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Phase 1/2, Prospective, Single Center, Randomized, ActiveControlled, Double-Blind, Age De-escalation Study to assess the safety and tolerability of SIILPCV10 administered as a single-dose regimen to healthy Gambian pneumococcal conjugate vaccine (PCV)-naïve young adults and PCV-primed toddlers through 4 weeks post vaccination.
Each adult and toddler subject will undergo a total of 4 clinic visits. Each infant subject will undergo a total of 9 scheduled visits. Blood will be collected from all subjects during the screening visit for safety and potential immunological assessments, and 28 days after completion of the vaccination schedule for immunological assessments. For adults, the vaccine was given intramuscularly into the mid-deltoid muscle of nondominant arm using a 24-gauge needle. For toddlers and infants, the vaccine will be given IM into the anterolateral aspect of the left thigh. Blood will be collected from adults and toddlers for safety labs at the Day 7 post-vaccination visit.
This was a prospective, single-center, randomized, active-controlled, double-blind, age de escalation study in healthy Gambian PCV-naïve adults (18-40 years old), PCV primed toddlers (12-15 months old) and PCV-naïve infants (6-8 weeks old).
In the adult cohort, at least 34 eligible PCV-naïve adults (18-40 years old) were planned to be randomized into the study to receive a single dose of either SIILPCV10 or Pneumovax 23 in a 1:1 ratio on Day 0 (V1), with stratification by sex (although no fixed proportion of males and females was required in the cohort as a whole).
In the toddler cohort, at least 112 eligible PCV-primed toddlers (12-15 months old) were planned to be randomized into the study to receive a single dose of either SIILPCV10 or Prevenar 13 in a 1:1 ratio on Day 0 (V1).
Each adult and toddler subject underwent a total of 4 clinic visits, including at least 1 screening visit (V0) no more than 14 days prior to Day 0, a vaccination visit on Day 0 (V1), and follow-up clinic visits at 7 (+3) and 28 (+14) days after vaccination (V2 and V3, respectively). A total of 3 blood samples were obtained for laboratory safety and immunogenicity assessments.
In the infant cohort, at least 200 eligible PCV-naïve infants (6 to 8 weeks old) were randomized into the study to receive 3 doses of either SIILPCV10 or Prevenar 13 in a 1:1 ratio along with standard Expanded Program on Immunisation (EPI) vaccinations (pentavalent diphtheria, tetanus, whole-cell pertussis, hepatitis B, and Haemophilus influenzae type b combined vaccine [DTwP-HepB-Hib], oral poliovirus vaccine [OPV], rotavirus vaccine [RV], and inactivated poliovirus vaccine [IPV]).
Each infant subject underwent a total of 9 scheduled visits for the primary series: at least 1 screening visit (V0); 3 primary vaccination visits at 28 (+14)-day intervals (V1, 3, 5); follow-up clinic visits at 7 (+3) days after each primary vaccination (V2, 4, 6); and 2 follow-up visits 28 and 84 days after the last primary vaccination (V7 and V8, respectively). Windows for follow-up and subsequent vaccination visits were calculated based on the actual calendar date of the prior vaccination, rather than relative to the day of randomization. Vaccinations included the blinded PCV study vaccine (SIILPCV10 or Prevenar 13) and the unblinded EPI vaccines (DTwP-HepB-Hib, OPV, RV, and IPV).
A total of 2 blood samples were obtained for the primary series (V0 and V7), with the first sample used for safety laboratory eligibility assessment, and if randomized, for baseline immunogenicity testing. Immunogenicity testing was also done on the second sample.
During the supplemental booster phase, infant subjects underwent 2 additional visits: a fourth (booster) vaccination visit (V9) at ≥ 9 months of age, and a follow-up visit 28 days after the booster dose (V10). The EPI vaccines scheduled for 9 months of age in The Gambia were not given as part of the study. However, study personnel contacted parents of infant subjects to remind them of the need to attend this EPI vaccination visit at the due date to allow for effective scheduling of the subsequent booster. The vaccine (SIILPCV10 or Prevenar 13) was given at least 4 weeks after the routine EPI vaccines given at 9 months of age in The Gambia (measles and rubella, yellow fever, and OPV). Infants who received SIILPCV10 at V9 were offered a booster dose of Prevenar 13 at least 56 days following the SIILPCV10 boost. Immunogenicity testing was performed on 2 additional blood samples collected during the booster phase (V9 and V10).
In the adult and toddler cohorts, on the day of vaccination, a malaria rapid test was performed using a finger prick to rule out parasitemia and a urine pregnancy test was performed (in adult women who were not surgically sterile) to rule out pregnancy before final eligibility was confirmed and randomization occurred. In the infant cohort, on each day of vaccination, a malaria rapid test was performed using a finger prick to rule out parasitemia before vaccination occurred. Any infant showing signs of acute illness or abnormal vital signs on the day of vaccination were not vaccinated until recovery was documented by the study team.
After all vaccinations, subjects were monitored for solicited reactogenicity. All adult and toddler subjects were monitored for AEs at each clinic visit until V3, and ongoing AEs at study exit were followed until last subject last visit (LSLV). Infant subjects were monitored for AEs at each clinic visit until V8. For infants who participated in the booster phase of the study, AEs were recorded at V10, and any conditions present at V9 were considered baseline.
