バングラデシュにおける新規の 1 型経口ポリオワクチンの研究
バングラデシュの健康な幼児、乳児、および新生児における新規生弱毒化 1 型経口ポリオワクチンの安全性と免疫原性を評価するための第 2 相、無作為化、観察者盲検、制御、年齢の段階的縮小、用量漸増研究
The purpose of this clinical trial is to assess the safety and tolerability (primary objective), immunogenicity (primary and secondary objectives), fecal shedding of vaccine viruses (secondary objective) and the potential for neurovirulence of shed virus (secondary objective) of a novel oral polio type 1 vaccine, nOPV1, as compared to Sabin monovalent type 1 vaccine controls (mOPV1), in healthy young children (192 subjects), infants (720 subjects), and neonates (1320 subjects).
調査の概要
状態
条件
詳細な説明
This single-center trial is the first clinical assessment of nOPV1 in a pediatric population. It will be a 15-arm, randomized, observer-blind, controlled trial, with Sabin monovalent type 1 vaccine (mOPV1) serving as the control. Enrollment in this pediatric study will be staggered into three age-descending cohorts, Cohort 1 composed of 192 healthy young children 1 to less than 5 years of age who have completed their full routine polio immunization series, Cohort 2 composed of 720 healthy infants 6 weeks of age (+6 days) who will receive only one dose of inactivated poliomyelitis vaccine (IPV) on Day 1, and finally Cohort 3, composed of 1320 healthy poliomyelitis unvaccinated neonates (day of birth +3 days). Participants will receive two or three doses of either nOPV1 at dose levels of 10^5.5 CCID50, 10^6.0 CCID50, 10^6.5 CCID50, 10^7.0 CCID50 or 10^7.5 CCID50 or the mOPV control vaccine. The second and third doses of vaccine will be given 28 days following the prior dose. In order to demonstrate the vaccine's ability to reduce fecal shedding following a challenge with the Sabin type 1 strain, the infant cohort will be challenged with mOPV 8 weeks after their last dose of nOPV. Participants will be followed until 28 weeks (young children and neonates) or 32 weeks (infants) after their Day 1 vaccination.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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Dhaka、バングラデシュ、1212
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria for all participants:
- Healthy, as defined by the absence of any clinically significant medical condition or congenital anomaly as determined by medical history, physical examination, and clinical assessment of the investigator
- Parent(s) or guardian(s) willing and able to provide written informed consent prior to performance of any study-specific procedure
- Resides in study area and parent understands and is able and willing to adhere to all study visits and procedures (as evidenced by a signed informed consent form [ICF] and assessment by the investigator)
- Parent agrees for participant to receive all routine infant and childhood immunizations as per the approved protocol-adjusted schedule
Inclusion Criteria for Cohort 1 (young children) participants only:
- Male or female child from 1 to less than 5 years of age at the time of initial study vaccination
- Based on documentation, previously received a 3 or 4 dose primary poliomyelitis immunization series containing OPV (may have also received IPV), with last dose received more than 3 months prior to initial study vaccination
Inclusion Criteria for Cohort 2 (infants) participants only:
- Male or female infant expected to be 6 weeks of age (43rd to 49th day of life [with day of birth being the first day of life], inclusive+ 6-day window), at the time of initial study vaccination
- Prior to study vaccination has received no doses of IPV or OPV, based on no evidence of such vaccination per available documentation.
Inclusion Criteria for Cohort 3 (neonates) participants only:
- Male or female newborn (1st day of life+ 3-day window, inclusive), at the time of initial study vaccination
- Prior to study vaccination has received no doses of IPV or OPV or rotavirus vaccine, based on no evidence of such vaccination per available documentation.
Exclusion Criteria for all participants:
- For all participants, the presence of anyone under 10 years of age in the participant's household (living in the same house or apartment unit) who does not have complete "age appropriate" vaccination status with respect to poliovirus vaccines at the time of study vaccine administration. For household members younger than 10 years of age, "age appropriate" vaccination is complete series of trivalent Oral Poliovirus Vaccine (tOPV) or at least three doses of bivalent (types 1 and 3) Oral Poliovirus Vaccine (bOPV) plus a booster fractional dose of IPV (fractional dose Inactivated Polio Vaccine; fIPV). Note: A vaccination series of tOPV or at least three doses of bOPV with our without a booster fractional dose of IPV will be considered sufficient.
