Clincosm LogoSign in Get a demo

Phase 3 Study of 10-valent Pneumococcal Conjugate Vaccine (PNEUMOSIL) in Healthy Infants

Sponsor
PATH (Other)
Overall Status
Completed
CT.gov ID
NCT03197376
Collaborator
(none)
2,250
Enrollment
1
Location
4
Arms
22.6
Actual Duration (Months)
99.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will examine the consistency of 3 batches of the Pneumosil vaccine by looking at the immune response in infants. In addition, the study will compare the immunogenicity of the Pneumosil vaccine to another WHO-prequalified vaccine, Synflorix.

Condition or Disease Intervention/Treatment Phase
  • Biological: Pneumosil
  • Biological: Synflorix
 Phase 3

Detailed Description

This is a randomized, active-controlled, double-blind, Phase 3 study in 2,250 healthy infants (6 to 8 weeks of age). Subjects will receive 3 doses of either PNEUMOSIL (3 groups receiving vaccine from different lots) or Synflorix (1 group) at 6, 10, and 14 weeks of age. The first 675 randomized subjects will receive a booster dose of either PNEUMOSIL or Synflorix at 9 months of age that matches the treatment assignment for the priming phase. Standard EPI vaccinations in The Gambia will be given concomitantly with all 4 doses of the study vaccines. Out of the 675 booster subjects, subjects who consented for further evaluation will participate for the assessment of immune persistence 12 (+1) months after the booster vaccination

The primary objectives are to demonstrate that the three lots of the Pneumosil vaccine is consistent by evaluating the immune responses, and to demonstrate that the immune responses generated by Pneumosil are non-inferior to those generated by Synflorix. The safety and tolerability of Pneumosil will also be evaluated.

Study Design

Study Type:
Interventional
Actual Enrollment :
2250 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
A Phase 3, Randomized, Double-Blind Study of the Safety, Tolerability, Lot-to-Lot Consistency, Immunogenicity & Non-Interference With Concomitant Vaccinations of Serum Institute of PNEUMOSIL in Healthy Infants in The Gambia
Actual Study Start Date :
Jun 21, 2017
Actual Primary Completion Date :
Jun 6, 2018
Actual Study Completion Date :
May 9, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pneumosil Lot 1

Pneumosil Lot 1

Biological: Pneumosil
10-Valent Pneumococcal Conjugate Vaccine
Experimental: Pneumosil Lot 2

Pneumosil Lot 2

Biological: Pneumosil
10-Valent Pneumococcal Conjugate Vaccine
Experimental: Pneumosil Lot 3

Pneumosil Lot 3

Biological: Pneumosil
10-Valent Pneumococcal Conjugate Vaccine
Active Comparator: Synflorix

Synflorix

Biological: Synflorix
Pneumococcal conjugate vaccine (Non-Typeable Haemophilus influenzae (NTHi) protein D, diphtheria or tetanus toxoid conjugates) adsorbed

Outcome Measures

Primary Outcome Measures

  1. Serotype-specific Geometric Mean Concentration of IgG Antibody [4 weeks after the third dose]

    Serotype-specific concentrations of immunoglobulin G (IgG) antibody measured by ELISA

  2. Number and Percentage of Subjects With Serotype-specific IgG Antibody Responses ≥ 0.35 μg/mL [4 weeks after the third dose]

    Number and Percentage of subjects with serotype-specific IgG Antibody Responses ≥ 0.35 μg/mL

  3. Serotype-specific Geometric Mean Concentration of IgG Antibody [4 weeks after the third dose]

    Serotype-specific immunoglobulin G (IgG) geometric mean concentration (GMC) 4 weeks after the primary series of PNEUMOSIL/Synflorix co-administered with pentavalent, RV and polio vaccines.

  4. Number and Percentage of Subjects With EPI Vaccine Immune Responses (Diphtheria, Tetanus, Hepatitis B, Hib, Polio and Rotavirus) [4 weeks after the third dose]

    Subjects with 1) anti-diphtheria toxoid (DT) and anti-tetanus toxoid (DT) IgG concentration ≥ 0.1 IU/mL; 2) anti-Hepatitis B surface antigen (HBsAg) IgG concentration ≥ 10 mIU/mL; 3) anti-Hib (polyribosylribitol phosphate [PRP]) IgG concentration ≥ 0.15 µg/mL; 4) anti-poliovirus types 1, 2 and 3 neutralizing antibody titers ≥ 1:8; 5) anti-rotavirus IgA concentration ≥ 20 U/mL.

  5. Anti-pertussis Toxoid GMCs for the Pertussis Antigen [4 weeks after the third dose]

    Anti-pertussis toxoid GMCs for the pertussis antigen

  6. Anti Fimbriae 2/3 IgG GMCs for the Pertussis Antigen [4 weeks after the third dose]

    Anti fimbriae 2/3 IgG GMCs for the pertussis antigen

  7. Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 1 [7 days (including day of vaccination)]

    In the primary reactogenicity cohort, local and systemic reactogenicity of the study vaccine was evaluated through day 6 for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [life threatening].

  8. Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 2 [7 days (including day of vaccination)]

    In the primary reactogenicity cohort, local and systemic reactogenicity of the study vaccine was evaluated through day 6 for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [life threatening].

  9. Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 3 [7 days (including day of vaccination)]

    In the primary reactogenicity cohort, local and systemic reactogenicity of the study vaccine was evaluated through day 6 for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [life threatening].

  10. Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Booster [7 days (including day of vaccination)]

    In the primary reactogenicity cohort, local and systemic reactogenicity of the study vaccine was evaluated through day 6 for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [life threatening].

  11. Number and Percentage of All AEs Including SAEs Occurring in Greater Than 1% Subjects by Severity and Relatedness [4 weeks post last vaccination]

    All subjects were followed up for AEs till 4 weeks post vaccination dose 3 and subjects in the booster cohort were followed up for AEs till 4 weeks post booster vaccination

  12. Number and Percentage of All SAEs by Severity and Relatedness [4 weeks post last vaccination]

    All subjects were followed up for SAEs till 4 weeks post vaccination dose 3 and subjects in the booster cohort were followed up for SAEs till 4 weeks post booster vaccination

Secondary Outcome Measures

  1. Number and Percentage of Subjects With 6A and 19A Serotype-specific Concentrations of Immunoglobulin G Antibody [4 weeks after the third dose]

    Subjects with 6A and 19A serotype-specific concentrations of immunoglobulin G (IgG) antibody measured by ELISA

  2. 6A and 19A Serotype Specific Geometric Mean Concentration of IgG Antibody [4 weeks after the third dose]

    6A and 19A Serotype Specific Immune Responses in terms of IgG GMCs measured by ELISA

  3. Number and Percentage of Subjects With Functional Antibody Responses [4 weeks after the third dose]

    Serotype-specific functional antibody titer measured by OPA

  4. Serotype-specific OPA Geometric Mean Titer [4 weeks after the third dose]

    Serotype-specific functional antibody titer measured by OPA and expressed as OPA GMT in a subset

  5. Comparison of Serotype-specific Geometric Mean Concentration of IgG Antibody Response 4 Weeks After a 3-dose Primary Series to 4 Weeks After a Booster Dose [4 weeks post booster vaccination]

    Comparison of Serotype-specific booster responses (antibody concentrations) measured by ELISA from 4 weeks after a 3-dose primary series to 4 weeks after a booster dose

  6. Serotype-specific Geometric Mean Concentration of IgG Antibody Response and Treatment-Group GMC Ratios 4 Weeks After a Booster Dose [4 weeks post booster vaccination]

    Comparison of Serotype-specific booster responses (antibody concentrations) to PNEUMOSIL in comparison to Synflorix 4 weeks after a booster dose

  7. Comparison of Functional Response (OPA) From 4 Weeks After a 3-dose Primary Series to 4 Weeks After a Booster Dose [4 weeks post booster vaccination]

    Comparison of Serotype-specific booster responses (functional response-OPA) from 4 weeks after a 3-dose primary series to 4 weeks after a booster dose

  8. Serotype-specific OPA GMT and Treatment-Group GMT Ratios 4 Weeks After a Booster Dose [4 weeks post booster vaccination]

    Comparison of Serotype-specific booster responses (functional response) to PNEUMOSIL in comparison to Synflorix 4 weeks after a booster dose

  9. Number and Percentage of Subjects With EPI Vaccine Immune Responses (Measles, Rubella and Yellow Fever) [4 weeks post booster vaccination]

    Anti-measles IgG, anti-rubella IgG and anti-yellow fever neutralizing antibody titer

Other Outcome Measures

  1. Proportions and Treatment Group Difference in Proportions of IgG Responders 1 Year Post Booster [One Year Post Booster Vaccination]

    Treatment group proportions and treatment-group difference in proportions of IgG responders (IgG concentration ≥ 0.35 μg/mL)

  2. Serotype-specific Geometric Mean Concentration of IgG Antibody Response and Treatment-Group GMC Ratios One Year Post Booster [One year post booster vaccination]

    Comparison of Serotype-specific immune persistence responses (antibody concentrations) to PNEUMOSIL in comparison to Synflorix one year post booster

  3. Comparison of Serotype-specific Geometric Mean Concentration of IgG Antibody Response 4 Weeks After a Booster Dose to One Year After a Booster Dose [One year post booster vaccination]

    Comparison of Serotype-specific responses (antibody concentrations) measured by ELISA from 4 weeks after a booster dose to one year after a booster dose

  4. Treatment Group Proportions and Treatment-group Difference in Proportions of Functional Antibody Responders (OPA) One Year Post Booster [One year post booster vaccination]

    Serotype-specific functional antibody titer measured by OPA

  5. Serotype-specific OPA Geometric Mean Titer One Year Post Booster [One year post booster vaccination]

    Serotype-specific functional antibody titer measured by OPA and expressed as OPA GMT in a subset one year post booster

  6. Comparison of Functional Response (OPA) From 4 Weeks After a Booster Dose to One Year Post Booster Dose [One year post booster vaccination]

    Comparison of Serotype-specific booster responses (functional response-OPA) from 4 weeks after a booster dose to one year post booster

Eligibility Criteria

Criteria

Ages Eligible for Study:
6 Weeks to 8 Weeks
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:

  • They are healthy infants based on medical history and clinical assessment.

  • They are between 6 and 8 weeks (ie 42 to 56 days) old, inclusive.

  • Subject's parent must provide voluntary written/thumb-printed informed consent and be willing to comply with study requirements and procedures.

Exclusion Criteria:

  • Use of any investigational medicinal product prior to randomization.

  • Previous vaccination against or infection with S. pneumoniae.

  • History of anaphylactic shock or an allergic reaction to any prior vaccination.

  • Any fever, illness (including malaria).

  • Receipt of another vaccine within 30 days of study start.

  • Chronic administration of an immunosuppressant or administration of immunoglobulins

  • History of blood disorder, primary immunodeficiency, or a sibling who has such a diagnosis or who died of suddenly without apparent cause.

  • History of meningitis, seizures or any neurological disorder.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Medical Research Council (MRC) Unit, The Gambia Fajara Gambia

Sponsors and Collaborators

  • PATH

Investigators

  • Principal Investigator: Ed Clarke, Medical Research Council (MRC) Unit, The Gambia

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
PATH
ClinicalTrials.gov Identifier:
NCT03197376
Other Study ID Numbers:
  • VAC-056
First Posted:
Jun 23, 2017
Last Update Posted:
Jul 14, 2020
Last Verified:
Aug 1, 2019
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Pneumonia, Pneumococcal

Study Results

Participant Flow

Recruitment Details Recruitment period: 21 June 2017 to 29 January 2018
Pre-assignment Detail Randomization took place only after a subject had satisfied all eligibility criteria. Subjects were randomized in a 2:2:2:3 ratio based on a pre-established randomization scheme.
Arm/Group Title Pneumosil Lot 1 Pneumosil Lot 2 Pneumosil Lot 3 Synflorix
Arm/Group Description 10-Valent Pneumococcal Conjugate Vaccine Lot 1 10-Valent Pneumococcal Conjugate Vaccine Lot 2 10-Valent Pneumococcal Conjugate Vaccine Lot 3 Pneumococcal conjugate vaccine (Non-Typeable Haemophilus influenzae (NTHi) protein D, diphtheria or tetanus toxoid conjugates) adsorbed
Period Title: Primary and Booster Phase
STARTED 502 501 500 747
Vaccinated-Dose 1 502 501 500 747
Vaccinated-Dose 2 495 495 491 738
Vaccinated-Dose 3 492 493 490 731
Primary Reactogenicity Cohort 251 243 257 364
Booster Cohort 150 151 150 224
Received Booster Vaccine 145 144 139 213
COMPLETED 487 488 480 722
NOT COMPLETED 15 13 20 25
Period Title: Primary and Booster Phase
STARTED 132 133 128 195
COMPLETED 127 129 123 190
NOT COMPLETED 5 4 5 5

Baseline Characteristics

Arm/Group Title Pneumosil Lot 1 Pneumosil Lot 2 Pneumosil Lot 3 Synflorix Total
Arm/Group Description Three doses of Pneumosil Lot 1 Three doses of Pneumosil Lot 2 Three doses of Pneumosil Lot 3 Three doses of Synflorix Total of all reporting groups
Overall Participants 502 501 500 747 2250
Age (Days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Days]
47.0
(3.78)
47.1
(4.10)
47.3
(4.03)
47.1
(4.05)
47.2
(4.01)
Sex: Female, Male (Count of Participants)
Female
252
50.2%
241
48.1%
245
49%
347
46.5%
1085
48.2%
Male
250
49.8%
260
51.9%
255
51%
400
53.5%
1165
51.8%
Race/Ethnicity, Customized (Count of Participants)
Race-African
502
100%
500
99.8%
500
100%
747
100%
2249
100%
Race-Other
0
0%
1
0.2%
0
0%
0
0%
1
0%
Ethnicity-Mandinka
264
52.6%
256
51.1%
257
51.4%
397
53.1%
1174
52.2%
Ethnicity-Wolof
47
9.4%
58
11.6%
51
10.2%
61
8.2%
217
9.6%
Ethnicity-Fula
61
12.2%
63
12.6%
62
12.4%
86
11.5%
272
12.1%
Ethnicity-Jola
63
12.5%
54
10.8%
63
12.6%
100
13.4%
280
12.4%
Ethnicity-Serahule
11
2.2%
16
3.2%
20
4%
29
3.9%
76
3.4%
Ethnicity-Serere
21
4.2%
14
2.8%
13
2.6%
21
2.8%
69
3.1%
Ethnicity-Manjago
8
1.6%
11
2.2%
5
1%
11
1.5%
35
1.6%
Ethnicity-Other
26
5.2%
29
5.8%
29
5.8%
42
5.6%
126
5.6%
Region of Enrollment (participants) [Number]
Gambia
502
100%
501
100%
500
100%
747
100%
2250
100%

