13-valent Pneumoccocal Conjugate Vaccine

Local reactions were recorded using an electronic diary (e-diary). Local reactions included redness, swelling and pain at the injection site. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 centimeter (cm). Redness and swelling were graded as mild (greater than \[\>\] 2.0 to 5.0 cm), moderate (\>5.0 to 10.0 cm) and severe (\>10.0 cm). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), and severe (prevented daily activity).

Systemic events fever, fatigue, headache, muscle pain and joint pain were recorded by using an e-diary. Fever was defined as temperature \>=38.0 degree Celsius (C) and categorized to \>=38.0 to 38.4 degree C, \>38.4 to 38.9 degree C, \>38.9 to 40.0 degree C and \>40.0 degree C. Fatigue, headache, muscle pain and joint pain were graded as mild (did not interfere with activity), moderate (some interference with activity) and severe (prevented daily routine activity).

An AE was any untoward medical occurrence in study participants who received study vaccine without regard to possibility of causal relationship with the treatment.

An SAE was any untoward medical occurrence at any dose that results in death; is life-threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); results in congenital anomaly/birth defect or that is considered to be an important medical event.

An NDCMC was defined as a disease or medical condition, not previously identified, that was expected to be persistent or was otherwise long-lasting in its effects.

OPA GMTs were determined for serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F and 33F. OPA titer was expressed as reciprocal of the highest serum dilution.

Serotype-specific IgG concentrations to the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in all participants from the blood samples taken 1 month after the infant series in Cohort 1 and the last dose 13vPnC in Cohorts 2, 3, 4. GMC and corresponding 2-sided 95% confidence intervals (CI) were evaluated. Geometric means (GMs) were calculated using all participants with available data for the specified blood draw.

Local reactions (redness, swelling, and tenderness) at the site of the investigational product injection were monitored daily for 7 days after each vaccination. Temperature were collected at bedtime daily for 7 days and at any time during the 7 days that fever is suspected. Fever is defined as temperature of greater than or equal to 38.0ºC (100.4ºF). Other systemic events (decreased appetite, drowsiness and irritability) were recorded for 7 days after each investigational product vaccination.

Local reactions (redness, swelling, and tenderness) at the site of the investigational product injection were monitored daily for 7 days after each vaccination. Temperature were collected at bedtime daily for 7 days and at any time during the 7 days that fever is suspected. Fever is defined as temperature of greater than or equal to 38.0ºC (100.4ºF). Other systemic events (decreased appetite, drowsiness and irritability) were recorded for 7 days after each investigational product vaccination.

Local reactions (redness, swelling, and tenderness) at the site of the investigational product injection were monitored daily for 7 days after each vaccination. Temperature were collected at bedtime daily for 7 days and at any time during the 7 days that fever is suspected. Fever is defined as temperature of greater than or equal to 38.0ºC (100.4ºF). Other systemic events (fatigue, headache, vomiting, diarrhea, muscle pain and joint pain) were recorded for 7 days after each investigational product vaccination.

An AE was any untoward medical occurrence in a study participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage.

Number of participants with NDCMCs from 1 month after the last study vaccination (13vPnC or Hib vaccine) to 6 months after the last study vaccination in Cohorts 2, 3, and 4. An NDCMC was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects.

An SAE was any untoward medical occurrence at any dose that resulted in death, was life-threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), resulted in congenital anomaly/birth defect or considered to be an important medical event.

Serotype-specific OPA GMTs for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in the blood samples of all the participants using a quantitative functional OPA assay. Confidence intervals (CIs) for GMT are back transformations of a CI based on the Student t distribution for the mean logarithm of the titers. Individual OPA assay values below the assay LLOQ (lower limit of quantification) were set at a titer of 0.5\*limit of detection (LOD \[8\]) = (titer of 4) for the purpose of calculating the OPA GMT.

Local reactions reported using an electronic diary. Redness and Swelling scaled as Any (redness present or swelling present), Mild (2.5 to 5.0 centimeters \[cm\]), Moderate (5.1 to 10.0 cm), Severe (\>10 cm). Pain at injection site scaled as Any (pain present), Mild (does not interfere with activity), Moderate (interferes with activity), Severe (prevents daily activity).