- For all participants, having a member of the participant's household (living in the same house or apartment unit) who has received OPV based on the vaccination records in the previous 3 months before study vaccine administration.
- Any participating children attending day care or pre-school during their participation in the study until one month after their last study vaccine administration.
- Moderate or severe (grade ≥ 2) acute illness at the time of enrollment/first study vaccination - temporary exclusion. Participant with mild (grade 1) acute illnesses may be enrolled at the discretion of the investigator.
- Presence of fever on the day of enrollment/first study vaccination (axillary temperature ≥37.5˚C) - (Temporary exclusion for Cohorts 1 and 2)
- A known allergy, hypersensitivity, or intolerance to any components of the study vaccines, including all macrolide and aminoglycoside antibiotics (e.g., erythromycin and kanamycin)
- Evidence of a clinically significant congenital or genetic defect as judged by the investigator
- History of chronic administration (defined as more than 14 days) of immunosuppressant medications, including corticosteroids (> 0.5mg/kg/day of prednisolone (or equivalent)). Topical and inhaler steroids are permitted (unless indicative of a significant chronic illness otherwise excluding the infant/young child)
- Any self-reported known or suspected immunosuppressive or immunodeficiency condition (including HIV infection) in the participant or household member (living under the same roof/in the same building rather than in the same compound)
- Receipt of any immune-modifying or immunosuppressant drugs within 6 months prior to the first study vaccine dose or planned use during the study of study participants or a household member
- Any known or suspected bleeding disorder in the participant that would pose a risk to venipuncture or intramuscular injection
- Presence of sever malnutrition [weight-for-length/height z-score greater than or equal to -3 SD median (per WHO published growth standards)] - temporary exclusion if marginal and subsequently gains weight.
- Participation in another investigational product (drug or vaccine) clinical trial within 30 days prior to entry in this study or receipt of any such investigational product other than the study vaccine within 30 days prior tot he first administration of study vaccine, or planned use during the study period.
- Receipt of transfusion of any blood product or immunoglobulins within 12 months prior to the first administration of study vaccine or planned use during the study period.
- Parent or participant has any condition that in the opinion of the investigator would increase the participant's health risks in the study participation or would increase the risk of not achieving the study's objectives (e.g., would compromise adherence to protocol requirements or interfere with planned safety and immunogenicity assessments.)
Exclusion Criteria for Cohort 2 & 3 participants only:
- Low birth weight (LBW) in newborn participants which is defined as a birth weight of less than 2500g (up to and including 2499b) at the time of birth or by the time of enrolment.
- Premature birth (less than 37 weeks gestation)
- From multiple birth (due to increased risk of OPV transmission between siblings)
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：防止
- 割り当て：ランダム化
- 介入モデル：順次割り当て
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：Group 1: Young Children, nOPV1 10^5.5 CCID50
48 young children aged 1 to <5 years will receive 2 doses of nOPV1 at a dose level of 10^5.5 CCID50 on Day 1 and Day 29 |
Drop counts of nOPV vaccine will be varied to achieve approximately 10^5.5, 10^6.0, 10^6.5 CCID50 or 10^7.0, 10^7.5 dose levels. |
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実験的：Group 3: Young Children, nOPV1 10^6.0 CCID50
48 young children aged 1 to <5 years will receive 2 doses of nOPV1 at a dose level of 10^6.0 CCID50 on Day 1 and Day 29 |
Drop counts of nOPV vaccine will be varied to achieve approximately 10^5.5, 10^6.0, 10^6.5 CCID50 or 10^7.0, 10^7.5 dose levels. |