Outcome Measures

1. Primary Outcome
Title Serotype-specific Geometric Mean Concentration of IgG Antibody
Description Serotype-specific concentrations of immunoglobulin G (IgG) antibody measured by ELISA
Time Frame 4 weeks after the third dose

Outcome Measure Data

Analysis Population Description
All subjects who received all primary series doses of study vaccines, had post-dose immunogenicity measurement(s) with no major protocol deviations
Arm/Group Title Lot 1 Lot 2 Lot 3
Arm/Group Description Three doses of Pneumosil Lot 1 Three doses of Pneumosil Lot 2 Three doses of Pneumosil Lot 3
Measure Participants 487 490 481
Pn IgG Type 1
4.08
4.24
4.58
Pn IgG Type 5
1.34
1.80
1.84
Pn IgG Type 6A
1.05
0.95
1.01
Pn IgG Type 6B
1.30
0.92
1.49
Pn IgG Type 7F
2.79
2.55
3.70
Pn IgG Type 9V
1.28
1.19
1.46
Pn IgG Type 14
4.99
5.37
5.25
Pn IgG Type 19A
1.53
1.66
1.74
Pn IgG Type 19F
4.20
5.02
3.89
Pn IgG Type 23F
1.61
1.57
1.56
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for each serotype 1, Lot 1 and Lot 2 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 1 GMC Ratio
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.88 to 1.05
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 5, Lot 1 and Lot 2 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 5 GMC Ratio
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.69 to 0.81
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 6A, Lot 1 and Lot 2 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6A GMC Ratio
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
0.96 to 1.26
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 6B, Lot 1 and Lot 2 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6B GMC Ratio
Estimated Value 1.41
Confidence Interval (2-Sided) 95%
1.18 to 1.69
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 7F, Lot 1 and Lot 2 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 7F GMC Ratio
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.99 to 1.20
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 9V, Lot 1 and Lot 2 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 9V GMC Ratio
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.98 to 1.18
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 14, Lot 1 and Lot 2 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 14 GMC Ratio
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.81 to 1.07
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 19A, Lot 1 and Lot 2 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19A GMC Ratio
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.83 to 1.04
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 19F, Lot 1 and Lot 2 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19F GMC Ratio
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.76 to 0.92
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 23F, Lot 1 and Lot 2 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 23F GMC Ratio
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.91 to 1.15
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 3
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 1, Lot 1 and Lot 3 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 1 GMC Ratio
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.82 to 0.97
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 3
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 5, Lot 1 and Lot 3 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 5 GMC Ratio
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.67 to 0.80
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 3
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 6A, Lot 1 and Lot 3 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6A GMC Ratio
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.91 to 1.20
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 3
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 6B, Lot 1 and Lot 3 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6B GMC Ratio
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.74 to 1.04
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 3
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 7F, Lot 1 and Lot 3 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 7F GMC Ratio
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.68 to 0.83
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 3
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 9V, Lot 1 and Lot 3 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 9V GMC Ratio
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.80 to 0.97
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 3
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 14, Lot 1 and Lot 3 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 14 GMC Ratio
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.83 to 1.09
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 3
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 19A, Lot 1 and Lot 3 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19A GMC Ratio
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.79 to 0.98
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 3
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 19F, Lot 1 and Lot 3 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19F GMC Ratio
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.97 to 1.20
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 3
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 24F, Lot 1 and Lot 3 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 23F GMC Ratio
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.92 to 1.15
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Lot 2, Lot 3
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 1, Lot 2 and Lot 3 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 1 GMC Ratio
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.85 to 1.01
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Lot 2, Lot 3
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 5, Lot 2 and Lot 3 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 5 GMC Ratio
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.90 to 1.07
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Lot 2, Lot 3
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 6A, Lot 2 and Lot 3 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6A GMC Ratio
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.82 to 1.09
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Lot 2, Lot 3
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 6B, Lot 2 and Lot 3 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6B GMC Ratio
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.52 to 0.74
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Lot 2, Lot 3
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 7F, Lot 2 and Lot 3 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 7F GMC Ratio
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.62 to 0.76
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Lot 2, Lot 3
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 9V, Lot 2 and Lot 3 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 9V GMC Ratio
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.74 to 0.90
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Lot 2, Lot 3
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 14, Lot 2 and Lot 3 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 14 GMC Ratio
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.89 to 1.17
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Lot 2, Lot 3
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 19A, Lot 2 and Lot 3 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19A GMC Ratio
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.85 to 1.06
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Lot 2, Lot 3
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 19F, Lot 2 and Lot 3 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19F GMC Ratio
Estimated Value 1.29
Confidence Interval (2-Sided) 95%
1.16 to 1.44
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Lot 2, Lot 3
Comments The 3 lots were to be considered equivalent if, for each serotype, all 3 CIs for IgG GMC ratios 4 weeks after the primary vaccination series lay within the interval (0.5, 2)
Type of Statistical Test Equivalence
Comments The equivalence margin was (0.5, 2.0). If the two sided 95% CIs for the ratio of the GMC of IgG antibody at one month following third vaccination was within this equivalence interval for serotype 23F, Lot 2 and Lot 3 would be equivalent with respect to the immune response to the vaccine lot
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 23F GMC Ratio
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.89 to 1.13
Parameter Dispersion Type:
Value:
Estimation Comments
2. Primary Outcome
Title Number and Percentage of Subjects With Serotype-specific IgG Antibody Responses ≥ 0.35 μg/mL
Description Number and Percentage of subjects with serotype-specific IgG Antibody Responses ≥ 0.35 μg/mL
Time Frame 4 weeks after the third dose

Outcome Measure Data

Analysis Population Description
Non-inferiority for each serotype is based on 2 non-inferiority criteria evaluation: for each serotype, non-inferiority was shown if a two-sided 97.5% CI for the absolute difference in proportions responding (PNEUMOSIL-Synflorix) had a lower limit >-0.10, or if a two-sided 97.5% CI for the IgG GMC ratio (PNEUMOSIL/Synflorix) had a lower limit >0.5.
Arm/Group Title Pneumosil Synflorix
Arm/Group Description Three doses of Pneumosil Three doses of Synflorix
Measure Participants 1458 724
Pn IgG Type 1
1454
289.6%
717
143.1%
Pn IgG Type 5
1435
285.9%
692
138.1%
Pn IgG Type 6A
1193
237.6%
555
110.8%
Pn IgG Type 6B
1142
227.5%
555
110.8%
Pn IgG Type 7F
1443
287.5%
709
141.5%
Pn IgG Type 9V
1391
277.1%
690
137.7%
Pn IgG Type 14
1437
286.3%
715
142.7%
Pn IgG Type 19A
1386
276.1%
555
110.8%
Pn IgG Type 19F
1427
284.3%
713
142.3%
Pn IgG Type 23F
1372
273.3%
557
111.2%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if either the lower limit of the 97.5% CI for the difference in proportions of IgG responders (PNEUMOSIL-Synflorix) exceeded -10%, for 7 or more of the 10 serotypes in PNEUMOSIL
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute Difference for Type 1
Estimated Value 0.7
Confidence Interval (2-Sided) 97.5%
-0.0 to 1.9
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if either the lower limit of the 97.5% CI for the difference in proportions of IgG responders (PNEUMOSIL-Synflorix) exceeded -10% for 7 or more of the 10 serotypes in PNEUMOSIL
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute Difference for Type 5
Estimated Value 2.8
Confidence Interval (2-Sided) 97.5%
1.2 to 5.0
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments Synflorix proportion of responders for serotype 6A was operationally defined as the lowest observed proportion of responders among the 8 serotypes in common with PNEUMOSIL
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if either the lower limit of the 97.5% CI for the difference in proportions of IgG responders (PNEUMOSIL-Synflorix) exceeded -10% for 7 or more of the 10 serotypes in PNEUMOSIL
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute Difference for Type 6A
Estimated Value 5.2
Confidence Interval (2-Sided) 97.5%
1.1 to 9.5
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if either the lower limit of the 97.5% CI for the difference in proportions of IgG responders (PNEUMOSIL-Synflorix) exceeded -10% for 7 or more of the 10 serotypes in PNEUMOSIL
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute Difference for Type 6B
Estimated Value 2.0
Confidence Interval (2-Sided) 97.5%
-2.2 to 6.4
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if either the lower limit of the 97.5% CI for the difference in proportions of IgG responders (PNEUMOSIL-Synflorix) exceeded -10% for 7 or more of the 10 serotypes in PNEUMOSIL
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute Difference for Type 7F
Estimated Value 1.0
Confidence Interval (2-Sided) 97.5%
-0.1 to 2.7
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if either the lower limit of the 97.5% CI for the difference in proportions of IgG responders (PNEUMOSIL-Synflorix) exceeded -10% for 7 or more of the 10 serotypes in PNEUMOSIL
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute Difference for Type 9V
Estimated Value 0.1
Confidence Interval (2-Sided) 97.5%
-1.9 to 2.5
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if either the lower limit of the 97.5% CI for the difference in proportions of IgG responders (PNEUMOSIL-Synflorix) exceeded -10% for 7 or more of the 10 serotypes in PNEUMOSIL
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute Difference for Type 14
Estimated Value -0.3
Confidence Interval (2-Sided) 97.5%
-1.4 to 1.0
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments Synflorix proportion of responders for serotype 19A was operationally defined as the lowest observed proportion of responders among the 8 serotypes in common with PNEUMOSIL
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if either the lower limit of the 97.5% CI for the difference in proportions of IgG responders (PNEUMOSIL-Synflorix) exceeded -10% for 7 or more of the 10 serotypes in PNEUMOSIL
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute Difference for Type 19A
Estimated Value 18.7
Confidence Interval (2-Sided) 97.5%
15.1 to 22.5
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if either the lower limit of the 97.5% CI for the difference in proportions of IgG responders (PNEUMOSIL-Synflorix) exceeded -10% for 7 or more of the 10 serotypes in PNEUMOSIL
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute Difference for Type 19F
Estimated Value -0.8
Confidence Interval (2-Sided) 97.5%
-1.9 to 0.5
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if either the lower limit of the 97.5% CI for the difference in proportions of IgG responders (PNEUMOSIL-Synflorix) exceeded -10% for 7 or more of the 10 serotypes in PNEUMOSIL
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute Difference for Type 23F
Estimated Value 17.2
Confidence Interval (2-Sided) 97.5%
13.6 to 21.1
Parameter Dispersion Type:
Value:
Estimation Comments
3. Primary Outcome
Title Serotype-specific Geometric Mean Concentration of IgG Antibody
Description Serotype-specific immunoglobulin G (IgG) geometric mean concentration (GMC) 4 weeks after the primary series of PNEUMOSIL/Synflorix co-administered with pentavalent, RV and polio vaccines.
Time Frame 4 weeks after the third dose

Outcome Measure Data

Analysis Population Description
Non-inferiority for each serotype is based on 2 non-inferiority criteria evaluation: for each serotype, non-inferiority was shown if a two-sided 97.5% CI for the absolute difference in proportions responding (PNEUMOSIL-Synflorix) had a lower limit >-0.10, or if a two-sided 97.5% CI for the IgG GMC ratio (PNEUMOSIL/Synflorix) had a lower limit >0.5.
Arm/Group Title Pneumosil Synflorix
Arm/Group Description IgG GMC after three doses of Pneumosil IgG GMC after three doses of Synflorix
Measure Participants 1458 724
Pn IgG Type 1
4.29
1.99
Pn IgG Type 5
1.65
1.20
Pn IgG Type 6A
1.00
1.13
Pn IgG Type 6B
1.21
1.13
Pn IgG Type 7F
2.97
2.29
Pn IgG Type 9V
1.31
1.42
Pn IgG Type 14
5.20
4.24
Pn IgG Type 19A
1.64
1.13
Pn IgG Type 19F
4.35
5.93
Pn IgG Type 23F
1.58
0.87
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if the lower limit of the 97.5% CI for the GMC ratio (PNEUMOSIL/Synflorix) exceeded 0.5, for 7 or more of the 10 serotypes in PNEUMOSIL
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 1 GMC Ratio
Estimated Value 2.15
Confidence Interval (2-Sided) 97.5%
2.00 to 2.32
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if the lower limit of the 97.5% CI for the GMC ratio (PNEUMOSIL/Synflorix) exceeded 0.5, for 7 or more of the 10 serotypes in PNEUMOSIL
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 5 GMC Ratio
Estimated Value 1.37
Confidence Interval (2-Sided) 97.5%
1.28 to 1.47
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments Synflorix proportion of responders for serotype 6A was operationally defined as the lowest observed proportion of responders among the 8 serotypes in common with PNEUMOSIL
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if the lower limit of the 97.5% CI for the GMC ratio (PNEUMOSIL/Synflorix) exceeded 0.5, for 7 or more of the 10 serotypes in PNEUMOSIL
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6A GMC Ratio
Estimated Value 0.89
Confidence Interval (2-Sided) 97.5%
0.78 to 1.01
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if the lower limit of the 97.5% CI for the GMC ratio (PNEUMOSIL/Synflorix) exceeded 0.5, for 7 or more of the 10 serotypes in PNEUMOSIL
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6B GMC Ratio
Estimated Value 1.07
Confidence Interval (2-Sided) 97.5%
0.93 to 1.24
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if the lower limit of the 97.5% CI for the GMC ratio (PNEUMOSIL/Synflorix) exceeded 0.5, for 7 or more of the 10 serotypes in PNEUMOSIL
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 7F GMC Ratio
Estimated Value 1.30
Confidence Interval (2-Sided) 97.5%
1.19 to 1.41
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if the lower limit of the 97.5% CI for the GMC ratio (PNEUMOSIL/Synflorix) exceeded 0.5, for 7 or more of the 10 serotypes in PNEUMOSIL
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 9V GMC Ratio
Estimated Value 0.92
Confidence Interval (2-Sided) 97.5%
0.85 to 1.00
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if the lower limit of the 97.5% CI for the GMC ratio (PNEUMOSIL/Synflorix) exceeded 0.5, for 7 or more of the 10 serotypes in PNEUMOSIL
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 14 GMC Ratio
Estimated Value 1.23
Confidence Interval (2-Sided) 97.5%
1.10 to 1.37
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments Synflorix proportion of responders for serotype 19A was operationally defined as the lowest observed proportion of responders among the 8 serotypes in common with PNEUMOSIL
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if the lower limit of the 97.5% CI for the GMC ratio (PNEUMOSIL/Synflorix) exceeded 0.5, for 7 or more of the 10 serotypes in PNEUMOSIL
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19A GMC Ratio
Estimated Value 1.45
Confidence Interval (2-Sided) 97.5%
1.30 to 1.63
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if the lower limit of the 97.5% CI for the GMC ratio (PNEUMOSIL/Synflorix) exceeded 0.5, for 7 or more of the 10 serotypes in PNEUMOSIL
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19F GMC Ratio
Estimated Value 0.73
Confidence Interval (2-Sided) 97.5%
0.67 to 0.80
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if the lower limit of the 97.5% CI for the GMC ratio (PNEUMOSIL/Synflorix) exceeded 0.5, for 7 or more of the 10 serotypes in PNEUMOSIL
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 23F GMC Ratio
Estimated Value 1.81
Confidence Interval (2-Sided) 97.5%
1.63 to 2.01
Parameter Dispersion Type:
Value:
Estimation Comments
4. Primary Outcome
Title Number and Percentage of Subjects With EPI Vaccine Immune Responses (Diphtheria, Tetanus, Hepatitis B, Hib, Polio and Rotavirus)
Description Subjects with 1) anti-diphtheria toxoid (DT) and anti-tetanus toxoid (DT) IgG concentration ≥ 0.1 IU/mL; 2) anti-Hepatitis B surface antigen (HBsAg) IgG concentration ≥ 10 mIU/mL; 3) anti-Hib (polyribosylribitol phosphate [PRP]) IgG concentration ≥ 0.15 µg/mL; 4) anti-poliovirus types 1, 2 and 3 neutralizing antibody titers ≥ 1:8; 5) anti-rotavirus IgA concentration ≥ 20 U/mL.
Time Frame 4 weeks after the third dose

