HPIV3血清陽性の小児24歳から鼻スプレーにより送達されるHMPVの融合糖タンパク質を発現する2種類の組換え生弱毒化B/HPIV3ベクターワクチンの感染力、安全性、免疫原性の研究
ヒトメタニューモウイルス（HMPV）の融合糖タンパク質を発現し、点鼻スプレーによりHPIV3に送達される2種類の組換え生弱毒化ウシ/ヒトパラインフルエンザウイルス3型（B/HPIV3）ベクター化ワクチンの感染力、安全性、免疫原性に関する第I相研究-血清陽性の子供（24歳から）
HPIV3 and HMPV are viruses that can cause breathing problems in children. The goal of this clinical trial is to look at the safety of 2 experimental HPIV3/HMPV vaccines in HPIV3-seropositive children ≥ 24 months to < 60 months of age. Children will receive B/HPIV3/HMPV-PreF-A vaccine, B/HPIV3/HMPV-F-B365 vaccine, or placebo, and participants will not know which study product they have received.
The main goals of the study are to find out whether these vaccines are well-tolerated and infectious in HPIV3-seropositive children.
The general procedures include daily temperature measurements and daily contact with the participant for the first 28 days, giving a single dose of one of the 2 study vaccines or placebo delivered by nasal sprayer, about 9 in-person visits, a physical examination, 7 clinical assessments, 2 blood samples, 9 nasal swabs and monthly contacts with the participant between Days 29-180.
Additional visits may occur if the child has a respiratory illness, fever, or ear infections. The illness visit will include a nasal swab and a clinical assessment.
調査の概要
状態
詳細な説明
This is a blinded, randomized, placebo-controlled study design will be used to evaluate the safety and immunogenicity of the study product in HPIV3-seropositive participants. The study will be performed in approximately 25 HPIV3-seropositive children ≥ 24 months to < 60 months of age. Subjects will be block randomized to receive a single dose of 10^5.6 PFU of B/HPIV3/HMPV-PreF-A, 10^5.6 PFU of B/HPIV3/HMPV-F-B365, or placebo in a 2:2:1 ratio. Enrollment will be continuous unless stopping rules are met or other safety concerns occur. During the enrollment period, the Data and Safety Monitoring Board (DSMB) will perform unblinded safety reviews. After completion of the Day 28 visit of the last participant, an unblinded review of all participants will be performed by the DSMB.
The first 28 days after inoculation are considered the Acute Phase of the study, and the participants' parents/guardians will be contacted daily during the Acute Phase. These contacts will consist either of an in-person evaluation of interim medical history, clinical assessment, and nasal swab, or an interim medical history conducted by a mutually agreed upon communication method. If a child develops a respiratory or febrile illness or otitis media during the acute phase, an in-person evaluation will be performed. During the Acute Phase, the participants will be evaluated for adverse events (AEs) or serious adverse events (SAEs). Between Days 29 and 180 parents/guardians will be asked to contact study staff to report Medically Attended Adverse Events (MAAEs), which will be reported per protocol. Between days 29-180, study staff will contact the participants' parents/guardians monthly and on Day 180 (±7 days) after inoculation to capture any previously unreported MAAEs.
Clinical assessments will be completed and nasal swabs will be obtained on study Days 0, 3, 4, 5, 6, 7, 10, 14 and 28 and whenever febrile or respiratory illnesses or otitis media (solicited AEs) are reported during the first 28 days following inoculation. The nasal swab will be tested for vaccine virus, for respiratory pathogens that are considered adventitious agents, including wild-type HPIV3 and HMPV, and for mucosal IgG and IgA antibody as listed in the schedule of events.
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
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Maryland
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Baltimore、Maryland、アメリカ、21205
- CIR - Rangos, Johns Hopkins Bloomberg School of Public Health
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Columbia、Maryland、アメリカ、21045
- CIR South
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New York
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Rochester、New York、アメリカ、14642
- University of Rochester Medical Center
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Tennessee
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Nashville、Tennessee、アメリカ、37232
- Vanderbilt University Medical Center
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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:
- ≥24 months of age and <60 months of age at the time of inoculation
- HAI Screening for HPIV3-neutralizing antibody is obtained within the calendar year of inoculation
- Seropositive for HPIV3 antibody, defined as serum HPIV3 HAI titer >1:8
- Pre-inoculation serum sample for HPIV3-neutralizing antibody specimen is obtained no more than 42 days prior to inoculation
- In good health based on review of the medical record, history, and physical examination at the time of inoculation
- Received routine immunizations appropriate for age based on the Advisory Committee on Immunization Practices (ACIP) Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger
- Growing normally for age as demonstrated on a World Health Organization (WHO) growth chart, AND has a current height and weight above the 3rd percentile for age
- Expected to be available for the duration of the study
- Parent/guardian is willing and able to provide written informed consent
Exclusion Criteria:
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<24 months of age and >60 months of age at the time of inoculation.