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実験的：Group 5: Young Children, nOPV1 10^6.5 CCID50
48 young children aged 1 to <5 years will receive 2 doses of nOPV1 at a dose level of 10^6.5 CCID50 on Day 1 and Day 29 |
Drop counts of nOPV vaccine will be varied to achieve approximately 10^5.5, 10^6.0, 10^6.5 CCID50 or 10^7.0, 10^7.5 dose levels. |
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アクティブコンパレータ：Groups 2, 4 and 6: Young Children, mOPV1
48 young children aged 1 to <5 years will receive 2 doses of mOPV1 at a dose level of ≥ 10^6.0 CCID50 on Day 1 and Day 29 |
The Sabin Monovalent Oral Poliomyelitis Vaccine Type 1 control and challenge vaccine (mOPV1) contains ≥ 10^6.0 CCID50 per 0.1 mL (2 drops) dose. |
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実験的：Group 7: Infants, nOPV1 10^5.5 CCID50
96 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 2 doses of nOPV1 at a dose level of 10^5.5 CCID50 on Day 29 and Day 57, and a challenge dose of mOPV on Day 113. |
Drop counts of nOPV vaccine will be varied to achieve approximately 10^5.5, 10^6.0, 10^6.5 CCID50 or 10^7.0, 10^7.5 dose levels. The Sabin Monovalent Oral Poliomyelitis Vaccine Type 1 control and challenge vaccine (mOPV1) contains ≥ 10^6.0 CCID50 per 0.1 mL (2 drops) dose. |
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実験的：Group 9: Infants, nOPV1 10^6.0 CCID50
96 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 2 doses of nOPV1 at a dose level of 10^6.0 CCID50 on Day 29 and Day 57, and a challenge dose of mOPV on Day 113. |
Drop counts of nOPV vaccine will be varied to achieve approximately 10^5.5, 10^6.0, 10^6.5 CCID50 or 10^7.0, 10^7.5 dose levels. The Sabin Monovalent Oral Poliomyelitis Vaccine Type 1 control and challenge vaccine (mOPV1) contains ≥ 10^6.0 CCID50 per 0.1 mL (2 drops) dose. |
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実験的：Group 11: Infants, nOPV1 10^6.5 CCID50
48 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 2 doses of nOPV1 at a dose level of 10^6.5 CCID50 on Day 29 and Day 57, and a challenge dose of mOPV on Day 113. |
Drop counts of nOPV vaccine will be varied to achieve approximately 10^5.5, 10^6.0, 10^6.5 CCID50 or 10^7.0, 10^7.5 dose levels. The Sabin Monovalent Oral Poliomyelitis Vaccine Type 1 control and challenge vaccine (mOPV1) contains ≥ 10^6.0 CCID50 per 0.1 mL (2 drops) dose. |
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実験的：Group 11b: Infants, nOPV1 10^6.5 CCID50
96 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 3 doses of nOPV1 at a dose level of 10^6.5 CCID50 on Day 29, Day 57 and Day 85, and a challenge dose of mOPV on Day 141. |
Drop counts of nOPV vaccine will be varied to achieve approximately 10^5.5, 10^6.0, 10^6.5 CCID50 or 10^7.0, 10^7.5 dose levels. The Sabin Monovalent Oral Poliomyelitis Vaccine Type 1 control and challenge vaccine (mOPV1) contains ≥ 10^6.0 CCID50 per 0.1 mL (2 drops) dose. |
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実験的：Group 13: Infants, nOPV1 10^7.0 CCID50
96 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 3 doses of nOPV1 at a dose level of 10^7.0 CCID50 on Day 29, Day 57 and Day 85, and a challenge dose of mOPV on Day 141. |
Drop counts of nOPV vaccine will be varied to achieve approximately 10^5.5, 10^6.0, 10^6.5 CCID50 or 10^7.0, 10^7.5 dose levels. The Sabin Monovalent Oral Poliomyelitis Vaccine Type 1 control and challenge vaccine (mOPV1) contains ≥ 10^6.0 CCID50 per 0.1 mL (2 drops) dose. |
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実験的：Group 15: Infants, nOPV1 10^7.5 CCID50
96 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 3 doses of nOPV1 at a dose level of 10^7.5 CCID50 on Day 29, Day 57 and Day 85, and a challenge dose of mOPV on Day 141. |
Drop counts of nOPV vaccine will be varied to achieve approximately 10^5.5, 10^6.0, 10^6.5 CCID50 or 10^7.0, 10^7.5 dose levels. The Sabin Monovalent Oral Poliomyelitis Vaccine Type 1 control and challenge vaccine (mOPV1) contains ≥ 10^6.0 CCID50 per 0.1 mL (2 drops) dose. |