Systemic events reported using electronic diary. Fever-Any:\>=38 degrees Celsius (C), Mild (M):\>=38 to \<38.5 degrees C, Moderate(Mod):\>=38.5 to \<39 degrees C, Severe (S):\>=39 to \<=40 degrees C, Potentially life threatening:\>40 degrees C. Headache, fatigue, muscle pain, joint pain- Any: present, M:did not interfere with activity, Mod:some interference, S:activity prevented. Vomiting- Any:present, M:1-2 times/day (d), Mod:\>2/d, S:required intravenous hydration. Diarrhoea- Any:present, M:2-3 loose stools/d, Mod:4-5/d, S:\>=6/d. All reports of fever \>40 degrees C were confirmed as data entry errors.

An AE was any untoward medical occurrence in a participant who received vaccine without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between vaccination and up to 1 month (28 to 42 days) after vaccination that were absent before treatment or that worsened relative to pre-treatment state.

GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from before 13vPnC Dose 1 to 1 month after 13vPnC Dose 3 were computed using the logarithmically transformed assay results. Confidence interval (CI) for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from both before 13vPnC Dose 1 and after 13vPnC Dose 3 blood draws.

GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from 1 month after 13vPnC Dose 1 to 1 month after 13vPnC Dose 2 were computed using the logarithmically transformed assay results. Confidence interval (CI) for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from both 1 month after 13vPnC Dose 1 and after 13vPnC Dose 2 blood draws. Here number of participants analyzed signifies the evaluable immunogenicity population and "N" signifies participants with a determinate IgG antibody concentration for the given serotype at both 1 Month After 13vPnC Dose 1 and 1 Month After 13vPnC Dose 2 blood draws. Participants may be represented in more than 1 category.

Antibody geometric mean concentration (GMC) as measured by micrograms per milliliter (mcg/mL) for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (Serotypes 1, 3, 5, 6A, 7F, and 19A) were presented. GMC (13vPnC) and corresponding 2-sided 95% confidence intervals (CI) were evaluated. GMCs were calculated using all participants with available data for the specified blood draw.

Percentages of participants achieving World Health Organization (WHO) predefined antibody threshold ≥ 0.35 μg/mL along with the corresponding 95% CI for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) are presented.

Local reactions included redness, swelling and pain at the injection site collected in an electronic diary (e-diary) or case report form(CRF). Redness and swelling were measured and recorded in measuring device units. One measuring device unit=0.5 centimeter (cm). Redness and swelling reported in e-diary were graded as mild: greater than (\>) 2.0 cm to 5.0 cm, moderate: \>5.0 cm to 10.0 cm and severe \> 10 cm. Pain at injection site was graded as mild: did not interfere with activity; moderate: interfered with activity; and severe: prevented daily activity. Severity definition from CRF: mild (does not interfere)/moderate (interferes to some extent)/severe(interferes significantly) with the participant's usual function. Exact 2-sided 95% confidence interval (CI) was based on the Clopper and Pearson method.

Systemic events included fever, fatigue, headache, muscle pain and joint pain and were collected in an e-diary or CRF. Fever was defined as temperature greater than or equal to (\>=) 38.0 degrees Celsius (C) and categorized as \>=38.0 to 38.4 degrees C, \>38.4 to 38.9 degrees C, \>38.9 to 40.0 degrees C and \>40.0 degrees C. Fatigue, headache, muscle pain and joint pain were graded as mild: did not interfere with activity; moderate: some interference with activity and severe: prevented daily routine activities. Severity definition from the CRF: mild (does not interfere)/moderate(interferes to some extent)/severe(interferes significantly) with the participant's usual function. Exact 2-sided 95% CI was based on the Clopper and Pearson method.

An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Exact 2-sided 95% CI was based on the Clopper and Pearson method.

An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event. Exact 2-sided 95% CI was based on the Clopper and Pearson method.