HIV-infected Pregnant Women, PNC Vaccine
Conditions
Keywords
PPV-23, PCV-10, HIV, Immunization, Pregnancy
Brief summary
The purpose of this study was to determine the safety, reactogenicity, immunogenicity, transplacental antibody transfer and interference with infant responses to childhood vaccination of maternal vaccination with pneumococcal conjugate 10-valent vaccine (PCV-10) or pneumococcal polysaccharide 23-valent vaccine (PPV-23) by comparison with placebo.
Detailed description
This was a multi-center, Phase II, randomized, double-blinded, placebo-controlled study of Human Immunodeficiency Virus (HIV)-infected pregnant women on Highly Active Antiretroviral Therapy (HAART) who were in the second or third trimester of pregnancy and of their infants. The study was designed to investigate the safety, reactogenicity, immunogenicity, transplacental antibody transfer and interference with infant responses to childhood vaccination of maternal vaccination with PCV-10 or PPV-23 by comparison with placebo. Mothers were randomized to one of three arms and received PCV-10, PPV-23, or placebo in a blinded fashion. They were followed for safety, immunogenicity and vaccine-specific anti-capsular pneumococcus (PNC) antibody persistence until 24 weeks post-delivery. Women who received placebo were randomized to a second study step and received PCV-10 or PPV-23 at 24 weeks post-delivery. Antibody responses to the vaccine administered 6 months postpartum were measured. Women who received placebo but cannot be randomized to a second study step due to ongoing new pregnancy were enrolled in a third study step and receive open label PCV-10 at the last study visit; no data were collected on these women and they were not followed after vaccine administration. All infants received PCV-10 vaccinations per local standard of care.
Interventions
BIOLOGICALPCV-10
PCV-10 was a conjugate PNC vaccine, licensed in Brazil, directed against 10 serotypes.
BIOLOGICALPPV-23
PPV-23 was a polysaccharide PNC vaccine, licensed in Brazil, directed against 23 serotypes.
OTHERNaCl
NaCl was the placebo for the study against which the two vaccines were compared during pregnancy.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Westat
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
Step 1 Inclusion Criteria for Pregnant Women: 1. Pregnant women ≥ 18 years old who provided written informed consent prior to study initiation. 2. Pregnant women \< 18 years old with parent or legal guardian able and willing to provide signed informed consent, or who had the capacity to consent for themselves, as defined by the local Institutional Review Board (IRB), and who provided written informed consent prior to study initiation. 3. Gestational age \[≥ 14 weeks (14 weeks 0 days) to \< 33 weeks (32 weeks 6 days)\] documented by the approximate date of the last menstrual period and corroborated by ultrasound if obtained as per local standard of care. Results of the ultrasound were recorded on the Abdominal Ultrasound Form. 4. Documentation of HIV-1 infection defined as positive results from two samples collected at different time points as per standard of care. Results and source documentation may have been obtained from the medical records. 5. Receipt of HAART (a regimen of at least three ARV drugs) for ≥ 4 weeks prior to enrollment. 6. Documented platelet count of \> 50,000/mm3 and an absolute neutrophil count (ANC) of \> 500/ mm3 ≤ 28 days prior to study entry. 7. Women who were willing and able to comply with the study visits. Step 1
Exclusion criteria
