A Phase 1/2, Prospective,Randomized, Active-Controlled, Double-Blind, Age De-escalation Study to Evaluate the Safety, Tolerability, Immunogenicity of Serum Institute of India's PCV10 in Healthy Adults, Toddlers, and Infants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 346
- 试验地点
- 1
- 主要终点
- Adult and Toddler Subjects Experiencing Local and Systemic Reactogenicity, by Severity
研究概览
简要总结
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.
详细描述
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]).
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
- 4 Weeks 至 40 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •• Healthy adults (18-40 yrs), toddlers (12-15 mo), full term infants (6-8 wks) and ≥ 3.5 kg
- •Able to provide informed consent (for themselves or child)
- •Willing to comply with study requirements and procedures.
- •Toddlers have completed their Gambian infant EPI schedule
- •Infants who have received the birth doses of BCG, HepB and OPV but who have not received any additional vaccines.
- •Infants and toddlers with a weight-to-height Z score of ≥ -
- •Subjects resident in the study area with no plans to travel outside the study area during the period of study participation.
排除标准
- •Use of any investigational medicinal product within 90 days prior to randomization and throughout the study.
- •Ingestion of herbal or other traditional local medication within 14 days of randomization.
- •Adults and infants who have previously been vaccinated against S. pneumoniae.
- •History of S. pneumoniae infection confirmed by culture from a normally sterile site.
- •History of allergic disease or history of a serious reaction to any prior vaccination or known hypersensitivity to any component of the study vaccines.
- •History of anaphylactic shock.
- •Screening laboratory test or vital signs outside the normal range.
- •HIV-positive or HbsAg- positive based on testing during screening.
- •Acute illness (moderate or severe) and/or fever (axillary temperature of ≥ 38.0°C for adults or ≥ 37.5°C for toddlers and infants).
- •Use of antibiotics within 5 days of randomization (excluding treatment for malaria).
- •A positive test for malaria at time of screening, which remains positive post treatment when retested at time of randomization (Day 0).
- •Administration of any non-study vaccine within 30 days prior to administration of study vaccine or planned vaccination during the course of study participation.
- •Chronic administration of immunosuppressant or other immune modifying drugs prior to the administration of the study. The use of topical and inhaled glucocorticoids will be permitted.
- •Administration of immunoglobulins and/or any blood products within the 6 months prior to administration of the study vaccine or during the study period.
- •History of known disturbance of coagulation or blood disorder that could cause anemia or excess bleeding.
- •Employee of, or direct descendant of any person employed by the Sponsor, the CRO, the PI, study site personnel, or site.
- •Adults only
- •Recent history or signs of alcohol or substance abuse.
- •History of major psychiatric disorder.
- •Female adult subjects who are pregnant or breast-feeding. Infants/Toddlers only
- •Family history of suspected primary immunodeficiency in first-degree relative.
- •Had a sibling die suddenly and without apparent other cause or preceding illness in the first year of life.
- •Evidence of a clinically significant congenital abnormality as judged by the PI.
- •Evidence of fetal alcohol syndrome or maternal history of alcohol abuse during pregnancy.
- •History of meningitis, seizures or any neurological disorder.
- •Evidence of exposure to an HIV-positive individual through maternal fetal transmission, breast milk, or other bloodborne mechanisms
研究组 & 干预措施
Adult SIILPCV10
Single dose of SIILPCV10 on day 0
干预措施: SIILPCV10 (Biological)
Toddler Prevenar 13
Single dose of Prevenar 13 on day 0
干预措施: Prevenar 13 (Biological)
Toddler SIILPCV10
Single dose of SIILPCV10 on day 0
干预措施: SIILPCV10 (Biological)
Adult Pneumovax 23
Single dose of Pneumovax 23 on day 0
干预措施: Pneumovax 23 (Biological)
Infant Booster Dose SIILPCV 10
One dose of SIILPCV 10 at 9 months of age
干预措施: SIILPCV10 (Biological)
Infants Prevenar 13
A three-dose series of Prevenar 13 on day 0, day 28, and day 56
干预措施: Prevenar 13 (Biological)
Infant Booster Dose Prevenar 13
One dose of SIILPCV 10 at 9 months of age
干预措施: Prevenar 13 (Biological)
Infants SIIL PCV10
A three-dose series of SIILPCV10 on day 0, day 28, and day 56
干预措施: SIILPCV10 (Biological)
结局指标
主要结局
Adult and Toddler Subjects Experiencing Local and Systemic Reactogenicity, by Severity
时间窗: 7 days
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: * At 60 (± 15) minutes following primary vaccination * Daily by field workers during Days 1 to 6 post vaccination * In the clinic on Day 7 (+3) following each vaccination (Visit 2 for adults and toddlers).
Infant Subjects Experiencing Local and Systemic Reactogenicity, by Severity: Vaccination 3
时间窗: 7 days
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: * At 60 (± 15) minutes following primary vaccination * Daily by field workers during Days 1 to 6 post vaccination * In the clinic on 7 days (+3) following each vaccination (Visit 2, 4, and 6 for infants).
Occurrence, Severity and Relatedness of All Adverse Events in Adults and Toddlers
时间窗: 28 days
Reported here are only adverse events occurring in 5% or more of subjects; unless specifically stated, AEs were regarded as unrelated.
Occurrence, Severity and Relatedness of Clinically Significant Hematological and Biochemistry Lab Values in Adults and Toddlers
时间窗: 7 days after vaccination
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.
Infant Subjects Experiencing Local and Systemic Reactogenicity, by Severity: Vaccination 1
时间窗: 7 days
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: * At 60 (± 15) minutes following primary vaccination * Daily by field workers during Days 1 to 6 post vaccination * In the clinic on 7 days (+3) following each vaccination (Visit 2, 4, and 6 for infants).
Infant Subjects Experiencing Local and Systemic Reactogenicity, by Severity: Vaccination 2
时间窗: 7 days
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: * At 60 (± 15) minutes following primary vaccination * Daily by field workers during Days 1 to 6 post vaccination * In the clinic on 7 days (+3) following each vaccination (Visit 2, 4, and 6 for infants).
Occurrence, Severity and Relatedness of All Adverse Events in Infants
时间窗: 12 weeks post last vaccination
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.
次要结局
- Geometric Mean Concentration of Immunoglobulin G (IgG) 4 Weeks After Vaccination for Infants(4 weeks after the third dose)
- Functional Antibody (OPA) Geometric Mean Titers(4 weeks after last vaccination)
- Number and Percentage of Immunoglobulin G (IgG) Seroresponders Against Pentavalent Vaccine Components(84 days)
- Geometric Mean Concentration of Immunoglobulin G (IgG) 4 Weeks After Vaccination for Toddlers(4 weeks after vaccination)
- Number and Percentage of Immunoglobulin G (IgG) Seroresponders Among Infants, by Serotype(4 weeks after third dose)
- Geometric Mean Concentration of Immunoglobulin G (IgG) for Adults(4 weeks after vaccination)
- Geometric Mean Fold Rise (GMFR) of Immunoglobulin G (IgG) in Toddlers, by Serotype(4 weeks after vaccination (28 days))
- Number and Percentage of Functional (OPA) Infant Seroresponders, by Serotype(84 days)