 74.3 188 119 63.3 56.0 70.2
≥ Grade 2 185 40 21.6 15.9 28.3 189 75 39.7 32.7 47.0 188 56 29.8 23.4 36.9
Grade 3 185 8 4.3 1.9 8.3 189 24 12.7 8.3 18.3 188 12
6.4
3.3 10.9
Medical 185 1 0.5 0.0 3.0 189 1 0.5 0.0 2.9 188 0
0.0
0.0 1.9
advice
ActHIB/HBV
Any
189 123 65.1 57.8 71.9 188 100 53.2 45.8 60.5
≥ Grade 2
189 66 34.9 28.1 42.2 188 45 23.9 18.0 30.7
Grade 3
189 22 11.6 7.4 17.1 188 10
5.3
2.6 9.6
Medical
189 1 0.5 0.0 2.9 188 0
0.0
0.0 1.9
advice
DTPa-HBVIPV/Hib/DTPaHBV-IPV/DTaPIPV/HIB
Redness
Total
ActHIB/HBV
DTPa-HBVIPV/Hib/DTPaHBV-IPV/DTaPIPV/HIB
Swelling
Total
ActHIB/HBV
DTPa-HBVIPV/Hib/DTPaHBV-IPV/DTaPIPV/HIB
Pain
Total
ActHIB/HBV
Any
185 94 50.8 43.4 58.2 189 113 59.8 52.4 66.8 188 115
61.2
53.8 68.2
≥ Grade 2
Grade 3
Medical
advice
Any
185 40 21.6 15.9 28.3 189 65 34.4 27.6 41.6 188 51
185 8 4.3 1.9 8.3 189 17 9.0 5.3 14.0 188 12
185 1 0.5 0.0 3.0 189 0 0.0 0.0 1.9 188 0
27.1
6.4
0.0
20.9 34.1
3.3 10.9
0.0 1.9
185 47 25.4 19.3 32.3 189 73 38.6 31.6 46.0 188 67
35.6
28.8 42.9
> 5 mm
185 15 8.1
4.6 13.0 189 27 14.3 9.6 20.1 188 27
14.4
9.7 20.2
>20 mm
Medical
advice
Any
> 5 mm
>20 mm
Medical
advice
Any
185 3
185 0
0.3 4.7 189 10 5.3 2.6 9.5 188 4
0.0 2.0 189 1 0.5 0.0 2.9 188 0
2.1
0.0
0.6
0.0
5.4
1.9
55
12
1
0
29.3
6.4
0.5
0.0
22.9
3.3
0.0
0.0
36.3
10.9
2.9
1.9
185 47 25.4 19.3 32.3 189 56 29.6 23.2 36.7 188 57
30.3
23.8 37.4
> 5 mm
>20 mm
Medical
advice
Any
> 5 mm
>20 mm
Medical
advice
Any
> 5 mm
>20 mm
Medical
advice
Any
185 15 8.1
185 3 1.6
185 0 0.0
4.6 13.0 189 15 7.9 4.5 12.8 188 20
0.3 4.7 189 4 2.1 0.6 5.3 188 3
0.0 2.0 189 0 0.0 0.0 1.9 188 0
10.6
1.6
0.0
6.6 16.0
0.3 4.6
0.0 1.9
185
185
185
185
11.7
2.6
0.1
0.0
1.6
0.0
189
189
189
189
31
10
2
0
26.7
6.2
1.8
0.0
40.5
15.3
8.2
2.9
188
188
188
188
46
18
7
1
24.3
9.5
3.7
0.5
18.4
5.7
1.5
0.0
31.1
14.6
7.5
2.9
188
188
188
188
53
24
11
0
28.2
12.8
5.9
0.0
21.9
8.4
3.0
0.0
35.2
18.4
10.2
1.9
189
189
189
189
41
14
6
1
21.7
7.4
3.2
0.5
16.0
4.1
1.2
0.0
28.3
12.1
6.8
2.9
188
188
188
188
39
14
3
0
20.7
7.4
1.6
0.0
15.2
4.1
0.3
0.0
27.2
12.2
4.6
1.9
185 31 16.8 11.7 22.9 189 35 18.5 13.3 24.8 188 45
23.9
18.0 30.7
> 5 mm
>20 mm
Medical
advice
185 10 5.4
185 2 1.1
185 0 0.0
2.6 9.7 189 14 7.4 4.1 12.1 188 24
0.1 3.9 189 3 1.6 0.3 4.6 188 11
0.0 2.0 189 0 0.0 0.0 1.9 188 0
12.8
5.9
0.0
8.4 18.4
3.0 10.2
0.0 1.9
Any
≥ Grade 2
Grade 3
Medical
advice
Any
≥ Grade 2
Grade 3
Medical
advice
182
182
182
182
Dose 2
38.8 53.7
9.1 19.6
0.0 3.0
0.0 2.0
46.2
13.7
0.5
0.0
22.9
9.7
3.9
2.0
33.3
10.1
4.2
0.5