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Born at less than 34 weeks gestation
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Maternal history of a positive HIV test before or during pregnancy.
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Evidence of chronic disease
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Known or suspected infection or impairment of immunological functions
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Bone marrow/solid organ transplant recipient
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Major congenital malformations, including congenital cleft palate or cytogenetic abnormalities
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Suspected or documented developmental disorder, delay, or other developmental problem
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Cardiac abnormality requiring treatment
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Lung disease or reactive airway disease
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More than one episode of medically diagnosed wheezing in the first year of life
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Wheezing episode or received bronchodilator therapy or racemic epinephrine within the past 12 months
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Wheezing episode or received bronchodilator therapy after the age of 12 months
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Previous receipt of supplemental oxygen therapy in a home setting
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Previous receipt of an investigational HPIV3 or HMPV vaccine
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Previous receipt or planned administration of human immunoglobulin within the past 6 months. Receipt of licensed monoclonal antibody products for passive prophylaxis against RSV (e.g., nirsevimab) within the past 6 months is not a cause for exclusion
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Previous receipt of any blood products within the past 6 months.
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Previous anaphylactic reaction
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Previous vaccine-associated adverse reaction that was Grade 3 or above.
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Known hypersensitivity to any study product component
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Member of a household that contains an infant who is less than 12 months of age at the date of inoculation through the 10th day after inoculation
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Member of a household that, at the date of inoculation through the 10th day after inoculation, contains an immunocompromised individual including but not limited to:
- a person who is HIV-infected
- a person who has cancer and has received chemotherapy within the 12 months prior to enrollment
- a person living with a solid organ or bone marrow transplant
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Attends a daycare facility that does not separate children by age and contains a child <12 months of age at the date of inoculation through the 10th day after inoculation
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Receipt of any of the following prior to enrollment:
- inactivated influenza vaccine within 3 days prior, or
- any other inactivated vaccine, messenger RNA (mRNA) vaccine, or live-attenuated rotavirus vaccine within the 14 days prior, or
- any live vaccine, other than rotavirus vaccine, within the 28 days prior, or
- another investigational vaccine or investigational drug within 28 days prior, or
- salicylate (aspirin) or salicylate-containing products within the past 28 days
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Scheduled administration of any of the following after planned inoculation:
- inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days after, or
- any live vaccine other than rotavirus within the 28 days after, or
- any salicylate or salicylate-containing products within the 28 days after, or
- another investigational vaccine or investigational drug in the 56 days after
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Receipt of any of the following medications within 3 days prior to study enrollment:
- systemic antibacterial, antiviral, antifungal, anti-parasitic, or antituberculous agents, whether for treatment or prophylaxis, or
- intranasal medications, or
- other prescription medications except the permitted concomitant medications listed below
- Permitted concomitant medications (prescription or non-prescription) include nutritional supplements, medications for gastroesophageal reflux, eye drops, and topical medications, including (but not limited to) cutaneous (topical) steroids, topical antibiotics, and topical antifungal agents
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Any of the following events at the time of enrollment:
- fever (temporal or rectal temperature of ≥100.4°F), or
- upper respiratory signs or symptoms (rhinorrhea, cough, or pharyngitis), or
- nasal congestion significant enough to interfere with successful inoculation, or
- otitis media, or
- contact with a person diagnosed with COVID-19 disease or active SARS-CoV-2 infection within the preceding 10 days
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：並列代入
- 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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アクティブコンパレータ：B/HPIV3/HMPV-PreF-A vaccine
A single dose of intranasal B/HPIV3/HMPV-PreF-A will be administered by a Vax300 VaxINator atomization device. |
B/HPIV3/HMPV-PreF-A is a live-attenuated vaccine candidate. The B/HPIV3/HMPV-PreF-A vaccine is provided in a sterile 2.0-mL cryovial, each containing 0.6 mL of vaccine with a titer of approximately 10^6.7 PFU/mL. The vaccine virus concentrate is diluted with Lactated Ringer's Solution for Injection to a dose of approximately 10^5.6 PFU in a 0.2 mL volume. |
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アクティブコンパレータ：B/HPIV3/HMPV-F-B365 vaccine
A single dose of intranasal B/HPIV3/HMPV-F-B365 will be administered by a Vax300 VaxINator atomization device. |
B/HPIV3/HMPV-F-B365 is a live-attenuated vaccine candidate. The B/HPIV3/HMPV-F-B365 vaccine is provided in a sterile 2.0-mL cryovial, each containing 0.6 mL of vaccine with a titer of approximately 10^6.3 PFU/mL. The vaccine virus concentrate is diluted with Lactated Ringer's Solution for Injection to a dose of approximately 10^5.6 PFU in a 0.2 mL volume. |
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プラセボコンパレーター：Placebo
A single dose of intranasal Lactated Ringer's Solution for Injection will be administered by a Vax300 VaxINator atomization device. |
Lactated Ringer's Injection, USP is a sterile, nonpyrogenic solution for fluid and electrolyte replenishment. It will be drawn up in a sterile syringe to a volume of 0.2 mL.