for Pregnant Women: 1. Receipt of any PCV or PPV-23 at any time prior to enrollment, documented by medical history or record. 2. Receipt of any live licensed vaccine ≤ 4 weeks or inactivated licensed vaccine ≤ 2 weeks prior to study entry. 3. Receipt of a non-licensed agent (vaccine, drug, biologic, device, blood product, or medication) ≤ 4 weeks prior to enrollment in this study, or expectations to receive another non-licensed agent before delivery unless approval from the protocol team is obtained. 4. Any significant (in the opinion of the site investigator) acute illness and/or oral temperature greater than or equal to 100.4 degrees F ≤ 24 hours prior to study entry. 5. Women who planed to terminate their pregnancy. 6. Women who had a prior history of lupus or other autoimmune disorders. 7. Use of anti-cancer systemic chemotherapy or radiation therapy ≤ 48 weeks of study enrollment, or evidence of immunosuppression as a result of an underlying illness (other than HIV-1 infection) or treatment. 8. Ongoing neoplastic disease (excluding non-melanoma skin cancer, and human papilloma virus-related cervical dysplasia, cervical intraepithelial neoplasia (CIN) grades 1, 2 or 3). 9. Long term use of glucocorticoids, including oral or parenteral prednisone ≥ 20 mg/day or equivalent for more than 2 consecutive weeks (or 2 weeks total) within 12 weeks of study entry. 10. Women who received last dose of corticosteroids for preterm labor ≤ 1 week prior to study entry. Note: A woman can be enrolled if more than 1 week has elapsed from the last dose of corticosteroids, i.e., enrollment may be delayed to satisfy this criterion. 11. Receipt of immunoglobulin or other blood products (with exception of Rho D immune globulin) ≤ 12 weeks prior to enrollment in this study or is scheduled to receive immunoglobulin or other blood products (with the exception of Rho D immune globulin) during pregnancy or for the first 24 weeks after delivery. 12. Receipt of Interleukin-2 (IL2), interferon (IFN), granulocyte-macrophage colony-stimulating factor (GMCSF) or other immune mediators ≤ 12 weeks before enrollment. 13. History of a severe adverse reaction to inactivated polysaccharide or conjugated vaccines. 14. Any condition that would, in the opinion of the site investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol. 15. Pregnancy complications (in the current pregnancy) such as pre-term labor, and pre-eclampsia or any other pregnancy related complication, which in the opinion of the investigator might jeopardize the results of the study. 16. Chronic hepatitis B infection that may require administration of Hepatitis B Hyperimmune Globulin to neonates. Step 2 Inclusion Criteria for Women: 1. 24 weeks ± 4 weeks postpartum. 2. Completion of Step 1. 3. Receipt of placebo on Step 1. Step 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Infant Participants With ELISA-measured IgG PNC Antibody Levels ≥ 0.35ug/mL at 8 Weeks of Age | 8 Weeks of Life | The number of infant participants with ELISA-measured IgG PNC antibody levels ≥ 0.35ug/mL at 8 weeks of age to 1 or more serotypes. |
| Number of Women Who Experienced Various Adverse Events (AEs) | up to 24 Weeks Post-Delivery for mother participants. | The number of women who experienced grade ≥ 3 adverse events (AEs) in the 4 weeks after vaccination in Step 1 and grade 4 AEs or death up to 24 weeks post-partum. AE grading (Grade 1- mild to Grade 4-life-threatening) was done by DAIDS AE Grading table v2.0 (see References). |
| Number of Women Who Experienced Grade ≥ 3 Adverse Events (AEs) in Step 2 | up to 4 Weeks after Step 2 vaccination for Mother Participants | The number of women who enrolled in Step 2, received vaccine and who experience grade ≥ 3 adverse events (AEs) in the 4 weeks after vaccination in Step 2 is presented. |