SAS software was used to analyze data.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Adult SIILPCV10 | Experimental | Single dose of SIILPCV10 on day 0 |
|
| Adult Pneumovax 23 | Active Comparator | Single dose of Pneumovax 23 on day 0 |
|
| Toddler SIILPCV10 | Experimental | Single dose of SIILPCV10 on day 0 |
|
| Toddler Prevenar 13 | Active Comparator | Single dose of Prevenar 13 on day 0 |
|
| Infants SIIL PCV10 | Experimental | A three-dose series of SIILPCV10 on day 0, day 28, and day 56 |
|
| Infants Prevenar 13 | Active Comparator | A three-dose series of Prevenar 13 on day 0, day 28, and day 56 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SIILPCV10 | Biological | 10-valent Pneumococcal Conjugate Vaccine (SIILPCV10) at a dosage of 2 µg for each serotype polysaccharide, except 4 µg for 6B serotype, conjugated to a carrier protein (CRM197), with adjuvant (aluminum phosphate [alum]) and preservative (thiomersal). |
| Measure | Description | Time Frame |
|---|---|---|
| Adult and Toddler Subjects Experiencing Local and Systemic Reactogenicity, by Severity | Local and systemic reactogenicity of the study vaccine was evaluated for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [potentially life threatening]) and relatedness to the vaccination. Injection site events were by definition considered related to study vaccine. Reactogenicity was monitored at the following times:
| 7 days |
| Infant Subjects Experiencing Local and Systemic Reactogenicity, by Severity: Vaccination 1 | Local and systemic reactogenicity of the study vaccine was evaluated for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [potentially life threatening]) and relatedness to the vaccination. Injection site events were by definition considered related to study vaccine. Reactogenicity was monitored at the following times:
| 7 days |
| Infant Subjects Experiencing Local and Systemic Reactogenicity, by Severity: Vaccination 2 | Local and systemic reactogenicity of the study vaccine was evaluated for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [potentially life threatening]) and relatedness to the vaccination. Injection site events were by definition considered related to study vaccine. Reactogenicity was monitored at the following times:
| 7 days |
| Infant Subjects Experiencing Local and Systemic Reactogenicity, by Severity: Vaccination 3 |
| Measure | Description | Time Frame |
|---|---|---|
| Geometric Mean Concentration of Immunoglobulin G (IgG) for Adults | Serum samples were collected 28 days after the vaccination in adults to determine the ELISA IgG concentration for all 10 serotypes contained in SIILPCV10. | 4 weeks after vaccination |
| Geometric Mean Concentration of Immunoglobulin G (IgG) 4 Weeks After Vaccination for Toddlers |
| Measure | Description | Time Frame |
|---|---|---|
| Infant Subjects Experiencing Local and Systemic Reactogenicity After Booster Vaccination, by Severity | Local and systemic reactogenicity of the study vaccine was evaluated for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [potentially life threatening]) and relatedness to the vaccination. Injection site events were by definition considered related to study vaccine. Reactogenicity was monitored at the following times:
|
Inclusion Criteria:
• Healthy adults (18-40 yrs), toddlers (12-15 mo), full term infants (6-8 wks) and ≥ 3.5 kg
Exclusion Criteria:
Adults only
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| Name | Affiliation | Role |
|---|---|---|
| Ed Clarke, MD PhD | Medical Research Council (MRC) Unit, The Gambia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical Research Council (MRC) Unit, The Gambia | Fajara | The Gambia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31843266 | Derived | Clarke E, Bashorun AO, Okoye M, Umesi A, Badjie Hydara M, Adigweme I, Dhere R, Sethna V, Kampmann B, Goldblatt D, Tate A, Weiner DH, Flores J, Alderson MR, Lamola S. Safety and immunogenicity of a novel 10-valent pneumococcal conjugate vaccine candidate in adults, toddlers, and infants in The Gambia-Results of a phase 1/2 randomized, double-blinded, controlled trial. Vaccine. 2020 Jan 10;38(2):399-410. doi: 10.1016/j.vaccine.2019.08.072. Epub 2019 Dec 14. |
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Adult cohort: 43 screened and 9 screen failures Toddler cohort: 173 screened and 61 screen failures Infant cohort: 262 screened and 62 screen failures
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| ID | Title | Description |
|---|---|---|
| FG000 | Adult SIILPCV10 | Single dose of SIILPCV10 on day 0 |
| FG001 | Adult Pneumovax 23 | Single dose of Pneumovax 23 on day 0 |
| FG002 | Toddler SIILPCV10 | Single dose of SIILPCV10 on day 0 |
| FG003 | Toddler Prevenar 13 | Single dose of Prevenar 13 on day 0 |
| FG004 | Infants SIILPCV10 | A three-dose series of SIILPCV10 on day 0, day 28, and day 56; Booster dose of SIILPCV 10 at 9 months of age. SIILPCV10: 10-valent Pneumococcal Conjugate Vaccine (SIILPCV10) at a dosage of 2 µg for each serotype polysaccharide, except 4 µg for 6B serotype, conjugated to a carrier protein (CRM197), with adjuvant (aluminum phosphate [alum]) and preservative (thiomersal). |
| FG005 | Infants Prevenar 13 | A three-dose series of Prevenar 13 on day 0, day 28, and day 56 Prevenar 13: 13-valent Pneumococcal Conjugate Vaccine (Prevenar 13; Pfizer-Wyeth) for the toddler and infant cohorts |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Adults--PCV 10 | Single dose of SIILPCV 10 on Day 0 |
| BG001 | Adults--Pneumovax 23 | Single dose of Pneumovax 23 on Day 0 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Only adults are included in this category. Infants and toddlers are included in their own separate categories. |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Adult and Toddler Subjects Experiencing Local and Systemic Reactogenicity, by Severity | Local and systemic reactogenicity of the study vaccine was evaluated for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [potentially life threatening]) and relatedness to the vaccination. Injection site events were by definition considered related to study vaccine. Reactogenicity was monitored at the following times:
| All subjects who received at least 1 study vaccination and had at least 1 post vaccination safety measurement. | Posted | Count of Participants | Participants | 7 days |
|
All adult and toddler subjects were monitored for AEs until 28 days after receipt of vaccine, and ongoing AEs at study exit were followed until last subject last visit (LSLV). Infant subjects were monitored for AEs until 28 days after receipt of three doses of the vaccine. For infants who participated in the booster phase of the study, AEs were recorded at 28 days post booster dose, and any conditions present at the visit when booster dose was given were considered baseline.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Adult SIILPCV 10 | Single dose of SIILPCV10 on Day 0 | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastroenteritis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Steve Lamola | PATH | 1-206-285-3500 | slamola@path.org |
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| ID | Term |
|---|---|
| D011008 | Pneumococcal Infections |
| ID | Term |
|---|---|
| D013290 | Streptococcal Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