他の名前：
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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 Grade 1 or Higher Solicited Adverse Events (AEs) by Grade
時間枠：Day 0 through Day 28
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Solicited adverse events include fever; otitis media; upper respiratory illness (URI); lower respiratory illness (LRI) and cough (without LRI) as defined in Appendix II of the protocol document. The number of participants who experienced solicited adverse events was presented. A participant was only counted once in each solicited AE category, and that is in the line corresponding to the highest grade adverse event they had in that category. These events were graded (Grade 1-mild to Grade 5-death) following protocol-defined grading system outlined in Table 13 and Table 14 in the protocol document. Details regarding LRIs will be noted in Primary Outcome Measure #2. |
Day 0 through Day 28
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Frequency of Lower Respiratory Illness (LRIs) by Grade
時間枠：Measured through Day 28
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LRI may include wheezing, pneumonia, laryngotracheobronchitis (croup), rhonchi and rales as defined in Appendix II of the protocol document. A participant was only counted once in each LRI category, and that is in the line corresponding to the highest grade adverse event they had in that category. These events were graded (Grade 1-mild to Grade 5-death) following protocol-defined grading system outlined in Table 13 in the protocol document. |
Measured through Day 28
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Percentage of Vaccinees With a ≥4-fold Rise in HPIV3 Serum Neutralizing Antibody Titer
時間枠：Measured at Day 0 and Day 28
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Serum HPIV3-neutralizing antibody titers were assessed by 60% HPIV3-plaque reduction neutralization titer (HPIV3-PRNT) assay. Antibody responses were defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points. |
Measured at Day 0 and Day 28
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Percentages of Vaccinees With a ≥4-fold Rise in HMPV-neutralizing Serum Antibody Titers
時間枠：Measured at Day 0 and Day 28
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Serum HMPV-neutralizing antibody titers were assessed by 60% HMPV-plaque reduction neutralization titer (HMPV-PRNT) assay. Antibody responses were defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points. |
Measured at Day 0 and Day 28
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Peak Titers of Vaccine Virus Shed
時間枠：Measured study days 0-28
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This is the highest value per participant of the titer of vaccine virus shed. It was measured by RT-qPCR. For the purposes of calculation, peak titers of 1.7 log10 copy number, which is the lower limit of detection of the RT-qPCR assay, were assigned to qPCR negative samples. Note that only 1 participant who received the B/HPIV3/HMPV-PreF-A vaccine and only 1 participant that received the B/HPIV3/HMPV-F-B365 vaccine shed vaccine virus. |
Measured study days 0-28
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Number of Vaccinees Infected With Vaccine Virus
時間枠：Measured through Day 28
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Infection with vaccine virus is determined by shedding of vaccine virus detected by immunoplaque assay and/or RT-qPCR, and/or ≥4 fold rise in HPIV3 or HMPV-specific serum antibodies, detected by neutralizing antibody assay or ELISA from study entry to Study Day 28 |
Measured through Day 28
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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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Frequency and Severity of Medically Attended Adverse Events (MAAEs) by Grade
時間枠：Measured from Day 29 through Day 180 (Observation Period)
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The number of participants who had medically attended illness (solicited and unsolicited adverse events). A participant was only counted once in each AE category, and that is in the line corresponding to the highest grade adverse event they had in that category. These events were graded (Grade 1-mild to Grade 5-death) following protocol-defined grading system outlined in Table 13 and Table 14 in the protocol document. |
Measured from Day 29 through Day 180 (Observation Period)
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Number of Participants Who Experienced Serious Adverse Events (SAEs)
時間枠：Measured Day 0 through Day 180 after inoculation
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A Serious Adverse Event (SAE) is an AE, whether considered related to the study product or not, that: Results in death during the period of protocol-defined surveillance; Is life threatening: defined as an event in which the patient was at immediate risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death were it more severe; Requires inpatient hospitalization (or prolongation of existing hospitalization): defined as at least an overnight stay in the hospital or emergency ward for treatment that would have been inappropriate if administered in the outpatient setting; Results in a persistent or significant disability/incapacity; Is a congenital anomaly or birth defect, OR Is an important medical event that may not be immediately life threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. |
Measured Day 0 through Day 180 after inoculation
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協力者と研究者
協力者
捜査官
- 主任研究者：Ruth Karron, M.D.、Center for Immunization Research, JHBSPH
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
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?
IPD プランの説明
Qualified researchers may request access to IPD that underlie results in a publication. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants.
IPD 共有時間枠
After publication
IPD 共有アクセス基準
Qualified researchers
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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