| Number of Infants With Various Adverse Events Following Maternal Vaccination With PCV10 and PPV23 Administered in Pregnancy | through 24 weeks of life for infant participants | The number of infants who experience grade ≥ 3 adverse events (AEs), congenital defects, HIV infections or pneumonia, meningitis or IPD after maternal vaccination in Step 1, assessed from birth through 24 weeks of life for infant participants. |
| Number of Women With a Two-fold or Higher Increase in ELISA-measured IgG PNC Antibody Concentrations | 28 days after Immunization in Step 1 | The number of participants with a two-fold or higher increase in ELISA-measured IgG PNC antibody concentrations from baseline to 28 days after immunization in Step 1 to 1 or more serotypes. The proportion of participants with \>=0.35ug/mL ELISA-measured IgG PNC antibody concentrations at 28 days after immunization in Step 1 to 1 or more serotypes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Two-fold or Higher Increase in ELISA-measured IgG PNC Antibody Concentrations at 28 Days After PCV-10 Vaccination in Step 1 and Step 2 | 28 days after Immunization in Step 1 and in Step 2 | The proportion of participants with a two-fold or higher increase in ELISA-measured IgG PNC antibody concentrations from baseline to 28 days after immunization in Step 1 vs from entry to Step 2 to 28 days after immunization in Step 2 to 1 or more serotypes. |
| Ratio of Infant/Mother PNC Antibody Levels | At Delivery for Mother Participants and Birth for Infant Participants | The ratios of infant/mother PNC antibody levels to study used serotypes. |
| Number of Participants With a >=0.35ug/mL ELISA-measured IgG PNC Antibody Concentrations at Labor/Delivery and 24 Weeks Post-partum | at Labor and Delivery and 24 Weeks Post-Delivery for Mother Participants | The number of participants with a \>=0.35ug/mL ELISA-measured IgG PNC antibody concentrations at the time points listed for 1 or more serotypes. |
| Number of Participants With a Two-fold or Higher Increase in ELISA-measured IgG PNC Antibody Concentrations at 28 Days After PPV-23 Vaccination in Step 1 and Step 2 | 28 days after Immunization in Step 1 and in Step 2 | The number of participants with a two-fold or higher increase in ELISA-measured IgG PNC antibody concentrations from baseline to 28 days after immunization in Step 1 vs from entry to Step 2 to 28 days after immunization in Step 2 to 1 or more serotypes. |
| Number of Infant Participants With ELISA-measured IgG PNC Antibody Levels ≥ 0.35ug/mL at 16 and 24 Weeks of Age | at weeks 16 and 24 of life | The number of infant participants with ELISA-measured IgG PNC antibody levels ≥ 0.35ug/mL at 16 and 24 weeks of age to 1 or more serotypes. |
Countries
Brazil
Participant flow
Recruitment details
Recruitment period was from April 2016 to November 2017. Participants were recruited from medical clinics.
Pre-assignment details
Of the 347 pregnant women enrolled in the study, 346 were randomized and received study vaccination. One discontinued study prior to receiving study vaccination. There were 349 infants born on the study, including 4 sets of twins. Two women discontinued study prior to delivering their child. Those children are not included in the outcome results.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1A (PPV-23) In Step 1, women in Arm 1A were administered a 0.5 milliliter (mL) dose of PPV-23 intramuscularly once.
PPV-23: PPV-23 was a polysaccharide PNC vaccine, licensed in Brazil, directed against 23 serotypes. | 115 |
| Arm 1B (PCV-10) In Step 1, women in Arm 1B were administered a 0.5 mL dose of PCV-10 intramuscularly once.
PCV-10: PCV-10 was a conjugate PNC vaccine, licensed in Brazil, directed against 10 serotypes. | 115 |
| Arm 1C (Placebo) In Step 1, women in Arm 1C were administered a 0.5 mL dose of 0.9 percent Sodium Chloride (NaCl) intramuscularly once.