189
189
189
189
84
25
1
0
16.8
5.4
1.1
0.0
63
19
8
1
184
184
184
184
112
54
10
0
60.9
29.3
5.4
0.0
53.4
22.9
2.6
0.0
68.0
36.5
9.8
2.0
179
179
179
179
93
32
6
0
52.0
17.9
3.4
0.0
44.4
12.6
1.2
0.0
59.5
24.3
7.2
2.0
184
184
184
184
104
47
9
0
56.5
25.5
4.9
0.0
49.0
19.4
2.3
0.0
63.8
32.5
9.1
2.0
13
13
13
13
6
2
0
0
46.2
15.4
0.0
0.0
19.2
1.9
0.0
0.0
74.9
45.4
24.7
24.7
DTPa-HBVIPV/Hib/DTPaHBV-IPV/DTaPIPV/HIB
Redness
Total
ActHIB/HBV
DTPa-HBVIPV/Hib/DTPaHBV-IPV/DTaPIPV/HIB
Swelling
Total
ActHIB/HBV
DTPa-HBVIPV/Hib/DTPaHBV-IPV/DTaPIPV/HIB
Pain
Total
ActHIB/HBV
Any
182 84 46.2 38.8 53.7 184 108 58.7 51.2 65.9 179 93
52.0
44.4 59.5
≥ Grade 2
Grade 3
Medical
advice
Any
> 5 mm
>20 mm
Medical
advice
Any
> 5 mm
>20 mm
Medical
advice
Any
182 25 13.7 9.1 19.6 184 44 23.9 17.9 30.7 179 31
182 1 0.5 0.0 3.0 184 7 3.8 1.5 7.7 179 6
182 0 0.0 0.0 2.0 184 0 0.0 0.0 2.0 179 0
17.3
3.4
0.0
12.1 23.7
1.2 7.2
0.0 2.0
182 57 31.3 24.7 38.6 184
182 15 8.2 4.7 13.2 184
182 3 1.6 0.3 4.7 184
184
77
22
3
0
41.8
12.0
1.6
0.0
34.6
7.6
0.3
0.0
49.3
17.5
4.7
2.0
179
179
179
13
64
16
2
0
35.8
8.9
1.1
0.0
28.7
5.2
0.1
0.0
43.2
14.1
4.0
24.7
184
184
184
0.0 2.0 184
66
17
1
0
35.9
9.2
0.5
0.0
28.9
5.5
0.0
0.0
43.3
14.4
3.0
2.0
13
13
13
179
5
1
0
0
38.5
7.7
0.0
0.0
13.9
0.2
0.0
0.0
68.4
36.0
24.7
2.0
182 57 31.3 24.7 38.6 184 61 33.2 26.4 40.5 179 64
35.8
28.7 43.2
> 5 mm
>20 mm
Medical
advice
Any
> 5 mm
>20 mm
Medical
advice
Any
> 5 mm
>20 mm
Medical
advice
Any
182 15 8.2
182 3 1.6
182 0 0.0
4.7 13.2 184 12 6.5 3.4 11.1 179 15
0.3 4.7 184 3 1.6 0.3 4.7 179 2
0.0 2.0 184 0 0.0 0.0 2.0 179 0
8.4
1.1
0.0
4.8 13.4
0.1 4.0
0.0 2.0
182
182
182
182
16.2
2.7
0.1
0.0
182 0
40
10
2
0
0.0
184
184
184
184
51
16
2
0
27.7
8.7
1.1
0.0
21.4
5.1
0.1
0.0
34.8
13.7
3.9
2.0
179
179
179
179
44
7
3
0
24.6
3.9
1.7
0.0
18.5
1.6
0.3
0.0
31.6
7.9
4.8
2.0
184
184
184
184
40
11
1
0
21.7
6.0
0.5
0.0
16.0
3.0
0.0
0.0
28.4
10.4
3.0
2.0
13
13
13
13
3
0
0
0
23.1
0.0
0.0
0.0
5.0
0.0
0.0
0.0
53.8
24.7
24.7
24.7
182 40 22.0 16.2 28.7 184 40 21.7 16.0 28.4 179 42
23.5
17.5 30.4
> 5 mm
>20 mm
Medical
advice
182 10 5.5
182 2 1.1
182 0 0.0
2.7 9.9 184 12 6.5 3.4 11.1 179 7
0.1 3.9 184 2 1.1 0.1 3.9 179 3
0.0 2.0 184 0 0.0 0.0 2.0 179 0
3.9
1.7
0.0
1.6
0.3
0.0
7.9
4.8
2.0
Any
≥ Grade 2
Grade 3
Medical
advice
Any
≥ Grade 2
Grade 3
Medical
advice
172
172
172
172
Dose 3
31.6 46.7
6.3 16.0
0.0 2.1
0.0 2.1
67
18
0
0
22.0
5.5
1.1
0.0
39.0
10.5
0.0
0.0
28.7
9.9
3.9
2.0
175
175
175
175
98
45
8
1
56.0
25.7
4.6
0.6
48.3
19.4
2.0
0.0
