Pneumococcal Infections
Conditions
Keywords
Pneumococcal Disease, Pneumococcal Conjugate Vaccine
Brief summary
The 13-valent pneumococcal conjugate vaccine (13vPnC) is being developed for adults to prevent pneumococcal diseases such as meningitis (inflammation of the brain lining), septicemia (blood poisoning), and pneumonia (inflammation of the lungs). As trivalent influenza vaccine (TIV) is frequently given to adults, it is important to show that both vaccines can safely be given together without affecting the immune response (body's ability to protect against disease).
Interventions
BIOLOGICAL13-valent pneumococcal conjugate vaccine
Single 0.5 milliliter (mL) 13-valent pneumococcal conjugate vaccine (13vPnC) and a single 0.5 mL trivalent inactivated influenza vaccine (TIV), administered intramuscularly (IM), followed by a single 0.5 mL vaccine 13vPnC placebo, 1 month later.
BIOLOGICAL13vPnC + TIV
Single 0.5 mL 13vPnC placebo vaccine and a single 0.5 mL TIV, administered IM, followed by a single 0.5 mL 13vPnC vaccine, 1 month later.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Generally healthy male or female adults 65 years of age or older. * Available for the duration of the trial - approximately 2 months. * No previous vaccination with any pneumococcal vaccine. * No history of severe adverse reaction associated with a vaccine. * No allergy to egg proteins (eggs or egg products) and chicken proteins.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TIV Comparisons: Percentage of Participants Achieving at Least a 4-fold Increase in the Titer of the Standard Hemagglutination Inhibition Assay (HAI) | Baseline and 1 month after TIV vaccination | Percentage of participants achieving at least a 4-fold increase in the titer of the standard HAI for each influenza virus subtype (A/H1N1, A/H3N2, and B) were compared. |
| 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | 1 month after 13vPnC vaccination | IgG GMC as measured by enzyme-linked immunosorbent assay (ELISA) and expressed in micrograms per mL (mcg/mL) for serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Pre-specified Local Reactions | Days 1 through 14 after 13vPnC vaccination | Local reactions were reported using an electronic diary. Pain was scaled as Any; Mild (awareness but easily tolerated); Moderate (discomfort enough to interfere with usual activity) and Severe (incapacitating the usual activity). Redness and swelling were scaled as Any; Mild (2.5 cm to 5.0 cm); Moderate (5.1 to 10.0 cm)and Severe (\> 10.0 cm). Limitation in arm movement were scaled as Any; Mild (some limitation); Moderate (unable to move above head but able to move above shoulder) and Severe (unable to move above shoulder). |
| Percentage of Participants With Pre-specified Systemic Events | Days 1 through 14 after 13vPnC vaccination | Systemic events (Any fever \>= 38 degrees Celsius \[C\]), fatigue, headache, chills, rash, vomiting, decreased appetite, new muscle pain, any aggravated muscle pain, new joint pain or any aggravated joint pain. Participants may be presented in more than one category. |
Participant flow
Pre-assignment details
A total of 1185 participants were enrolled, of which 1160 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| 13vPnC+TIV Followed by Placebo 1 Month Later Single 0.5 milliliter (mL) 13-valent pneumococcal conjugate vaccine (13vPnC) and a single 0.5 mL trivalent inactivated influenza vaccine (TIV), administered intramuscularly (IM), followed by a single 0.5 mL 13vPnC placebo vaccine, 1 month later. | 576 |
| Placebo+TIV Followed by 13vPnC 1 Month Later Single 0.5 mL 13vPnC placebo vaccine and a single 0.5 mL TIV, administered IM, followed by a single 0.5 mL 13vPnC, 1 month later. | 575 |
| Total | 1,151 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Failed to return | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other | 2 | 2 |
| Overall Study | Protocol Violation | 7 | 8 |
| Overall Study | Subject request | 12 | 11 |
Baseline characteristics
| Characteristic | 13vPnC+TIV Followed by Placebo 1 Month Later | Placebo+TIV Followed by 13vPnC 1 Month Later | Total |
|---|---|---|---|
| Age Continuous | 72.1 years STANDARD_DEVIATION 5.6 | 72.1 years STANDARD_DEVIATION 5.5 | 72.1 years STANDARD_DEVIATION 5.5 |
| Sex: Female, Male Female | 289 Participants | 290 Participants | 579 Participants |
| Sex: Female, Male Male | 287 Participants | 285 Participants | 572 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 307 / 576 | 194 / 559 | 256 / 575 | 237 / 558 |
| serious Total, serious adverse events | 4 / 576 | 8 / 559 | 0 / 575 | 5 / 558 |
Outcome results
Primary
13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC)
IgG GMC as measured by enzyme-linked immunosorbent assay (ELISA) and expressed in micrograms per mL (mcg/mL) for serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.