Outcome Measure Data

Analysis Population Description
Evaluated in a subset who got 3 primary doses, had postdose immunogenicity data with no major protocol deviations.For each Ag in the pentavalent, RV, OPV vaccines, non-inferiority shown if 2-sided 95% CI for difference in response proportions (PNEUMOSIL-Synflorix) had lower limit >-0.10. For this, pooled PNUEMOSIL data was used as specified in SAP.
Arm/Group Title Pneumosil Synflorix
Arm/Group Description EPI vaccine immune responses after three doses of Pneumosil EPI vaccine immune responses after three doses of Synflorix
Measure Participants 447 225
Anti-Diphtheria Toxoid ≥ 0.1 IU/mL
447
89%
225
44.9%
Anti-Tetanus Toxoid ≥ 0.1 IU/mL
447
89%
225
44.9%
Anti-HBsAg concentration ≥ 10 mIU/mL
447
89%
224
44.7%
Anti-PRP concentration ≥ 0.15 μg/mL
441
87.8%
224
44.7%
Anti-Polio titer ≥ 1:8 (type 1)
446
88.8%
225
44.9%
Anti-Polio titer ≥ 1:8 (type 2)
374
74.5%
182
36.3%
Anti-Polio titer ≥ 1:8 (type 3)
437
87.1%
222
44.3%
Anti-Rotavirus concentration ≥ 20 U/mL
122
24.3%
61
12.2%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if the lower limit of the 95% CI exceeded -10% (for comparisons based on the difference in proportions of antibody responders to EPI vaccines between PNEUMOSIL and Synflorix)
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute difference for diphtheria
Estimated Value 0.0
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments CI could not be computed due to 100% response rate
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if the lower limit of the 95% CI exceeded -10% (for comparisons based on the difference in proportions of antibody responders to EPI vaccines between PNEUMOSIL and Synflorix)
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute difference for Tetanus
Estimated Value 0.0
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments CI could not be computed due to 100% response rate
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if the lower limit of the 95% CI exceeded -10% (for comparisons based on the difference in proportions of antibody responders to EPI vaccines between PNEUMOSIL and Synflorix)
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute difference for Hepatitis B
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.4 to 2.5
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if the lower limit of the 95% CI exceeded -10% (for comparisons based on the difference in proportions of antibody responders to EPI vaccines between PNEUMOSIL and Synflorix)
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute difference for Hib
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-2.5 to 1.2
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if the lower limit of the 95% CI exceeded -10% (for comparisons based on the difference in proportions of antibody responders to EPI vaccines between PNEUMOSIL and Synflorix)
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute difference for Polio type 1
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-1.3 to 1.5
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if the lower limit of the 95% CI exceeded -10% (for comparisons based on the difference in proportions of antibody responders to EPI vaccines between PNEUMOSIL and Synflorix)
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute difference for Polio type 2
Estimated Value 2.8
Confidence Interval (2-Sided) 95%
-3.2 to 9.3
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if the lower limit of the 95% CI exceeded -10% (for comparisons based on the difference in proportions of antibody responders to EPI vaccines between PNEUMOSIL and Synflorix)
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute difference for Polio type 3
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-3.0 to 1.8
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if the lower limit of the 95% CI exceeded -10% (for comparisons based on the difference in proportions of antibody responders to EPI vaccines between PNEUMOSIL and Synflorix)
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute difference for Rotavirus
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-7.1 to 7.1
Parameter Dispersion Type:
Value:
Estimation Comments
5. Primary Outcome
Title Anti-pertussis Toxoid GMCs for the Pertussis Antigen
Description Anti-pertussis toxoid GMCs for the pertussis antigen
Time Frame 4 weeks after the third dose

Outcome Measure Data

Analysis Population Description
Evaluated in a subset who got 3 primary doses, had postdose immunogenicity data with no major protocol deviations.Non-inferiority was defined as 2-sided 95% CI for the GMC ratio (PNEUMOSIL/Synflorix) with lower limit>0.5 for each of 2 separate antigens (pertussis toxoid and fimbriae).For this analysis, pooled PNUEMOSIL data used as specified in SAP
Arm/Group Title Pneumosil Synflorix
Arm/Group Description EPI vaccine immune responses after three doses of Pneumosil EPI vaccine immune responses after three doses of Synflorix
Measure Participants 447 225
Geometric Mean (95% Confidence Interval) [IU/mL]
50.95
61.82
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if the lower limit of the 95% CI for the GMC ratio exceeded 0.5 (for pertussis antigens).
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMC Ratio for anti-pertussis toxoid
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.62 to 1.09
Parameter Dispersion Type:
Value:
Estimation Comments
6. Primary Outcome
Title Anti Fimbriae 2/3 IgG GMCs for the Pertussis Antigen
Description Anti fimbriae 2/3 IgG GMCs for the pertussis antigen
Time Frame 4 weeks after the third dose

Outcome Measure Data

Analysis Population Description
Evaluated in a subset of subjects who received all primary series doses, had postdose immunogenicity results with no major protocol deviations. Non-inferiority was defined as a two-sided 95% CI for the GMC ratio (PNEUMOSIL/Synflorix) with lower limit > 0.5 for each of 2 separate antigens (pertussis toxoid and fimbriae).
Arm/Group Title Pneumosil Synflorix
Arm/Group Description EPI vaccine immune responses after three doses of Pneumosil EPI vaccine immune responses after three doses of Synflorix
Measure Participants 447 225
Geometric Mean (95% Confidence Interval) [U/mL]
317.97
324.87
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was to be shown if the lower limit of the 95% CI for the GMC ratio exceeded 0.5 (for pertussis antigens).
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMC Ratio for anti-fimbriae 2/3
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.77 to 1.25
Parameter Dispersion Type:
Value:
Estimation Comments
7. Primary Outcome
Title Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 1
Description In the primary reactogenicity cohort, local and systemic reactogenicity of the study vaccine was evaluated through day 6 for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [life threatening].
Time Frame 7 days (including day of vaccination)

Outcome Measure Data

Analysis Population Description
Sample size for evaluation of solicited local and systemic AEs was approx. 1,125. Evaluated in a subset of subjects who got a study vaccine and had some post-vaccination safety data. Lotwise data was used for clinical lot equivalence evaluation, for safety analyses pooled PNUEMOSIL data was used as specified in SAP.
Arm/Group Title Pneumosil Synflorix
Arm/Group Description Subjects who have received one dose of Pneumosil vaccine Subjects who have received one dose of Synflorix vaccine
Measure Participants 751 364
Grade 0
516
102.8%
249
49.7%
Grade 1
183
36.5%
88
17.6%
Grade 2
52
10.4%
27
5.4%
Grade 0
731
145.6%
353
70.5%
Grade 1
19
3.8%
10
2%
Grade 2
1
0.2%
1
0.2%
Grade 0
619
123.3%
301
60.1%
Grade 1
127
25.3%
57
11.4%
Grade 2
5
1%
6
1.2%
Grade 0
732
145.8%
352
70.3%
Grade 1
19
3.8%
12
2.4%
Grade 2
0
0%
0
0%
Grade 0
728
145%
349
69.7%
Grade 1
22
4.4%
12
2.4%
Grade 2
1
0.2%
3
0.6%
Grade 0
539
107.4%
251
50.1%
Grade 1
185
36.9%
93
18.6%
Grade 2
27
5.4%
20
4%
Grade 0
736
146.6%
350
69.9%
Grade 1
15
3%
13
2.6%
Grade 2
0
0%
1
0.2%
Grade 0
731
145.6%
345
68.9%
Grade 1
17
3.4%
16
3.2%
Grade 2
3
0.6%
3
0.6%
8. Primary Outcome
Title Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 2
Description In the primary reactogenicity cohort, local and systemic reactogenicity of the study vaccine was evaluated through day 6 for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [life threatening].
Time Frame 7 days (including day of vaccination)

Outcome Measure Data

Analysis Population Description
Sample size for evaluation of solicited local and systemic AEs was approx. 1,125. Evaluated in a subset of subjects who got a study vaccine and had some post-vaccination safety data. Lotwise data was used for clinical lot equivalence evaluation, for safety analyses pooled PNUEMOSIL data was used as specified in SAP.
Arm/Group Title Pneumosil Synflorix
Arm/Group Description Subjects who have received two doses of Pneumosil vaccine Subjects who have received two doses of Synflorix vaccine
Measure Participants 739 361
Grade 0
590
117.5%
271
54.1%
Grade 1
121
24.1%
70
14%
Grade 2
25
5%
19
3.8%
Grade 3
3
0.6%
1
0.2%
Grade 0
727
144.8%
355
70.9%
Grade 1
10
2%
4
0.8%
Grade 2
2
0.4%
1
0.2%
Grade 3
0
0%
1
0.2%
Grade 0
646
128.7%
324
64.7%
Grade 1
84
16.7%
36
7.2%
Grade 2
8
1.6%
1
0.2%
Grade 3
1
0.2%
0
0%
Grade 0
726
144.6%
359
71.7%
Grade 1
13
2.6%
2
0.4%
Grade 2
0
0%
0
0%
Grade 3
0
0%
0
0%
Grade 0
728
145%
354
70.7%
Grade 1
10
2%
4
0.8%
Grade 2
0
0%
3
0.6%
Grade 3
1
0.2%
0
0%
Grade 0
585
116.5%
283
56.5%
Grade 1
127
25.3%
63
12.6%
Grade 2
27
5.4%
15
3%
Grade 3
0
0%
0
0%
Grade 0
725
144.4%
356
71.1%
Grade 1
14
2.8%
5
1%
Grade 2
0
0%
0
0%
Grade 3
0
0%
0
0%
Grade 0
724
144.2%
348
69.5%
Grade 1
14
2.8%
11
2.2%
Grade 2
1
0.2%
2
0.4%
Grade 3
0
0%
0
0%
9. Primary Outcome
Title Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 3
Description In the primary reactogenicity cohort, local and systemic reactogenicity of the study vaccine was evaluated through day 6 for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [life threatening].
Time Frame 7 days (including day of vaccination)

Outcome Measure Data

Analysis Population Description
Sample size for evaluation of solicited local and systemic AEs was approx. 1,125. Evaluated in a subset of subjects who got a study vaccine and had some post-vaccination safety data. Lotwise data was used for clinical lot equivalence evaluation, for safety analyses pooled PNUEMOSIL data was used as specified in SAP.
Arm/Group Title Pneumosil Synflorix
Arm/Group Description Subjects who have received three doses of Pneumosil vaccine Subjects who have received three doses of Synflorix vaccine
Measure Participants 735 360
Grade 0
576
114.7%
301
60.1%
Grade 1
122
24.3%
51
10.2%
Grade 2
37
7.4%
7
1.4%
Grade 3
0
0%
1
0.2%
Grade 4
0
0%
0
0%
Grade 0
726
144.6%
358
71.5%
Grade 1
9
1.8%
2
0.4%
Grade 2
0
0%
0
0%
Grade 3
0
0%
0
0%
Grade 4
0
0%
0
0%
Grade 0
657
130.9%
316
63.1%
Grade 1
74
14.7%
41
8.2%
Grade 2
3
0.6%
3
0.6%
Grade 3
0
0%
0
0%
Grade 4
1
0.2%
0
0%
Grade 0
717
142.8%
352
70.3%
Grade 1
17
3.4%
8
1.6%
Grade 2
0
0%
0
0%
Grade 3
1
0.2%
0
0%
Grade 4
0
0%
0
0%
Grade 0
716
142.6%
353
70.5%
Grade 1
17
3.4%
6
1.2%
Grade 2
1
0.2%
0
0%
Grade 3
1
0.2%
1
0.2%
Grade 4
0
0%
0
0%
Grade 0
605
120.5%
296
59.1%
Grade 1
110
21.9%
55
11%
Grade 2
20
4%
9
1.8%
Grade 3
0
0%
0
0%
Grade 4
0
0%
0
0%
Grade 0
730
145.4%
357
71.3%
Grade 1
4
0.8%
3
0.6%
Grade 2
1
0.2%
0
0%
Grade 3
0
0%
0
0%
Grade 4
0
0%
0
0%
Grade 0
727
144.8%
353
70.5%
Grade 1
7
1.4%
6
1.2%
Grade 2
1
0.2%
1
0.2%
Grade 3
0
0%
0
0%
Grade 4
0
0%
0
0%
10. Primary Outcome
Title Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Booster
Description In the primary reactogenicity cohort, local and systemic reactogenicity of the study vaccine was evaluated through day 6 for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [life threatening].
Time Frame 7 days (including day of vaccination)