63.5
32.9
8.8
3.1
171
171
171
171
83
28
7
0
48.5
16.4
4.1
0.0
40.8
11.2
1.7
0.0
56.3
22.8
8.3
2.1
175
175
175
175
93
41
7
1
53.1
23.4
4.0
0.6
45.5
17.4
1.6
0.0
60.7
30.4
8.1
3.1
169
169
169
169
75
25
5
0
44.4
14.8
3.0
0.0
36.8
9.8
1.0
0.0
52.2
21.1
6.8
2.2
DTPa-HBVIPV/Hib/DTPaHBV-IPV/DTaPIPV/HIB
Redness
Total
ActHIB/HBV
DTPa-HBVIPV/Hib/DTPaHBV-IPV/DTaPIPV/HIB
Swelling
Total
ActHIB/HBV
DTPa-HBVIPV/Hib/DTPaHBV-IPV/DTaPIPV/HIB
Pain
Total
ActHIB/HBV
Any
172 67 39.0 31.6 46.7 175 90 51.4 43.8 59.0 170 76
44.7
37.1 52.5
≥ Grade 2
Grade 3
Medical
advice
Any
> 5 mm
>20 mm
Medical
advice
Any
> 5 mm
>20 mm
Medical
advice
Any
172 18 10.5 6.3 16.0 175 39 22.3 16.4 29.2 170 20
172 0 0.0 0.0 2.1 175 7 4.0 1.6 8.1 170 7
172 0 0.0 0.0 2.1 175 1 0.6 0.0 3.1 170 0
11.8
4.1
0.0
7.3 17.6
1.7 8.3
0.0 2.1
172
172
172
172
175
175
175
175
81
14
4
1
46.3
8.0
2.3
0.6
38.7
4.4
0.6
0.0
54.0
13.1
5.7
3.1
171
171
171
171
65
16
2
0
38.0
9.4
1.2
0.0
30.7
5.4
0.1
0.0
45.7
14.7
4.2
2.1
175
175
175
175
69
7
1
0
39.4
4.0
0.6
0.0
32.1
1.6
0.0
0.0
47.1
8.1
3.1
2.1
169
169
169
169
51
9
2
0
30.2
5.3
1.2
0.0
23.4
2.5
0.1
0.0
37.7
9.9
4.2
2.2
172 63 36.6 29.4 44.3 175 66 37.7 30.5 45.3 170 56
32.9
25.9 40.6
> 5 mm
>20 mm
Medical
advice
Any
> 5 mm
>20 mm
Medical
advice
Any
> 5 mm
>20 mm
Medical
advice
Any
172 7
172 2
172 0
4.1
1.2
0.0
1.7 8.2 175 12 6.9 3.6 11.7 170 11
0.1 4.1 175 3 1.7 0.4 4.9 170 0
0.0 2.1 175 1 0.6 0.0 3.1 170 0
6.5
0.0
0.0
3.3 11.3
0.0 2.1
0.0 2.1
172
172
172
172
25.0
4.1
0.6
0.0
18.7
1.7
0.0
0.0
> 5 mm
>20 mm
Medical
advice
Any
63
7
2
0
43
7
1
0
36.6
4.1
1.2
0.0
29.4
1.7
0.1
0.0
44.3
8.2
4.1
2.1
175
175
175
175
53
12
3
1
30.3
6.9
1.7
0.6
23.6
3.6
0.4
0.0
37.7
11.7
4.9
3.1
171
171
171
171
44
8
0
0
25.7
4.7
0.0
0.0
19.4
2.0
0.0
0.0
33.0
9.0
2.1
2.1
175
175
175
175
42
7
1
0
24.0
4.0
0.6
0.0
17.9
1.6
0.0
0.0
31.0
8.1
3.1
2.1
169
169
169
169
37
7
0
0
21.9
4.1
0.0
0.0
15.9
1.7
0.0
0.0
28.9
8.3
2.2
2.2
172 43 25.0 18.7 32.2 175 44 25.1 18.9 32.2 170 35
20.6
14.8 27.5
172 7
172 1
172 0
2.4
0.0
0.0
0.6
0.0
0.0
Across doses
67.9 60.7 74.5 189 155 82.0 75.8 87.2 188 150
79.8
73.3 85.3
31.0 24.5 38.2 189 104 55.0 47.6 62.3 188 88
4.3 1.9 8.3 189 34 18.0 12.8 24.2 188 22
0.5 0.0 2.9 189 2 1.1 0.1 3.8 188 0
46.8
11.7
0.0
39.5 54.2
7.5 17.2
0.0 1.9
189 148 78.3 71.7 84.0 188 127
189 96 50.8 43.4 58.1 188 62
189 30 15.9 11.0 21.9 188 14
67.6
33.0
7.4
60.4 74.2
26.3 40.2
4.1 12.2
187 12
7
≥ Grade 2 187 58
Grade 3 187 8
Medical 187 1
advice
Any
≥ Grade 2
Grade 3
4.1
0.6
0.0
32.2
8.2
3.2
2.1