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| ID | Term |
|---|---|
| C414006 | 23-valent pneumococcal capsular polysaccharide vaccine |
| C538862 | 13-valent pneumococcal vaccine |
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| Infant Booster Dose SIILPCV 10 | Experimental | One dose of SIILPCV 10 at 9 months of age |
|
| Infant Booster Dose Prevenar 13 | Active Comparator | One dose of SIILPCV 10 at 9 months of age |
|
| Pneumovax 23 | Biological | 23-valent Pneumococcal Polysaccharide Vaccine (Pneumovax 23; MSD Pharmaceuticals) for the adult cohort. |
|
|
| Prevenar 13 | Biological | 13-valent Pneumococcal Conjugate Vaccine (Prevenar 13; Pfizer-Wyeth) for the toddler and infant cohorts |
|
|
Local and systemic reactogenicity of the study vaccine was evaluated for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [potentially life threatening]) and relatedness to the vaccination. Injection site events were by definition considered related to study vaccine. Reactogenicity was monitored at the following times:
|
| 7 days |
| Occurrence, Severity and Relatedness of All Adverse Events in Adults and Toddlers | Reported here are only adverse events occurring in 5% or more of subjects; unless specifically stated, AEs were regarded as unrelated. | 28 days |
| Occurrence, Severity and Relatedness of All Adverse Events in Infants | Reported here are adverse events that occurred in 5% or more of the infant cohort. Booster dose safety results are reported separately. Unless stated, AEs are regarded as unrelated. | 12 weeks post last vaccination |
| Occurrence, Severity and Relatedness of Clinically Significant Hematological and Biochemistry Lab Values in Adults and Toddlers | Blood samples were collected for safety hematology and clinical chemistry evaluations, organ function tests, and, for adults, coagulation panel evaluation. Laboratory assessments were only performed at baseline for infants. Testing for HIV was undertaken only following pre-test counseling of the subject/subject's parent as to the implications of the test result. Post test counseling was also undertaken, and on the basis of a positive result the subject and subject's parents would have been referred on for HIV care according to normal local practice in The Gambia. | 7 days after vaccination |
Serum samples were collected 28 days after vaccination for toddlers to determine the ELISA IgG concentration for all 10 serotypes contained in SIILPCV10. |
| 4 weeks after vaccination |
| Geometric Mean Concentration of Immunoglobulin G (IgG) 4 Weeks After Vaccination for Infants | Serum samples were collected 28 days after the third vaccination for infants to determine the ELISA IgG concentration for all 10 serotypes contained in SIILPCV10. | 4 weeks after the third dose |
| Geometric Mean Fold Rise (GMFR) of Immunoglobulin G (IgG) in Toddlers, by Serotype | Serum samples were collected before the first vaccination and 28 days after the last vaccination for adults and toddlers and 28 days after the completion of the primary series for infants to determine the ELISA IgG concentration for all 10 serotypes contained in SIILPCV10. Blood samples were also collected for immunogenicity testing before and 28 days after the booster dose for infants. Baseline serum samples for infants and adults were not assayed. The IgG concentration was also determined for each component of the co administered pentavalent vaccine (DTwP-HepB-Hib) in sera from the infant cohort. If there were limitations to blood volumes, appropriate subsets and priorities for immune testing were established with the immunology laboratories to ensure measurements were unbiased and representative of the entire cohort. | 4 weeks after vaccination (28 days) |
| Number and Percentage of Immunoglobulin G (IgG) Seroresponders Among Infants, by Serotype | Seroresponse was defined as ≥ 0.35 µg/mL. In infants, serum samples were collected 28 days after receipt of three doses of the vaccine to determine the ELISA IgG concentration for all 10 serotypes contained in SIILPCV10. | 4 weeks after third dose |
| Functional Antibody (OPA) Geometric Mean Titers | The functional activity of the IgG response to the 10 serotypes contained in SIILPCV10 was determined in randomly selected subsets of the infant and toddler cohorts and all adult subjects in the same serum samples collected 28 days after the last vaccinations. This activity was determined using the 4-fold multiplexed OPA developed at the University of Alabama at Birmingham. | 4 weeks after last vaccination |
| Number and Percentage of Functional (OPA) Infant Seroresponders, by Serotype | The functional activity of the immune response to the 10 serotypes contained in SIILPCV10 was determined in randomly selected subsets of the infant cohort in the same serum samples collected 28 days after the completion of the primary series. This activity was determined using the 4-fold multiplexed OPA developed at the University of Alabama at Birmingham. | 84 days |
| Number and Percentage of Immunoglobulin G (IgG) Seroresponders Against Pentavalent Vaccine Components | Serum samples were collected 28 days after the third vaccination for infants to determine the ELISA IgG concentration for each component of the co administered pentavalent vaccine (DTwP-HepB-Hib) . Seroresponse was defined as equal to or greater concentrations for:
| 84 days |
| 7 days |
| Occurrence of All Adverse Events (AEs) and SAEs Following a Booster Vaccination Among Infants, by Type and Severity | Unsolicited adverse events following a booster dose of SIILPCV10 occurring in 5% or greater of study participants. Unless specifically stated, AEs are considered unrelated. | 4 weeks (28 days) |
| Geometric Mean Concentration (GMC) of Immunoglobulin G (IgG) by Time Point (4 Weeks Post Vaccination 3, Pre Booster, 4 Weeks Post Booster) Among Infants Receiving Booster Dose | Using enzyme-linked immunosorbent assay (ELISA). Blood samples were collected for immunogenicity testing at 4 weeks post vaccination 3, and before and 28 days after the booster dose for infants. | 4 weeks (28 days) |
| Geometric Mean Fold Rise (GMFR) in Immunoglobulin G (IgG) Among Infants Receiving a Booster Dose | Using enzyme-linked immunosorbent assay (ELISA). Blood samples were collected for immunogenicity testing before and 28 days after the booster dose for infants. | 4 weeks (28 days) |
| Antibody Persistence of Immunoglobulin G (IgG) Geometric Mean Concentration Among Infants Receiving a Booster Dose | Defined as the ratio of IgG geometric mean concentration (GMC) measured prior to the infant booster dose, to GMC measured 4 weeks after the 3-dose primary series. Infants received the booster dose at least four weeks after they received routine Expanded Program on Immunization (EPI) vaccines, which occurred at 9 months of age. Thus, the time frame was at least 20 weeks but may have been longer. | 20-23 weeks |
| Booster Effect: Ratio of Immunoglobulin G (IgG) Geometric Mean Concentration 4 Weeks Post Vaccination 3 Versus 4 Weeks Post Booster Among Infants Receiving a Booster Dose | Defined as the ratio of IgG geometric mean concentration (GMC) measured 4 weeks post-infant booster dose, to GMC measured 4 weeks after the 3-dose primary series. Infants received the booster dose at least four weeks after they received routine Expanded Program on Immunization (EPI) vaccines, which occurred at 9 months of age. Thus, the time frame was at least 24 weeks but may have been longer. | 24-26 weeks |
