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临床试验/NCT03553940
NCT03553940已完成1 期

A Phase I Trial to Evaluate the Safety and Immunogenicity of an Influenza Vaccination Strategy Including a H3N2 M2SR Prime Followed by a Seasonal Quadrivalent Inactivated Vaccine Boost in a Pediatric Population 9-17 Years Old

National Institute of Allergy and Infectious Diseases (NIAID)2 个研究点 分布在 1 个国家目标入组 43 人开始时间: 2018年8月15日最近更新:
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适应症

试验速览

阶段
1 期
状态
已完成
入组人数
43
试验地点
2
主要终点
Number of Participants With Serious Adverse Events (SAEs)
研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a Phase I double-blind, randomized, placebo-controlled study in 50 healthy adolescents and children, 9-17 years of age, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety and immunogenicity of a prime-boost regimen of H3N2 M2SR intranasal influenza vaccine (manufactured by FluGen) followed by licensed inactivated Quadrivalent Influenza Vaccine (QIV) boost administered intramuscularly Subjects will be enrolled in one of two groups in a 1:1 ratio. Arm 1 will receive one dose of M2SR intranasally on Day 1 and one dose of QIV on Day 92. Arm 2 will receive one dose of placebo (saline) intranasally on Day 1, and one dose of QIV on Day 92. Study duration will be approximately 28 months with patient participation duration approximately 13 months. The primary study objective is to assess the safety and reactogenicity of a monovalent live attenuated influenza H3N2 M2SR vaccine.

详细描述

This is a Phase I double-blind, randomized, placebo-controlled study in 50 healthy adolescents and children, 9-17 years of age, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety and immunogenicity of a prime-boost regimen of H3N2 M2SR intranasal influenza vaccine (manufactured by FluGen) followed by licensed inactivated Quadrivalent Influenza Vaccine (QIV) boost administered intramuscularly. Subjects will be enrolled in one of two groups in a 1:1 ratio. Arm 1 will receive one dose of M2SR intranasally on Day 1 and one dose of QIV on Day 92. Arm 2 will receive one dose of placebo (saline) intranasally on Day 1, and one dose of QIV on Day 92. Study duration will be approximately 28 months with patient participation duration approximately 13 months. The primary study objective is to assess the safety and reactogenicity of a monovalent live attenuated influenza H3N2 M2SR vaccine. The secondary study objectives are to identify circulating and mucosal antibody responses induced by H3N2 M2SR vaccination and to identify cellular immune responses induced by H3N2 M2SR vaccination.

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
9 Years 至 17 Years（Child）
性别
All
接受健康志愿者
是

入选标准

  • •Parent(s)/legal guardian(s) must provide written informed consent prior to initiation of any study procedures, and subject must provide assent.
  • •Are able to understand and comply with planned study procedures and be available for all study visits.
  • •Are males or non-pregnant females, 9-17 years old, inclusive at the time of enrollment.
  • •Are in good health*.
  • •*As determined by medical history and physical examination to evaluate acute or currently ongoing chronic medical diagnoses or conditions, defined as those that have been present for at least 90 days, which would affect the assessment of the safety of subjects or the immunogenicity of study vaccinations. Chronic medical diagnoses or conditions should be stable for the last 60 days (no hospitalizations, ER, or urgent care for condition and no adverse symptoms that need medical intervention). This includes no change in chronic prescription medication, dose, or frequency as a result of deterioration of the chronic medical diagnosis or condition in the 60 days prior to enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or that is done for financial reasons, as long as in the same class of medication, will not be considered a deviation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the site principal investigator or appropriate sub-investigator, will not be considered a deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening of medical diagnosis or condition. Similarly, medication changes subsequent to enrollment and study vaccination are acceptable provided there was no deterioration in the subject's chronic medical condition that necessitated a medication change, and there is no additional risk to the subject or interference with the evaluation of responses to study vaccination. Note: Low dose topical steroids, herbals, vitamins, and supplements are permitted.
  • •Oral temperature is less than 100.0 degrees Fahrenheit.
  • •For female adolescent of child-bearing potential* must agree to correctly use an acceptable method of contraception** from 30 days prior to vaccination until 30 days after the last study vaccination.
  • •*Defined by the onset of menses, and not sterilized via tubal ligation, bilateral oophorectomy, hysterectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating.
  • •**Includes non-male sexual relationships, abstinence from sexual intercourse with a male partner, monogamous relationship with a vasectomized partner, and correct use of male condoms with the use of applied spermicide, intrauterine devices, NuvaRing(R), and licensed hormonal methods such as implants, injectables, contraceptive patches or oral contraceptives ("the pill"). Method of contraception will be captured on the appropriate data collection form.
  • •Female adolescent of childbearing potential must have a negative urine pregnancy test within 24 hours prior to study vaccination.
  • •Males who are sexually active with a female of childbearing potential must agree not to father a child for 30 days after receipt of the first study vaccination.
  • •Agrees not to participate in another clinical trial during the study period.
  • •Agrees not to donate blood or blood products to a blood bank for 12 months after receiving the investigational vaccine.
  • •Weight = / > 34 kg or 75 pounds.
  • •Hemoglobin = / > 11.5 g/dL.
  • •Hematocrit > 35%.
  • •Ferritin level = / > 15 ng/mL.
  • •Parent/legal guardian must provide consent to future use of stored samples.

