A Randomized, Observer-Blind, Controlled Phase 1/2 Trial to Evaluate the Safety, Tolerability and Immunogenicity of Different Doses of a Stand-alone Trivalent, Inactivated Poliomyelitis Vaccine From Sabin Strains in Healthy Infants, With a Safety and Tolerability Age-Step Down Lead-in in Healthy Adults Followed by Healthy Toddlers
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 340
- 试验地点
- 8
- 主要终点
- Percentage of Participants With a Body Temperature ≥ 38°C (Defined as Fever) During the 7-day Period (Including Day of Vaccination) After Third Primary Immunization Dose of sIPV on Day 57
研究概览
简要总结
The purpose of this study is to select the optimal antigen dosage of the three Sabin poliovirus strains (types 1, 2, and 3) entering the composition of the stand-alone trivalent Sabin-based inactivated poliomyelitis vaccine (sIPV) to take forward into advanced stage studies. The selection will be carried out comparing the three sIPV study arms based on the safety and tolerability profile after each dose of primary immunization and the immune response to poliovirus types 1, 2, and 3 for both Sabin and Salk strains, after the final dose of a three dose primary immunization series (Day 85).
详细描述
The vaccine being tested in this study is called sIPV. sIPV is used to prevent poliomyelitis. This study will look at the safety, tolerability of sIPV in healthy adults, toddlers and infants as well as safety and immunogenicity in toddlers and infants. .
The study will enroll approximately 340 participants including 40 adults, 60 toddlers and 240 infants. Adult participants will be randomly assigned to one of the two treatment groups-which will remain undisclosed to study doctor and participants during the study (unless there is an urgent medical need):
- sIPV High Dose
- Placebo (saline control - 0.9% sodium chloride)
Toddler participants will be randomly assigned to one of the following treatment groups:
- sIPV High Dose
- Reference 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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 6 Weeks 至 49 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adult Lead-in Cohort
- •Individuals who are in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and clinical judgment of the investigator.
- •Completed primary immunization against poliomyelitis according to local recommendations.
- •Toddler Lead-in Cohort
- •Toddlers in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and clinical judgment of the investigator.
- •Completed primary immunization against poliomyelitis, preferably with IPV, according to local recommendations.
- •Infant Dose Ranging Cohort
- •Infants are in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and clinical judgment of the investigator.
- •3. Infants must have been born full term (37-42 weeks of gestation).
排除标准
- •Adult Lead-in Cohort
- •1. Has body mass index (BMI) greater than or equal to 35 kg/m^2 (= weight in kg [height in meters * height in meters].
- •Toddler Lead-in Cohort
- •Last polio vaccination (either inactivated or oral) received within 5 months prior to first trial visit.
- •Household member/sibling who had received or is/are scheduled to receive Oral Poliomyelitis Vaccine (OPV) in the previous 3 months until 5 weeks post participant's inclusion in the study.
- •Prior vaccination with booster dose of diphtheria, tetanus, pertussis (acellular or whole cell), polio (either inactivated or oral), or Haemophilus influenzae type b (Hib) vaccines.
- •Infant Dose Ranging Cohort
- •Infants with low birth weight according to local standards.
- •Prior vaccination with polio vaccines (either inactivated or oral).
- •Household member/sibling that had received or is/are scheduled to receive OPV in the previous 3 months until 5 weeks after the third dose of the primary immunization series.
- •Prior vaccination with any diphtheria, tetanus, pertussis (acellular or whole cell), Haemophilus influenzae type b (Hib) vaccine or polio vaccine (OPV or IPV). Note, bacillus Calmette Guérin (BCG) at birth and prior vaccination with Hepatitis B vaccine given at least 4 weeks prior to first trial visit are not exclusion criteria.
- •All Cohorts
- •Any significant chronic infection.
- •Any clinically significant active infection (as assessed by the investigator) or temperature ≥38.0°C (>100.4°F), within 3 days of intended trial vaccination.
- •Known or suspected impairment/alteration of immune function, including:
- •Chronic use of oral steroids (equivalent to 20 mg/day prednisone for ≥12 weeks/≥2 mg/kg body weight/day for ≥2 weeks) within 60 days prior to Day 1 (use of inhaled, intranasal, or topical corticosteroids is allowed).