Outcome Measure Data

Analysis Population Description
Reported in a subset of subjects who got 3 doses and booster dose of the study vaccine and had post-vaccination safety data.Treatment groups (PNUEMOSIL or Synflorix) were based on actual treatment received at Visit 1. Lotwise data was used for clinical lot equivalence evaluation, for safety analyses pooled PNUEMOSIL data was used (specified in SAP)
Arm/Group Title Pneumosil Synflorix
Arm/Group Description Three doses + 1 booster dose of Pneumosil Three doses + 1 booster dose of Synflorix
Measure Participants 428 213
Grade 0
404
80.5%
197
39.3%
Grade 1
14
2.8%
12
2.4%
Grade 2
9
1.8%
4
0.8%
Grade 3
1
0.2%
0
0%
Grade 0
424
84.5%
211
42.1%
Grade 1
4
0.8%
2
0.4%
Grade 2
0
0%
0
0%
Grade 3
0
0%
0
0%
Grade 0
415
82.7%
207
41.3%
Grade 1
12
2.4%
6
1.2%
Grade 2
1
0.2%
0
0%
Grade 3
0
0%
0
0%
Grade 0
418
83.3%
208
41.5%
Grade 1
9
1.8%
5
1%
Grade 2
0
0%
0
0%
Grade 3
1
0.2%
0
0%
Grade 0
425
84.7%
211
42.1%
Grade 1
2
0.4%
2
0.4%
Grade 2
1
0.2%
0
0%
Grade 3
0
0%
0
0%
Grade 0
395
78.7%
200
39.9%
Grade 1
28
5.6%
9
1.8%
Grade 2
5
1%
4
0.8%
Grade 3
0
0%
0
0%
Grade 0
428
85.3%
213
42.5%
Grade 1
0
0%
0
0%
Grade 2
0
0%
0
0%
Grade 3
0
0%
0
0%
Grade 0
423
84.3%
209
41.7%
Grade 1
5
1%
4
0.8%
Grade 2
0
0%
0
0%
Grade 3
0
0%
0
0%
11. Primary Outcome
Title Number and Percentage of All AEs Including SAEs Occurring in Greater Than 1% Subjects by Severity and Relatedness
Description All subjects were followed up for AEs till 4 weeks post vaccination dose 3 and subjects in the booster cohort were followed up for AEs till 4 weeks post booster vaccination
Time Frame 4 weeks post last vaccination

Outcome Measure Data

Analysis Population Description
Evaluated in all subjects who received a study vaccination and provided some post-vaccination safety data. Treatment groups (PNUEMOSIL or Synflorix) were based on actual treatment received at Visit 1. Lotwise data was used for clinical lot equivalence evaluation, for safety analyses pooled PNUEMOSIL data was used as specified in SAP.
Arm/Group Title Pneumosil Synflorix
Arm/Group Description Primary series who have received three doses and booster cohort who have received three doses + a booster dose of Pneumosil Primary series who have received three doses and booster cohort who have received three doses + a booster dose of Synflorix
Measure Participants 1503 747
Mild-Related
0
0%
0
0%
Mild-Not related
714
142.2%
366
73.1%
Moderate-Related
0
0%
0
0%
Moderate-Not related
48
9.6%
26
5.2%
Severe-Related
0
0%
0
0%
Severe-Not related
2
0.4%
0
0%
None
739
147.2%
355
70.9%
Mild-Related
0
0%
0
0%
Mild-Not related
142
28.3%
62
12.4%
Moderate-Related
0
0%
0
0%
Moderate-Not related
11
2.2%
3
0.6%
Severe-Related
0
0%
0
0%
Severe-Not related
0
0%
0
0%
None
1350
268.9%
682
136.1%
Mild-Related
0
0%
0
0%
Mild-Not related
125
24.9%
67
13.4%
Moderate-Related
0
0%
0
0%
Moderate-Not related
27
5.4%
7
1.4%
Severe-Related
0
0%
0
0%
Severe-Not related
5
1%
3
0.6%
None
1346
268.1%
670
133.7%
Mild-Related
0
0%
0
0%
Mild-Not related
103
20.5%
62
12.4%
Moderate-Related
0
0%
0
0%
Moderate-Not related
8
1.6%
2
0.4%
Severe-Related
0
0%
0
0%
Severe-Not related
0
0%
0
0%
None
1392
277.3%
683
136.3%
Mild-Related
0
0%
0
0%
Mild-Not related
30
6%
32
6.4%
Moderate-Related
0
0%
0
0%
Moderate-Not related
20
4%
8
1.6%
Severe-Related
0
0%
0
0%
Severe-Not related
13
2.6%
4
0.8%
None
1440
286.9%
703
140.3%
Mild-Related
0
0%
0
0%
Mild-Not related
59
11.8%
21
4.2%
Moderate-Related
0
0%
0
0%
Moderate-Not related
3
0.6%
1
0.2%
Severe-Related
0
0%
0
0%
Severe-Not related
0
0%
0
0%
None
1441
287.1%
725
144.7%
Mild-Related
0
0%
0
0%
Mild-Not related
44
8.8%
20
4%
Moderate-Related
0
0%
0
0%
Moderate-Not related
9
1.8%
7
1.4%
Severe-Related
0
0%
0
0%
Severe-Not related
0
0%
1
0.2%
None
1450
288.8%
719
143.5%
Mild-Related
0
0%
0
0%
Mild-Not related
17
3.4%
10
2%
Moderate-Related
0
0%
0
0%
Moderate-Not related
21
4.2%
5
1%
Severe-Related
0
0%
0
0%
Severe-Not related
5
1%
6
1.2%
None
1460
290.8%
726
144.9%
Mild-Related
0
0%
0
0%
Mild-Not related
29
5.8%
22
4.4%
Moderate-Related
0
0%
0
0%
Moderate-Not related
0
0%
0
0%
Severe-Related
0
0%
0
0%
Severe-Not related
0
0%
0
0%
None
1474
293.6%
725
144.7%
Mild-Related
0
0%
0
0%
Mild-Not related
31
6.2%
15
3%
Moderate-Related
0
0%
0
0%
Moderate-Not related
4
0.8%
0
0%
Severe-Related
0
0%
0
0%
Severe-Not related
0
0%
0
0%
None
1468
292.4%
732
146.1%
Mild-Related
0
0%
0
0%
Mild-Not related
27
5.4%
18
3.6%
Moderate-Related
0
0%
0
0%
Moderate-Not related
2
0.4%
0
0%
Severe-Related
0
0%
0
0%
Severe-Not related
0
0%
0
0%
None
1474
293.6%
729
145.5%
Mild-Related
0
0%
0
0%
Mild-Not related
24
4.8%
19
3.8%
Moderate-Related
0
0%
0
0%
Moderate-Not related
3
0.6%
0
0%
Severe-Related
0
0%
0
0%
Severe-Not related
0
0%
0
0%
None
1476
294%
728
145.3%
Mild-Related
0
0%
0
0%
Mild-Not related
25
5%
15
3%
Moderate-Related
0
0%
0
0%
Moderate-Not related
0
0%
1
0.2%
Severe-Related
0
0%
0
0%
Severe-Not related
0
0%
0
0%
None
1478
294.4%
731
145.9%
Mild-Related
0
0%
0
0%
Mild-Not related
14
2.8%
11
2.2%
Moderate-Related
0
0%
0
0%
Moderate-Not related
0
0%
0
0%
Severe-Related
0
0%
0
0%
Severe-Not related
0
0%
0
0%
None
1489
296.6%
736
146.9%
Mild-Related
1
0.2%
0
0%
Mild-Not related
268
53.4%
130
25.9%
Moderate-Related
0
0%
0
0%
Moderate-Not related
16
3.2%
3
0.6%
Severe-Related
0
0%
0
0%
Severe-Not related
0
0%
0
0%
None
1218
242.6%
614
122.6%
Mild-Related
0
0%
1
0.2%
Mild-Not related
22
4.4%
12
2.4%
Moderate-Related
0
0%
0
0%
Moderate-Not related
2
0.4%
0
0%
Severe-Related
0
0%
0
0%
Severe-Not related
1
0.2%
0
0%
None
1478
294.4%
734
146.5%
Mild-Related
0
0%
0
0%
Mild-Not related
34
6.8%
27
5.4%
Moderate-Related
0
0%
0
0%
Moderate-Not related
2
0.4%
1
0.2%
Severe-Related
0
0%
0
0%
Severe-Not related
0
0%
0
0%
None
1467
292.2%
719
143.5%
Mild-Related
0
0%
1
0.2%
Mild-Not related
37
7.4%
14
2.8%
Moderate-Related
0
0%
0
0%
Moderate-Not related
0
0%
2
0.4%
Severe-Related
0
0%
0
0%
Severe-Not related
0
0%
0
0%
None
1466
292%
730
145.7%
Mild-Related
1
0.2%
0
0%
Mild-Not related
19
3.8%
11
2.2%
Moderate-Related
0
0%
0
0%
Moderate-Not related
0
0%
0
0%
Severe-Related
0
0%
0
0%
Severe-Not related
0
0%
0
0%
None
1483
295.4%
736
146.9%
Mild-Related
0
0%
0
0%
Mild-Not related
16
3.2%
7
1.4%
Moderate-Related
0
0%
0
0%
Moderate-Not related
2
0.4%
0
0%
Severe-Related
0
0%
0
0%
Severe-Not related
0
0%
0
0%
None
1485
295.8%
740
147.7%
Mild-Related
0
0%
0
0%
Mild-Not related
12
2.4%
10
2%
Moderate-Related
0
0%
0
0%
Moderate-Not related
0
0%
1
0.2%
Severe-Related
0
0%
0
0%
Severe-Not related
0
0%
0
0%
None
1491
297%
736
146.9%
Mild-Related
0
0%
0
0%
Mild-Not related
16
3.2%
5
1%
Moderate-Related
0
0%
0
0%
Moderate-Not related
1
0.2%
0
0%
Severe-Related
0
0%
0
0%
Severe-Not related
0
0%
0
0%
None
1486
296%
742
148.1%
Mild-Related
0
0%
0
0%
Mild-Not related
95
18.9%
38
7.6%
Moderate-Related
0
0%
0
0%
Moderate-Not related
0
0%
1
0.2%
Severe-Related
0
0%
0
0%
Severe-Not related
0
0%
0
0%
None
1408
280.5%
708
141.3%
Mild-Related
1
0.2%
0
0%
Mild-Not related
17
3.4%
15
3%
Moderate-Related
1
0.2%
0
0%
Moderate-Not related
8
1.6%
1
0.2%
Severe-Related
3
0.6%
0
0%
Severe-Not related
1
0.2%
0
0%
None
1472
293.2%
731
145.9%
Mild-Related
0
0%
0
0%
Mild-Not related
7
1.4%
10
2%
Moderate-Related
0
0%
0
0%
Moderate-Not related
2
0.4%
1
0.2%
Severe-Related
0
0%
0
0%
Severe-Not related
0
0%
0
0%
None
1494
297.6%
736
146.9%
12. Primary Outcome
Title Number and Percentage of All SAEs by Severity and Relatedness
Description All subjects were followed up for SAEs till 4 weeks post vaccination dose 3 and subjects in the booster cohort were followed up for SAEs till 4 weeks post booster vaccination
Time Frame 4 weeks post last vaccination

Outcome Measure Data

Analysis Population Description
Evaluated in all subjects who received a study vaccination and provided some post-vaccination safety data. Treatment groups (PNUEMOSIL or Synflorix) were based on actual treatment received at Visit 1. Lotwise data was used for clinical lot equivalence evaluation, for safety analyses pooled PNUEMOSIL data was used as specified in SAP.
Arm/Group Title Pneumosil Synflorix
Arm/Group Description Primary series who have received three doses and booster cohort who have received three doses + a booster dose of Pneumosil Primary series who have received three doses and booster cohort who have received three doses + a booster dose of Synflorix
Measure Participants 1503 747
Moderate-Not Related
0
0%
0
0%
Severe-Not Related
13
2.6%
4
0.8%
None
1490
296.8%
743
148.3%
Moderate-Not Related
4
0.8%
0
0%
Severe-Not Related
5
1%
3
0.6%
None
1494
297.6%
744
148.5%
Moderate-Not Related
0
0%
0
0%
Severe-Not Related
4
0.8%
6
1.2%
None
1499
298.6%
741
147.9%
Moderate-Not Related
0
0%
0
0%
Severe-Not Related
0
0%
1
0.2%
None
1503
299.4%
746
148.9%
Moderate-Not Related
0
0%
1
0.2%
Severe-Not Related
0
0%
0
0%
None
1503
299.4%
746
148.9%
Moderate-Not Related
0
0%
0
0%
Severe-Not Related
0
0%
1
0.2%
None
1503
299.4%
746
148.9%
Moderate-Not Related
0
0%
0
0%
Severe-Not Related
1
0.2%
0
0%
None
1502
299.2%
747
149.1%
Moderate-Not Related
0
0%
0
0%
Severe-Not Related
0
0%
1
0.2%
None
1503
299.4%
746
148.9%
Moderate-Not Related
0
0%
0
0%
Severe-Not Related
0
0%
1
0.2%
None
1503
299.4%
746
148.9%
Moderate-Not Related
0
0%
0
0%
Severe-Not Related
1
0.2%
0
0%
None
1502
299.2%
747
149.1%
Moderate-Not Related
0
0%
0
0%
Severe-Not Related
1
0.2%
1
0.2%
None
1502
299.2%
746
148.9%
Moderate-Not Related
0
0%
0
0%
Severe-Not Related
2
0.4%
0
0%
None
1501
299%
747
149.1%
Moderate-Not Related
0
0%
0
0%
Severe-Not Related
1
0.2%
0
0%
None
1502
299.2%
747
149.1%
Moderate-Not Related
0
0%
0
0%
Severe-Not Related
2
0.4%
0
0%
None
1501
299%
747
149.1%
Moderate-Not Related
0
0%
0
0%
Severe-Not Related
1
0.2%
0
0%
None
1502
299.2%
747
149.1%
Moderate-Not Related
0
0%
0
0%
Severe-Not Related
1
0.2%
0
0%
None
1502
299.2%
747
149.1%
Moderate-Not Related
0
0%
0
0%
Severe-Not Related
1
0.2%
0
0%
None
1502
299.2%
747
149.1%
Moderate-Not Related
0
0%
0
0%
Severe-Not Related
0
0%
1
0.2%
None
1503
299.4%
746
148.9%
Moderate-Not Related
0
0%
0
0%
Severe-Not Related
1
0.2%
0
0%
None
1502
299.2%
747
149.1%
Moderate-Not Related
0
0%
0
0%
Severe-Not Related
1
0.2%
0
0%
None
1502
299.2%
747
149.1%
Moderate-Not Related
0
0%
0
0%
Severe-Not Related
1
0.2%
0
0%
None
1502
299.2%
747
149.1%
13. Secondary Outcome
Title Number and Percentage of Subjects With 6A and 19A Serotype-specific Concentrations of Immunoglobulin G Antibody
Description Subjects with 6A and 19A serotype-specific concentrations of immunoglobulin G (IgG) antibody measured by ELISA
Time Frame 4 weeks after the third dose