NaCl: NaCl was the placebo for the study against which the two vaccines were compared during pregnancy. | 116 |
| Total | 346 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| First Intervention (Step 1) | Death | 0 | 0 | 1 |
| First Intervention (Step 1) | Lost to Follow-up | 4 | 7 | 3 |
| First Intervention (Step 1) | Withdrawal by Subject | 2 | 0 | 1 |
| Second Intervention (Step 2 or Step 3) | Lost to Follow-up | 0 | 0 | 4 |
Baseline characteristics
| Characteristic | Arm 1A (PPV-23) | Arm 1B (PCV-10) | Arm 1C (Placebo) | Total |
|---|---|---|---|---|
| Age, Continuous | 28 years STANDARD_DEVIATION 6 | 27 years STANDARD_DEVIATION 6 | 28 years STANDARD_DEVIATION 6 | 28 years STANDARD_DEVIATION 6 |
| CD4% at Randomization | 32 percent STANDARD_DEVIATION 9 | 32 percent STANDARD_DEVIATION 9 | 31 percent STANDARD_DEVIATION 9 | 32 percent STANDARD_DEVIATION 9 |
| CD4 Count at Randomization | 585 cells/microliter STANDARD_DEVIATION 257 | 596 cells/microliter STANDARD_DEVIATION 243 | 564 cells/microliter STANDARD_DEVIATION 297 | 582 cells/microliter STANDARD_DEVIATION 266 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 110 Participants | 112 Participants | 113 Participants | 335 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 2 Participants | 2 Participants | 8 Participants |
| Gestational Age at Randomization | 25 weeks STANDARD_DEVIATION 5 | 25 weeks STANDARD_DEVIATION 5 | 26 weeks STANDARD_DEVIATION 5 | 26 weeks STANDARD_DEVIATION 5 |
| Log10 RNA Copies at Randomization | 1.9 log10(copies)/mL STANDARD_DEVIATION 0.6 | 1.9 log10(copies)/mL STANDARD_DEVIATION 0.5 | 1.8 log10(copies)/mL STANDARD_DEVIATION 0.6 | 1.9 log10(copies)/mL STANDARD_DEVIATION 0.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 57 Participants | 51 Participants | 61 Participants | 169 Participants |
| Race (NIH/OMB) More than one race | 36 Participants | 40 Participants | 28 Participants | 104 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) White | 19 Participants | 24 Participants | 25 Participants | 68 Participants |
| Region of Enrollment Brazil | 115 participants | 115 participants | 116 participants | 346 participants |
| RNA Copies at Randomization | 569 copies/mL STANDARD_DEVIATION 1825 | 307 copies/mL STANDARD_DEVIATION 1278 | 1144 copies/mL STANDARD_DEVIATION 7864 | 674 copies/mL STANDARD_DEVIATION 4730 |
| Sex: Female, Male Female | 115 Participants | 115 Participants | 116 Participants | 346 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 115 | 0 / 115 | 1 / 116 | 0 / 53 | 0 / 53 | 1 / 114 | 1 / 116 | 0 / 119 |
| other Total, other adverse events | 66 / 115 | 63 / 115 | 62 / 116 | 5 / 53 | 7 / 53 | 9 / 115 | 8 / 117 | 17 / 119 |
| serious Total, serious adverse events | 15 / 115 | 15 / 115 | 16 / 116 | 0 / 53 | 0 / 53 | 20 / 114 | 21 / 116 | 19 / 119 |
Outcome results
Primary
Number of Infant Participants With ELISA-measured IgG PNC Antibody Levels ≥ 0.35ug/mL at 8 Weeks of Age
The number of infant participants with ELISA-measured IgG PNC antibody levels ≥ 0.35ug/mL at 8 weeks of age to 1 or more serotypes.
Time frame: 8 Weeks of Life
Population: The are the infants who were born on study and who had blood drawn for the week 8 evaluation prior to receiving their PCV-10 vaccination.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1A (PPV-23) | Number of Infant Participants With ELISA-measured IgG PNC Antibody Levels ≥ 0.35ug/mL at 8 Weeks of Age | 87 Participants |
| Arm 1B (PCV-10) | Number of Infant Participants With ELISA-measured IgG PNC Antibody Levels ≥ 0.35ug/mL at 8 Weeks of Age | 95 Participants |
| Arm 1C (Placebo) | Number of Infant Participants With ELISA-measured IgG PNC Antibody Levels ≥ 0.35ug/mL at 8 Weeks of Age | 46 Participants |
p-value: 0.29Chi-squared
Primary
Number of Infants With Various Adverse Events Following Maternal Vaccination With PCV10 and PPV23 Administered in Pregnancy
The number of infants who experience grade ≥ 3 adverse events (AEs), congenital defects, HIV infections or pneumonia, meningitis or IPD after maternal vaccination in Step 1, assessed from birth through 24 weeks of life for infant participants.
