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
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 297
- 试验地点
- 1
- 主要终点
- Prevalence of Streptococcus Pneumoniae in Nasopharynx
研究概览
简要总结
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.
详细描述
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:
-
- PATH-wSP + Booster
-
- PATH-wSP Only
-
- Booster Only
Participants who did not participate in VAC-010:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 12 Months 至 15 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For Toddlers Enrolled in VAC-010 (NCT02097472):
- •Randomization in VAC-
- •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-
- •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.
排除标准
- •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.
结局指标
主要结局
Prevalence of Streptococcus Pneumoniae in Nasopharynx
时间窗: Week 0, Week 12, Week 16, Week 20, Week 32
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
Density of Streptococcus Pneumoniae in the Nasopharynx
时间窗: Week 0, Week 12, Week 16, Week 20, Week 32
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
次要结局
- Geometric Mean Fold Change of Immunoglobulin G (IgG) Antibodies Against Pneumococcal Proteins(Baseline and Week 32)
- Prevalence of Streptococcus Pneumoniae Serotype 15B/C [15B] in the Nasopharynx(Week 0, Week 12, Week 16, Week 20, Week 32)
- Prevalence of Streptococcus Pneumoniae Serotype 3 in the Nasopharynx(Week 0, Week 12, Week 16, Week 20, Week 32)
- Number of Participants With Neutralizing Antibody Response to Pneumolysin(Baseline (Week 0) and 6 months post-vaccination 2 (Week 32))
- Prevalence of Streptococcus Pneumoniae Serotype 35B in the Nasopharynx(Week 0, Week 12, Week 16, Week 20, Week 32)
- Prevalence of Streptococcus Pneumoniae Serotype 13 in the Nasopharynx(Week 0, Week 12, Week 16, Week 20, Week 32)
- Geometric Mean Concentration (GMC) of Immunoglobulin G (IgG) Antibodies Against Pneumococcal Proteins(Baseline (Week 0), 4 weeks post-vaccination 2 (Week 12), and 6 months post-vaccination 2 (Week 32).)
- Geometric Mean Concentration Ratios of Immunoglobulin G (IgG) Antibodies Against Pneumococcal Proteins for PATH-wSP Groups Versus the Booster Only Group(Week 32)
- Prevalence of Streptococcus Pneumoniae Serotype 11A/D/E [11A] in the Nasopharynx(Week 0, Week 12, Week 16, Week 20, Week 32)
- Density of Streptococcus Pneumoniae Serotype 15A in the Nasopharynx(Week 0, Week 12, Week 16, Week 20, Week 32)
- Density of Streptococcus Pneumoniae Serotype 19A in the Nasopharynx(Week 0, Week 12, Week 16, Week 20, Week 32)
- Percentage of Participants Meeting Seroresponse Fold-Rise Categories at 6 Months Post Vaccination 2(Baseline and Week 32)
- Number of Adverse Events (AE)(32 weeks; for participants enrolled concurrently in Study VAC-010 adverse events were collected after the last VAC-010 visit through to Week 32.)
- Prevalence of Streptococcus Pneumoniae Serotype 19A in the Nasopharynx(Week 0, Week 12, Week 16, Week 20, Week 32)
- Prevalence of Streptococcus Pneumoniae Serotype 15A in the Nasopharynx(Week 0, Week 12, Week 16, Week 20, Week 32)
- Density of Streptococcus Pneumoniae Serotype 11A/D/E [11A] in the Nasopharynx(Week 0, Week 12, Week 16, Week 20, Week 32)
- Density of Streptococcus Pneumoniae Serotype 13 in the Nasopharynx(Week 0, Week 12, Week 16, Week 20, Week 32)
- Density of Streptococcus Pneumoniae Serotype 6A/B [6A] in the Nasopharynx(Week 0, Week 12, Week 16, Week 20, Week 32)
- Prevalence of Streptococcus Pneumoniae Serotype 19F in the Nasopharynx(Week 0, Week 12, Week 16, Week 20, Week 32)
- Prevalence of Streptococcus Pneumoniae Serotype 6A/B [6A] in the Nasopharynx(Week 0, Week 12, Week 16, Week 20, Week 32)
- Prevalence of Streptococcus Pneumoniae Serotype NT4b in the Nasopharynx(Week 0, Week 12, Week 16, Week 20, Week 32)
- Density of Streptococcus Pneumoniae Serotype 3 in the Nasopharynx(Week 0, Week 12, Week 16, Week 20, Week 32)
- Density of Streptococcus Pneumoniae Serotype 15B/C [15B] in the Nasopharynx(Week 0, Week 12, Week 16, Week 20, Week 32)
- Density of Streptococcus Pneumoniae Serotype 35B in the Nasopharynx(Week 0, Week 12, Week 16, Week 20, Week 32)
- Density of Streptococcus Pneumoniae Serotype 19F in the Nasopharynx(Week 0, Week 12, Week 16, Week 20, Week 32)
- Density of Streptococcus Pneumoniae Serotype NT4b in the Nasopharynx(Week 0, Week 12, Week 16, Week 20, Week 32)