- •Receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥2 mg/kg body weight/day for ≥2 weeks) within 60 days prior to Day
- •Administration of immunoglobulins and/or any blood or blood products within the 3 months preceding the administration of the trial vaccine or planned administration during the trial
- •Receipt of immunostimulants within 60 days prior to Day
- •Genetic immunodeficiency.
- •Has a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
结局指标
主要结局
Percentage of Participants With a Body Temperature ≥ 38°C (Defined as Fever) During the 7-day Period (Including Day of Vaccination) After Third Primary Immunization Dose of sIPV on Day 57
时间窗: Within 7 days of the Third Dose given on Day 57
A systemic AE of fever (defined as ≥38°C or ≥100.4°F) was derived from a daily temperature reading recorded within 7 days after each Immunization. Data is only reported for those categories with at least 1 participant.
Percentage of Participants Experiencing Non-serious Unsolicited AEs Within the 28-day Period (Including Day of Vaccination) After Each Primary Immunization Dose of sIPV in Infant Dose Ranging Cohort
时间窗: Within 28 days of primary vaccinations given on Days 1, 29 and 57 (Up to Day 85)
An AE is defined as any untoward medical occurrence in a participant who has enrolled in a study; it does not necessarily have a causal relationship with this treatment. Non-serious unsolicited AEs indicates any and all AEs (other than serious adverse events \[SAEs\]) that occurred other than those that are solicited.
Percentage of Participants With Solicited Local Reactions Within 7-day Period (Including Day of Vaccination) After Third Primary Immunization Dose of sIPV in Infant Dose Ranging Cohort by Severity on Day 57
时间窗: Within 7 Days of the Third Dose given on Day 57
Solicited local AEs (at injection site) were collected by participants using diary cards within 7 days after vaccination and included pain (none, mild: no interference with daily activity, moderate: interference with daily activity with or without treatment, severe: prevents daily activity with or without treatment), erythema, induration and swelling (any: \<25 mm, mild: \>25 - ≤ 50 mm, moderate: \> 50 - ≤ 100 mm, severe: \> 100 mm). Data is only reported for those categories with at least 1 participant.
Percentage of Participants With Solicited Systemic Adverse Events (AEs) Within 7-day Period (Including Day of Vaccination) After Third Primary Immunization Dose of sIPV in Infant Dose Ranging Cohort by Severity on Day 57
时间窗: Within 7 Days of the Third Dose given on Day 57
Solicited systemic AEs were collected within 7 days after vaccination using a diary and included drowsiness, graded as 0-behavior as usual, 1-mild: drowsiness easily tolerated, 2-moderate: drowsiness that interferes with normal activity and 3-severe: prevents normal activity with or without treatment; irritability/fussiness, graded as 0-behavior as usual, mild: crying more than usual/no effect on normal activity, moderate: crying more than usual/interferes with normal activity and severe: crying that cannot be comforted/prevents normal; loss of appetite, graded as 0-apetite as usual, mild: eating less than usual/no effect on normal activity, moderate: eating less than usual/interferes with normal activity and severe: not eating at all. Data is only reported for those categories with at least 1 participant.
Percentage of Participants With Solicited Local Reactions Within 7-day Period (Including Day of Vaccination) After First Primary Immunization Dose of sIPV in Infant Dose Ranging Cohort by Severity on Day 1
时间窗: Within 7 days of the First Dose given on Day 1
Solicited local AEs (at injection site) were collected by participants using diary cards within 7 days after vaccination and included pain (none, mild: no interference with daily activity, moderate: interference with daily activity with or without treatment, severe: prevents daily activity with or without treatment), erythema, induration and swelling (any: \<25 mm, mild: \>25 - ≤ 50 mm, moderate: \> 50 - ≤ 100 mm, severe: \> 100 mm). Data is only reported for those categories with at least 1 participant.
Percentage of Participants With Seroconversion
时间窗: Day 85
Seroconversion is defined as i) initially seronegative infants (titer \<8 at Day 1) having a titer ≥8 at Day 85, or ii) initially seropositive infants (titer ≥8 at Day 1) with a 4-fold rise in antibody titers over the expected level of maternal antibodies at Day 85, calculated using a decline from the Day 1 titer with a half-life of 28 days.
