Nasopharyngeal Carriage Study in Healthy Kenyan Toddlers | NCT02146365

NCT02146365

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Detailed Description

This study enrolled healthy Kenyan toddlers (12-15 months of age) who participated in the randomized control trial of VAC-010 (NCT02097472), as well as healthy toddlers aged 12 to 15 months who had not participated in the VAC-010 Study. All participants must have received a primary dose of pneumococcal conjugate vaccine (PCV) per local practice prior to enrollment in either VAC-010 or VAC-011. No treatments were administered during this study.

The study consisted of the following four groups:

Participants who were randomized in study VAC-010 (2:2:1 ratio), defined according to the treatment received in VAC-010:

1. PATH-wSP + Booster
2. PATH-wSP Only
3. Booster Only

Participants who did not participate in VAC-010:

4. No Intervention

Each group consisted of 2 cohorts of participants, Cohort 1 (300 µg PATH-wSP) and Cohort 2 (600 µg PATH-wSP). Enrollment into Cohorts 1 and 2 occurred sequentially; participants in groups 3 and 4 who did not receive PATH-wSP were also enrolled over time and allocated into one of the two cohorts (300 and 600 µg) in order to control for potential seasonal variation in the NPC of S. pneumoniae.

Each participant completed a total of 5 scheduled visits. For toddlers enrolled simultaneously in VAC-010, visits corresponded to enrollment (Baseline) and 4, 8, 12, and 24 weeks post final vaccination in VAC-010. For toddlers in the No Intervention group, the first visit corresponded to Baseline and the second to fifth visits corresponded to 12, 16, 20, and 32 weeks later. Nasopharyngeal swabs were taken at each visit following World Health Organization (WHO) guidelines for analysis of nasopharyngeal burden.

Treatments received during VAC-010 included:

PATH-wSP: Streptococcus pneumoniae whole cell vaccine with aluminum hydroxide adjuvant
Synflorix™ booster vaccine: pneumococcal polysaccharide conjugate vaccine (adsorbed)
Pentavac booster vaccine: diphtheria, tetanus, pertussis (Whole Cell), hepatitis B (recombinant deoxyribonucleic acid [rDNA]) and Haemophilus influenzae type b conjugate vaccine (adsorbed).
Saline control

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
PATH-wSP 300 µg + Booster		Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later.
PATH-wSP 300 µg Only		Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later.
PATH-wSP 600 µg + Booster		Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later.
PATH-wSP 600 µg Only		Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later.
Booster Only (300 µg)		Toddlers who enrolled in Cohort 1 of Study VAC-010 and received one saline injection and the two booster vaccines (Synflorix and Pentavac) followed by a 2nd saline injection 8 weeks later.
Booster Only (600 µg)		Toddlers who enrolled in Cohort 2 of Study VAC-010 and received one saline injection and the two booster vaccines (Synflorix and Pentavac) followed by a 2nd saline injection 8 weeks later.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Prevalence of Streptococcus Pneumoniae in Nasopharynx	The prevalence of Streptococcus pneumoniae (SPn) in the nasopharynx was measured by the number (and percentage) of participants positive for SPn detected by quantitative polymerase chain reaction (qPCR) from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only plus non-interventional participants enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only plus non-interventional participants enrolled during Cohort 2	Week 0, Week 12, Week 16, Week 20, Week 32
Density of Streptococcus Pneumoniae in the Nasopharynx	The density of Streptococcus pneumoniae (SPn) in the nasopharynx was measured by the number of autolysin (LytA) gene copies detected by quantitative polymerase chain reaction (qPCR) from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2	Week 0, Week 12, Week 16, Week 20, Week 32

Secondary Outcomes

Measure	Description	Time Frame
Geometric Mean Concentration (GMC) of Immunoglobulin G (IgG) Antibodies Against Pneumococcal Proteins	Immunogenicity was evaluated based on the following assays: Immunoglobulin (IgG) response to pneumolysoid [L460D] and pneumococcal surface protein A family 1 [PspA-Fam1] was measured by enzyme-linked immunosorbent assay (ELISA). IgG response to the following pneumococcal proteins was measured using the Meso Scale Discovery (MSD) platform: L460D PspA-Fam1 Pneumococcal histidine triad D (PhtD) Boston Children's Hospital protein 785 (BCH0785) Serine threonine kinase protein (StkP) Pneumococcal choline-binding protein A (PcpA) Streptococcus pneumonia whole cell antigen (SPWCA) Pneumococcal iron uptake protein A (PiuA) Pneumococcal iron acquisition protein A (PiaA)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

- For Toddlers Enrolled in VAC-010 (NCT02097472):

Randomization in VAC-010.
Subject's parent must provide voluntary written informed consent for subject to participate in the study, is fully capable of comprehending and complying with study requirements and procedures, able and willing to return for all scheduled follow-up visits, and has expressed availability for the required study period, with access to a consistent means of telephone contact. An illiterate parent will require an impartial witness to be present during consenting process to include discussing the consent form, verbal consent and thumb-printing.
Subject has not completed his or her final vaccination in VAC-010.