1.7 8.2 175 10 5.7 2.8 10.3 170 4
0.0 3.2 175 3 1.7 0.4 4.9 170 0
0.0 2.1 175 1 0.6 0.0 3.1 170 0
5.9
2.1
2.1
DTPa-HBVIPV/Hib/DTPaHBV-IPV/DTaPIPV/HIB
Redness
Total
ActHIB/HBV
DTPa-HBVIPV/Hib/DTPaHBV-IPV/DTaPIPV/HIB
Swelling
Total
ActHIB/HBV
DTPa-HBVIPV/Hib/DTPaHBV-IPV/DTaPIPV/HIB
Medical
advice
Any
189 2
1.1 0.1 3.8 188 0
0.0
0.0
1.9
187 12
7
≥ Grade 2 187 58
Grade 3 187 8
Medical 187 1
advice
Any
187 93
> 5 mm 187 27
>20 mm 187 7
Medical 187 0
advice
Any
> 5 mm
>20
Medical
advice
Any
187 93
> 5 mm 187 27
>20 mm 187 7
67.9 60.7 74.5 189 151 79.9 73.5 85.4 188 147
78.2
71.6 83.9
31.0 24.5 38.2 189 93 49.2 41.9 56.6 188 80
4.3 1.9 8.3 189 27 14.3 9.6 20.1 188 22
0.5 0.0 2.9 189 1 0.5 0.0 2.9 188 0
42.6
11.7
0.0
35.4 50.0
7.5 17.2
0.0 1.9
49.7
14.4
3.7
0.0
Medical
advice
Any
> 5 mm
>20 mm
Medical
advice
Any
> 5 mm
>20 mm
Medical
advice
Any
> 5 mm
>20 mm
189
189
189
189
120
49
15
2
63.5
25.9
7.9
1.1
56.2
19.8
4.5
0.1
70.4
32.8
12.8
3.8
188
188
188
188
106
45
8
0
56.4
23.9
4.3
0.0
49.0
18.0
1.9
0.0
63.6
30.7
8.2
1.9
189
189
189
189
108
38
10
1
57.1
20.1
5.3
0.5
49.8
14.6
2.6
0.0
64.3
26.5
9.5
2.9
188
188
188
188
77
20
3
0
41.0
10.6
1.6
0.0
33.9
6.6
0.3
0.0
48.3
16.0
4.6
1.9
49.7 42.4 57.1 189 98 51.9 44.5 59.2 188 97
14.4 9.7 20.3 189 32 16.9 11.9 23.1 188 37
3.7 1.5 7.6 189 9 4.8 2.2 8.8 188 5
51.6
19.7
2.7
44.2 58.9
14.3 26.1
0.9 6.1
187 0
0.0
0.0 2.0 189 1
0.5 0.0 2.9 188 0
0.0
0.0
1.9
187
187
187
187
38.5
10.7
2.1
0.0
31.5
6.7
0.6
0.0
72
20
4
0
42.4
9.7
1.5
0.0
57.1
20.3
7.6
2.0
45.9
16.0
5.4
2.0
189
189
189
189
88
34
11
2
46.6
18.0
5.8
1.1
39.3
12.8
2.9
0.1
53.9
24.2
10.2
3.8
188
188
188
188
81
29
12
0
43.1
15.4
6.4
0.0
35.9
10.6
3.3
0.0
50.5
21.4
10.9
1.9
189
189
189
189
78
25
7
1
41.3
13.2
3.7
0.5
34.2
8.7
1.5
0.0
48.6
18.9
7.5
2.9
188
188
188
188
64
18
3
0
34.0
9.6
1.6
0.0
27.3
5.8
0.3
0.0
41.3
14.7
4.6
1.9
187 72 38.5 31.5 45.9 189 70 37.0 30.1 44.3 188 72
187 20 10.7 6.7 16.0 189 26 13.8 9.2 19.5 188 26
187 4 2.1 0.6 5.4 189 7 3.7 1.5 7.5 188 12
38.3
13.8
6.4
31.3 45.7
9.2 19.6
3.3 10.9
Medical 187 0 0.0 0.0 2.0 189 1 0.5 0.0 2.9 188 0
0.0
0.0 1.9
advice
N = number of subjects with at least one documented dose
n/% = number/percentage of subjects reporting the symptom at least once95%CI = Exact 95% confidence interval; LL = lower
limit, UL = upper limit
Any = any reports of the specified symptom irrespective of intensity grade
Grade 2 Pain = Moderate: Cries/protests on touch
Grade 3 Pain = Severe: Cries when limb is moved/spontaneously painful.