Percentage of Participants With Solicited Local Reactions Within 7-day Period (Including Day of Vaccination) After Second Primary Immunization Dose of sIPV in Infant Dose Ranging Cohort by Severity on Day 29
时间窗: Within 7 days of the Second Dose given on Day 29
Solicited local AEs (at injection site) were collected by participants using diary cards within 7 days after vaccination and included pain (none, mild: no interference with daily activity, moderate: interference with daily activity with or without treatment, severe: prevents daily activity with or without treatment), erythema, induration and swelling (any: \<25 mm, mild: \>25 - ≤ 50 mm, moderate: \> 50 - ≤ 100 mm, severe: \> 100 mm). Data is only reported for those categories with at least 1 participant.
Percentage of Participants With a Body Temperature ≥ 38°C (Defined as Fever) During the 7-day Period (Including Day of Vaccination) After First Primary Immunization Dose of sIPV on Day 1
时间窗: Within 7 days of the First Dose given on Day 1
A systemic adverse event (AE) of fever (defined as ≥38°C or ≥100.4°F) was derived from a daily temperature reading recorded within 7 days after each Immunization. Data is only reported for those categories with at least 1 participant.
Percentage of Participants With a Body Temperature ≥ 38°C (Defined as Fever) During the 7-day Period (Including Day of Vaccination) After Second Primary Immunization Dose of sIPV on Day 29
时间窗: Within 7 days of the Second Dose given on Day 29
A systemic AE of fever (defined as ≥38°C or ≥100.4°F) was derived from a daily temperature reading recorded within 7 days after each Immunization. Data is only reported for those categories with at least 1 participant.
Percentage of Participants With Solicited Systemic Adverse Events (AEs) Within 7-day Period (Including Day of Vaccination) After First Primary Immunization Dose of sIPV in Infant Dose Ranging Cohort by Severity on Day 1
时间窗: Within 7 days of the First Dose given on Day 1
Solicited systemic AEs were collected within 7 days after vaccination using a diary and included drowsiness, graded as 0-behavior as usual, 1-mild: drowsiness easily tolerated, 2-moderate: drowsiness that interferes with normal activity and 3-severe: prevents normal activity with or without treatment; irritability/fussiness, graded as 0-behavior as usual, mild: crying more than usual/no effect on normal activity, moderate: crying more than usual/interferes with normal activity and severe: crying that cannot be comforted/prevents normal; loss of appetite, graded as 0-apetite as usual, mild: eating less than usual/no effect on normal activity, moderate: eating less than usual/interferes with normal activity and severe: not eating at all. Data is only reported for those categories with at least 1 participant.
Percentage of Participants With Solicited Systemic Adverse Events (AEs) Within 7-day Period (Including Day of Vaccination) After Second Primary Immunization Dose of sIPV in Infant Dose Ranging Cohort by Severity on Day 29
时间窗: Within 7 days of the Second Dose given on Day 29
Solicited systemic AEs were collected within 7 days after vaccination using a diary and included drowsiness, graded as 0-behavior as usual, 1-mild: drowsiness easily tolerated, 2-moderate: drowsiness that interferes with normal activity and 3-severe: prevents normal activity with or without treatment; irritability/fussiness, graded as 0-behavior as usual, mild: crying more than usual/no effect on normal activity, moderate: crying more than usual/interferes with normal activity and severe: crying that cannot be comforted/prevents normal; loss of appetite, graded as 0-apetite as usual, mild: eating less than usual/no effect on normal activity, moderate: eating less than usual/interferes with normal activity and severe: not eating at all. Data is only reported for those categories with at least 1 participant.
Percentage of Participants Experiencing SAEs Throughout the Entire Trial Duration in the sIPV Study Arms in Infant Dose Ranging Cohort
时间窗: Day 1 up to Day 547
An SAE is defined as any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically important due to other reasons than the above mentioned criteria.