Outcome Measure Data

Analysis Population Description
For 6A and 19A serotypes, proportions with IgG concentration ≥ 0.35 µg/mL were compared using a z-test for proportions.Test was done at the 2-sided 2.5% significance level to adjust for superiority test. Analysis was done on pooled PNEUMOSIL data as specified in SAP
Arm/Group Title Pneumosil Synflorix
Arm/Group Description Three doses of Pneumosil Three doses of Synflorix
Measure Participants 1458 724
Pn IgG Type 6A
1193
237.6%
62
12.4%
Pn IgG Type 19A
1386
276.1%
293
58.5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Superiority
Comments Proportions with IgG concentration ≥ 0.35 µg/mL will be compared using a z-test for proportions. The test will be done at the two-sided 2.5% significance level to adjust for the two superiority tests. 97.5% CIs for treatment-group differences in response, will also be reported
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference for Type 6A
Estimated Value 73.3
Confidence Interval (2-Sided) 97.5%
69.8 to 76.3
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Superiority
Comments Proportions with IgG concentration ≥ 0.35 µg/mL will be compared using a z-test for proportions. The test will be done at the two-sided 2.5% significance level to adjust for the two superiority tests. 97.5% CIs for treatment-group differences in response, will also be reported
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference for Type 19A
Estimated Value 54.7
Confidence Interval (2-Sided) 97.5%
50.3 to 58.9
Parameter Dispersion Type:
Value:
Estimation Comments
14. Secondary Outcome
Title 6A and 19A Serotype Specific Geometric Mean Concentration of IgG Antibody
Description 6A and 19A Serotype Specific Immune Responses in terms of IgG GMCs measured by ELISA
Time Frame 4 weeks after the third dose

Outcome Measure Data

Analysis Population Description
For 6A and 19A serotypes, GMCs were compared by a two-sample t-test on the difference.Test was done at the 2-sided 2.5% significance level to adjust for superiority test.The 95% CIs around treatment-group responses, and 97.5% CIs for treatment-group differences in response were reported.Analysis was done on pooled PNEUMOSIL data as specified in SAP
Arm/Group Title Pneumosil Synflorix
Arm/Group Description Three doses of Pneumosil Three doses of Synflorix
Measure Participants 1458 724
Pn IgG Type 6A
1.00
0.12
Pn IgG Type 19A
1.64
0.29
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Superiority
Comments For each of the two serotypes, GMCs are compared by a two-sample t-test on the difference between means of log10 (antibody). The test was done at the two-sided 2.5% significance level to adjust for the two superiority tests. 97.5% CIs for treatment-group differences in response, are also be reported
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6A GMC Ratio
Estimated Value 8.51
Confidence Interval (2-Sided) 97.5%
7.68 to 9.43
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Superiority
Comments For each of the two serotypes, GMCs are compared by a two-sample t-test on the difference between means of log10 (antibody). The test was done at the two-sided 2.5% significance level to adjust for the two superiority tests. 97.5% CIs for treatment-group differences in response, are also be reported
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19A GMC Ratio
Estimated Value 5.64
Confidence Interval (2-Sided) 97.5%
5.14 to 6.18
Parameter Dispersion Type:
Value:
Estimation Comments
15. Secondary Outcome
Title Number and Percentage of Subjects With Functional Antibody Responses
Description Serotype-specific functional antibody titer measured by OPA
Time Frame 4 weeks after the third dose

Outcome Measure Data

Analysis Population Description
In a subset of subjects who got 3 primary doses of study vaccines, had postdose immunogenicity measurement and no major protocol deviations, functional immune responses induced by PNEUMOSIL were compared to Synflorix for 10 serotypes in PNEUMOSIL, i.e., OPA seroresponse rate (titer≥1:8) differences.Pooled PNEUMOSIL data was used as noted in the SAP
Arm/Group Title Pneumosil Synflorix
Arm/Group Description Three doses of Pneumosil Three doses of Synflorix
Measure Participants 247 250
OPA Type 1
229
45.6%
188
37.5%
OPA Type 5
244
48.6%
239
47.7%
OPA Type 6A
240
47.8%
36
7.2%
OPA Type 6B
233
46.4%
212
42.3%
OPA Type 7F
247
49.2%
249
49.7%
OPA Type 9V
242
48.2%
249
49.7%
OPA Type 14
237
47.2%
242
48.3%
OPA Type 19A
228
45.4%
92
18.4%
OPA Type 19F
239
47.6%
246
49.1%
OPA Type 23F
246
49%
243
48.5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA titer to Pneumosil in comparison with Synflorix for each of the 10 serotypes
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA Type 1
Estimated Value 17.2
Confidence Interval (2-Sided) 95%
11.0 to 23.6
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA titer to Pneumosil in comparison with Synflorix for each of the 10 serotypes
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA Type 5
Estimated Value 2.8
Confidence Interval (2-Sided) 95%
-0.0 to 6.2
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA titer to Pneumosil in comparison with Synflorix for each of the 10 serotypes
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA Type 6A
Estimated Value 82.2
Confidence Interval (2-Sided) 95%
76.7 to 86.6
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA titer to Pneumosil in comparison with Synflorix for each of the 10 serotypes
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA Type 6B
Estimated Value 9.4
Confidence Interval (2-Sided) 95%
4.5 to 14.6
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA titer to Pneumosil in comparison with Synflorix for each of the 10 serotypes
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA Type 7F
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-1.1 to 2.2
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA titer to Pneumosil in comparison with Synflorix for each of the 10 serotypes
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA Type 9V
Estimated Value 0.0
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments CI could not be computed due to 100% response rate
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA titer to Pneumosil in comparison with Synflorix for each of the 10 serotypes
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA Type14
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-4.0 to 2.2
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA titer to Pneumosil in comparison with Synflorix for each of the 10 serotypes
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA Type 19A
Estimated Value 53.3
Confidence Interval (2-Sided) 95%
46.0 to 60.1
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA titer to Pneumosil in comparison with Synflorix for each of the 10 serotypes
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA Type 19F
Estimated Value -1.6
Confidence Interval (2-Sided) 95%
-4.9 to 1.2
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA titer to Pneumosil in comparison with Synflorix for each of the 10 serotypes
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA Type 23F
Estimated Value 0.0
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments CI could not be computed due to 100% response rate
16. Secondary Outcome
Title Serotype-specific OPA Geometric Mean Titer
Description Serotype-specific functional antibody titer measured by OPA and expressed as OPA GMT in a subset
Time Frame 4 weeks after the third dose

Outcome Measure Data

Analysis Population Description
In a subset of subjects who got 3 primary doses of study vaccines, had postdose immunogenicity measurement and no major protocol deviations, functional immune responses induced by PNEUMOSIL were compared to Synflorix for 10 serotypes in PNEUMOSIL, i.e., ratio of OPA GMTs (and corresponding 95% CIs).Pooled PNEUMOSIL data was used as noted in the SAP
Arm/Group Title Pneumosil Synflorix
Arm/Group Description Three doses of Pneumosil Three doses of Synflorix
Measure Participants 247 250
OPA Type 1
85.17
27.55
OPA Type 5
161.34
115.93
OPA Type 6A
1317.16
7.06
OPA Type 6B
913.52
467.65
OPA Type 7F
1833.71
1586.75
OPA Type 9V
141.72
376.77
OPA Type 14
1019.34
1102.64
OPA 19A
148.59
11.09
OPA 19F
594.27
895.39
OPA 23F
767.24
253.09
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA to Pneumosil in comparison with Synflorix for each of the 10 serotypes (GMT Ratio)
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 1
Estimated Value 3.09
Confidence Interval (2-Sided) 95%
2.40 to 3.98
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA to Pneumosil in comparison with Synflorix for each of the 10 serotypes (GMT Ratio)
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 5
Estimated Value 1.39
Confidence Interval (2-Sided) 95%
1.12 to 1.72
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA to Pneumosil in comparison with Synflorix for each of the 10 serotypes (GMT Ratio)
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 6A
Estimated Value 186
Confidence Interval (2-Sided) 95%
144 to 241
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA to Pneumosil in comparison with Synflorix for each of the 10 serotypes (GMT Ratio)
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 6B
Estimated Value 1.95
Confidence Interval (2-Sided) 95%
1.42 to 2.69
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA to Pneumosil in comparison with Synflorix for each of the 10 serotypes (GMT Ratio)
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 7F
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.96 to 1.39
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA to Pneumosil in comparison with Synflorix for each of the 10 serotypes (GMT Ratio)
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 9V
Estimated Value 0.38
Confidence Interval (2-Sided) 95%
0.29 to 0.49
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA to Pneumosil in comparison with Synflorix for each of the 10 serotypes (GMT Ratio)
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 14
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.67 to 1.27
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA to Pneumosil in comparison with Synflorix for each of the 10 serotypes (GMT Ratio)
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 19A
Estimated Value 13.4
Confidence Interval (2-Sided) 95%
10.2 to 17.7
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA to Pneumosil in comparison with Synflorix for each of the 10 serotypes (GMT Ratio)
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 19F
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.54 to 0.81
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA to Pneumosil in comparison with Synflorix for each of the 10 serotypes (GMT Ratio)
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 23F
Estimated Value 3.03
Confidence Interval (2-Sided) 95%
2.25 to 4.09
Parameter Dispersion Type:
Value:
Estimation Comments
17. Secondary Outcome
Title Comparison of Serotype-specific Geometric Mean Concentration of IgG Antibody Response 4 Weeks After a 3-dose Primary Series to 4 Weeks After a Booster Dose
Description Comparison of Serotype-specific booster responses (antibody concentrations) measured by ELISA from 4 weeks after a 3-dose primary series to 4 weeks after a booster dose
Time Frame 4 weeks post booster vaccination

Outcome Measure Data

Analysis Population Description
In a subset who got 3 primary series+booster dose of study vaccines, had postdose immunogenicity measurement & no major PDs, comparisons based on ratios of IgG GMC post booster to IgG GMC post primary series. Comparison done using ratios of the ratios for the 2 treatment groups (PNEUMOSIL ratio/Synflorix ratio), & corresponding 95% CIs.
Arm/Group Title 4 Weeks Post Dose 3-Pneumosil 4 Weeks Post Booster-Pneumosil 4 Weeks Post Dose 3-Synflorix 4 Weeks Post Booster-Synflorix
Arm/Group Description Three doses of Pneumosil in a subset Three doses + 1 booster dose of Pneumosil in a subset Three doses of Synflorix in a subset Three doses + 1 booster dose of Synflorix in a subset
Measure Participants 436 425 216 209
Pn IgG Type 1
4.05
5.71
2.12
2.47
Pn IgG Type 5
1.49
1.31
1.26
0.84
Pn IgG Type 6A
1.09
4.86
0.12
0.42
Pn IgG Type 6B
1.29
8.32
1.15
4.44
Pn IgG Type 7F
3.12
6.36
2.49
4.07
Pn IgG Type 9V
1.29
1.80
1.43
2.08
Pn IgG Type 14
5.06
6.84
3.86
4.67
Pn IgG Type 19A
1.50
3.97
0.26
0.95
Pn IgG Type 19F
4.16
6.18
6.31
9.79
Pn IgG Type 23F
1.65
4.11
0.94
2.15
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC post-booster to the IgG GMC post-primary series in the Booster Cohort restricted to subjects who contributed relevant data at both time points.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 1 GMC Ratio
Estimated Value 1.41
Confidence Interval (2-Sided) 95%
1.31 to 1.52
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC post-booster to the IgG GMC post-primary series in the Booster Cohort restricted to subjects who contributed relevant data at both time points.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 5 GMC Ratio
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.81 to 0.95
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC post-booster to the IgG GMC post-primary series in the Booster Cohort restricted to subjects who contributed relevant data at both time points.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6A GMC Ratio
Estimated Value 4.46
Confidence Interval (2-Sided) 95%
4.01 to 4.96
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC post-booster to the IgG GMC post-primary series in the Booster Cohort restricted to subjects who contributed relevant data at both time points.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6B GMC Ratio
Estimated Value 6.43
Confidence Interval (2-Sided) 95%
5.70 to 7.26
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC post-booster to the IgG GMC post-primary series in the Booster Cohort restricted to subjects who contributed relevant data at both time points.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 7F GMC Ratio
Estimated Value 2.04
Confidence Interval (2-Sided) 95%
1.89 to 2.19
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC post-booster to the IgG GMC post-primary series in the Booster Cohort restricted to subjects who contributed relevant data at both time points.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 9V GMC Ratio
Estimated Value 1.39
Confidence Interval (2-Sided) 95%
1.29 to 1.50
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC post-booster to the IgG GMC post-primary series in the Booster Cohort restricted to subjects who contributed relevant data at both time points.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 14 GMC Ratio
Estimated Value 1.35
Confidence Interval (2-Sided) 95%
1.21 to 1.51
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC post-booster to the IgG GMC post-primary series in the Booster Cohort restricted to subjects who contributed relevant data at both time points.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19A GMC Ratio
Estimated Value 2.64
Confidence Interval (2-Sided) 95%
2.40 to 2.91
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC post-booster to the IgG GMC post-primary series in the Booster Cohort restricted to subjects who contributed relevant data at both time points.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19F GMC Ratio
Estimated Value 1.49
Confidence Interval (2-Sided) 95%
1.36 to 1.63
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC post-booster to the IgG GMC post-primary series in the Booster Cohort restricted to subjects who contributed relevant data at both time points.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 23F GMC Ratio
Estimated Value 2.50
Confidence Interval (2-Sided) 95%
2.29 to 2.72
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC post-booster to the IgG GMC post-primary series in the Booster Cohort restricted to subjects who contributed relevant data at both time points.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 1 GMC Ratio
Estimated Value 1.17
Confidence Interval (2-Sided) 95%
1.06 to 1.28
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC post-booster to the IgG GMC post-primary series in the Booster Cohort restricted to subjects who contributed relevant data at both time points.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 5 GMC Ratio
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
0.61 to 0.74
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC post-booster to the IgG GMC post-primary series in the Booster Cohort restricted to subjects who contributed relevant data at both time points.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6A GMC Ratio
Estimated Value 3.49
Confidence Interval (2-Sided) 95%
2.97 to 4.11
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC post-booster to the IgG GMC post-primary series in the Booster Cohort restricted to subjects who contributed relevant data at both time points.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6B GMC Ratio
Estimated Value 3.85
Confidence Interval (2-Sided) 95%
3.23 to 4.59
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC post-booster to the IgG GMC post-primary series in the Booster Cohort restricted to subjects who contributed relevant data at both time points.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 7F GMC Ratio
Estimated Value 1.63
Confidence Interval (2-Sided) 95%
1.47 to 1.82
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC post-booster to the IgG GMC post-primary series in the Booster Cohort restricted to subjects who contributed relevant data at both time points.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 9V GMC Ratio
Estimated Value 1.46
Confidence Interval (2-Sided) 95%
1.31 to 1.62
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC post-booster to the IgG GMC post-primary series in the Booster Cohort restricted to subjects who contributed relevant data at both time points.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 14 GMC Ratio
Estimated Value 1.21
Confidence Interval (2-Sided) 95%
1.03 to 1.42
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC post-booster to the IgG GMC post-primary series in the Booster Cohort restricted to subjects who contributed relevant data at both time points.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19A GMC Ratio
Estimated Value 3.60
Confidence Interval (2-Sided) 95%
2.99 to 4.33
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC post-booster to the IgG GMC post-primary series in the Booster Cohort restricted to subjects who contributed relevant data at both time points.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19F GMC Ratio
Estimated Value 1.55
Confidence Interval (2-Sided) 95%
1.38 to 1.75
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC post-booster to the IgG GMC post-primary series in the Booster Cohort restricted to subjects who contributed relevant data at both time points.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 23F GMC Ratio
Estimated Value 2.29
Confidence Interval (2-Sided) 95%
1.98 to 2.65
Parameter Dispersion Type:
Value:
Estimation Comments
18. Secondary Outcome
Title Serotype-specific Geometric Mean Concentration of IgG Antibody Response and Treatment-Group GMC Ratios 4 Weeks After a Booster Dose
Description Comparison of Serotype-specific booster responses (antibody concentrations) to PNEUMOSIL in comparison to Synflorix 4 weeks after a booster dose
Time Frame 4 weeks post booster vaccination