Grade 2 Redness/Swelling: > 5 mm
Grade 3 Redness/Swelling: >20 mm
Secondary Outcome Results: Number (%) of subjects reporting solicited general symptom during the 4-day (Days 0-3) postvaccination period following each dose and across doses (Primary Total Vaccinated cohort)
DTPa-HBV/Hib Group
DTPa-HBV Group
DTaP/HIB Group
95 % CI
95 % CI
95 % CI
Symptom
Intensity/Relati N
n
% LL UL N
n
% LL UL N
n
% LL UL
onship
Dose 1
Drowsiness
Any
185 114 61.6 54.2 68.7 189 143 75.7 68.9 81.6 188 149 79.3 72.8 84.8
Irritability / Fussiness
Loss Of Appetite
Temperature
Drowsiness
Irritability / Fussiness
Loss Of Appetite
Temperature
≥ Grade 2
Grade 3
Related
Grade 3
Related
Medical advice
Any
≥ Grade 2
Grade 3
Related
Grade 3
Related
Medical advice
Any
≥ Grade 2
Grade 3
Related
Grade 3
Related
Medical advice
≥ 38.0°C
>39.0 °C
>40.0°C
Related
>40.0 °C
Related
Medical advice
185 36 19.5
185 3 1.6
185 112 60.5
185 3 1.6
Any
≥ Grade 2
Grade 3
Related
Grade 3
Related
Medical advice
Any
≥ Grade 2
Grade 3
Related
Grade 3
Related
Medical advice
Any
≥ Grade 2
Grade 3
Related
Grade 3
Related
Medical advice
≥ 38.0°C
>39.0°C
>40.0°C
Related
>40.0°C
Related
Medical advice
182
182
182
182
182
14.0
0.3
53.1
0.3
25.9
4.7
67.6
4.7
189 56 29.6
189 8 4.2
189 136 72.0
189 7 3.7
23.2
1.8
65.0
1.5
36.7
8.2
78.2
7.5
188 53 28.2
188 12 6.4
188 141 75.0
188 12 6.4
21.9
3.3
68.2
3.3
35.2
10.9
81.0
10.9
185 1 0.5 0.0 3.0 189 0 0.0 0.0 1.9 188 0 0.0 0.0 1.9
185 115 62.2 54.8 69.2 189 165 87.3 81.7 91.7 188 153 81.4 75.1 86.7
185 42 22.7 16.9 29.4 189 79 41.8 34.7 49.2 188 68 36.2 29.3 43.5
185 9 4.9 2.2 9.0 189 17 9.0 5.3 14.0 188 15 8.0 4.5 12.8
185 113 61.1 53.7 68.1 189 163 86.2 80.5 90.8 188 147 78.2 71.6 83.9
185 9 4.9 2.2 9.0 189 17 9.0 5.3 14.0 188 15 8.0 4.5 12.8
185
185
185
185
185
185
1 0.5 0.0 3.0 189
53 28.6 22.3 35.7 189
8 4.3 1.9 8.3 189
0 0.0 0.0 2.0 189
48 25.9 19.8 32.9 189
0 0.0 0.0 2.0 189
0 0.0 0.0 1.9 188
76 40.2 33.2 47.6 188
13 6.9 3.7 11.5 188
1 0.5 0.0 2.9 188
73 38.6 31.6 46.0 188
1 0.5 0.0 2.9 188
0 0.0 0.0 1.9
80 42.6 35.4 50.0
26 13.8 9.2 19.6
4 2.1 0.6 5.4
77 41.0 33.9 48.3
4 2.1 0.6 5.4
185
185
185
185
185
185
0 0.0 0.0 2.0 189
22 11.9 7.6 17.4 189
0 0.0 0.0 2.0 189
0 0.0 0.0 2.0 189
15 8.1 4.6 13.0 189
0 0.0 0.0 2.0 189
0 0.0 0.0 1.9 188
34 18.0 12.8 24.2 188
0 0.0 0.0 1.9 188
0 0.0 0.0 1.9 188
31 16.4 11.4 22.5 188
0 0.0 0.0 1.9 188
0 0.0 0.0 1.9
29 15.4 10.6 21.4
2 1.1 0.1 3.8
0 0.0 0.0 1.9
27 14.4 9.7 20.2
0 0.0 0.0 1.9
185
0
0
0
0.0 0.0 2.0
Dose 2
97 53.3 45.8 60.7
31 17.0 11.9 23.3
8 4.4 1.9 8.5
94 51.6 44.1 59.1
7 3.8 1.6 7.8
189
0.0 0.0 1.9 188
0.0 0.0
1.9
184 132 71.7 64.6 78.1 179 109 60.9 53.3 68.1
184 43 23.4 17.5 30.2 179 39 21.8 16.0 28.6
184 7 3.8 1.5 7.7 179 4 2.2 0.6 5.6
184 126 68.5 61.2 75.1 179 108 60.3 52.8 67.6
184 7 3.8 1.5 7.7 179 3 1.7 0.3 4.8
182 0 0.0 0.0 2.0 184 0 0.0 0.0 2.0 179 0 0.0 0.0 2.0
182 128 70.3 63.1 76.9 184 147 79.9 73.4 85.4 179 136 76.0 69.0 82.0
182 53 29.1 22.6 36.3 184 70 38.0 31.0 45.5 179 61 34.1 27.2 41.5