| BG002 | Toddler--PCV 10 | Single dose of SIILPCV 10 on Day 0 |
| BG003 | Toddler--Prevenar 13 | Single dose of Prevenar 13 on Day 0 |
| BG004 | Infant--PCV 10 | A 3-dose series of SIILPCV 10 on Day 0, Day 28, and Day 56. |
| BG005 | Infant--Prevenar 13 | A 3-dose series of Prevenar 13 on Day 0, Day 28, and Day 56. |
| BG006 | Infant Boost--PCV 10 | [Subset of infants in main study] Booster dose of SIILPCV 10 at 9 months of age |
| BG007 | Infant Boost--Prevenar 13 | [Subset of infants in main study] Booster dose of Prevenar 13 at 9 months of age |
| BG008 | Total | Total of all reporting groups |
| Mean |
| Standard Deviation |
| years |
|
| Age, Continuous | Only infants are represented here. Adults, toddlers and infants in booster cohort are represented separately. | Mean | Standard Deviation | Days |
|
| Age, Continuous | Only toddlers are represented here. Adults and infants are presented separately. | Mean | Standard Deviation | Months |
|
| Age, Continuous | This includes data from infant booster cohort. Data from adults, toddlers and infants are represented separately | Mean | Standard Deviation | months |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Ethnicity | Count of Participants | Participants |
|
| OG001 | Adults--Pneumovax 23 | A single dose of Pneumovax 23 at Day 0 |
| OG002 | Toddler--PCV 10 | A single dose of SIIL PCV 10 at Day 0 |
| OG003 | Toddler--Prevenar 13 | A single dose of Prevenar 13 at Day 0 |
|
|
| Primary | Infant Subjects Experiencing Local and Systemic Reactogenicity, by Severity: Vaccination 1 | Local and systemic reactogenicity of the study vaccine was evaluated for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [potentially life threatening]) and relatedness to the vaccination. Injection site events were by definition considered related to study vaccine. Reactogenicity was monitored at the following times:
| Safety population | Posted | Count of Participants | Participants | 7 days |
|
|
|
| Primary | Infant Subjects Experiencing Local and Systemic Reactogenicity, by Severity: Vaccination 2 | Local and systemic reactogenicity of the study vaccine was evaluated for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [potentially life threatening]) and relatedness to the vaccination. Injection site events were by definition considered related to study vaccine. Reactogenicity was monitored at the following times:
| Safety population | Posted | Count of Participants | Participants | 7 days |
|
|
|
| Primary | Infant Subjects Experiencing Local and Systemic Reactogenicity, by Severity: Vaccination 3 | Local and systemic reactogenicity of the study vaccine was evaluated for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [potentially life threatening]) and relatedness to the vaccination. Injection site events were by definition considered related to study vaccine. Reactogenicity was monitored at the following times:
| Safety population | Posted | Count of Participants | Participants | 7 days |
|
|
|
| Primary | Occurrence, Severity and Relatedness of All Adverse Events in Adults and Toddlers | Reported here are only adverse events occurring in 5% or more of subjects; unless specifically stated, AEs were regarded as unrelated. | All subjects who received at least 1 study vaccination and had at least 1 post vaccination safety measurement and experienced an AE at a rate of 5% or more. | Posted | Count of Participants | Participants | 28 days |
|
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| Primary | Occurrence, Severity and Relatedness of All Adverse Events in Infants | Reported here are adverse events that occurred in 5% or more of the infant cohort. Booster dose safety results are reported separately. Unless stated, AEs are regarded as unrelated. | Safety population | Posted | Count of Participants | Participants | 12 weeks post last vaccination |
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| Primary | Occurrence, Severity and Relatedness of Clinically Significant Hematological and Biochemistry Lab Values in Adults and Toddlers | Blood samples were collected for safety hematology and clinical chemistry evaluations, organ function tests, and, for adults, coagulation panel evaluation. Laboratory assessments were only performed at baseline for infants. Testing for HIV was undertaken only following pre-test counseling of the subject/subject's parent as to the implications of the test result. Post test counseling was also undertaken, and on the basis of a positive result the subject and subject's parents would have been referred on for HIV care according to normal local practice in The Gambia. | This table displays vaccinated adults and toddlers only. Infants had laboratory tests only at screening. | Posted | Count of Participants | Participants | 7 days after vaccination |
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| Secondary | Geometric Mean Concentration of Immunoglobulin G (IgG) for Adults | Serum samples were collected 28 days after the vaccination in adults to determine the ELISA IgG concentration for all 10 serotypes contained in SIILPCV10. | All subjects who received the study vaccine per the assigned treatment group, and had post-dose immunogenicity measurement(s) with no major protocol violations that were determined to potentially interfere with immune response to the study vaccine. | Posted | Geometric Mean | 90% Confidence Interval | µg/mL | 4 weeks after vaccination |
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| Secondary | Geometric Mean Concentration of Immunoglobulin G (IgG) 4 Weeks After Vaccination for Toddlers | Serum samples were collected 28 days after vaccination for toddlers to determine the ELISA IgG concentration for all 10 serotypes contained in SIILPCV10. | All subjects who received the study vaccine per the assigned treatment group, and had post-dose immunogenicity measurement(s) with no major protocol violations that were determined to potentially interfere with immune response to the study vaccine. | Posted | Geometric Mean | 90% Confidence Interval | µg/mL | 4 weeks after vaccination |
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| Secondary | Geometric Mean Concentration of Immunoglobulin G (IgG) 4 Weeks After Vaccination for Infants | Serum samples were collected 28 days after the third vaccination for infants to determine the ELISA IgG concentration for all 10 serotypes contained in SIILPCV10. | All subjects who received all study vaccines per the assigned treatment group, and had post-dose immunogenicity measurement(s) with no major protocol violations that were determined to potentially interfere with immune response to the study vaccine. | Posted | Geometric Mean | 90% Confidence Interval | µg/mL | 4 weeks after the third dose |