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アクティブコンパレータ：Groups 8, 10, 12, 12b, 14, 16: Infants mOPV1
192 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1 then 2 to 3 doses of mOPV1 at a dose level of ≥10^6.0 CCID50 on Day 29, Day 57, Day 85 (groups 12b, 14 & 16 only) and a challenge dose of mOPV on Day 113 (groups 8, 10 & 12) on Day 141 (groups 12b, 14 & 16) |
Drop counts of nOPV vaccine will be varied to achieve approximately 10^5.5, 10^6.0, 10^6.5 CCID50 or 10^7.0, 10^7.5 dose levels. The Sabin Monovalent Oral Poliomyelitis Vaccine Type 1 control and challenge vaccine (mOPV1) contains ≥ 10^6.0 CCID50 per 0.1 mL (2 drops) dose. |
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実験的：Group 17: Neonates, nOPV1 10^6.5 CCID50
330 neonates (day of birth +3 days) will receive 3 doses of nOPV1 at a dose level of 10^6.5 CCID50 on Day 1, Day 29 & Day 57 |
Drop counts of nOPV vaccine will be varied to achieve approximately 10^5.5, 10^6.0, 10^6.5 CCID50 or 10^7.0, 10^7.5 dose levels. |
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実験的：Group 19: Neonates, nOPV1 10^7.0 CCID50
330 neonates (day of birth +3 days) will receive 3 doses of nOPV1 at a dose level of 10^7.0 CCID50 on Day 1, Day 29 & Day 57 |
Drop counts of nOPV vaccine will be varied to achieve approximately 10^5.5, 10^6.0, 10^6.5 CCID50 or 10^7.0, 10^7.5 dose levels. |
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実験的：Group 21: Neonates, nOPV1 10^7.5 CCID50
330 neonates (day of birth +3 days) will receive 3 doses of nOPV1 at a dose level of 10^7.5 CCID50 on Day 1, Day 29 & Day 57 |
Drop counts of nOPV vaccine will be varied to achieve approximately 10^5.5, 10^6.0, 10^6.5 CCID50 or 10^7.0, 10^7.5 dose levels. |
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アクティブコンパレータ：Groups 18, 20 & 22: Neonates, mOPV1
330 neonates (day of birth +3 days) will receive 3 doses of mOPV1 at a dose level of ≥ 10^6.0 CCID50 on Day 1, Day 29 & Day 57 |
The Sabin Monovalent Oral Poliomyelitis Vaccine Type 1 control and challenge vaccine (mOPV1) contains ≥ 10^6.0 CCID50 per 0.1 mL (2 drops) dose. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Frequency of serious adverse events (SAEs) from the time of first study vaccination through the end of the study
時間枠：From Day 1 to end of study, up to Day 197 (young children and neonates) or Day 225 (infants)
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Serious adverse event is any adverse event that results in any of the following outcomes:
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From Day 1 to end of study, up to Day 197 (young children and neonates) or Day 225 (infants)
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Frequency of solicited adverse events (AEs) for 7 days (day of vaccination and 6 following days) after each vaccination
時間枠：From vaccination to 7 days post vaccination
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Solicited AEs are pre-specific AEs that are common or known to be associated with vaccination that are actively monitored as potential indicators of vaccine reactogenicity. The following specific solicited AEs will be monitored for this trial:
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From vaccination to 7 days post vaccination
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Frequency of unsolicited AEs for 28 days (day of vaccination and 27 following days) after each vaccination
時間枠：From vaccination to 28 days post vaccination
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Unsolicited AEs are any AEs reported spontaneously by the participant's parent, observed by the study personnel during study visits or identified during review of medical records or source documents. In the absence of a diagnosis, abnormal physical examination findings or abnormal clinical safety laboratory test results that are assessed by the investigator to be clinically significant will be reported as an AE. |
From vaccination to 28 days post vaccination
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Post-vaccination frequency of seroconversion of type 1 anti-polio serum neutralizing antibody (NAb).