次要结局
- Percentage of Participants Experiencing SAEs Throughout the Entire Trial Duration in the sIPV or IPV Study Arms in Infant Dose Ranging Cohort(Day 1 up to Day 547)
- Percentage of Participants With Solicited Local Reactions Within 7-day Period (Including Day of Vaccination) After Booster Vaccination in Infant Dose Ranging Cohort(Within 7 days of booster vaccination given on Day 365)
- Percentage of Participants With a Body Temperature ≥ 38°C (Defined as Fever) During the 7-day Period (Including Day of Vaccination) After Each Primary Immunization Dose of sIPV or IPV in Infant Dose Ranging Cohort(Within 7 days of primary vaccinations (First Dose given on Day 1, Second Dose given on Day 29, Third Dose given on Day 57))
- Percentage of Participants Experiencing Non-serious Unsolicited AEs Within the 28-day Period (Including Day of Vaccination) After Each Primary Immunization Dose of sIPV or IPV in Infant Dose Ranging Cohort(Within 28 Days of primary vaccinations (Up to 85 days))
- Percentage of Participants With a Body Temperature ≥ 38°C (Defined as Fever) During the 7-day Period (Including Day of Vaccination) After Booster Vaccination in Infant Dose Ranging Cohort(Within 7 days of booster vaccination given on Day 365)
- Percentage of Participants With Solicited Local Reactions Within 7-day Period (Including Day of Vaccination) After Booster Vaccination in Toddler Lead-in Cohort(Within 7 days of booster vaccination given on Day 365)
- Number of Participants With Solicited Local Reactions Within 7-day Period (Including Day of Vaccination) After a Single Dose of sIPV or Placebo in Adult Lead-in Cohort(Within 7 days of sIPV or placebo vaccination)
- Percentage of Participants With Solicited Local Reactions Within 7-day Period (Including Day of Vaccination) After Each Primary Immunization Dose of sIPV or IPV by Severity in Infant Dose Ranging Cohort(Within 7 days of primary vaccinations (First Dose given on Day 1, Second Dose given on Day 29, Third Dose given on Day 57))
- Percentage of Participants With a Body Temperature ≥ 38°C (Defined as Fever) During the 7-day Period (Including Day of Vaccination) After Booster Vaccination in Toddler Lead-in Cohort(Within 7 days of booster vaccination given on Day 365)
- Percentage of Participants With Solicited Systemic Adverse Events (AEs) Within 7-day Period (Including Day of Vaccination) After Each Primary Immunization Dose of sIPV or IPV by Severity in Infant Dose Ranging Cohort(Within 7 days of primary vaccinations (First Dose given on Day 1, Second Dose given on Day 29, Third Dose given on Day 57))
- Percentage of Participants With Solicited Systemic AEs Within 7-day Period (Including Day of Vaccination) After Booster Vaccination in Infant Dose Ranging Cohort(Within 7 days of booster vaccination given on Day 365)
- Number of Participants With a Body Temperature ≥ 38°C (Defined as Fever) During the 7-day Period (Including Day of Vaccination) After a Single Dose of sIPV or Placebo in Adult Lead-in Cohort(Within 7 days of sIPV or placebo vaccination dose given on Day 1)
- Number of Participants Experiencing Non-serious Unsolicited AEs Within the 7-day Period (Including Day of Vaccination) After a Single Dose of sIPV or Placebo in Adult Lead-in Cohort(Within 7 days of sIPV or placebo vaccination)
- Seropositivity/Seroprotection Rate (SPR) on Days 85, 365 and 393 in Infant Dose Ranging Cohort(Days 85, 365 and 393)
- Percentage of Participants Experiencing Non-serious Unsolicited AEs Within the 28-day Period (Including Day of Vaccination) After Booster Vaccination in Infant Dose Ranging Cohort(Within 28 days of booster vaccination given on Day 365)
- Percentage of Participants With Solicited Systemic AEs Within 7-day Period (Including Day of Vaccination) After Booster Vaccination in Toddler Lead-in Cohort(Within 7 days of booster vaccination given on Day 365)
- Percentage of Participants Experiencing Non-serious Unsolicited AEs Within the 28-day Period (Including Day of Vaccination) After Booster Vaccination in Toddler Lead-in Cohort(Within 28 Days of booster vaccination given on Day 365)
- Percentage of Participants Experiencing SAEs Throughout the Entire Trial Duration in Toddler Lead-in Cohort(Day 1 up to Day 183)
- Number of Participants Experiencing SAEs Throughout the Entire Trial Duration in Adult Lead-in Cohort(Day 1 up to Day 8)
- Geometric Mean Titers (GMT) on Days 85, 365 and 393 in Infant Dose Ranging Cohort(Days 85, 365 and 393)
- Vaccine Response Rate (VRR) on Day 393 in Infant Dose Ranging Cohort(Day 393)
- Number of Participants With Solicited Systemic AEs Within 7-day Period (Including Day of Vaccination) After a Single Dose of sIPV or Placebo in Adult Lead-in Cohort(Within 7 days of sIPV or placebo vaccination)