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| Secondary | Geometric Mean Fold Rise (GMFR) of Immunoglobulin G (IgG) in Toddlers, by Serotype | Serum samples were collected before the first vaccination and 28 days after the last vaccination for adults and toddlers and 28 days after the completion of the primary series for infants to determine the ELISA IgG concentration for all 10 serotypes contained in SIILPCV10. Blood samples were also collected for immunogenicity testing before and 28 days after the booster dose for infants. Baseline serum samples for infants and adults were not assayed. The IgG concentration was also determined for each component of the co administered pentavalent vaccine (DTwP-HepB-Hib) in sera from the infant cohort. If there were limitations to blood volumes, appropriate subsets and priorities for immune testing were established with the immunology laboratories to ensure measurements were unbiased and representative of the entire cohort. | The evaluable group differs for individual serotypes due to non-reportable results. | Posted | Geometric Mean | 90% Confidence Interval | fold change | 4 weeks after vaccination (28 days) |
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| Secondary | Number and Percentage of Immunoglobulin G (IgG) Seroresponders Among Infants, by Serotype | Seroresponse was defined as ≥ 0.35 µg/mL. In infants, serum samples were collected 28 days after receipt of three doses of the vaccine to determine the ELISA IgG concentration for all 10 serotypes contained in SIILPCV10. | All subjects who received all study vaccines per the assigned treatment group, and had post-dose immunogenicity measurement(s) with no major protocol violations that were determined to potentially interfere with immune response to the study vaccine. | Posted | Count of Participants | Participants | 4 weeks after third dose |
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| Secondary | Functional Antibody (OPA) Geometric Mean Titers | The functional activity of the IgG response to the 10 serotypes contained in SIILPCV10 was determined in randomly selected subsets of the infant and toddler cohorts and all adult subjects in the same serum samples collected 28 days after the last vaccinations. This activity was determined using the 4-fold multiplexed OPA developed at the University of Alabama at Birmingham. | Randomly selected subsets of the infant and toddler cohorts and all adult subjects | Posted | Geometric Mean | 90% Confidence Interval | titer | 4 weeks after last vaccination |
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| Secondary | Number and Percentage of Functional (OPA) Infant Seroresponders, by Serotype | The functional activity of the immune response to the 10 serotypes contained in SIILPCV10 was determined in randomly selected subsets of the infant cohort in the same serum samples collected 28 days after the completion of the primary series. This activity was determined using the 4-fold multiplexed OPA developed at the University of Alabama at Birmingham. | Randomly selected subsets of the infant cohort | Posted | Count of Participants | Participants | 84 days |
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|
| Secondary | Number and Percentage of Immunoglobulin G (IgG) Seroresponders Against Pentavalent Vaccine Components | Serum samples were collected 28 days after the third vaccination for infants to determine the ELISA IgG concentration for each component of the co administered pentavalent vaccine (DTwP-HepB-Hib) . Seroresponse was defined as equal to or greater concentrations for:
| All subjects who receive all study vaccines per the assigned treatment group, and had post-dose immunogenicity measurement(s) with no major protocol violations that were determined to potentially interfere with immune response to the study vaccine. | Posted | Count of Participants | Participants | 84 days |
|
|
|
| Other Pre-specified | Infant Subjects Experiencing Local and Systemic Reactogenicity After Booster Vaccination, by Severity | Local and systemic reactogenicity of the study vaccine was evaluated for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [potentially life threatening]) and relatedness to the vaccination. Injection site events were by definition considered related to study vaccine. Reactogenicity was monitored at the following times:
| A subset of the infant cohort who were eligible for the booster phase, had not yet received the Prevenar 13 booster that was offered to infants in the SIILPCV10 group as part of the primary phase of the study and who contributed at least some safety and/or immunogenicity data. | Posted | Count of Participants | Participants | 7 days |
|
|
|
| Other Pre-specified | Occurrence of All Adverse Events (AEs) and SAEs Following a Booster Vaccination Among Infants, by Type and Severity | Unsolicited adverse events following a booster dose of SIILPCV10 occurring in 5% or greater of study participants. Unless specifically stated, AEs are considered unrelated. | A subset of the infant cohort PP_IMM who were eligible for the booster phase, had not yet received the Prevenar 13 booster that was offered to infants in the SIILPCV10 group as part of the primary phase of the study and who contributed at least some safety and/or immunogenicity data. | Posted | Count of Participants | Participants | 4 weeks (28 days) |
|
|
|
| Other Pre-specified | Geometric Mean Concentration (GMC) of Immunoglobulin G (IgG) by Time Point (4 Weeks Post Vaccination 3, Pre Booster, 4 Weeks Post Booster) Among Infants Receiving Booster Dose | Using enzyme-linked immunosorbent assay (ELISA). Blood samples were collected for immunogenicity testing at 4 weeks post vaccination 3, and before and 28 days after the booster dose for infants. | This is the population of infants who received a booster dose of either PCV-10 or Prevenar-13. The evaluable group differs for individual serotypes due to NR results. | Posted | Geometric Mean | 90% Confidence Interval | µg/mL | 4 weeks (28 days) |
|
|
|
| Other Pre-specified | Geometric Mean Fold Rise (GMFR) in Immunoglobulin G (IgG) Among Infants Receiving a Booster Dose | Using enzyme-linked immunosorbent assay (ELISA). Blood samples were collected for immunogenicity testing before and 28 days after the booster dose for infants. | This population is infants who had a booster vaccination of either PCV-10 or Prevenar-13. The evaluable group differs for individual serotypes due to NR results. | Posted | Geometric Mean | 90% Confidence Interval | fold change | 4 weeks (28 days) |
|
|
|
| Other Pre-specified | Antibody Persistence of Immunoglobulin G (IgG) Geometric Mean Concentration Among Infants Receiving a Booster Dose | Defined as the ratio of IgG geometric mean concentration (GMC) measured prior to the infant booster dose, to GMC measured 4 weeks after the 3-dose primary series. Infants received the booster dose at least four weeks after they received routine Expanded Program on Immunization (EPI) vaccines, which occurred at 9 months of age. Thus, the time frame was at least 20 weeks but may have been longer. | This population is infants who had a booster vaccination of either PCV-10 or Prevenar-13. The evaluable group differs for individual serotypes due to non-reportable results. | Posted | Geometric Mean | 90% Confidence Interval | concentration ratio | 20-23 weeks |
|
|
|