Time frame: 1 month after 13vPnC vaccination
Population: Evaluable immunogenicity population: had participants who adhered to protocol requirements, had valid and determinate assay results, and had no major protocol violations.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 4 | 2.15 mcg/mL |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 9V | 4.97 mcg/mL |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 6A | 4.61 mcg/mL |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 14 | 8.95 mcg/mL |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 3 | 1.08 mcg/mL |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 18C | 8.88 mcg/mL |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 6B | 6.24 mcg/mL |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 19A | 11.93 mcg/mL |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 5 | 4.74 mcg/mL |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 19F | 4.78 mcg/mL |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 7F | 7.63 mcg/mL |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 23F | 5.82 mcg/mL |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 1 | 2.52 mcg/mL |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 23F | 6.11 mcg/mL |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 1 | 3.20 mcg/mL |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 3 | 1.15 mcg/mL |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 4 | 3.24 mcg/mL |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 5 | 6.90 mcg/mL |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 6A | 6.10 mcg/mL |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 6B | 6.43 mcg/mL |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 7F | 9.04 mcg/mL |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 9V | 6.21 mcg/mL |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 14 | 12.44 mcg/mL |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 18C | 11.07 mcg/mL |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 19A | 17.10 mcg/mL |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) | Serotype 19F | 7.39 mcg/mL |
Comparison: Serotype 1. The primary null hypothesis was: the log of the GMC in the group receiving 13vPnC and TIV concomitantly, minus the log of the GMC in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.6, 1.04]
Comparison: Serotype 3. The primary null hypothesis was: the log of the GMC in the group receiving 13vPnC and TIV concomitantly, minus the log of the GMC in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.78, 1.13]
Comparison: Serotype 4. The primary null hypothesis was: the log of the GMC in the group receiving 13vPnC and TIV concomitantly, minus the log of the GMC in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.51, 0.87]
Comparison: Serotype 5. The primary null hypothesis was: the log of the GMC in the group receiving 13vPnC and TIV concomitantly, minus the log of the GMC in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.55, 0.86]
Comparison: Serotype 6A. The primary null hypothesis was: the log of the GMC in the group receiving 13vPnC and TIV concomitantly, minus the log of the GMC in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.61, 0.94]
Comparison: Serotype 6B. The primary null hypothesis was: the log of the GMC in the group receiving 13vPnC and TIV concomitantly, minus the log of the GMC in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.75, 1.25]
Comparison: Serotype 7F. The primary null hypothesis was: the log of the GMC in the group receiving 13vPnC and TIV concomitantly, minus the log of the GMC in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.67, 1.07]
Comparison: Serotype 9V. The primary null hypothesis was: the log of the GMC in the group receiving 13vPnC and TIV concomitantly, minus the log of the GMC in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.63, 1.02]
Comparison: Serotype 14. The primary null hypothesis was: the log of the GMC in the group receiving 13vPnC and TIV concomitantly, minus the log of the GMC in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.53, 0.97]
Comparison: Serotype 18C. The primary null hypothesis was: the log of the GMC in the group receiving 13vPnC and TIV concomitantly, minus the log of the GMC in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.64, 1.01]
Comparison: Serotype 19A. The primary null hypothesis was: the log of the GMC in the group receiving 13vPnC and TIV concomitantly, minus the log of the GMC in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.56, 0.87]
Comparison: Serotype 19F. The primary null hypothesis was: the log of the GMC in the group receiving 13vPnC and TIV concomitantly, minus the log of the GMC in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.49, 0.85]
Comparison: Serotype 23F. The primary null hypothesis was: the log of the GMC in the group receiving 13vPnC and TIV concomitantly, minus the log of the GMC in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.71, 1.27]
Primary
TIV Comparisons: Percentage of Participants Achieving at Least a 4-fold Increase in the Titer of the Standard Hemagglutination Inhibition Assay (HAI)
Percentage of participants achieving at least a 4-fold increase in the titer of the standard HAI for each influenza virus subtype (A/H1N1, A/H3N2, and B) were compared.