182 6 3.3 1.2 7.0 184 14 7.6 4.2 12.4 179 11 6.1 3.1 10.7
182 125 68.7 61.4 75.3 184 143 77.7 71.0 83.5 179 133 74.3 67.2 80.5
182 6 3.3 1.2 7.0 184 13 7.1 3.8 11.8 179 11 6.1 3.1 10.7
182
182
182
182
182
182
0 0.0 0.0 2.0 184
56 30.8 24.2 38.0 184
17 9.3 5.5 14.5 184
1 0.5 0.0 3.0 184
52 28.6 22.1 35.7 184
1 0.5 0.0 3.0 184
0 0.0 0.0 2.0 179
55 29.9 23.4 37.1 179
15 8.2 4.6 13.1 179
1 0.5 0.0 3.0 179
51 27.7 21.4 34.8 179
1 0.5 0.0 3.0 179
2 1.1 0.1 4.0
56 31.3 24.6 38.6
15 8.4 4.8 13.4
2 1.1 0.1 4.0
55 30.7 24.1 38.0
2 1.1 0.1 4.0
182
182
182
182
182
182
0 0.0 0.0 2.0 184
47 25.8 19.6 32.8 184
2 1.1 0.1 3.9 184
0 0.0 0.0 2.0 184
37 20.3 14.7 26.9 184
0 0.0 0.0 2.0 184
0 0.0 0.0 2.0 179
36 19.6 14.1 26.0 179
3 1.6 0.3 4.7 179
0 0.0 0.0 2.0 179
32 17.4 12.2 23.7 179
0 0.0 0.0 2.0 179
1 0.6 0.0 3.1
34 19.0 13.5 25.5
2 1.1 0.1 4.0
0 0.0 0.0 2.0
32 17.9 12.6 24.3
0 0.0 0.0 2.0
182
0
0
0
0.0 0.0 2.0 184
0.0 0.0 2.0 179
0.0 0.0
2.0
Drowsiness
Irritability / Fussiness
Loss Of Appetite
Temperature
Drowsiness
Irritability / Fussiness
Loss Of Appetite
Temperature
Dose 3
86 50.0 42.3 57.7 175 108 61.7 54.1 68.9 170
24 14.0 9.1 20.0 175 37 21.1 15.3 27.9 170
3 1.7 0.4 5.0 175 5 2.9 0.9 6.5 170
82 47.7 40.0 55.4 175 106 60.6 52.9 67.9 170
3 1.7 0.4 5.0 175 5 2.9 0.9 6.5 170
Any
≥ Grade 2
Grade 3
Related
Grade 3
Related
Medical advice
Any
≥ Grade 2
Grade 3
Related
Grade 3
Related
Medical advice
Any
≥ Grade 2
Grade 3
Related
Grade 3
Related
Medical advice
≥ 38.0°C
>39.0°C
>40.0°C
Related
>40.0°C
Related
Medical advice
172
172
172
172
172
Any
≥ Grade 2
Grade 3
Related
Grade 3
Related
Medical advice
Any
≥ Grade 2
Grade 3
Related
Grade 3
Related
Medical advice
Any
≥ Grade 2
Grade 3
Related
Grade 3
Related
Medical advice
≥ 38.0°C
>39.0°C
>40.0°C
Related
187 148
187 67
187 11
187 145
187 11
88 51.8 44.0 59.5
25 14.7 9.7 20.9
9 5.3 2.4 9.8
86 50.6 42.8 58.3
9 5.3 2.4 9.8
172 0 0.0 0.0 2.1 175 2 1.1 0.1 4.1 170 1 0.6 0.0 3.2
172 126 73.3 66.0 79.7 175 135 77.1 70.2 83.1 170 122 71.8 64.4 78.4
172 46 26.7 20.3 34.0 175 58 33.1 26.2 40.6 170 58 34.1 27.0 41.8
172 6 3.5 1.3 7.4 175 15 8.6 4.9 13.7 170 11 6.5 3.3 11.3
172 121 70.3 62.9 77.1 175 130 74.3 67.1 80.6 170 120 70.6 63.1 77.3
172 6 3.5 1.3 7.4 175 13 7.4 4.0 12.4 170 11 6.5 3.3 11.3
172
172
172
172
172
172
0 0.0 0.0 2.1 175
46 26.7 20.3 34.0 175
11 6.4 3.2 11.2 175
1 0.6 0.0 3.2 175
44 25.6 19.2 32.8 175
1 0.6 0.0 3.2 175
3 1.7 0.4 4.9 170
58 33.1 26.2 40.6 170
13 7.4 4.0 12.4 170
2 1.1 0.1 4.1 170
57 32.6 25.7 40.1 170
2 1.1 0.1 4.1 170
1 0.6 0.0 3.2
53 31.2 24.3 38.7
15 8.8 5.0 14.1
2 1.2 0.1 4.2
52 30.6 23.8 38.1
2 1.2 0.1 4.2
172
172
172
172
172
172
0 0.0 0.0 2.1 175
40 23.3 17.2 30.3 175
4 2.3 0.6 5.8 175
0 0.0 0.0 2.1 175
35 20.3 14.6 27.1 175
0 0.0 0.0 2.1 175
1 0.6 0.0 3.1 170
45 25.7 19.4 32.9 170
11 6.3 3.2 11.0 170
2 1.1 0.1 4.1 170
39 22.3 16.4 29.2 170
2 1.1 0.1 4.1 170
0 0.0 0.0 2.1
37 21.8 15.8 28.7
7 4.1 1.7 8.3
0 0.0 0.0 2.1
35 20.6 14.8 27.5
0 0.0 0.0 2.1
172
1
0.6 0.0 3.2 175 2 1.1 0.1 4.1 170 1 0.6 0.0 3.2
Across doses