| Other Pre-specified | Booster Effect: Ratio of Immunoglobulin G (IgG) Geometric Mean Concentration 4 Weeks Post Vaccination 3 Versus 4 Weeks Post Booster Among Infants Receiving a Booster Dose | Defined as the ratio of IgG geometric mean concentration (GMC) measured 4 weeks post-infant booster dose, to GMC measured 4 weeks after the 3-dose primary series. Infants received the booster dose at least four weeks after they received routine Expanded Program on Immunization (EPI) vaccines, which occurred at 9 months of age. Thus, the time frame was at least 24 weeks but may have been longer. | This population is infants who had a booster vaccination of either PCV-10 or Prevenar-13. The evaluable group differs for individual serotypes due to non-reportable results. | Posted | Geometric Mean | 90% Confidence Interval | concentration ratio | 24-26 weeks |
|
|
|
| 17 |
| 0 |
| 17 |
| 4 |
| 17 |
| EG001 | Adult Pneumovax 23 | Single dose of Pneumovax 23 on Day 0 | 0 | 17 | 0 | 17 | 10 | 17 |
| EG002 | Toddler SIILPCV 10 | Single dose of SIILPCV10 on Day 0 | 0 | 56 | 1 | 56 | 35 | 56 |
| EG003 | Toddler Prevenar 13 | Single dose of Prevenar 13 on Day 0 | 0 | 56 | 1 | 56 | 36 | 56 |
| EG004 | Infants SIILPCV 10 | A 3-dose series of SIILPCV 10 on Days 0, 28, & 56 | 0 | 100 | 6 | 100 | 97 | 100 |
| EG005 | Infants Prevenar 13 | A 3-dose series of Prevenar 13 on Days 0, 28, & 56 | 0 | 100 | 2 | 100 | 96 | 100 |
| EG006 | Booster Infants SIILPCV 10 | Booster dose of SIILPCV 10 at 9 months of age | 0 | 49 | 1 | 49 | 25 | 49 |
| EG007 | Booster Infants Prevenar 13 | Booster dose of Prevenar 13 at 9 months of age | 0 | 47 | 0 | 47 | 24 | 47 |
| Malaria | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Food poisoning | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Axillary pain | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Vaccination site pruritis | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Vaccination site swelling | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Abscess | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Tonsillitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Impetigo | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Rash Pustular | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Vaccination site reaction | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Bronchiolitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Conjunctivitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Furuncle | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Tinea infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Cough | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Papular rash | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Microcytic anemia | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
Not provided
Not provided
| D007239 | Infections |
| Male |
|
|
|
|
|
|
|
|
|
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| None reported/normal (temp) |
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| None reported/normal (temp) |
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| None reported/normal (temp) |
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| None reported/normal (temp) |
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| None reported/normal (temp) |
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| None reported/normal (temp) |
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| None reported/normal (temp) |
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| None reported/normal (temp) |
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| None reported/normal (temp) |
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| None reported/normal (temp) |
|
| None |
|
| Irritability |
|
| Drowsiness |
|
| Decreased appetite |
|
| Tenderness at injection site |
|
| Erythema/redness at injection site |
|
| Induration/swelling at injection site |
|
| None |
|
| Irritability |
|
| Drowsiness |
|
| Decreased appetite |
|
| Tenderness at injection site |
|
| Erythema/redness at injection site |
|
| Induration/swelling at injection site |
|
| Grade 3 |
|
| None |
|
| Irritability |
|
| Drowsiness |
|
| Decreased appetite |
|
| Tenderness at injection site |
|
| Erythema/redness at injection site |
|
| Induration/swelling at injection site |
|
| Moderate |
|
| Severe |
|
| None |
|
| Diarrhea (Both) |
|
| Diarrhea--related |
|
| Pyrexia (Toddlers) |
|
| Furuncle (Toddlers) |
|
| Gastroenteritis (Toddlers) |
|
| Nasopharyngitis (Toddlers) |
|
| Tinea infection (Toddlers) |
|
| Upper respiratory infection (Both) |
|
| Abdominal pain (Adults) |
|
| Food poisoning (Adults) |
|
| Toothache (Adults) |
|
| Axillary pain (Adults) |
|
| Axillary pain--related |
|
| Vaccination site pruritis (Both) |
|
| Vaccination site pruritis--related |
|
| Vaccination site swelling (Adults) |
|
| Vaccination site swelling--related |
|
| Abscess (Adults) |
|
| Otitis media (Adults) |
|
| Tonsillitis (Adults) |
|
| Urinary tract infection (Adults) |
|
| Dizziness (Adults) |
|
| Dizziness--related |
|
| Vaccination site reaction (routine vaccines) |
|
| Vaccination site swelling (routine vaccines) |
|
| Vaccination site swelling (study vaccine) |
|
| Bronchiolitis |
|
| Conjunctivitis |
|
| Furuncle |
|
| Gastroenteritis |
|
| Impetigo |
|
| Nasopharyngitis |
|
| Otitis media--acute |
|
| Pneumonia |
|
| Tinea infection |
|
| Upper respiratory tract infection |
|
| Cough |
|
| Diaper dermatitis |
|
| Papular rash |
|
| Serious Adverse Event (SAE): Diarrhea |
|
| SAE: Gastroenteritis |
|
| SAE: Bronchiolitis |
|
| SAE: Atypical pneumonia |
|
| SAE: Sepsis |
|
| Moderate |
|
| Severe |
|
| None |
|
| Decreased WBCs--vaccine related |
|
| Increased WBCs--not related |
|
| Increased WBCs--vaccine related |
|
| Decreased hemoglobin--not related |
|
| Decreased hemoglobin--vaccine related |
|
| Increased ALT--not related |
|
| Increased ALT--vaccine related |
|
| Decreased platelets--not related |
|
| Decreased platelets--vaccine related |
|
| PnC-IgG-ELISA type 5 |
|
|
| PnC-IgG-ELISA type 6A |
|
|
| PnC-IgG-ELISA type 6B |
|
|
| PnC-IgG-ELISA type 7F |
|
|
| PnC-IgG-ELISA type 9V |
|
|
| PnC-IgG-ELISA type 14 |
|
|
| PnC-IgG-ELISA type 19A |
|
|
| PnC-IgG-ELISA type 19F |
|
|
| PnC-IgG-ELISA type 23F |
|
|
| 0.4540 |
| Pn IgG type 5 GMC Ratio |
| 0.74 |
| 2-Sided |
| 90 |
| 0.38 |
| 1.45 |
| Other |
GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. |
| t-test, 2 sided | 0.0003 | Pn IgG type 6A GMC Ratio | 4.69 | 2-Sided | 90 | 2.46 | 8.94 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. |
| t-test, 2 sided | 0.0460 | Pn IgG type 6B GMC Ratio | 2.22 | 2-Sided | 90 | 1.16 | 4.24 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. |
| t-test, 2 sided | 0.3365 | Pn IgG type 7F GMC Ratio | 0.76 | 2-Sided | 90 | 0.47 | 1.22 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. |
| t-test, 2 sided | 0.0313 | Pn IgG type 9V GMC Ratio | 0.56 | 2-Sided | 90 | 0.37 | 0.87 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. |
| t-test, 2 sided | 0.8060 | Pn IgG type 14 GMC Ratio | 1.08 | 2-Sided | 90 | 0.65 | 1.79 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. |
| t-test, 2 sided | 0.2044 | Pn IgG type 19A GMC Ratio | 1.74 | 2-Sided | 90 | 0.84 | 3.58 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. |
| t-test, 2 sided | 0.1490 | Pn IgG type 19F GMC Ratio | 1.67 | 2-Sided | 90 | 0.93 | 3.02 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. |
| t-test, 2 sided | 0.7565 | Pn IgG type 23F GMC Ratio | 1.13 | 2-Sided | 90 | 0.59 | 2.15 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. |
| PnC-IgG-ELISA type 5: Baseline |
|
| PnC-IgG-ELISA type 5: Post-vaccination |
|
| PnC-IgG-ELISA type 6A: Baseline |
|
| PnC-IgG-ELISA type 6A: Post-vaccination |