Outcome Measure Data

Analysis Population Description
In a subset of subjects who got 3 primary series and a booster dose of study vaccines, had postdose immunogenicity measurement(s) with no major protocol deviations, serotype-specific GMC of IgG Antibody and treatment group ratios of IgG GMCs (with corresponding 95% CIs) were evaluated. Pooled PNEUMOSIL data was used for this analysis as per SAP
Arm/Group Title Pneumosil Synflorix
Arm/Group Description Three doses + 1 booster dose of Pneumosil Three doses + 1 booster dose of Synflorix
Measure Participants 425 209
Pn IgG Type 1
5.73
2.45
Pn IgG Type 5
1.31
0.83
Pn IgG Type 6A
4.87
0.42
Pn IgG Type 6B
8.33
4.42
Pn IgG Type 7F
6.37
4.06
Pn IgG Type 9V
1.81
2.07
Pn IgG Type 14
6.85
4.62
Pn IgG Type 19A
3.97
0.94
Pn IgG Type 19F
6.16
9.70
Pn IgG Type 23F
4.08
2.13
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines were compared using the ratios of the GMC ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs based on log linear random effects models
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 1 GMC Ratio
Estimated Value 2.34
Confidence Interval (2-Sided) 95%
2.02 to 2.71
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines were compared using the ratios of the GMC ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs based on log linear random effects models
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 5 GMC Ratio
Estimated Value 1.57
Confidence Interval (2-Sided) 95%
1.38 to 1.79
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines were compared using the ratios of the GMC ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs based on log linear random effects models
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6A GMC Ratio
Estimated Value 11.6
Confidence Interval (2-Sided) 95%
9.67 to 14.0
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines were compared using the ratios of the GMC ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs based on log linear random effects models
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6B GMC Ratio
Estimated Value 1.89
Confidence Interval (2-Sided) 95%
1.65 to 2.15
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines were compared using the ratios of the GMC ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs based on log linear random effects models
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 7F GMC Ratio
Estimated Value 1.57
Confidence Interval (2-Sided) 95%
1.37 to 1.80
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines were compared using the ratios of the GMC ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs based on log linear random effects models
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 9V GMC Ratio
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.76 to 0.99
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines were compared using the ratios of the GMC ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs based on log linear random effects models
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 14 GMC Ratio
Estimated Value 1.48
Confidence Interval (2-Sided) 95%
1.21 to 1.82
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines were compared using the ratios of the GMC ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs based on log linear random effects models
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19A GMC Ratio
Estimated Value 4.22
Confidence Interval (2-Sided) 95%
3.52 to 5.06
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines were compared using the ratios of the GMC ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs based on log linear random effects models
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19F GMC Ratio
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.55 to 0.73
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines were compared using the ratios of the GMC ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs based on log linear random effects models
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 23F GMC Ratio
Estimated Value 1.91
Confidence Interval (2-Sided) 95%
1.63 to 2.24
Parameter Dispersion Type:
Value:
Estimation Comments
19. Secondary Outcome
Title Comparison of Functional Response (OPA) From 4 Weeks After a 3-dose Primary Series to 4 Weeks After a Booster Dose
Description Comparison of Serotype-specific booster responses (functional response-OPA) from 4 weeks after a 3-dose primary series to 4 weeks after a booster dose
Time Frame 4 weeks post booster vaccination

Outcome Measure Data

Analysis Population Description
In a subset who got 3 primary series+booster dose of study vaccines, had postdose immunogenicity measurement & no major PDs, comparisons based on ratios of OPA GMT post booster to OPA GMT post primary series. Comparison done using ratios of the ratios for the 2 treatment groups (PNEUMOSIL ratio/Synflorix ratio), & corresponding 95% CIs.
Arm/Group Title 4 Weeks Post Dose 3-Pneumosil 4 Weeks Post Booster-Pneumosil 4 Weeks Post Dose 3-Synflorix 4 Weeks Post Booster-Synflorix
Arm/Group Description Three doses of Pneumosil in a subset Three doses + 1 booster dose of Pneumosil in a subset Three doses of Synflorix in a subset Three doses + 1 booster dose of Synflorix in a subset
Measure Participants 239 99 214 100
OPA Type 1
99.21
344.5
29.76
187.2
OPA Type 5
161.2
409.9
112.9
360.6
OPA Type 6A
1225
3063
6.44
39.96
OPA Type 6B
771.4
2897
495.2
1610
OPA Type 7F
1795
6977
1438
4036
OPA Type 9V
168.7
1155
417.0
1229
OPA Type 14
1254
3069
866.8
1401
OPA Type 19A
177.5
645.6
8.89
53.15
OPA Type 19F
669.9
1592
801.0
1580
OPA Type 23F
774.5
3847
211.7
1213
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post primary series and 4 weeks post booster for the OPA subset of the booster cohort. It was restricted to subjects who contributed relevant data at both time points
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 1
Estimated Value 3.47
Confidence Interval (2-Sided) 95%
2.72 to 4.44
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post primary series and 4 weeks post booster for the OPA subset of the booster cohort. It was restricted to subjects who contributed relevant data at both time points
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 5
Estimated Value 2.54
Confidence Interval (2-Sided) 95%
2.06 to 3.13
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post primary series and 4 weeks post booster for the OPA subset of the booster cohort. It was restricted to subjects who contributed relevant data at both time points
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 6A
Estimated Value 2.50
Confidence Interval (2-Sided) 95%
1.83 to 3.42
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post primary series and 4 weeks post booster for the OPA subset of the booster cohort. It was restricted to subjects who contributed relevant data at both time points
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 6B
Estimated Value 3.76
Confidence Interval (2-Sided) 95%
2.48 to 5.69
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post primary series and 4 weeks post booster for the OPA subset of the booster cohort. It was restricted to subjects who contributed relevant data at both time points
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 7F
Estimated Value 3.89
Confidence Interval (2-Sided) 95%
2.92 to 5.18
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post primary series and 4 weeks post booster for the OPA subset of the booster cohort. It was restricted to subjects who contributed relevant data at both time points
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 9V
Estimated Value 6.85
Confidence Interval (2-Sided) 95%
4.45 to 10.52
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post primary series and 4 weeks post booster for the OPA subset of the booster cohort. It was restricted to subjects who contributed relevant data at both time points
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 14
Estimated Value 2.45
Confidence Interval (2-Sided) 95%
1.64 to 3.65
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post primary series and 4 weeks post booster for the OPA subset of the booster cohort. It was restricted to subjects who contributed relevant data at both time points
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 19A
Estimated Value 3.64
Confidence Interval (2-Sided) 95%
2.47 to 5.36
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post primary series and 4 weeks post booster for the OPA subset of the booster cohort. It was restricted to subjects who contributed relevant data at both time points
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 19F
Estimated Value 2.38
Confidence Interval (2-Sided) 95%
1.80 to 3.14
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post primary series and 4 weeks post booster for the OPA subset of the booster cohort. It was restricted to subjects who contributed relevant data at both time points
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 23F
Estimated Value 4.97
Confidence Interval (2-Sided) 95%
3.49 to 7.06
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post primary series and 4 weeks post booster for the OPA subset of the booster cohort. It was restricted to subjects who contributed relevant data at both time points
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 1
Estimated Value 6.29
Confidence Interval (2-Sided) 95%
4.97 to 7.96
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post primary series and 4 weeks post booster for the OPA subset of the booster cohort. It was restricted to subjects who contributed relevant data at both time points
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 5
Estimated Value 3.19
Confidence Interval (2-Sided) 95%
2.56 to 3.98
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post primary series and 4 weeks post booster for the OPA subset of the booster cohort. It was restricted to subjects who contributed relevant data at both time points
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 6A
Estimated Value 6.21
Confidence Interval (2-Sided) 95%
3.55 to 10.84
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post primary series and 4 weeks post booster for the OPA subset of the booster cohort. It was restricted to subjects who contributed relevant data at both time points
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 6B
Estimated Value 3.25
Confidence Interval (2-Sided) 95%
2.25 to 4.70
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post primary series and 4 weeks post booster for the OPA subset of the booster cohort. It was restricted to subjects who contributed relevant data at both time points
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 7F
Estimated Value 2.81
Confidence Interval (2-Sided) 95%
2.13 to 3.69
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post primary series and 4 weeks post booster for the OPA subset of the booster cohort. It was restricted to subjects who contributed relevant data at both time points
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 9V
Estimated Value 2.95
Confidence Interval (2-Sided) 95%
2.15 to 4.04
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post primary series and 4 weeks post booster for the OPA subset of the booster cohort. It was restricted to subjects who contributed relevant data at both time points
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 14
Estimated Value 1.62
Confidence Interval (2-Sided) 95%
1.06 to 2.46
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post primary series and 4 weeks post booster for the OPA subset of the booster cohort. It was restricted to subjects who contributed relevant data at both time points
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 19A
Estimated Value 5.98
Confidence Interval (2-Sided) 95%
3.88 to 9.21
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post primary series and 4 weeks post booster for the OPA subset of the booster cohort. It was restricted to subjects who contributed relevant data at both time points
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 19F
Estimated Value 1.97
Confidence Interval (2-Sided) 95%
1.45 to 2.68
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post primary series and 4 weeks post booster for the OPA subset of the booster cohort. It was restricted to subjects who contributed relevant data at both time points
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 23F
Estimated Value 5.73
Confidence Interval (2-Sided) 95%
3.80 to 8.63
Parameter Dispersion Type:
Value:
Estimation Comments
20. Secondary Outcome
Title Serotype-specific OPA GMT and Treatment-Group GMT Ratios 4 Weeks After a Booster Dose
Description Comparison of Serotype-specific booster responses (functional response) to PNEUMOSIL in comparison to Synflorix 4 weeks after a booster dose
Time Frame 4 weeks post booster vaccination

Outcome Measure Data

Analysis Population Description
In a subset of subjects who got 3 primary series and a booster dose of study vaccines, had postdose immunogenicity measurement(s) with no major protocol deviations, serotype-specific OPA GMT and treatment group ratios of OPA GMT (with corresponding 95% CIs) were evaluated. Pooled PNEUMOSIL data was used for this analysis as per SAP
Arm/Group Title Pneumosil Synflorix
Arm/Group Description Three doses + 1 booster dose of Pneumosil Three doses + 1 booster dose of Synflorix
Measure Participants 99 100
OPA Type 1
344.53
187.16
OPA Type 5
409.87
360.59
OPA Type 6A
3063.37
44.98
OPA Type 6B
2824.56
1610.81
OPA Type 7F
6977.27
4036.08
OPA Type 9V
1137.28
1229.05
OPA Type 14
3114.71
1411.94
OPA Type 19A
645.56
51.47
OPA Type 19F
1592.40
1580.46
OPA Type 23F
3846.82
1226.89
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines will be compared using the ratios of the GMT ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs based on log linear random effects models
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 1
Estimated Value 1.84
Confidence Interval (2-Sided) 95%
1.25 to 2.72
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines will be compared using the ratios of the GMT ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs based on log linear random effects models
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 5
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
0.79 to 1.64
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines will be compared using the ratios of the GMT ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs based on log linear random effects models
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 6A
Estimated Value 68.10
Confidence Interval (2-Sided) 95%
37.07 to 125.09
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines will be compared using the ratios of the GMT ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs based on log linear random effects models
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 6B
Estimated Value 1.75
Confidence Interval (2-Sided) 95%
1.25 to 2.46
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines will be compared using the ratios of the GMT ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs based on log linear random effects models
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 7F
Estimated Value 1.73
Confidence Interval (2-Sided) 95%
1.28 to 2.34
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines will be compared using the ratios of the GMT ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs based on log linear random effects models
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 9V
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.65 to 1.32
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines will be compared using the ratios of the GMT ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs based on log linear random effects models
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 14
Estimated Value 2.21
Confidence Interval (2-Sided) 95%
1.38 to 3.51
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines will be compared using the ratios of the GMT ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs based on log linear random effects models
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 19A
Estimated Value 12.54
Confidence Interval (2-Sided) 95%
7.36 to 21.37
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines will be compared using the ratios of the GMT ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs based on log linear random effects models
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 19F
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.70 to 1.46
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines will be compared using the ratios of the GMT ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs based on log linear random effects models
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 23F
Estimated Value 3.14
Confidence Interval (2-Sided) 95%
2.21 to 4.45
Parameter Dispersion Type:
Value:
Estimation Comments
21. Secondary Outcome
Title Number and Percentage of Subjects With EPI Vaccine Immune Responses (Measles, Rubella and Yellow Fever)
Description Anti-measles IgG, anti-rubella IgG and anti-yellow fever neutralizing antibody titer
Time Frame 4 weeks post booster vaccination

Outcome Measure Data

Analysis Population Description
Evaluated in a subset who got 3 primary doses and a booster dose, had postdose immunogenicity data with no major protocol deviations. Non-inferiority shown if 2-sided 95% CI for difference in response proportions (PNEUMOSIL-Synflorix) had lower limit >-0.10. For this, pooled PNUEMOSIL data was used as specified in SAP.
Arm/Group Title Pneumosil Synflorix
Arm/Group Description Three primary doses + 1 booster dose of Pneumosil Three primary doses + 1 booster dose of Synflorix
Measure Participants 425 208
Anti-Measles IgG ≥ 150 mIU/mL
381
75.9%
183
36.5%
Anti- Rubella IgG ≥ 4 IU/mL
421
83.9%
204
40.7%
Anti-Yellow Fever neutralizing Ab titer ≥ 1:8
420
83.7%
201
40.1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority will be shown if a two-sided 95% CI for the treatment-group difference in response proportions (proportion with Synflorix co-administration minus proportion with PNEUMOSIL co-administration) has an upper limit of < 0.10.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute difference for measles
Estimated Value 1.7
Confidence Interval (2-Sided) 95%
-3.3 to 7.4
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority will be shown if a two-sided 95% CI for the treatment-group difference in response proportions (proportion with Synflorix co-administration minus proportion with PNEUMOSIL co-administration) has an upper limit of < 0.10.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute difference for rubella
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
-0.9 to 4.0
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority will be shown if a two-sided 95% CI for the treatment-group difference in response proportions (proportion with Synflorix co-administration minus proportion with PNEUMOSIL co-administration) has an upper limit of < 0.10.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute difference for yellow fever
Estimated Value 2.4
Confidence Interval (2-Sided) 95%
0.2 to 5.9
Parameter Dispersion Type:
Value:
Estimation Comments
22. Other Pre-specified Outcome
Title Proportions and Treatment Group Difference in Proportions of IgG Responders 1 Year Post Booster
Description Treatment group proportions and treatment-group difference in proportions of IgG responders (IgG concentration ≥ 0.35 μg/mL)
Time Frame One Year Post Booster Vaccination