Time frame: Baseline and 1 month after TIV vaccination
Population: Evaluable immunogenicity population: had participants who adhered to protocol requirements, had valid and determinate assay results, and had no major protocol violations.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 13vPnC+TIV | TIV Comparisons: Percentage of Participants Achieving at Least a 4-fold Increase in the Titer of the Standard Hemagglutination Inhibition Assay (HAI) | Influenza virus subtype: A/H1N1 | 80.3 Percentage of participants |
| 13vPnC+TIV | TIV Comparisons: Percentage of Participants Achieving at Least a 4-fold Increase in the Titer of the Standard Hemagglutination Inhibition Assay (HAI) | Influenza virus subtype: A/H3N2 | 58.0 Percentage of participants |
| 13vPnC+TIV | TIV Comparisons: Percentage of Participants Achieving at Least a 4-fold Increase in the Titer of the Standard Hemagglutination Inhibition Assay (HAI) | Influenza virus subtype: B | 52.2 Percentage of participants |
| Placebo+TIV | TIV Comparisons: Percentage of Participants Achieving at Least a 4-fold Increase in the Titer of the Standard Hemagglutination Inhibition Assay (HAI) | Influenza virus subtype: A/H1N1 | 78.6 Percentage of participants |
| Placebo+TIV | TIV Comparisons: Percentage of Participants Achieving at Least a 4-fold Increase in the Titer of the Standard Hemagglutination Inhibition Assay (HAI) | Influenza virus subtype: A/H3N2 | 62.6 Percentage of participants |
| Placebo+TIV | TIV Comparisons: Percentage of Participants Achieving at Least a 4-fold Increase in the Titer of the Standard Hemagglutination Inhibition Assay (HAI) | Influenza virus subtype: B | 54.0 Percentage of participants |
Comparison: Influenza virus subtype: A/H1N1. Primary null hypothesis for each of the influenza virus subtypes is: proportion of participants achieving a 4-fold increase in titer when 13vPnC+TIV were administered concomitantly, minus the proportion of participants achieving a 4-fold increase in titer when TIV was administered alone (with placebo) \<= -0.10.95% CI: [-3.1, 6.5]
Comparison: Influenza virus subtype: A/H3N2. Primary null hypothesis for each of the influenza virus subtypes is: proportion of participants achieving a 4-fold increase in titer when 13vPnC+TIV were administered concomitantly, minus the proportion of participants achieving a 4-fold increase in titer when TIV was administered alone (with placebo) \<= -0.10.95% CI: [-10.4, 1.3]
Comparison: Influenza virus subtype: B. Primary null hypothesis for each of the influenza virus subtypes is: proportion of participants achieving a 4-fold increase in titer when 13vPnC+TIV were administered concomitantly, minus the proportion of participants achieving a 4-fold increase in titer when TIV was administered alone (with placebo) \<= -0.10.95% CI: [-7.8, 4.1]
Post Hoc
13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT)
Pneumococcal OPA GMTs for 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in the blood samples of a subset of participants using a microcolony OPA (mcOPA) assay.
Time frame: 1 month after 13vPnC vaccination
Population: Evaluable immunogenicity population: had participants who adhered to protocol requirements, had valid and determinate assay results, and had no major protocol violations. n= number of participants with a determinate OPA antibody titer to the given serotype.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 4 (n= 247, 245) | 997 Geometric mean titers |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 9V (n= 247, 242) | 477 Geometric mean titers |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 6A (n= 250, 252) | 1220 Geometric mean titers |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 14 (n= 247, 236) | 975 Geometric mean titers |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 3 (n= 235, 237) | 46 Geometric mean titers |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 18C (n= 250, 244) | 1158 Geometric mean titers |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 6B (n= 259, 248) | 1564 Geometric mean titers |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 19A (n= 251, 247) | 445 Geometric mean titers |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 5 (n= 245, 234) | 124 Geometric mean titers |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 19F (n= 247, 242) | 378 Geometric mean titers |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 7F (n= 246, 248) | 607 Geometric mean titers |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 23F (n= 252, 242) | 245 Geometric mean titers |
| 13vPnC+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 1 (n= 256, 255) | 88 Geometric mean titers |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 23F (n= 252, 242) | 295 Geometric mean titers |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 1 (n= 256, 255) | 95 Geometric mean titers |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 3 (n= 235, 237) | 51 Geometric mean titers |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 4 (n= 247, 245) | 1486 Geometric mean titers |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 5 (n= 245, 234) | 112 Geometric mean titers |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 6A (n= 250, 252) | 1597 Geometric mean titers |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 6B (n= 259, 248) | 2017 Geometric mean titers |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 7F (n= 246, 248) | 835 Geometric mean titers |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 9V (n= 247, 242) | 723 Geometric mean titers |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 14 (n= 247, 236) | 1088 Geometric mean titers |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 18C (n= 250, 244) | 1415 Geometric mean titers |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 19A (n= 251, 247) | 539 Geometric mean titers |