Time frame: through 24 weeks of life for infant participants
Population: Infants who were born on the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1A (PPV-23) | Number of Infants With Various Adverse Events Following Maternal Vaccination With PCV10 and PPV23 Administered in Pregnancy | HIV Infected | 0 Participants |
| Arm 1A (PPV-23) | Number of Infants With Various Adverse Events Following Maternal Vaccination With PCV10 and PPV23 Administered in Pregnancy | Grade 3+ AEs, | 23 Participants |
| Arm 1A (PPV-23) | Number of Infants With Various Adverse Events Following Maternal Vaccination With PCV10 and PPV23 Administered in Pregnancy | Pneumonia, meningitis or IPD | 5 Participants |
| Arm 1A (PPV-23) | Number of Infants With Various Adverse Events Following Maternal Vaccination With PCV10 and PPV23 Administered in Pregnancy | Congenital Anomalies | 19 Participants |
| Arm 1B (PCV-10) | Number of Infants With Various Adverse Events Following Maternal Vaccination With PCV10 and PPV23 Administered in Pregnancy | HIV Infected | 0 Participants |
| Arm 1B (PCV-10) | Number of Infants With Various Adverse Events Following Maternal Vaccination With PCV10 and PPV23 Administered in Pregnancy | Congenital Anomalies | 25 Participants |
| Arm 1B (PCV-10) | Number of Infants With Various Adverse Events Following Maternal Vaccination With PCV10 and PPV23 Administered in Pregnancy | Pneumonia, meningitis or IPD | 8 Participants |
| Arm 1B (PCV-10) | Number of Infants With Various Adverse Events Following Maternal Vaccination With PCV10 and PPV23 Administered in Pregnancy | Grade 3+ AEs, | 23 Participants |
| Arm 1C (Placebo) | Number of Infants With Various Adverse Events Following Maternal Vaccination With PCV10 and PPV23 Administered in Pregnancy | Pneumonia, meningitis or IPD | 8 Participants |
| Arm 1C (Placebo) | Number of Infants With Various Adverse Events Following Maternal Vaccination With PCV10 and PPV23 Administered in Pregnancy | Grade 3+ AEs, | 24 Participants |
| Arm 1C (Placebo) | Number of Infants With Various Adverse Events Following Maternal Vaccination With PCV10 and PPV23 Administered in Pregnancy | Congenital Anomalies | 15 Participants |
| Arm 1C (Placebo) | Number of Infants With Various Adverse Events Following Maternal Vaccination With PCV10 and PPV23 Administered in Pregnancy | HIV Infected | 0 Participants |
90% CI: [14, 28]
90% CI: [14, 27]
90% CI: [14, 27]
90% CI: [11, 24]
90% CI: [15, 29]
90% CI: [8, 19]
90% CI: [0, 3]
90% CI: [0, 3]
90% CI: [0, 2]
90% CI: [2, 9]
90% CI: [3, 12]
90% CI: [3, 12]
Primary
Number of Women Who Experienced Grade ≥ 3 Adverse Events (AEs) in Step 2
The number of women who enrolled in Step 2, received vaccine and who experience grade ≥ 3 adverse events (AEs) in the 4 weeks after vaccination in Step 2 is presented.
Time frame: up to 4 Weeks after Step 2 vaccination for Mother Participants
Population: Women who received Placebo in Step 1 and who were eligible and were randomized to Step 2.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1A (PPV-23) | Number of Women Who Experienced Grade ≥ 3 Adverse Events (AEs) in Step 2 | Grade 3+ AEs, up to week 4, Step 2 | 0 Participants |
| Arm 1A (PPV-23) | Number of Women Who Experienced Grade ≥ 3 Adverse Events (AEs) in Step 2 | Grade 3+ AEs related to treatment, Step 2 | 0 Participants |
| Arm 1B (PCV-10) | Number of Women Who Experienced Grade ≥ 3 Adverse Events (AEs) in Step 2 | Grade 3+ AEs related to treatment, Step 2 | 0 Participants |
| Arm 1B (PCV-10) | Number of Women Who Experienced Grade ≥ 3 Adverse Events (AEs) in Step 2 | Grade 3+ AEs, up to week 4, Step 2 | 0 Participants |
90% CI: [0, 5]
90% CI: [0, 5]
Primary
Number of Women Who Experienced Various Adverse Events (AEs)
The number of women who experienced grade ≥ 3 adverse events (AEs) in the 4 weeks after vaccination in Step 1 and grade 4 AEs or death up to 24 weeks post-partum. AE grading (Grade 1- mild to Grade 4-life-threatening) was done by DAIDS AE Grading table v2.0 (see References).