For Toddlers NOT Enrolled in VAC-010 (PCV-primed-only cohort):

Healthy Kenyan toddlers between 12 to 15 (inclusive) months of age who have completed their primary Expanded Programme on Immunization (EPI) vaccines, with the exception that the birth dose of oral polio vaccine is not required.
Subjects who have not received a PCV booster following primary PCV series.
Subject's parent must provide voluntary written informed consent for subject to participate in the study, is fully capable of comprehending and complying with study requirements and procedures, able and willing to return for all scheduled follow-up visits, and has expressed availability for the required study period, with access to a consistent means of telephone contact. An illiterate parent will require an impartial witness to be present during consenting process to include discussing the consent form, verbal consent and thumb-printing.
Subjects who were not born premature, had a birth weight of > 2.5 kg, and who have a weight-to-height Z-score of ≥ -2 at the time of enrollment.

Exclusion Criteria:

- For Toddlers NOT enrolled in VAC-010 (PCV-primed only):

Use of any investigational or non-registered drug within 90 days prior to screening, or planned during the course of study participation.
Immunosuppression or immunodeficiency (inclusive of human immunodeficiency virus [HIV]) by medical history (inclusive of possible HIV through maternal fetal transfer at time of birth or through breast milk).
Chronic, clinically significant pulmonary, cardiovascular, hepatobiliary, gastrointestinal, renal, neurological, or hematological functional abnormality or major congenital defects or illness that requires medical therapy, by medical history or clinical assessment. This includes abnormal vital signs as assessed by toxicity scoring.
Any medical or social condition that in the opinion of the investigator may interfere with the study objectives, pose a risk to the study subject, or prevent the subject from completing the study.
An employee (or first degree relative of employee) of the Sponsor, the Clinical Research Organization (CRO), the investigator or any site personnel.
Disorders that required chronic administration (defined as more than 14 consecutive days) of immunosuppressants or other immune-modifying drugs within the 6 months prior to enrollment. An immunosuppressant dose of glucocorticoid will be defined as a systemic dose >10 mg of prednisone (adult dosage) adjusted for equivalent dosing in toddlers by weight. The use of topical glucocorticoids will be permitted.
Administration of immunoglobulins and/or any blood products within the 6 months preceding enrollment in the study; or anticipation of such administration during the study period.
History of meningitis, seizures or any neurological disorder.
Subject who has evidence of congenital abnormality or developmental delay.
Any evidence of fetal alcohol syndrome or history of alcohol abuse in mother during pregnancy.

Name	Affiliation	Role
Nekoye Otsyula, MB ChB MSc	Kenya Medical Research Institute/Walter Reed Project	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Kenya Medical Research Institute/Walter Reed Project		Kisumu		40100	Kenya

Arm/Group Information

ID	Title	Description
FG000	PATH-wSP 300 µg + Booster	Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later.
FG001	PATH-wSP 300 µg Only	Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later.
FG002	PATH-wSP 600 µg + Booster	Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later.
FG003	PATH-wSP 600 µg Only	Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later.
FG004	Booster Only (300 µg)	Toddlers who enrolled in Cohort 1 of Study VAC-010 and received one saline injection and the two booster vaccines (Synflorix and Pentavac) followed by a 2nd saline injection 8 weeks later.
FG005	Booster Only (600 µg)	Toddlers who enrolled in Cohort 2 of Study VAC-010 and received one saline injection and the two booster vaccines (Synflorix and Pentavac) followed by a 2nd saline injection 8 weeks later.
FG006	No Intervention (300 µg)	Toddlers who enrolled during Cohort 1 who did not participate in Study VAC-010 and did not receive either PATH-wSP or either of the booster vaccines (Pentavac or Synflorix).
FG007	No Intervention (600 µg)	Toddlers who enrolled during Cohort 2 who did not participate in Study VAC-010 and did not receive either PATH-wSP or either of the booster vaccines (Pentavac or Synflorix).

ID	Title	Description
BG000	PATH-wSP 300 µg + Booster	Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later.
BG001	PATH-wSP 300 µg Only

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

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

Prevalence of Streptococcus Pneumoniae in Nasopharynx

The prevalence of Streptococcus pneumoniae (SPn) in the nasopharynx was measured by the number (and percentage) of participants positive for SPn detected by quantitative polymerase chain reaction (qPCR) from nasopharyngeal swabs taken at each study visit.

NPC endpoints were analyzed within combined study groups:

PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster
Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only plus non-interventional participants enrolled during Cohort 1
PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster
Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only plus non-interventional participants enrolled during Cohort 2

The Nasopharyngeal Carriage (NPC) population included enrolled participants with at least one post-enrollment swab measurement not associated with a protocol violation that may have interfered with the assessment of NPC outcomes. VAC-010 participants who did not receive both vaccinations were excluded.

Posted

Count of Participants

Participants

Week 0, Week 12, Week 16, Week 20, Week 32

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	PATH-wSP 300 µg + Booster	Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later.

ID	Term
D013290	Streptococcal Infections
D016908	Gram-Positive Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses

OG000	Combined PATH-wSP 300 µg	All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups.
OG001	Combined Control (300 µg)	Participants enrolled during Cohort 1 who received booster-only or no intervention.
OG002	Combined PATH-wSP 600 µg	All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups.
OG003	Combined Control (600 µg)	All participants enrolled during Cohort 2 who received booster-only or no intervention.