79.1 72.6 84.7 189 172 91.0 86.0 94.7 188 168 89.4 84.0 93.4
35.8 29.0 43.2 189 88 46.6 39.3 53.9 188 81 43.1 35.9 50.5
5.9 3.0 10.3 189 19 10.1 6.2 15.3 188 22 11.7 7.5 17.2
77.5 70.9 83.3 189 170 89.9 84.7 93.8 188 166 88.3 82.8 92.5
5.9 3.0 10.3 189 18 9.5 5.7 14.6 188 21 11.2 7.0 16.6
187 1 0.5 0.0 2.9 189 2 1.1 0.1 3.8 188 1 0.5 0.0 2.9
187 164 87.7 82.1 92.0 189 182 96.3 92.5 98.5 188 177 94.1 89.8 97.0
187 96 51.3 43.9 58.7 189 128 67.7 60.6 74.3 188 120 63.8 56.5 70.7
187 18 9.6 5.8 14.8 189 35 18.5 13.3 24.8 188 30 16.0 11.0 22.0
187 161 86.1 80.3 90.7 189 180 95.2 91.2 97.8 188 175 93.1 88.5 96.3
187 18 9.6 5.8 14.8 189 34 18.0 12.8 24.2 188 30 16.0 11.0 22.0
187
187
187
187
187
187
1 0.5 0.0 2.9 189 3 1.6 0.3 4.6 188 3 1.6 0.3 4.6
95 50.8 43.4 58.2 189 111 58.7 51.4 65.8 188 117 62.2 54.9 69.2
28 15.0 10.2 20.9 189 32 16.9 11.9 23.1 188 39 20.7 15.2 27.2
2 1.1 0.1 3.8 189 3 1.6 0.3 4.6 188 6 3.2 1.2 6.8
91 48.7 41.3 56.1 189 109 57.7 50.3 64.8 188 116 61.7 54.3 68.7
2 1.1 0.1 3.8 189 3 1.6 0.3 4.6 188 6 3.2 1.2 6.8
187
187
187
187
187
0 0.0 0.0 2.0 189
72 38.5 31.5 45.9 189
6 3.2 1.2 6.9 189
0 0.0 0.0 2.0 189
61 32.6 26.0 39.8 189
1 0.5 0.0 2.9 188
78 41.3 34.2 48.6 188
14 7.4 4.1 12.1 188
2 1.1 0.1 3.8 188
74 39.2 32.2 46.5 188
1 0.5 0.0 2.9
71 37.8 30.8 45.1
10 5.3 2.6 9.6
0 0.0 0.0 1.9
68 36.2 29.3 43.5
>40.0°C
187 0 0.0 0.0 2.0 189 2 1.1 0.1 3.8 188 0 0.0 0.0 1.9
Related
Medical advice 187 1 0.5 0.0 2.9 189 2 1.1 0.1 3.8 188 1 0.5 0.0 2.9
N = number of subjects with at least one documented dose
n/% = number/percentage of subjects reporting the symptom at least once
95%CI = Exact 95% confidence interval; LL = lower limit, UL = upper limit
Any = any reports of the specified symptom irrespective of intensity grade
Related = Symptoms which is assessed by the investigator as related to vaccination
Grade 2 Drowsiness, Irritability/Fussiness: Moderate: Interfered with normal activity
Grade 2 Loss of appetite: Moderate: Ate less than usual/interfered with normal activity
Grade 3 Drowsiness: Severe: Drowsiness that prevents normal activity
Grade 3 Irritability: Severe: Crying that cannot be comforted/prevents normal activity
Grade 3 Loss of appetite: Severe: Not eating at all
Grade 2 Temperature: >39.0°C
Grade 3 Temperature: >40.0°C
Secondary Outcome Results: Number (%) of subjects with NOCD events reported till Database Freeze date (19 Jun 2015) for
Primary Epoch analysis (Primary Total Vaccinated cohort)
Most frequent adverse events DTPa-HBV/Hib
DTPa-HBV
DTaP/HIB Group
On-Therapy (up to the database freeze date)
Group
Group
N = 196
N = 195
N = 194
Subjects with any AE(s), n (%)
4 (2.1)
2 (1.0)
3 (1.5)
Dermatitis atopic
2 (1.0)
2 (1.0)
Bronchial hyperreactivity
2 (1.0)
Asthma
1 (0.5)
Drug hypersensitivity
1 (0.5)
Food allergy
1 (0.5)
Hypersensitivity
1 (0.5)
- : Adverse event absent
Note: The data presented represents data up to the date of the database freeze, which was before the completion of the full 6
months of safety following up after dose 3.