Time frame: up to 24 Weeks Post-Delivery for mother participants.
Population: All women randomized to vaccine or placebo, and who received the study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1A (PPV-23) | Number of Women Who Experienced Various Adverse Events (AEs) | Grade 4+ AEs, after week 4, Step 1 | 1 Participants |
| Arm 1A (PPV-23) | Number of Women Who Experienced Various Adverse Events (AEs) | Grade 3+ AEs, up to week 4, Step 1 | 2 Participants |
| Arm 1A (PPV-23) | Number of Women Who Experienced Various Adverse Events (AEs) | Grade 3+ AEs related to treatment, Step 1 | 1 Participants |
| Arm 1B (PCV-10) | Number of Women Who Experienced Various Adverse Events (AEs) | Grade 4+ AEs, after week 4, Step 1 | 2 Participants |
| Arm 1B (PCV-10) | Number of Women Who Experienced Various Adverse Events (AEs) | Grade 3+ AEs, up to week 4, Step 1 | 3 Participants |
| Arm 1B (PCV-10) | Number of Women Who Experienced Various Adverse Events (AEs) | Grade 3+ AEs related to treatment, Step 1 | 1 Participants |
| Arm 1C (Placebo) | Number of Women Who Experienced Various Adverse Events (AEs) | Grade 3+ AEs, up to week 4, Step 1 | 4 Participants |
| Arm 1C (Placebo) | Number of Women Who Experienced Various Adverse Events (AEs) | Grade 3+ AEs related to treatment, Step 1 | 1 Participants |
| Arm 1C (Placebo) | Number of Women Who Experienced Various Adverse Events (AEs) | Grade 4+ AEs, after week 4, Step 1 | 4 Participants |
90% CI: [0, 5]
90% CI: [1, 7]
90% CI: [1, 8]
90% CI: [0, 4]
90% CI: [0, 5]
90% CI: [1, 8]
90% CI: [0, 4]
90% CI: [0, 4]
90% CI: [0, 4]
Primary
Number of Women With a Two-fold or Higher Increase in ELISA-measured IgG PNC Antibody Concentrations
The number of participants with a two-fold or higher increase in ELISA-measured IgG PNC antibody concentrations from baseline to 28 days after immunization in Step 1 to 1 or more serotypes. The proportion of participants with \>=0.35ug/mL ELISA-measured IgG PNC antibody concentrations at 28 days after immunization in Step 1 to 1 or more serotypes.