時間枠：28 days post second vaccination
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Following two doses of nOPV1, at dose levels of 10^6.5 and 10^7.0 CCID50/dose, compared to mOPV1, in healthy neonates. For unvaccinated neonates, seroconversion will be defined as either a minimum 4-fold higher antibody titer relative to the expected level of maternal antibody and seropositivity (reciprocal titer ≥ 8) at the post-vaccination time point among those initially seropositive, or post-vaccination seropositivity among those initially seronegative. |
28 days post second vaccination
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Post-vaccination frequency of seroconversion of type 1 anti-polio serum NAb.
時間枠：Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)
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To assess the seroconversion rate elicited by nOPV1 at dose levels of 10^6.5, 10^7.0 and 10^7.5 CCID50/dose following one and three doses in healthy neonates compared to mOPV1. To assess the seroconversion rate elicited by nOPV1 at dose levels of 10^5.5, 10^6.0 and 10^6.5 CCID50/dose following one or two doses in healthy young children compared to mOPV1. To assess the seroconversion rate elicited by nOPV1 at dose levels of 10^5.5 and 10^6.0 CCID50/dose following one or two doses in healthy infants compared to mOPV1. |
Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)
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Median type 1 anti-polio serum NAb titers.
時間枠：Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)
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Elicited by nOPV1, compared to that of mOPV1, following one or two doses in healthy young children, and one, two or three doses in infants and neonates. |
Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)
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Type 1 anti-polio serum NAb Geometric Mean Titer (GMT).
時間枠：Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)
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Elicited by nOPV1, compared to that of mOPV1, following one or two doses in healthy young children, and one, two or three doses in infants and neonates. |
Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)
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Post-vaccination GMT ratios of type 1 anti-polio serum NAb, adjusted for baseline immunity.
時間枠：Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)
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Elicited by nOPV1, compared to that of mOPV1, following one or two doses in healthy young children, and one, two or three doses in infants and neonates. |
Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)
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Seroprotection rate, defined as type 1 anti-polio serum NAb reciprocal titer ≥ 8.
時間枠：Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)
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Elicited by nOPV1, compared to that of mOPV1, following one or two doses in healthy young children, and one, two or three doses in infants and neonates. |
Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)
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Geometric mean fold rise (GMFR) in NAb titer relative to baseline
時間枠：Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)
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Elicited by nOPV1, compared to that of mOPV1, following one or two doses in healthy young children, and one, two or three doses in infants and neonates. |
Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)
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Proportion of participants shedding type 1 poliovirus at any and at each post-vaccination stool collection, as assessed by polymerase chain reaction (PCR) in infants and neonates.
時間枠：Baseline through to 28 days post initial vaccination (Day 29 through to Day 57 for infants; Day 1 through to Day 29 for neonates)
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28 days after the initial dose of nOPV1, compared to mOPV1. |
Baseline through to 28 days post initial vaccination (Day 29 through to Day 57 for infants; Day 1 through to Day 29 for neonates)
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Proportion of participants shedding type 1 poliovirus at any and at each post-challenge stool collection, as assessed by PCR in infants.
時間枠：Day of challenge through to 28 days post challenge (Day 113 through to Day 141 or 169, for infants)
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28 days after mOPV challenge compared to mOPV1 |
Day of challenge through to 28 days post challenge (Day 113 through to Day 141 or 169, for infants)
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Neurovirulence of shed study vaccine virus from select stool samples as measured by a transgenic mouse neurovirulence test in a subset of infants.
時間枠：Baseline through to 28 days post initial vaccination (Day 29 through 57 for infants)
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Within 28 days of an initial nOPV dose and compared to that of mOPV1. |
Baseline through to 28 days post initial vaccination (Day 29 through 57 for infants)
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協力者と研究者
スポンサー
協力者
捜査官
- 主任研究者：K. Zaman, MBBS, MPH, PhD, FRCP、International Centre for Diarrhoeal Disease Research, Bangladesh
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- CVIA 093
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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