Outcome Measure Data

Analysis Population Description
In a subset of subjects who got 3 primary and a booster dose of study vaccines, had postdose immunogenicity measurement(s) one year post booster with no major protocol deviations, serotype-specific IgG responders and treatment group comparisons (with corresponding 95% CIs) were evaluated. Pooled PNEUMOSIL data was used for this analysis as per SAP
Arm/Group Title Pneumosil Synflorix
Arm/Group Description Three doses + 1 booster dose of Pneumosil Three doses + 1 booster dose of Synflorix
Measure Participants 378 190
Pn IgG Type 1
150
29.9%
44
8.8%
Pn IgG Type 5
223
44.4%
99
19.8%
Pn IgG Type 6A
306
61%
97
19.4%
Pn IgG Type 6B
344
68.5%
143
28.5%
Pn IgG Type 7F
296
59%
117
23.4%
Pn IgG Type 9V
209
41.6%
106
21.2%
Pn IgG Type 14
322
64.1%
134
26.7%
Pn IgG Type 19A
316
62.9%
128
25.5%
Pn IgG Type 19F
301
60%
174
34.7%
Pn IgG Type 23F
224
44.6%
79
15.8%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Treatment group difference in proportions
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute Difference for Type 1
Estimated Value 16.2
Confidence Interval (2-Sided) 95%
8.0 to 23.7
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Treatment group difference in proportions
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute Difference for Type 5
Estimated Value 7.2
Confidence Interval (2-Sided) 95%
-1.4 to 15.8
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Treatment group difference in proportions
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute Difference for Type 6A
Estimated Value 30.0
Confidence Interval (2-Sided) 95%
21.8 to 38.1
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Treatment group difference in proportions
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute Difference for Type 6B
Estimated Value 16.5
Confidence Interval (2-Sided) 95%
10.1 to 23.6
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Treatment group difference in proportions
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute Difference for Type 7F
Estimated Value 16.4
Confidence Interval (2-Sided) 95%
8.4 to 24.5
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Treatment group difference in proportions
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute Difference for Type 9V
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-8.8 to 8.5
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Treatment group difference in proportions
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute Difference for Type 14
Estimated Value 14.7
Confidence Interval (2-Sided) 95%
7.5 to 22.3
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Treatment group difference in proportions
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute Difference for Type 19A
Estimated Value 14.7
Confidence Interval (2-Sided) 95%
7.3 to 22.5
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Treatment group difference in proportions
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute Difference for Type 19F
Estimated Value -13.7
Confidence Interval (2-Sided) 95%
-19.0 to -8.0
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Treatment group difference in proportions
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Absolute Difference for Type 23F
Estimated Value 16.9
Confidence Interval (2-Sided) 95%
8.2 to 25.4
Parameter Dispersion Type:
Value:
Estimation Comments
23. Other Pre-specified Outcome
Title Serotype-specific Geometric Mean Concentration of IgG Antibody Response and Treatment-Group GMC Ratios One Year Post Booster
Description Comparison of Serotype-specific immune persistence responses (antibody concentrations) to PNEUMOSIL in comparison to Synflorix one year post booster
Time Frame One year post booster vaccination

Outcome Measure Data

Analysis Population Description
Subset of subjects who got 3 primary and a booster dose of study vaccines, had postdose immunogenicity measurement(s) one year post booster with no major protocol deviations, serotype-specific GMC of IgG Antibody and treatment group ratios of IgG GMCs (with corresponding 95% CIs) evaluated. Pooled PNEUMOSIL data was used for this analysis
Arm/Group Title Pneumosil Synflorix
Arm/Group Description Three primary doses + 1 booster dose of Pneumosil Three primary doses + 1 booster dose of Synflorix
Measure Participants 378 190
Pn IgG Type 1
0.30
0.18
Pn IgG Type 5
0.40
0.34
Pn IgG Type 6A
0.73
0.31
Pn IgG Type 6B
0.90
0.62
Pn IgG Type 7F
0.64
0.49
Pn IgG Type 9V
0.38
0.41
Pn IgG Type 14
0.99
0.71
Pn IgG Type 19A
0.91
0.66
Pn IgG Type 19F
0.82
1.35
Pn IgG Type 23F
0.43
0.29
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines were compared using the ratios of the GMC ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 1 GMC Ratio
Estimated Value 1.64
Confidence Interval (2-Sided) 95%
1.42 to 1.89
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines were compared using the ratios of the GMC ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 5 GMC Ratio
Estimated Value 1.20
Confidence Interval (2-Sided) 95%
1.03 to 1.40
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines were compared using the ratios of the GMC ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6A GMC Ratio
Estimated Value 2.36
Confidence Interval (2-Sided) 95%
2.01 to 2.78
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines were compared using the ratios of the GMC ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6B GMC Ratio
Estimated Value 1.45
Confidence Interval (2-Sided) 95%
1.27 to 1.66
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines were compared using the ratios of the GMC ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 7F GMC Ratio
Estimated Value 1.29
Confidence Interval (2-Sided) 95%
1.12 to 1.49
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines were compared using the ratios of the GMC ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 9V GMC Ratio
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.81 to 1.09
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines were compared using the ratios of the GMC ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 14 GMC Ratio
Estimated Value 1.41
Confidence Interval (2-Sided) 95%
1.15 to 1.72
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines were compared using the ratios of the GMC ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19A GMC Ratio
Estimated Value 1.38
Confidence Interval (2-Sided) 95%
1.14 to 1.68
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines were compared using the ratios of the GMC ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19F GMC Ratio
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.50 to 0.74
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The vaccines were compared using the ratios of the GMC ratios for the two treatment groups, i.e., the PNEUMOSIL ratio divided by the Synflorix ratio, and the corresponding 95% CIs
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 23F GMC Ratio
Estimated Value 1.50
Confidence Interval (2-Sided) 95%
1.24 to 1.81
Parameter Dispersion Type:
Value:
Estimation Comments
24. Other Pre-specified Outcome
Title Comparison of Serotype-specific Geometric Mean Concentration of IgG Antibody Response 4 Weeks After a Booster Dose to One Year After a Booster Dose
Description Comparison of Serotype-specific responses (antibody concentrations) measured by ELISA from 4 weeks after a booster dose to one year after a booster dose
Time Frame One year post booster vaccination

Outcome Measure Data

Analysis Population Description
Subset who got 3 primary series+booster dose of study vaccines, had postdose immunogenicity measurements post booster, no major PDs, comparisons based on ratios of IgG GMC one year post booster to IgG GMC four weeks post booster. Comparison done using ratios of the ratios for the 2 treatment groups & corresponding 95% CIs.
Arm/Group Title 4 Weeks Post Booster Dose-Pneumosil One Year Post Booster-Pneumosil 4 Weeks Post Booster Dose-Synflorix One Year Post Booster-Synflorix
Arm/Group Description Three doses + 1 booster dose of Pneumosil in a subset Three doses + 1 booster dose of Pneumosil in a subset Three doses + 1 booster dose of Synflorix in a subset Three doses + 1 booster dose of Synflorix in a subset
Measure Participants 378 378 189 190
Pn IgG Type 1
5.87
0.30
2.52
0.18
Pn IgG Type 5
1.35
0.40
0.85
0.34
Pn IgG Type 6A
4.86
0.73
0.43
0.31
Pn IgG Type 6B
8.48
0.90
4.45
0.62
Pn IgG Type 7F
6.40
0.64
4.14
0.49
Pn IgG Type 9V
1.86
0.38
2.08
0.41
Pn IgG Type 14
6.58
0.99
4.61
0.71
Pn IgG Type 19A
4.02
0.91
1.00
0.66
Pn IgG Type 19F
6.17
0.82
9.80
1.35
Pn IgG Type 23F
4.03
0.43
2.12
0.29
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC one year post-booster to the IgG GMC 4 weeks post booster in the Booster Cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 1 GMC Ratio
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
0.05 to 0.06
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC one year post-booster to the IgG GMC 4 weeks post booster in the Booster Cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 5 GMC Ratio
Estimated Value 0.30
Confidence Interval (2-Sided) 95%
0.27 to 0.33
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC one year post-booster to the IgG GMC 4 weeks post booster in the Booster Cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6A GMC Ratio
Estimated Value 0.15
Confidence Interval (2-Sided) 95%
0.13 to 0.16
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC one year post-booster to the IgG GMC 4 weeks post booster in the Booster Cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6B GMC Ratio
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
0.10 to 0.11
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC one year post-booster to the IgG GMC 4 weeks post booster in the Booster Cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 7F GMC Ratio
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
0.09 to 0.11
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC one year post-booster to the IgG GMC 4 weeks post booster in the Booster Cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 9V GMC Ratio
Estimated Value 0.21
Confidence Interval (2-Sided) 95%
0.19 to 0.23
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC one year post-booster to the IgG GMC 4 weeks post booster in the Booster Cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 14 GMC Ratio
Estimated Value 0.15
Confidence Interval (2-Sided) 95%
0.13 to 0.17
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC one year post-booster to the IgG GMC 4 weeks post booster in the Booster Cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19A GMC Ratio
Estimated Value 0.23
Confidence Interval (2-Sided) 95%
0.20 to 0.26
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC one year post-booster to the IgG GMC 4 weeks post booster in the Booster Cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19F GMC Ratio
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
0.12 to 0.15
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC one year post-booster to the IgG GMC 4 weeks post booster in the Booster Cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 23F GMC Ratio
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
0.10 to 0.12
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC one year post-booster to the IgG GMC 4 weeks post booster in the Booster Cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 1 GMC Ratio
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
0.06 to 0.08
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC one year post-booster to the IgG GMC 4 weeks post booster in the Booster Cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 5 GMC Ratio
Estimated Value 0.40
Confidence Interval (2-Sided) 95%
0.35 to 0.45
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC one year post-booster to the IgG GMC 4 weeks post booster in the Booster Cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6A GMC Ratio
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.62 to 0.86
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC one year post-booster to the IgG GMC 4 weeks post booster in the Booster Cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 6B GMC Ratio
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
0.12 to 0.16
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC one year post-booster to the IgG GMC 4 weeks post booster in the Booster Cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 7F GMC Ratio
Estimated Value 0.12
Confidence Interval (2-Sided) 95%
0.11 to 0.13
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC one year post-booster to the IgG GMC 4 weeks post booster in the Booster Cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 9V GMC Ratio
Estimated Value 0.20
Confidence Interval (2-Sided) 95%
0.18 to 0.22
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC one year post-booster to the IgG GMC 4 weeks post booster in the Booster Cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 14 GMC Ratio
Estimated Value 0.15
Confidence Interval (2-Sided) 95%
0.13 to 0.19
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC one year post-booster to the IgG GMC 4 weeks post booster in the Booster Cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19A GMC Ratio
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.52 to 0.78
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC one year post-booster to the IgG GMC 4 weeks post booster in the Booster Cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 19F GMC Ratio
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
0.12 to 0.16
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on the ratio of IgG GMC one year post-booster to the IgG GMC 4 weeks post booster in the Booster Cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Pn IgG type 23F GMC Ratio
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
0.12 to 0.16
Parameter Dispersion Type:
Value:
Estimation Comments
25. Other Pre-specified Outcome
Title Treatment Group Proportions and Treatment-group Difference in Proportions of Functional Antibody Responders (OPA) One Year Post Booster
Description Serotype-specific functional antibody titer measured by OPA
Time Frame One year post booster vaccination

Outcome Measure Data

Analysis Population Description
Subset of subjects who got 3 primary doses + booster dose, had postdose immunogenicity measurement one year after booster, no major protocol deviations, functional immune responses induced by PNEUMOSIL were compared to Synflorix for 10 serotypes OPA Type 1[OPA seroresponse rate (titer≥1:8)] differences.Pooled PNEUMOSIL data was used.
Arm/Group Title Pneumosil Synflorix
Arm/Group Description Three primary doses + 1 booster dose of Pneumosil Three primary doses + 1 booster dose of Synflorix
Measure Participants 50 50
OPA Type 1
27
5.4%
14
2.8%
OPA Type 5
39
7.8%
37
7.4%
OPA Type 6A
42
8.4%
9
1.8%
OPA Type 6B
43
8.6%
31
6.2%
OPA Type 7F
50
10%
48
9.6%
OPA Type 9V
43
8.6%
40
8%
OPA Type 14
45
9%
41
8.2%
OPA Type 19A
43
8.6%
24
4.8%
OPA Type 19F
44
8.8%
39
7.8%
OPA Type 23F
49
9.8%
43
8.6%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA titer to Pneumosil in comparison with Synflorix for each of the 10 serotypes one year post booster
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA Type 1
Estimated Value 24.2
Confidence Interval (2-Sided) 95%
4.5 to 42.1
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA titer to Pneumosil in comparison with Synflorix for each of the 10 serotypes one year post booster
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA Type 5
Estimated Value 9.9
Confidence Interval (2-Sided) 95%
-5.8 to 25.5
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA titer to Pneumosil in comparison with Synflorix for each of the 10 serotypes one year post booster
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA Type 6A
Estimated Value 65.6
Confidence Interval (2-Sided) 95%
48.3 to 78.0
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA titer to Pneumosil in comparison with Synflorix for each of the 10 serotypes one year post booster
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA Type 6B
Estimated Value 23.2
Confidence Interval (2-Sided) 95%
6.4 to 39.4
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA titer to Pneumosil in comparison with Synflorix for each of the 10 serotypes one year post booster
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA Type 7F
Estimated Value 2.0
Confidence Interval (2-Sided) 95%
-5.2 to 10.8
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA titer to Pneumosil in comparison with Synflorix for each of the 10 serotypes one year post booster
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA Type 9V
Estimated Value 0.0
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments CI could not be computed due to 100% response rate
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA titer to Pneumosil in comparison with Synflorix for each of the 10 serotypes one year post booster
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA Type14
Estimated Value 4.6
Confidence Interval (2-Sided) 95%
-8.5 to 18.3
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA titer to Pneumosil in comparison with Synflorix for each of the 10 serotypes one year post booster
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA Type 19A
Estimated Value 34.4
Confidence Interval (2-Sided) 95%
16.5 to 50.8
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA titer to Pneumosil in comparison with Synflorix for each of the 10 serotypes one year post booster
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA Type 19F
Estimated Value 5.0
Confidence Interval (2-Sided) 95%
-8.4 to 19.2
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA titer to Pneumosil in comparison with Synflorix for each of the 10 serotypes one year post booster
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA Type 23F
Estimated Value 0.0
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments CI could not be computed due to 100% response rate
26. Other Pre-specified Outcome
Title Serotype-specific OPA Geometric Mean Titer One Year Post Booster
Description Serotype-specific functional antibody titer measured by OPA and expressed as OPA GMT in a subset one year post booster
Time Frame One year post booster vaccination

