Clinical trial NCT02146365: Nasopharyngeal Carriage Study in Healthy Kenyan Toddlers
Official title: A Prospective Study to Assess the Nasopharyngeal Carriage of Streptococcus Pneumoniae (SPn), Long Term Safety and Immune Persistence in Healthy Kenyan PCV-Primed Toddlers (12-15 Months of Age) Who Received a Whole Cell Pneumococcal Vaccine (PATH-wSP) Compared to Controls
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pneumococcal Disease
Lead sponsor: PATH
Sponsor class: OTHER
First posted: 2014-05-23
Enrollment: 297
Sex: ALL
Minimum age (years): 12
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Healthy PCV- primed Kenyan toddlers; some of whom have participated in VAC-010 (n=250) and some of whom have not (n=50)

Brief summary: This study evaluated the change in nasopharyngeal carriage (NPC) of Streptococcus pneumoniae (SPn), hypothesizing that it would be reduced post-vaccination with Streptococcus pneumoniae whole cell vaccine with aluminum hydroxide adjuvant (PATH-wSP) and that PATH-wSP would remain safe and well-tolerated over the course of the study.

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

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.

Primary outcomes:
measure: Prevalence of Streptococcus Pneumoniae in Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
measure: Density of Streptococcus Pneumoniae in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
Secondary outcomes:
measure: Geometric Mean Concentration (GMC) of Immunoglobulin G (IgG) Antibodies Against Pneumococcal Proteins
timeFrame: Baseline (Week 0), 4 weeks post-vaccination 2 (Week 12), and 6 months post-vaccination 2 (Week 32).
measure: Geometric Mean Concentration Ratios of Immunoglobulin G (IgG) Antibodies Against Pneumococcal Proteins for PATH-wSP Groups Versus the Booster Only Group
timeFrame: Week 32
measure: Geometric Mean Fold Change of Immunoglobulin G (IgG) Antibodies Against Pneumococcal Proteins
timeFrame: Baseline and Week 32
measure: Percentage of Participants Meeting Seroresponse Fold-Rise Categories at 6 Months Post Vaccination 2
timeFrame: Baseline and Week 32
measure: Number of Participants With Neutralizing Antibody Response to Pneumolysin
timeFrame: Baseline (Week 0) and 6 months post-vaccination 2 (Week 32)
measure: Number of Adverse Events (AE)
timeFrame: 32 weeks; for participants enrolled concurrently in Study VAC-010 adverse events were collected after the last VAC-010 visit through to Week 32.
measure: Prevalence of Streptococcus Pneumoniae Serotype 11A/D/E [11A] in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
measure: Prevalence of Streptococcus Pneumoniae Serotype 13 in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
measure: Prevalence of Streptococcus Pneumoniae Serotype 15A in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
measure: Prevalence of Streptococcus Pneumoniae Serotype 15B/C [15B] in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
measure: Prevalence of Streptococcus Pneumoniae Serotype 19A in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
measure: Prevalence of Streptococcus Pneumoniae Serotype 19F in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
measure: Prevalence of Streptococcus Pneumoniae Serotype 3 in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
measure: Prevalence of Streptococcus Pneumoniae Serotype 35B in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
measure: Prevalence of Streptococcus Pneumoniae Serotype 6A/B [6A] in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
measure: Prevalence of Streptococcus Pneumoniae Serotype NT4b in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
measure: Density of Streptococcus Pneumoniae Serotype 11A/D/E [11A] in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
measure: Density of Streptococcus Pneumoniae Serotype 13 in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
measure: Density of Streptococcus Pneumoniae Serotype 15A in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
measure: Density of Streptococcus Pneumoniae Serotype 15B/C [15B] in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
measure: Density of Streptococcus Pneumoniae Serotype 19A in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
measure: Density of Streptococcus Pneumoniae Serotype 19F in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
measure: Density of Streptococcus Pneumoniae Serotype 3 in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
measure: Density of Streptococcus Pneumoniae Serotype 35B in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
measure: Density of Streptococcus Pneumoniae Serotype 6A/B [6A] in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
measure: Density of Streptococcus Pneumoniae Serotype NT4b in the Nasopharynx
timeFrame: Week 0, Week 12, Week 16, Week 20, Week 32
Other outcomes:
Locations:
city: Kisumu
country: Kenya
facility: Kenya Medical Research Institute/Walter Reed Project
Study officials:
affiliation: Kenya Medical Research Institute/Walter Reed Project
name: Nekoye Otsyula, MB ChB MSc
role: PRINCIPAL_INVESTIGATOR
References: