Phase 1-2 Safety and Immunogenicity Study of PATH-wSP in Kenyan Adults and Toddlers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 248
- 试验地点
- 2
- 主要终点
- Highest Grade of Reactogenicity Events in the Adult Cohort: Vaccination 1
研究概览
简要总结
This study aimed to determine whether PATH-wSP, a vaccine against a germ that causes pneumonia, is safe and induces immune responses in adults and toddlers. The study vaccine was compared to placebo. First adults received 2 injections of a lower dose of the vaccine or placebo, 28 days apart. Since the lower dose was considered safe, a higher dose was tested. Once the safety was established in adults the lower and higher dose was tested in toddlers, starting with the lower dose and then the higher dose.
详细描述
S. pneumoniae whole cell vaccine (SPWCV) is a vaccine candidate made from whole unencapsulated pneumococcal cells and adsorbed to aluminum hydroxide adjuvant (Alum). After adsorption of the Alum to SPWCV, the vaccine is referred to as PATH-wSP. PATH-wSP has been previously tested in Phase 1/2 studies in healthy US adults (VAC-002), and in healthy Kenyan adults and toddlers (VAC-010) and showed a favorable safety, tolerability, and immunogenicity profile. The SPWCV and Alum used in previous Phase 1/2 trials were supplied separately in a two-vial configuration; the SPWCV was manufactured at Walter Reed Army Institute of Research and the Alum at Instituto Butantan. A single-vial formulation of PATH wSP, an adsorbed suspension of SPWCV and Alum, has now been manufactured by PT Bio Farma, Indonesia. The purpose of this study was to assess the safety and tolerability of this new formulation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Year 至 40 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adults who are 18 to 40 years old, or toddlers who are 12 to 19 months old.
- •Must provide voluntary written/thumb-printed informed consent
- •Must comply with study requirements and procedures.
- •Must have an identifiable place of residence to allow home visits, and a consistent means of telephone contact
- •Must be resident in the study area with no plans to travel outside the study area during the study
- •Must be willing to not take herbal or other local traditional medications within 28 days of randomization and during the course of the study
- •Adult female subjects must have a negative serum pregnancy test at screening and urine pregnancy test prior to each vaccination
- •Toddlers must have been born full-term, and have a mid-upper arm circumference > 11.5 cm at the time of enrollment.
- •Toddlers must have completed their Kenyan infant EPI schedule through 9 months including 1 birth dose of BCG, 3 doses of DTwPHibHep, 3 doses of OPV (birth dose is not required), 3 doses of PCV, and 1 dose of measles vaccine
排除标准
- •Use of any investigational or nonregistered drug within 90 days of enrollment
- •Use of any potentially hepatotoxic drug
- •Receipt of any licensed vaccine within 14 days of administration of study vaccine.
- •Chronic, clinically significant pulmonary, cardiovascular, hepatobiliary, gastrointestinal, renal, neurological, or hematological functional abnormality or major congenital defects or illness that requires medical therapy, based on medical history or clinical assessment
- •History of anaphylactic shock
- •History of a serious reaction to any prior vaccination or known hypersensitivity to any component of the study vaccines
- •History of immunosuppression or immunodeficiency, inclusive of human immunodeficiency virus (HIV) infection by medical history (including that of an enrolled toddler's mother) or by HIV testing at screening
- •Evidence of active hepatitis infection (B or C) by serologic testing at screening.
- •Any screening laboratory test (chemistry or hematology) or vital sign measurement with toxicity grade ≥ 1
- •Acute illness (moderate or severe) and/or fever (axillary temperature ≥ 37.5°C)
- •Positive test for malaria (blood film) at screening that remains positive post treatment when retested prior to vaccination
- •Disorders that require chronic administration (defined as more than 14 consecutive days) of immunosuppressants or other immune-modifying drugs within the past 6 months prior to the administration of the study vaccine.
- •Administration of immunoglobulins and/or any blood products within the 6 months preceding enrollment in the study
- •Known disturbance of coagulation or other blood disorder (e.g., thalassemia, sickle cell disease, thrombocytopenia, disorders of the lymphocytes, severe anemia at birth) in adult subject or in self/first-degree relative of toddler subject; or receipt of anticoagulants in the past three weeks (aspirin as needed and nonsteroidal anti-inflammatory drugs are acceptable)
- •History of meningitis, seizures or any neurological disorder (all participants) or major psychiatric disorder (adults)
- •Any medical or social condition that in the opinion of the investigator will interfere with the study objectives or pose a risk to the study subject
- •An employee (or first-degree relative of employee) of the Sponsor, the CRO, or any investigator or site personnel
- •Female adult subjects who are pregnant or breast-feeding
- •Adults with a recent history (within the past year) of alcohol or substance abuse.
- •Toddlers who have already received a pentavalent booster (following the primary series).
- •Toddlers with a family history of suspected primary immunodeficiency in first-degree relative.
- •Toddlers who had a sibling die of likely sudden infant death syndrome (SIDS) or die suddenly and without apparent other cause or preceding illness in the first year of life.
- •Toddlers with evidence of a clinically significant congenital abnormality as judged by the PI.
- •Toddlers with evidence of fetal alcohol syndrome or maternal history of alcohol abuse during pregnancy
研究组 & 干预措施
Toddler 0.6mg PATH-wSP
Two 0.6 mg doses of PATH-wSP with a 28 day interval between doses
干预措施: PATH-wSP (Biological)
Adult Placebo High Dose
Two injections of normal saline with a 28 day interval between injections
干预措施: Placebo (Biological)
Toddler Placebo Low Dose
Two injections of normal saline with a 28 day interval between injections
干预措施: Placebo (Biological)
Toddler Placebo High Dose
Two injections of normal saline with a 28 day interval between injections
干预措施: Placebo (Biological)
Adult Placebo Low Dose
Two injections of normal saline with a 28 day interval between injections
干预措施: Placebo (Biological)
Toddler 1.0 mg PATH-wSP
Two 1 mg doses of PATH-wSP with a 28 day interval between doses
干预措施: PATH-wSP (Biological)
Adult 1.0 mg PATH-wSP
Two 1 mg doses of PATH-wSP with a 28 day interval between doses
干预措施: PATH-wSP (Biological)
Adult 0.6mg PATH-wSP
Two 0.6 mg doses of PATH-wSP with a 28 day interval between doses
干预措施: PATH-wSP (Biological)
结局指标
主要结局
Highest Grade of Reactogenicity Events in the Adult Cohort: Vaccination 1
时间窗: 7 days after the first dose (Day 7)
Solicited adverse events (AEs) were referred to as reactogenicity events (REs). Local REs included pain, induration/swelling, and erythema/redness at the injection site for adults; and pain/tenderness, redness, and induration/swelling for toddlers. Solicited systemic REs included cutaneous rash, headache, axillary fever/temperature, fatigue/malaise, and arthralgia/myalgia. Solicited REs were assessed for all subjects during the 60 minutes post-vaccination, daily for the first week, and at the clinic visit 1 week post-vaccination. Within the first week post-vaccination, fieldworkers visited the subject at home daily to assess and record solicited reactogenicity and determine whether the subject needed to be seen by the principal investigator (PI) for any medical condition or issue. Generally, grade 1 was no interference with activity, grade 2 was some interference with activity, and grade 3 was prevents daily activity. Grade 0 is equivalent to no event.
Number of Adverse Events (AE), by Relation to Vaccine and Seriousness
时间窗: 112 days
Only treatment-emergent adverse events (TEAEs) were included in the analysis; adverse events (AEs) that were not TEAEs were to have been listed.
Highest Grade of Reactogenicity Events in the Adult Cohort: Vaccination 2
时间窗: 7 days after the second dose (Day 35)
Solicited adverse events (AEs) were referred to as reactogenicity events (REs). Local REs included pain, induration/swelling, and erythema/redness at the injection site for adults; and pain/tenderness, redness, and induration/swelling for toddlers. Solicited systemic REs included cutaneous rash, headache, axillary fever/temperature, fatigue/malaise, and arthralgia/myalgia. Solicited REs were assessed for all subjects during the 60 minutes post-vaccination, daily for the first week, and at the clinic visit 1 week post-vaccination. Within the first week post-vaccination, fieldworkers visited the subject at home daily to assess and record solicited reactogenicity and determine whether the subject needed to be seen by the principal investigator (PI) for any medical condition or issue. Generally, grade 1 was no interference with activity, grade 2 was some interference with activity, and grade 3 was prevents daily activity.
Highest Grade of Reactogenicity Events in the Toddler Cohort: Vaccination 1
时间窗: 7 days after the first dose (Day 7)
Solicited adverse events (AEs) were referred to as reactogenicity events (REs). Local REs included pain, induration/swelling, and erythema/redness at the injection site for adults; and pain/tenderness, redness, and induration/swelling for toddlers. Solicited systemic REs included cutaneous rash, axillary fever/temperature, drowsiness, irritability, and decreased appetite. Solicited REs were assessed for all subjects during the 60 minutes post-vaccination, daily for the first week, and at the clinic visit 1 week post-vaccination. Within the first week post-vaccination, fieldworkers visited the subject at home daily to assess and record solicited reactogenicity and determine whether the subject needed to be seen by the PI for any medical condition or issue. Generally, grade 1 was no interference with activity, grade 2 was some interference with activity, and grade 3 was prevents daily activity. Grade 0 is equivalent to no event.
Highest Grade of Reactogenicity Events in the Toddler Cohort: Vaccination 2
时间窗: 7 days after the second dose (Day 35)
Solicited adverse events (AEs) were referred to as reactogenicity events (REs). Local REs included pain, induration/swelling, and erythema/redness at the injection site for adults; and pain/tenderness, redness, and induration/swelling for toddlers. Solicited systemic REs included cutaneous rash, axillary fever/temperature, drowsiness, irritability, and decreased appetite. Solicited REs were assessed for all subjects during the 60 minutes post-vaccination, daily for the first week, and at the clinic visit 1 week post-vaccination. Within the first week post-vaccination, fieldworkers visited the subject at home daily to assess and record solicited reactogenicity and determine whether the subject needed to be seen by the PI for any medical condition or issue. Generally, grade 1 was no interference with activity, grade 2 was some interference with activity, and grade 3 was prevents daily activity. Grade 0 is equivalent to no event.
次要结局
- Immunoglobulin G (IgG) Antibody Geometric Mean Concentration Against Pneumococcal Proteins(Baseline and 12 weeks after vaccination 2 (Day 0 and Day 112))
- Immunoglobulin G (IgG) Antibody Geometric Mean Fold Change Against Pneumococcal Proteins(Baseline and 12 weeks after vaccination 2 (Day 0 and Day 112))
- Number of Subjects With Immunoglobulin G (IgG) Seroresponse(Baseline and 12 weeks after vaccination 2 (Day 0 and Day 112))