|
| PnC-IgG-ELISA type 6B: Baseline |
|
| PnC-IgG-ELISA type 6B: Post-vaccination |
|
| PnC-IgG-ELISA type 7F: Baseline |
|
| PnC-IgG-ELISA type 7F: Post-vaccination |
|
| PnC-IgG-ELISA type 9V: Baseline |
|
| PnC-IgG-ELISA type 9V: Post-vaccination |
|
| PnC-IgG-ELISA type 14: Baseline |
|
| PnC-IgG-ELISA type 14: Post-vaccination |
|
| PnC-IgG-ELISA type 19A: Baseline |
|
| PnC-IgG-ELISA type 19A: Post-vaccination |
|
| PnC-IgG-ELISA type 19F: Baseline |
|
| PnC-IgG-ELISA type 19F: Post-vaccination |
|
| PnC-IgG-ELISA type 23F: Baseline |
|
| PnC-IgG-ELISA type 23F: Post-vaccination |
|
| Two-tailed from z-test |
| 0.2059 |
| Pn IgG type 5 GMC Ratio |
| 0.69 |
| 2-Sided |
| 90 |
| 0.45 |
| 1.20 |
| Other |
GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. Due to distributional characteristics, confidence intervals around GMCs and treatment-group ratio are estimated using bootstrap resampling (10,000 bootstrap samples). |
| Two-tailed from z-test | 0.5664 | Pn IgG type 6A GMC Ratio | 0.84 | 2-Sided | 90 | 0.55 | 1.54 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. Due to distributional characteristics, confidence intervals around GMCs and treatment-group ratio are estimated using bootstrap resampling (10,000 bootstrap samples). |
| Two-tailed from z-test | 0.4456 | Pn IgG type 6B GMC Ratio | 0.82 | 2-Sided | 90 | 0.57 | 1.31 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. Due to distributional characteristics, confidence intervals around GMCs and treatment-group ratio are estimated using bootstrap resampling (10,000 bootstrap samples). |
| Two-tailed from z-test | 0.2189 | Pn IgG type 7F GMC Ratio | 0.74 | 2-Sided | 90 | 0.52 | 1.14 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. Due to distributional characteristics, confidence intervals around GMCs and treatment-group ratio are estimated using bootstrap resampling (10,000 bootstrap samples). |
| Two-tailed from z-test | 0.0970 | Pn IgG type 9V GMC Ratio | 0.60 | 2-Sided | 90 | 0.38 | 1.03 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. Due to distributional characteristics, confidence intervals around GMCs and treatment-group ratio are estimated using bootstrap resampling (10,000 bootstrap samples). |
| Two-tailed from z-test | 0.0713 | Pn IgG type 14 GMC Ratio | 1.76 | 2-Sided | 90 | 1.02 | 2.79 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. Due to distributional characteristics, confidence intervals around GMCs and treatment-group ratio are estimated using bootstrap resampling (10,000 bootstrap samples). |
| Two-tailed from z-test | 0.3443 | Pn IgG type 19A GMC Ratio | 0.71 | 2-Sided | 90 | 0.42 | 1.35 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. Due to distributional characteristics, confidence intervals around GMCs and treatment-group ratio are estimated using bootstrap resampling (10,000 bootstrap samples). |
| Two-tailed from z-test | 0.3278 | Pn IgG type 19F GMC Ratio | 0.76 | 2-Sided | 90 | 0.48 | 1.23 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. Due to distributional characteristics, confidence intervals around GMCs and treatment-group ratio are estimated using bootstrap resampling (10,000 bootstrap samples). |
| Two-tailed from z-test | 0.2039 | Pn IgG type 23F GMC Ratio | 0.65 | 2-Sided | 90 | 0.40 | 1.16 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. Due to distributional characteristics, confidence intervals around GMCs and treatment-group ratio are estimated using bootstrap resampling (10,000 bootstrap samples). |
| PnC-IgG-ELISA type 5 |
|
|
| PnC-IgG-ELISA type 6A |
|
|
| PnC-IgG-ELISA type 6B |
|
|
| PnC-IgG-ELISA type 7F |
|
|
| PnC-IgG-ELISA type 9V |
|
|
| PnC-IgG-ELISA type 14 |
|
|
| PnC-IgG-ELISA type 19A |
|
|
| PnC-IgG-ELISA type 19F |
|
|
| PnC-IgG-ELISA type 23F |
|
|
| 0.0865 |
| Pn IgG type 5 GMC Ratio |
| 1.20 |
| 2-Sided |
| 90 |
| 1.01 |
| 1.43 |
| Other |
GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. |
| t-test, 2 sided | 0.0006 | Pn IgG type 6A GMC Ratio | 0.56 | 2-Sided | 90 | 0.43 | 0.74 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. |
| t-test, 2 sided | <0.0001 | Pn IgG type 6B GMC Ratio | 0.43 | 2-Sided | 90 | 0.33 | 0.57 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. |
| t-test, 2 sided | <0.0001 | Pn IgG type 7F GMC Ratio | 0.56 | 2-Sided | 90 | 0.47 | 0.68 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. |
| t-test, 2 sided | <0.0001 | Pn IgG type 9V GMC Ratio | 0.49 | 2-Sided | 90 | 0.41 | 0.59 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. |
| t-test, 2 sided | 0.5234 | Pn IgG type 14 GMC Ratio | 1.11 | 2-Sided | 90 | 0.85 | 1.45 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. |
| t-test, 2 sided | <0.0001 | Pn IgG type 19A GMC Ratio | 0.29 | 2-Sided | 90 | 0.22 | 0.36 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. |
| t-test, 2 sided | 0.0040 | Pn IgG type 19F GMC Ratio | 0.72 | 2-Sided | 90 | 0.60 | 0.87 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. |
| t-test, 2 sided | 0.0001 | Pn IgG type 23F GMC Ratio | 0.58 | 2-Sided | 90 | 0.46 | 0.73 | Other | GMC will be summarized by treatment group with corresponding two-sided 90% CIs based on the t-distribution to provide population estimates. |
| PnC-IgG-ELISA type 6A |
|
| PnC-IgG-ELISA type 6B |
|
| PnC-IgG-ELISA type 7F |
|
| PnC-IgG-ELISA type 9V |
|
| PnC-IgG-ELISA type 14 |
|
| PnC-IgG-ELISA type 19A |
|
| PnC-IgG-ELISA type 19F |
|
| PnC-IgG-ELISA type 23F |
|
| Pn-IgG-ELISA type 6A |
|
| Pn-IgG-ELISA type 6B |
|
| Pn-IgG-ELISA type 7F |
|
| Pn-IgG-ELISA type 9V |
|
| Pn-IgG-ELISA type 14 |
|
| Pn-IgG-ELISA type 19A |
|
| Pn-IgG-ELISA type 19F |
|
| Pn-IgG-ELISA type 23F |
|
| Absolute Difference for Type 5 | 3.0 | 2-Sided | 90 | -1.10 | 7.95 | Other | Treatment group differences were estimated by the difference in proportion of seroresponders, with 2-sided exact 90% CIs around the difference calculated using the unconditional exact method of Newcombe. Although inference regarding seroresponse was not of primary concern in this study, a 2-sided 90% CI that excluded 0 was indicative of statistically significant difference at p ≤ 0.10 not corrected for multiplicity analysis. |
| Absolute Difference for Type 6A | -12.0 | 2-Sided | 90 | -20.94 | -2.97 | Other | Treatment group differences were estimated by the difference in proportion of seroresponders, with 2-sided exact 90% CIs around the difference calculated using the unconditional exact method of Newcombe. Although inference regarding seroresponse was not of primary concern in this study, a 2-sided 90% CI that excluded 0 was indicative of statistically significant difference at p ≤ 0.10 not corrected for multiplicity analysis. |
| Absolute Difference for Type 6B | -7.9 | 2-Sided | 90 | -15.0 | -1.01 | Other | Treatment group differences were estimated by the difference in proportion of seroresponders, with 2-sided exact 90% CIs around the difference calculated using the unconditional exact method of Newcombe. Although inference regarding seroresponse was not of primary concern in this study, a 2-sided 90% CI that excluded 0 was indicative of statistically significant difference at p ≤ 0.10 not corrected for multiplicity analysis. |
| Absolute Difference for Type 7F | -3.0 | 2-Sided | 90 | -7.95 | 1.10 | Other | Treatment group differences were estimated by the difference in proportion of seroresponders, with 2-sided exact 90% CIs around the difference calculated using the unconditional exact method of Newcombe. Although inference regarding seroresponse was not of primary concern in this study, a 2-sided 90% CI that excluded 0 was indicative of statistically significant difference at p ≤ 0.10 not corrected for multiplicity analysis. |
| Absolute Difference for Type 9V | -3.0 | 2-Sided | 90 | -9.17 | 2.90 | Other | Treatment group differences were estimated by the difference in proportion of seroresponders, with 2-sided exact 90% CIs around the difference calculated using the unconditional exact method of Newcombe. Although inference regarding seroresponse was not of primary concern in this study, a 2-sided 90% CI that excluded 0 was indicative of statistically significant difference at p ≤ 0.10 not corrected for multiplicity analysis. |
| Absolute Difference for Type 14 | 1.00 | 2-Sided | 90 | -4.00 | 6.27 | Other | Treatment group differences were estimated by the difference in proportion of seroresponders, with 2-sided exact 90% CIs around the difference calculated using the unconditional exact method of Newcombe. Although inference regarding seroresponse was not of primary concern in this study, a 2-sided 90% CI that excluded 0 was indicative of statistically significant difference at p ≤ 0.10 not corrected for multiplicity analysis. |
| Absolute Difference for Type 19A | -5.9 | 2-Sided | 90 | -12.38 | 0.17 | Other | Treatment group differences were estimated by the difference in proportion of seroresponders, with 2-sided exact 90% CIs around the difference calculated using the unconditional exact method of Newcombe. Although inference regarding seroresponse was not of primary concern in this study, a 2-sided 90% CI that excluded 0 was indicative of statistically significant difference at p ≤ 0.10 not corrected for multiplicity analysis. |
| Absolute Difference for Type 19F | 0.0 | 2-Sided | 90 | -4.22 | 4.33 | Other | Treatment group differences were estimated by the difference in proportion of seroresponders, with 2-sided exact 90% CIs around the difference calculated using the unconditional exact method of Newcombe. Although inference regarding seroresponse was not of primary concern in this study, a 2-sided 90% CI that excluded 0 was indicative of statistically significant difference at p ≤ 0.10 not corrected for multiplicity analysis. |
| Absolute Difference for Type 23F | -6.0 | 2-Sided | 90 | -12.77 | 0.40 | Other | Treatment group differences were estimated by the difference in proportion of seroresponders, with 2-sided exact 90% CIs around the difference calculated using the unconditional exact method of Newcombe. Although inference regarding seroresponse was not of primary concern in this study, a 2-sided 90% CI that excluded 0 was indicative of statistically significant difference at p ≤ 0.10 not corrected for multiplicity analysis. |
| MOPA - Pn 5 |
|
| MOPA - Pn 6A |
|
| MOPA - 6B |
|
| MOPA - 7F |
|
| MOPA - 9V |
|
| MOPA - 14 |
|
| MOPA - 19A |
|
| MOPA - 19F |
|
| MOPA - 23F |
|
| MOPA - Pn 5 |
|
|
| MOPA - Pn 6A |
|
|
| MOPA - 6B |
|
|
| MOPA - 7F |
|
|
| MOPA - 9V |
|
|
| MOPA - 14 |
|
|
| MOPA - 19A |
|
|
| MOPA - 19F |
|
|
| MOPA - 23F |
|
|
| Absolute difference for MOPA type 5 |
| 0.0 |
| 2-Sided |
| 90 |
| -18.56 |
| 18.56 |
| Other |
Exact confidence intervals around treatment group differences are calculated based on Newcombe score. Calculation of difference and confidence interval around the difference is not possible when all subjects in both groups are responders |
| Absolute difference for MOPA type 6B | 5.0 | 2-Sided | 90 | -12.35 | 22.97 | Other | Exact confidence intervals around treatment group differences are calculated based on Newcombe score. Calculation of difference and confidence interval around the difference is not possible when all subjects in both groups are responders |
| Absolute difference for MOPA type 14 | 5.3 | 2-Sided | 90 | -12.15 | 24.01 | Other | Exact confidence intervals around treatment group differences are calculated based on Newcombe score. Calculation of difference and confidence interval around the difference is not possible when all subjects in both groups are responders |
| Absolute difference for MOPA type 19A | -5.9 | 2-Sided | 90 | -26.41 | 11.01 | Other | Exact confidence intervals around treatment group differences are calculated based on Newcombe score. Calculation of difference and confidence interval around the difference is not possible when all subjects in both groups are responders |
| Absolute difference for MOPA type 19F | 5.0 | 2-Sided | 90 | -11.64 | 22.97 | Other | Exact confidence intervals around treatment group differences are calculated based on Newcombe score. Calculation of difference and confidence interval around the difference is not possible when all subjects in both groups are responders |
| Hib (anti-PRP antibodies) |
|
| Tetanus toxoid |
|
| Grade 3 |
|
| Grade 4 |
|
| None reported/normal (temp) |
|
| Cutaneous Rash |
|
| Irritability |
|
| Drowsiness |
|
| Decreased appetite |
|
| Injection site tenderness |
|
| Erythema |
|
| Induration/Swelling |
|
| Grade 3 |
|
| Grade 4 |
|
| None reported |
|
| Dermatitis |
|
| Diarrhea |
|
| Impetigo |
|
| Rash pustular |
|
| Pyrexia |
|
| SAE--severe malaria with severe anemia |
|
| PnC-IgG-ELISA Type 1: Pre Booster |
|
|
| PnC-IgG-ELISA Type 1: Post Booster |
|
|
| PnC-IgG-ELISA Type 5: 4 weeks post Vac 3 |
|
|
| PnC-IgG-ELISA Type 5: Pre Booster |
|
|
| ELISA Type 5: Post Booster |
|
|
| PnC-IgG-ELISA Type 6A: 4 weeks post Vac 3 |
|
|
| PnC-IgG-ELISA Type 6A: Pre Booster |
|
|
| PnC-IgG-ELISA Type 6A: Post Booster |
|
|
| PnC-IgG-ELISA Type 6B: 4 weeks post Vac 3 |
|
|
| PnC-IgG-ELISA Type 6B: Pre Booster |
|
|
| PnC-IgG-ELISA Type 6B: Post Booster |
|
|
| PnC-IgG-ELISA Type 7F: 4 weeks post Vac 3 |
|
|
| PnC-IgG-ELISA Type 7F: Pre Booster |
|
|
| PnC-IgG-ELISA Type 7F: Post Booster |
|
|
| PnC-IgG-ELISA Type 9V: 4 weeks post Vac 3 |
|
|
| PnC-IgG-ELISA Type 9V: Pre Booster |
|
|
| PnC-IgG-ELISA Type 9V: Post Booster |
|
|
| PnC-IgG-ELISA Type 14: 4 weeks post Vac 3 |
|
|
| PnC-IgG-ELISA Type 14: Pre Booster |
|
|
| PnC-IgG-ELISA Type 14: Post Booster |
|
|
| PnC-IgG-ELISA Type 19A: 4 weeks post Vac 3 |
|
|
| PnC-IgG-ELISA Type 19A: Pre Booster |
|
|
| PnC-IgG-ELISA Type 19A: Post Booster |
|
|
| PnC-IgG-ELISA Type 19F: 4 weeks post Vac 3 |
|
|
| PnC-IgG-ELISA Type 19F: Pre Booster |
|
|
| PnC-IgG-ELISA Type 19F: Post Booster |
|
|
| PnC-IgG-ELISA Type 23F: 4 weeks post Vac 3 |
|
|
| PnC-IgG-ELISA Type 23F: Pre Booster |
|
|
| PnC-IgG-ELISA Type 23F: Post Booster |
|
|
| PnC-IgG-ELISA type 5 |
|
|
| PnC-IgG-ELISA type 6A |
|
|
| PnC-IgG-ELISA type 6B |
|
|
| PnC-IgG-ELISA type 7F |
|
|
| PnC-IgG-ELISA type 9V |
|
|
| PnC-IgG-ELISA type 14 |
|
|
| PnC-IgG-ELISA Type 19A |
|
|
| PnC-IgG-ELISA Type 19F |
|
|
| PnC-IgG-ELISA Type 23F |
|
|
| PnC-IgG-ELISA type 6A |
|
| PnC-IgG-ELISA type 6B |
|
| PnC-IgG-ELISA type 7F |
|
| PnC-IgG-ELISA type 9V |
|
| PnC-IgG-ELISA type 14 |
|
| PnC-IgG-ELISA Type 19A |
|
| PnC-IgG-ELISA Type 19F |
|
| PnC-IgG-ELISA Type 23F |
|
| PnC-IgG-ELISA type 6A |
|
| PnC-IgG-ELISA type 6B |
|
| PnC-IgG-ELISA type 7F |
|
| PnC-IgG-ELISA type 9V |
|
| PnC-IgG-ELISA type 14 |
|
| PnC-IgG-ELISA Type 19A |
|
| PnC-IgG-ELISA Type 19F |
|
| PnC-IgG-ELISA Type 23F |
|