| Placebo+TIV | 13vPnC Comparisons: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Serotype 19F (n= 247, 242) | 467 Geometric mean titers |
Comparison: Serotype 1. The primary null hypothesis was: the log of the GMT in the group receiving 13vPnC + TIV minus the log of the GMT in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.68, 1.24]
Comparison: Serotype 3. The primary null hypothesis was: the log of the GMT in the group receiving 13vPnC + TIV minus the log of the GMT in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.69, 1.2]
Comparison: Serotype 4. The primary null hypothesis was: the log of the GMT in the group receiving 13vPnC + TIV minus the log of the GMT in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.47, 0.95]
Comparison: Serotype 5. The primary null hypothesis was: the log of the GMT in the group receiving 13vPnC + TIV minus the log of the GMT in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.77, 1.6]
Comparison: Serotype 6A. The primary null hypothesis was: the log of the GMT in the group receiving 13vPnC + TIV minus the log of the GMT in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.54, 1.08]
Comparison: Serotype 6B. The primary null hypothesis was: the log of the GMT in the group receiving 13vPnC + TIV minus the log of the GMT in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.55, 1.09]
Comparison: Serotype 7F. The primary null hypothesis was: the log of the GMT in the group receiving 13vPnC + TIV minus the log of the GMT in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.47, 1.12]
Comparison: Serotype 9V. The primary null hypothesis was: the log of the GMT in the group receiving 13vPnC + TIV minus the log of the GMT in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.42, 1.03]
Comparison: Serotype 14. The primary null hypothesis was: the log of the GMT in the group receiving 13vPnC + TIV minus the log of the GMT in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.65, 1.24]
Comparison: Serotype 18C. The primary null hypothesis was: the log of the GMT in the group receiving 13vPnC + TIV minus the log of the GMT in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.59, 1.14]
Comparison: Serotype 19A. The primary null hypothesis was: the log of the GMT in the group receiving 13vPnC + TIV minus the log of the GMT in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.61, 1.12]
Comparison: Serotype 19F. The primary null hypothesis was: the log of the GMT in the group receiving 13vPnC + TIV minus the log of the GMT in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.57, 1.16]
Comparison: Serotype 23F. The primary null hypothesis was: the log of the GMT in the group receiving 13vPnC + TIV minus the log of the GMT in the group receiving 13vPnC alone (1 month after TIV) \<= -0.693.95% CI: [0.54, 1.27]
Other Pre-specified
Percentage of Participants With Pre-specified Local Reactions
Local reactions were reported using an electronic diary. Pain was scaled as Any; Mild (awareness but easily tolerated); Moderate (discomfort enough to interfere with usual activity) and Severe (incapacitating the usual activity). Redness and swelling were scaled as Any; Mild (2.5 cm to 5.0 cm); Moderate (5.1 to 10.0 cm)and Severe (\> 10.0 cm). Limitation in arm movement were scaled as Any; Mild (some limitation); Moderate (unable to move above head but able to move above shoulder) and Severe (unable to move above shoulder).
Time frame: Days 1 through 14 after 13vPnC vaccination
Population: Safety population: included all participants who received at least 1 dose of study vaccine. n=number of participants at each timepoint, in each group respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 13vPnC+TIV | Percentage of Participants With Pre-specified Local Reactions | Pain: Any (n= 480, 470) | 40.0 percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Local Reactions | Pain: Mild (n= 470, 462) | 34.3 percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Local Reactions | Swelling: Any (n= 441, 431) | 13.8 percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Local Reactions | Pain: Moderate (n= 447, 442) | 14.8 percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Local Reactions | Redness: Moderate (n= 433, 424) | 6.0 percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Local Reactions | Pain: Severe (n= 429, 421) | 1.4 percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Local Reactions | Swelling: Mild (n= 440, 430) | 11.8 percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Local Reactions | Limitation of arm movement: Any (n= 445, 432) | 13.9 percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Local Reactions | Redness: Mild (n= 438, 432) | 14.4 percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Local Reactions | Limitation of arm movement: Mild (n= 444, 432) | 13.1 percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Local Reactions | Swelling: Moderate (n= 432, 423) | 4.2 percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Local Reactions | Limitation of arm movement:Moderate (n= 430, 420) | 1.4 percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Local Reactions | Redness: Severe (n= 429, 420) | 0.7 percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Local Reactions | Limitation of arm movement: Severe (n= 429, 420) | 1.9 percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Local Reactions | Swelling: Severe (n= 428, 420) | 0.2 percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Local Reactions | Any local reaction (n= 488, 470) | 46.9 percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Local Reactions | Redness: Any (n= 440, 432) | 16.6 percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Local Reactions | Any local reaction (n= 488, 470) | 46.6 percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Local Reactions | Redness: Any (n= 440, 432) | 12.3 percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Local Reactions | Redness: Mild (n= 438, 432) | 9.7 percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Local Reactions | Redness: Moderate (n= 433, 424) | 6.1 percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Local Reactions | Redness: Severe (n= 429, 420) | 1.0 percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Local Reactions | Swelling: Any (n= 441, 431) | 10.2 percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Local Reactions | Swelling: Mild (n= 440, 430) | 8.1 percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Local Reactions | Swelling: Moderate (n= 432, 423) | 5.0 percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Local Reactions | Swelling: Severe (n= 428, 420) | 0.0 percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Local Reactions | Pain: Mild (n= 470, 462) | 37.9 percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Local Reactions | Pain: Moderate (n= 447, 442) | 19.7 percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Local Reactions | Pain: Severe (n= 429, 421) | 2.6 percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Local Reactions | Limitation of arm movement: Any (n= 445, 432) | 14.8 percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Local Reactions | Limitation of arm movement: Mild (n= 444, 432) | 13.4 percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Local Reactions | Limitation of arm movement:Moderate (n= 430, 420) | 1.0 percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Local Reactions | Limitation of arm movement: Severe (n= 429, 420) | 1.4 percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Local Reactions | Pain: Any (n= 480, 470) | 43.4 percentage of participants |
Other Pre-specified
Percentage of Participants With Pre-specified Systemic Events
Systemic events (Any fever \>= 38 degrees Celsius \[C\]), fatigue, headache, chills, rash, vomiting, decreased appetite, new muscle pain, any aggravated muscle pain, new joint pain or any aggravated joint pain. Participants may be presented in more than one category.
Time frame: Days 1 through 14 after 13vPnC vaccination
Population: Safety population: included all participants who received at least 1 dose of study vaccine. n=number of participants at each timepoint, in each group respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 13vPnC+TIV | Percentage of Participants With Pre-specified Systemic Events | Fatigue (n= 476, 456) | 37.4 Percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Systemic Events | Vomiting (n= 432, 424) | 3.0 Percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Systemic Events | Fever >=38.5 degreesC but <39 degreesC (n=430,421) | 1.4 Percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Systemic Events | Decreased appetite (n= 450, 434) | 16.9 Percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Systemic Events | Headache (n= 472, 449) | 32.6 Percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Systemic Events | New muscle pain (n= 468, 448) | 26.9 Percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Systemic Events | Fever >40.0 degrees C (n= 429, 422) | 1.4 Percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Systemic Events | Any aggravated muscle pain (n= 454, 439) | 18.7 Percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Systemic Events | Chills (n= 443, 429) | 13.8 Percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Systemic Events | New joint pain (n= 452, 435) | 16.2 Percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Systemic Events | Fever >=39degreesC but <=40.0degreesC (n=428,420) | 0.0 Percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Systemic Events | Any aggravated joint pain (n= 452, 428) | 15.7 Percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Systemic Events | Rash (n= 433, 427) | 6.9 Percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Systemic Events | Any systemic event (n= 510, 488) | 60.2 Percentage of participants |
| 13vPnC+TIV | Percentage of Participants With Pre-specified Systemic Events | Fever >=38 degreesC but <38.5 degreesC (n=434,423) | 3.0 Percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Systemic Events | Any systemic event (n= 510, 488) | 48.6 Percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Systemic Events | Fever >=38 degreesC but <38.5 degreesC (n=434,423) | 3.1 Percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Systemic Events | Fever >=38.5 degreesC but <39 degreesC (n=430,421) | 1.0 Percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Systemic Events | Fever >=39degreesC but <=40.0degreesC (n=428,420) | 0.0 Percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Systemic Events | Fever >40.0 degrees C (n= 429, 422) | 0.7 Percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Systemic Events | Fatigue (n= 476, 456) | 28.5 Percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Systemic Events | Headache (n= 472, 449) | 24.7 Percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Systemic Events | Chills (n= 443, 429) | 9.1 Percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Systemic Events | Rash (n= 433, 427) | 6.8 Percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Systemic Events | Vomiting (n= 432, 424) | 1.7 Percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Systemic Events | Decreased appetite (n= 450, 434) | 11.3 Percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Systemic Events | New muscle pain (n= 468, 448) | 23.4 Percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Systemic Events | Any aggravated muscle pain (n= 454, 439) | 15.0 Percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Systemic Events | New joint pain (n= 452, 435) | 11.5 Percentage of participants |
| Placebo+TIV | Percentage of Participants With Pre-specified Systemic Events | Any aggravated joint pain (n= 452, 428) | 8.6 Percentage of participants |