Outcome Measure Data

Analysis Population Description
In a subset of subjects who got 3 primary + booster dose of study vaccines, had postdose immunogenicity measurement one year post booster and no major protocol deviations, functional immune responses induced by PNEUMOSIL were compared to Synflorix for 10 serotypes, i.e., ratio of OPA GMTs (and corresponding 95% CIs).Pooled PNEUMOSIL data was used.
Arm/Group Title Pneumosil Synflorix
Arm/Group Description Three primary doses + 1 booster dose of Pneumosil Three primary doses + 1 booster dose of Synflorix
Measure Participants 50 50
OPA Type 1
11.0
8.7
OPA Type 5
41.4
31.6
OPA Type 6A
118.1
8.3
OPA Type 6B
116.3
31.1
OPA Type 7F
1765.9
1851.8
OPA Type 9V
114.5
158.2
OPA Type 14
215.1
193.4
OPA Type 19A
89.7
17.6
OPA Type 19F
133.5
139.8
OPA Type 23F
393.8
91.6
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA to Pneumosil in comparison with Synflorix for each of the 10 serotypes (GMT Ratio) one year post booster dose
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 1
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
0.8 to 2.1
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA to Pneumosil in comparison with Synflorix for each of the 10 serotypes (GMT Ratio) one year post booster dose
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 5
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
0.7 to 2.4
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA to Pneumosil in comparison with Synflorix for each of the 10 serotypes (GMT Ratio) one year post booster dose
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 6A
Estimated Value 14.3
Confidence Interval (2-Sided) 95%
6.3 to 32.1
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA to Pneumosil in comparison with Synflorix for each of the 10 serotypes (GMT Ratio) one year post booster dose
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 6B
Estimated Value 3.7
Confidence Interval (2-Sided) 95%
2.1 to 6.8
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA to Pneumosil in comparison with Synflorix for each of the 10 serotypes (GMT Ratio) one year post booster dose
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 7F
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
0.6 to 1.6
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA to Pneumosil in comparison with Synflorix for each of the 10 serotypes (GMT Ratio) one year post booster dose
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 9V
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
0.3 to 1.7
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA to Pneumosil in comparison with Synflorix for each of the 10 serotypes (GMT Ratio) one year post booster dose
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 14
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
0.5 to 2.4
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA to Pneumosil in comparison with Synflorix for each of the 10 serotypes (GMT Ratio) one year post booster dose
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 19A
Estimated Value 5.1
Confidence Interval (2-Sided) 95%
2.4 to 10.8
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA to Pneumosil in comparison with Synflorix for each of the 10 serotypes (GMT Ratio) one year post booster dose
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 19F
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
0.4 to 2.3
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments Serotype specific functional antibody responses measured by OPA to Pneumosil in comparison with Synflorix for each of the 10 serotypes (GMT Ratio) one year post booster dose
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 23F
Estimated Value 4.3
Confidence Interval (2-Sided) 95%
2.0 to 9.4
Parameter Dispersion Type:
Value:
Estimation Comments
27. Other Pre-specified Outcome
Title Comparison of Functional Response (OPA) From 4 Weeks After a Booster Dose to One Year Post Booster Dose
Description Comparison of Serotype-specific booster responses (functional response-OPA) from 4 weeks after a booster dose to one year post booster
Time Frame One year post booster vaccination

Outcome Measure Data

Analysis Population Description
In a subset who got 3 primary series+booster dose of study vaccines, had postdose immunogenicity measurements & no major PDs, comparisons based on ratios of OPA GMT one year post booster to OPA GMT 4 weeks post booster. Comparison done using ratios of the ratios for the 2 treatment groups (PNEUMOSIL ratio/Synflorix ratio), & corresponding 95% CIs.
Arm/Group Title 4 Weeks Post Booster Dose-Pneumosil One Year Post Booster-Pneumosil 4 Weeks Post Booster Dose-Synflorix One Year Post Booster-Synflorix
Arm/Group Description Three doses + 1 booster dose of Pneumosil in a subset Three doses + 1 booster dose of Pneumosil in a subset Three doses + 1 booster dose of Synflorix in a subset Three doses + 1 booster dose of Synflorix in a subset
Measure Participants 88 50 91 50
OPA Type 1
345.8
11.0
191.7
8.7
OPA Type 5
422.9
41.4
369.6
31.6
OPA Type 6A
3119.4
118.1
49.9
8.3
OPA Type 6B
3012.0
116.3
1613.8
31.1
OPA Type 7F
6757.8
1765.9
4033.5
1851.8
OPA Type 9V
1114.9
114.5
1231.4
158.2
OPA Type 14
3128.9
215.1
1423.1
193.4
OPA Type 19A
643.6
89.7
54.6
17.6
OPA Type 19F
1651.1
133.5
1611.8
139.8
OPA Type 23F
3933.9
393.8
1219.8
91.6
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post booster and one year post booster for the OPA subset of the booster cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 1
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
0.03 to 0.06
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post booster and one year post booster for the OPA subset of the booster cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 5
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
0.09 to 0.14
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post booster and one year post booster for the OPA subset of the booster cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 6A
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
0.03 to 0.08
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post booster and one year post booster for the OPA subset of the booster cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 6B
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
0.03 to 0.07
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post booster and one year post booster for the OPA subset of the booster cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 7F
Estimated Value 0.26
Confidence Interval (2-Sided) 95%
0.18 to 0.38
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post booster and one year post booster for the OPA subset of the booster cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 9V
Estimated Value 0.12
Confidence Interval (2-Sided) 95%
0.06 to 0.23
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post booster and one year post booster for the OPA subset of the booster cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 14
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
0.05 to 0.11
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post booster and one year post booster for the OPA subset of the booster cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 19A
Estimated Value 0.16
Confidence Interval (2-Sided) 95%
0.09 to 0.30
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post booster and one year post booster for the OPA subset of the booster cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 19F
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
0.05 to 0.18
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Lot 1, Lot 2
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post booster and one year post booster for the OPA subset of the booster cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 23F
Estimated Value 0.12
Confidence Interval (2-Sided) 95%
0.08 to 0.18
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post booster and one year post booster for the OPA subset of the booster cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 1
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
0.03 to 0.06
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post booster and one year post booster for the OPA subset of the booster cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 5
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
0.05 to 0.10
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post booster and one year post booster for the OPA subset of the booster cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 6A
Estimated Value 0.21
Confidence Interval (2-Sided) 95%
0.09 to 0.48
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post booster and one year post booster for the OPA subset of the booster cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 6B
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
0.01 to 0.03
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post booster and one year post booster for the OPA subset of the booster cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 7F
Estimated Value 0.44
Confidence Interval (2-Sided) 95%
0.30 to 0.65
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post booster and one year post booster for the OPA subset of the booster cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 9V
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
0.06 to 0.20
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post booster and one year post booster for the OPA subset of the booster cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 14
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
0.06 to 0.22
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post booster and one year post booster for the OPA subset of the booster cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 19A
Estimated Value 0.26
Confidence Interval (2-Sided) 95%
0.14 to 0.49
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post booster and one year post booster for the OPA subset of the booster cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 19F
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
0.06 to 0.14
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Lot 3, 4 Weeks Post Booster-Synflorix
Comments
Type of Statistical Test Other
Comments The comparisons were based on OPA GMTs 4 weeks post booster and one year post booster for the OPA subset of the booster cohort.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter OPA GMT Ratio-Type 23F
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
0.05 to 0.12
Parameter Dispersion Type:
Value:
Estimation Comments

Adverse Events

Time Frame Recording and reporting of all AEs occurred from signing of the ICF (6-8 weeks of age) through the EOS visit for each subject enrolled in the priming phase of the study (upto 18-20 weeks of age), and through Visit 6 for each study subject enrolled in the booster phase (upto 12 months of age). Subjects included in the third phase for immune persistence evaluation, serious adverse events were monitored from 4 weeks post booster to 12 months after booster.
Adverse Event Reporting Description Immediate solicited local and systemic reactogenicity events and vital signs were assessed 30 minutes following vaccination in all subjects. Half of the subjects in each treatment group were randomly selected to be part of the primary reactogenicity cohort. These subjects and those who received a booster dose were monitored daily at home for 6 days after each study vaccine dose by field workers. As stated in the SAP, pooled PNEUMOSIL data was used for safety analyses.
Arm/Group Title Pneumosil Synflorix
Arm/Group Description Three doses of Pneumosil in primary series cohort and three + 1 booster dose in booster cohort Three doses of Synflorix in primary series cohort and three + 1 booster dose in booster cohort
All Cause Mortality
Pneumosil Synflorix
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/1503 (0.1%) 2/747 (0.3%)
Serious Adverse Events
Pneumosil Synflorix
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 51/1503 (3.4%) 26/747 (3.5%)
Congenital, familial and genetic disorders
Fallot's tetralogy 1/1503 (0.1%) 1 1/747 (0.1%) 1
Trisomy 21 2/1503 (0.1%) 2 0/747 (0%) 0
Atrioventricular septal defect 1/1503 (0.1%) 1 0/747 (0%) 0
Gastrointestinal disorders
Intussusception 2/1503 (0.1%) 2 0/747 (0%) 0
Diarrhoea haemorrhagic 1/1503 (0.1%) 1 0/747 (0%) 0
Vomiting 3/1503 (0.2%) 3 0/747 (0%) 0
General disorders
Developmental delay 1/1503 (0.1%) 1 0/747 (0%) 0
Infections and infestations
Bronchiolitis 14/1503 (0.9%) 14 4/747 (0.5%) 4
Gastroenteritis 15/1503 (1%) 17 9/747 (1.2%) 9
Pneumonia 4/1503 (0.3%) 4 6/747 (0.8%) 6
Dysentery 0/1503 (0%) 0 1/747 (0.1%) 1
Febrile infection 0/1503 (0%) 0 1/747 (0.1%) 1
HIV infection WHO clinical stage IV 0/1503 (0%) 0 1/747 (0.1%) 1
Meningitis pneumococcal 1/1503 (0.1%) 1 0/747 (0%) 0
Perinatal HIV infection 0/1503 (0%) 0 1/747 (0.1%) 1
Periorbital cellulitis 3/1503 (0.2%) 3 1/747 (0.1%) 1
Upper respiratory tract infection 4/1503 (0.3%) 4 0/747 (0%) 0
Abdominal wall abscess 0/1503 (0%) 0 1/747 (0.1%) 1
Abscess neck 0/1503 (0%) 0 1/747 (0.1%) 1
Otitis media acute 0/1503 (0%) 0 1/747 (0.1%) 1
Subcutaneous abscess 1/1503 (0.1%) 1 0/747 (0%) 0
Injury, poisoning and procedural complications
Thermal burn 1/1503 (0.1%) 1 0/747 (0%) 0
Metabolism and nutrition disorders
Malnutrition 0/1503 (0%) 0 1/747 (0.1%) 1
Nervous system disorders
Seizure 1/1503 (0.1%) 1 0/747 (0%) 0
Respiratory, thoracic and mediastinal disorders
Epistaxis 1/1503 (0.1%) 1 0/747 (0%) 0
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome 1/1503 (0.1%) 1 0/747 (0%) 0
Other (Not Including Serious) Adverse Events
Pneumosil Synflorix
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1131/1503 (75.2%) 572/747 (76.6%)
Gastrointestinal disorders
Diarrhoea 281/1503 (18.7%) 317 132/747 (17.7%) 139
Vomiting 25/1503 (1.7%) 25 13/747 (1.7%) 13
General disorders
Pyrexia 31/1503 (2.1%) 31 16/747 (2.1%) 16
Infections and infestations
Upper respiratory tract infection 730/1503 (48.6%) 1041 379/747 (50.7%) 552
Furuncle 150/1503 (10%) 183 65/747 (8.7%) 77
Gastroenteritis 154/1503 (10.2%) 169 76/747 (10.2%) 80
Conjunctivitis 110/1503 (7.3%) 116 64/747 (8.6%) 67
Bronchiolitis 59/1503 (3.9%) 65 42/747 (5.6%) 47
Tinea infection 62/1503 (4.1%) 62 22/747 (2.9%) 22
Febrile infection 52/1503 (3.5%) 54 25/747 (3.3%) 28
Pneumonia 41/1503 (2.7%) 44 21/747 (2.8%) 21
Tinea capitis 29/1503 (1.9%) 30 22/747 (2.9%) 23
Oral candidiasis 33/1503 (2.2%) 37 15/747 (2%) 15
Body tinea 29/1503 (1.9%) 29 18/747 (2.4%) 18
Impetigo 27/1503 (1.8%) 27 19/747 (2.5%) 19
Rash pustular 25/1503 (1.7%) 26 16/747 (2.1%) 16
Skin candida 14/1503 (0.9%) 14 11/747 (1.5%) 11
Otitis media acute 6/1503 (0.4%) 6 8/747 (1.1%) 8
Injury, poisoning and procedural complications
Thermal burn 9/1503 (0.6%) 9 11/747 (1.5%) 11
Respiratory, thoracic and mediastinal disorders
Cough 95/1503 (6.3%) 103 39/747 (5.2%) 39
Skin and subcutaneous tissue disorders
Dermatitis diaper 36/1503 (2.4%) 37 28/747 (3.7%) 31
Rash maculo-papular 37/1503 (2.5%) 37 16/747 (2.1%) 17
Rash papular 20/1503 (1.3%) 22 11/747 (1.5%) 13
Dermatitis contact 17/1503 (1.1%) 18 7/747 (0.9%) 7
Dermatitis atopic 12/1503 (0.8%) 12 11/747 (1.5%) 11
Seborrhoeic dermatitis 17/1503 (1.1%) 17 5/747 (0.7%) 5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Dr. Steve Lamola
Organization PATH
Phone + 1 206.302.6067
Email slamola@path.org
Responsible Party:
PATH
ClinicalTrials.gov Identifier:
NCT03197376
Other Study ID Numbers:
  • VAC-056
First Posted:
Jun 23, 2017
Last Update Posted:
Jul 14, 2020
Last Verified:
Aug 1, 2019