Time frame: 28 days after Immunization in Step 1
Population: Pregnant women who received the vaccination and did not deliver prior to the day 28 study visit and who had ELISA-measured IgG PNC antibody concentrations measured at baseline and at 28 days after immunization.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1A (PPV-23) | Number of Women With a Two-fold or Higher Increase in ELISA-measured IgG PNC Antibody Concentrations | >=2 fold change from baseline to day 28 | 106 Participants |
| Arm 1A (PPV-23) | Number of Women With a Two-fold or Higher Increase in ELISA-measured IgG PNC Antibody Concentrations | >=0.35ug.mL at day 28 | 109 Participants |
| Arm 1B (PCV-10) | Number of Women With a Two-fold or Higher Increase in ELISA-measured IgG PNC Antibody Concentrations | >=2 fold change from baseline to day 28 | 112 Participants |
| Arm 1B (PCV-10) | Number of Women With a Two-fold or Higher Increase in ELISA-measured IgG PNC Antibody Concentrations | >=0.35ug.mL at day 28 | 114 Participants |
| Arm 1C (Placebo) | Number of Women With a Two-fold or Higher Increase in ELISA-measured IgG PNC Antibody Concentrations | >=2 fold change from baseline to day 28 | 7 Participants |
| Arm 1C (Placebo) | Number of Women With a Two-fold or Higher Increase in ELISA-measured IgG PNC Antibody Concentrations | >=0.35ug.mL at day 28 | 106 Participants |
p-value: 0.44Fisher Exact
p-value: 0.49Fisher Exact
95% CI: [91, 99]
95% CI: [94, 100]
95% CI: [3, 12]
95% CI: [95, 100]
95% CI: [97, 100]
95% CI: [88, 97]
Secondary
Number of Infant Participants With ELISA-measured IgG PNC Antibody Levels ≥ 0.35ug/mL at 16 and 24 Weeks of Age
The number of infant participants with ELISA-measured IgG PNC antibody levels ≥ 0.35ug/mL at 16 and 24 weeks of age to 1 or more serotypes.
Time frame: at weeks 16 and 24 of life
Population: These are the infants who were born on study and received the PCV-10 vaccination in the windows allowed by the protocol (prior to week 8 and prior to week 16). The number of infants with nonmissing data who received the vaccination as required are indicated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1A (PPV-23) | Number of Infant Participants With ELISA-measured IgG PNC Antibody Levels ≥ 0.35ug/mL at 16 and 24 Weeks of Age | at week 16 | 100 Participants |
| Arm 1A (PPV-23) | Number of Infant Participants With ELISA-measured IgG PNC Antibody Levels ≥ 0.35ug/mL at 16 and 24 Weeks of Age | at week 24 | 102 Participants |
| Arm 1B (PCV-10) | Number of Infant Participants With ELISA-measured IgG PNC Antibody Levels ≥ 0.35ug/mL at 16 and 24 Weeks of Age | at week 16 | 94 Participants |
| Arm 1B (PCV-10) | Number of Infant Participants With ELISA-measured IgG PNC Antibody Levels ≥ 0.35ug/mL at 16 and 24 Weeks of Age | at week 24 | 98 Participants |
| Arm 1C (Placebo) | Number of Infant Participants With ELISA-measured IgG PNC Antibody Levels ≥ 0.35ug/mL at 16 and 24 Weeks of Age | at week 24 | 97 Participants |
| Arm 1C (Placebo) | Number of Infant Participants With ELISA-measured IgG PNC Antibody Levels ≥ 0.35ug/mL at 16 and 24 Weeks of Age | at week 16 | 95 Participants |
95% CI: [96, 100]
95% CI: [93, 100]
95% CI: [91, 99]
95% CI: [96, 100]
95% CI: [95, 100]
95% CI: [93, 100]
Secondary
Number of Participants With a >=0.35ug/mL ELISA-measured IgG PNC Antibody Concentrations at Labor/Delivery and 24 Weeks Post-partum
The number of participants with a \>=0.35ug/mL ELISA-measured IgG PNC antibody concentrations at the time points listed for 1 or more serotypes.