Safety Results: Number (%) of subjects with AEs reported during 31-day (Days 0-30) post-vaccination period (Primary Total
Vaccinated cohort)
Most frequent adverse events DTPa-HBV/Hib
DTPa-HBV
DTaP/HIB Group
On-Therapy (occurring within day 0-30 following
Group
Group
N = 196
vaccination)
N = 195
N = 194
Subjects with any AE(s), n (%)
111 (56.9)
108 (55.7)
96 (49.0)
Upper respiratory tract infection
29 (14.9)
23 (11.9)
26 (13.3)
Pyrexia
11 (5.6)
5 (2.6)
15 (7.7)
Cough
15 (7.7)
7 (3.6)
7 (3.6)
Vomiting
9 (4.6)
8 (4.1)
10 (5.1)
Otitis media
9 (4.6)
7 (3.6)
9 (4.6)
Diarrhoea
6 (3.1)
5 (2.6)
10 (5.1)
Teething
5 (2.6)
8 (4.1)
8 (4.1)
Conjunctivitis
10 (5.1)
8 (4.1)
Injection site pain
4 (2.1)
6 (3.1)
7 (3.6)
Dermatitis diaper
9 (4.6)
Eczema
4 (2.1)
5 (2.6)
Gastrooesophageal reflux disease
8 (4.1)
Constipation
6 (3.1)
Nasal congestion
6 (3.1)
Rash
6 (3.1)
Injection site erythema
4 (2.1)
Injection site swelling
4 (2.1)
Irritability
4 (2.1)
-
Counting rule applied: As there were more than 30 subjects per treatment group and ≤ 3 groups, only the 10 most frequent
events in each treatment group are to be listed.
-: Implies that adverse event was not reported in the particular group or that the adverse event was reported in the particular
group but did not fall within the pre-defined counting rule of 10 most frequent events for that group.
Safety Results: Number (%) of subjects with SAEs reported till DBF date (19 Jun 2015) for Primary Epoch analysis (Primary
Total Vaccinated cohort)
Serious adverse event, n (%) [n considered by the investigator to be related to study medication]
All SAEs
DTPa-HBV/Hib
DTPa-HBV
DTaP/HIB Group
Group
Group
N = 196
N = 195
N = 194
Subjects with any SAE(s), n (%) [n assessed by the investigator
7 (3.6) [2]
1 (0.5) [0]
7 (3.6) [0]
as related]
Gastroenteritis viral
1 (0.5) [0]
1 (0.5) [0]
0 (0.0) [0]
Parainfluenzae virus infection
0 (0.0) [0]
0 (0.0) [0]
2 (1.0) [0]
Respiratory distress
2 (1.0) [0]
0 (0.0) [0]
0 (0.0) [0]
Respiratory syncytial virus bronchiolitis
1 (0.5) [0]
0 (0.0) [0]
1 (0.5) [0]
Apparent life threatening event
1 (0.5) [1]
0 (0.0) [0]
0 (0.0) [0]
Choking
1 (0.5) [0]
0 (0.0) [0]
0 (0.0) [0]
Dehydration
0 (0.0) [0]
0 (0.0) [0]
1 (0.5) [0]
Febrile convulsion
0 (0.0) [0]
0 (0.0) [0]
1 (0.5) [0]
Gastrooesophageal reflux disease
1 (0.5) [0]
0 (0.0) [0]
0 (0.0) [0]
Hypoxia
1 (0.5) [0]
0 (0.0) [0]
0 (0.0) [0]
Lethargy
1 (0.5) [1]
0 (0.0) [0]
0 (0.0) [0]
Leukocytosis
1 (0.5) [1]
0 (0.0) [0]
0 (0.0) [0]
Meningitis viral
1 (0.5) [0]
0 (0.0) [0]
0 (0.0) [0]
Mental status changes
0 (0.0) [0]
0 (0.0) [0]
1 (0.5) [0]
Pneumonia
0 (0.0) [0]
0 (0.0) [0]
1 (0.5) [0]
Respiratory syncytial virus infection
0 (0.0) [0]
0 (0.0) [0]
1 (0.5) [0]
Road traffic accident
0 (0.0) [0]
0 (0.0) [0]
1 (0.5) [0]
Seizure
1 (0.5) [0]
0 (0.0) [0]
0 (0.0) [0]
Fatal SAEs
DTPa/Hib Group DTPa Group DTaP-IPV/HIB Group
N = 195
N = 194
N = 196
Subjects with fatal SAE(s), n (%) [n assessed by the investigator
0 (0.0) [0]
0 (0.0) [0]
0 (0.0) [0]
as related]
Conclusion: During the 31-day (Days 0-30) period following primary vaccination, at least one unsolicited symptom was
reported for 111 (56.9%) subjects in the DTPa-HBV/Hib Group, 108 (55.7%) of subjects in the DTPa-HBV Group and 96
(49.0%) subjects in the DTaP/HIB Group. During the Primary Phase of the study (Months 0-10), SAEs were reported for 7, 1
and 7 subjects from the DTPa-HBV/Hib, DTPa-HBV and DTaP/HIB groups, respectively. SAEs that were assessed by the
investigator to be causally related to study vaccination were reported for two subjects in the DTPa-HBV/Hib Group
(Lethargy in one subject and Apparent life threatening event and Leukocytosis in the other subject). No fatal SAEs were
reported.
Date updated: 29-September-2015