Time frame: at Labor and Delivery and 24 Weeks Post-Delivery for Mother Participants
Population: Pregnant women who received the vaccination and did not deliver prior to the day 28 study visit and who had ELISA-measured IgG PNC antibody concentrations measured at the timepoints listed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1A (PPV-23) | Number of Participants With a >=0.35ug/mL ELISA-measured IgG PNC Antibody Concentrations at Labor/Delivery and 24 Weeks Post-partum | at labor and delivery | 109 Participants |
| Arm 1A (PPV-23) | Number of Participants With a >=0.35ug/mL ELISA-measured IgG PNC Antibody Concentrations at Labor/Delivery and 24 Weeks Post-partum | at 24 weeks post partum | 105 Participants |
| Arm 1B (PCV-10) | Number of Participants With a >=0.35ug/mL ELISA-measured IgG PNC Antibody Concentrations at Labor/Delivery and 24 Weeks Post-partum | at labor and delivery | 115 Participants |
| Arm 1B (PCV-10) | Number of Participants With a >=0.35ug/mL ELISA-measured IgG PNC Antibody Concentrations at Labor/Delivery and 24 Weeks Post-partum | at 24 weeks post partum | 107 Participants |
| Arm 1C (Placebo) | Number of Participants With a >=0.35ug/mL ELISA-measured IgG PNC Antibody Concentrations at Labor/Delivery and 24 Weeks Post-partum | at labor and delivery | 16 Participants |
| Arm 1C (Placebo) | Number of Participants With a >=0.35ug/mL ELISA-measured IgG PNC Antibody Concentrations at Labor/Delivery and 24 Weeks Post-partum | at 24 weeks post partum | 58 Participants |
p-value: 0.37Chi-squared
p-value: 0.21Fisher Exact
Secondary
Number of Participants With a Two-fold or Higher Increase in ELISA-measured IgG PNC Antibody Concentrations at 28 Days After PCV-10 Vaccination in Step 1 and Step 2
The proportion of participants with a two-fold or higher increase in ELISA-measured IgG PNC antibody concentrations from baseline to 28 days after immunization in Step 1 vs from entry to Step 2 to 28 days after immunization in Step 2 to 1 or more serotypes.
Time frame: 28 days after Immunization in Step 1 and in Step 2
Population: Women who received PCV-10 in Step 1 or in Step 2 and who had ELISA-measured IgG PNC antibody concentrations data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1A (PPV-23) | Number of Participants With a Two-fold or Higher Increase in ELISA-measured IgG PNC Antibody Concentrations at 28 Days After PCV-10 Vaccination in Step 1 and Step 2 | 112 Participants |
| Arm 1B (PCV-10) | Number of Participants With a Two-fold or Higher Increase in ELISA-measured IgG PNC Antibody Concentrations at 28 Days After PCV-10 Vaccination in Step 1 and Step 2 | 48 Participants |
95% CI: [94, 100]
95% CI: [93, 100]
Secondary
Number of Participants With a Two-fold or Higher Increase in ELISA-measured IgG PNC Antibody Concentrations at 28 Days After PPV-23 Vaccination in Step 1 and Step 2
The number of participants with a two-fold or higher increase in ELISA-measured IgG PNC antibody concentrations from baseline to 28 days after immunization in Step 1 vs from entry to Step 2 to 28 days after immunization in Step 2 to 1 or more serotypes.
Time frame: 28 days after Immunization in Step 1 and in Step 2
Population: Women who received PPV-23 in Step 1 or in Step 2 and who had ELISA-measured IgG PNC antibody concentrations data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1A (PPV-23) | Number of Participants With a Two-fold or Higher Increase in ELISA-measured IgG PNC Antibody Concentrations at 28 Days After PPV-23 Vaccination in Step 1 and Step 2 | 106 Participants |
| Arm 1B (PCV-10) | Number of Participants With a Two-fold or Higher Increase in ELISA-measured IgG PNC Antibody Concentrations at 28 Days After PPV-23 Vaccination in Step 1 and Step 2 | 49 Participants |
95% CI: [91, 99]
95% CI: [89, 100]
Secondary
Ratio of Infant/Mother PNC Antibody Levels
The ratios of infant/mother PNC antibody levels to study used serotypes.
Time frame: At Delivery for Mother Participants and Birth for Infant Participants
Population: These are the mother-infant pairs who meet the criteria of receipt of study product for the moms and have data for delivery/birth time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm 1A (PPV-23) | Ratio of Infant/Mother PNC Antibody Levels | 0.92 ratio |
| Arm 1B (PCV-10) | Ratio of Infant/Mother PNC Antibody Levels | 0.93 ratio |
| Arm 1C (Placebo) | Ratio of Infant/Mother PNC Antibody Levels | 0.90 ratio |
p-value: 0.08t-test, 2 sided