排除标准

  • •Have an acute illness*, as determined by the site PI or appropriate sub-investigator, within 72 hours prior to each study vaccination.
  • •*An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.
  • •Have any medical disease or condition that, in the opinion of the site PI or appropriate sub-investigator, is a contraindication to study participation*.
  • •*Including acute or chronic medical disease or condition, defined as persisting for at least 90 days, that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this study.
  • •Have immunosuppression as a result of an underlying illness or treatment, or use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination.
  • •Have known active neoplastic disease or a history of any hematologic malignancy. Non-melanoma skin cancers that are not active are permitted.
  • •Have known HIV, hepatitis B, or hepatitis C infection.
  • •Have a history of severe reactions following previous immunization with licensed or unlicensed influenza vaccines.
  • •History of anatomic disorder of the nares or nasopharynx (Deviated septum is allowed).
  • •History of chronic sinus infections.
  • •Have a history of Guillain-Barre Syndrome.
  • •Have a history of alcohol or drug abuse prior to study vaccination.
  • •Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations.
  • •Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others prior to study vaccination.
  • •Have taken oral and/or nasal corticosteroids of any dose within 30 days prior to each study vaccination or plan to take in the 30 days following the first study vaccination.
  • •Have taken high-dose*,** inhaled corticosteroids within 30 days (prior to study vaccination).
  • •*High-dose defined as per age as using inhaled high dose per reference chart.
  • •**https://www.nhlbi.nih.gov/files/docs/guidelines/asthma_org.pdf.
  • •Use of aspirin or salicylate-containing products 30 days prior to the first vaccination.
  • •Recurring or active wheezing or diagnosis of asthma, or history of significant wheezing*.
  • •*Medically significant wheezing: defined as wheezing on physical exam plus sign of respiratory distress (tachypnea, retractions, or dyspnea), hypoxemia (O2 saturation < 95%), or new bronchodilator prescription, or use of daily bronchodilator therapy (not on an "as needed" basis).
  • •Received any licensed live or inactivated vaccine within 30 days prior to or plan to receive any licensed live or inactivated vaccine within 30 days after each study vaccination.
  • •Received any influenza vaccine (inactivated or live) within 6 months prior to the first study vaccination and until the end of the study.
  • •Received immunoglobulin or other blood products within 6 months prior to study vaccination.
  • •Received an experimental agent* within 30 days prior to the first study vaccination, or expects to receive an experimental agent** during the 12-month trial-reporting period.
  • •*Including vaccine, drug, biologic, device, blood product, or medication.
  • •**Other than from participation in this study.
  • •Are participating or plan to participate in another clinical trial with an interventional agent* that will be received during the 12-month trial-reporting period.
  • •*Including agent (licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication) during the 12-month study period.
  • •Prior history of H3N2 actual or potential exposure or infection prior to the first study vaccination, or receipt of experimental vaccines within the past year prior to the first study vaccine.
  • •Female adolescent subject who is breastfeeding or plans to breastfeed at any given time from the first study vaccination until 30 days after the last study vaccination.
  • •Blood donation within 30 days prior to the study vaccination through 30 days after the last blood drawn for this study.
  • •Have signs or symptoms that could confound or confuse assessment of study vaccine reactogenicity*.
  • •*The study vaccination should be postponed/deferred until signs or symptoms have resolved and if within the acceptable protocol-specified window for that visit.
  • •Have received any antiviral drug within 3 days of study vaccination.

结局指标

主要结局

Number of Participants With Serious Adverse Events (SAEs)

时间窗: Day 1 through Day 366

SAEs included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation or a congenital anomaly/birth defect.

Number of Participants With Unsolicited Non-Serious Adverse Events

时间窗: Day 1 through Day 22

Adverse events were defined as any untoward medical occurrence in a participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Non-serious AEs were collected from the time of first study vaccination through 21 days after first vaccination. Adverse events were MedDRA coded and are summarized by MedDRA System Organ Class (SOC).

Number of Participants With Adverse Events of Special Interest (AESIs)

时间窗: Day 1 through Day 92

Adverse Events of Special Interest (AESIs) included medically significant wheezing and otitis media. AESIs were collected from receipt of the first study vaccination through 3 months after first vaccination.

Number of Participants With New Onset Chronic Medical Conditions (NOCMCs)

时间窗: Day 1 through Day 92

Participants were queried at each visit for the occurrence of new onset chronic medical conditions (NOCMCs). NOCMCs were collected from receipt of the first study vaccination through 3 months after first vaccination.

Number of Participants With Solicited Reactogenicity

时间窗: Day 1 through Day 8

Reactogenicity assessments included an assessment of solicited AEs occurring from the time of first study vaccination through 7 days after first vaccination. For upper respiratory symptoms, this included an assessment of runny nose, stuffy nose/ congestion, sneezing, nasal pain/irritation/nasal dryness, nasal bleeding/epistaxis, sinus pressure/pain, sore throat/sore/scratchy, itchy or painful throat, cough, and trouble breathing/shortness of breath. For general systemic symptoms, this included an assessment of reactions including fever, feverishness (chills/shivering/sweating), fatigue (tiredness), malaise, myalgia (body aches/muscular pain), arthralgia (joint pain), headache, flushing, decreased activity, decreased appetite, abdominal pain, nausea, vomiting, diarrhea, eye pruritus, eye redness (conjunctivitis), allergy, and wheezing.

次要结局

  • Frequency of Influenza H3 HA-specific Spot Forming Cells for the H3N2 QIV-like Virus A/North Carolina/04/2016(Day 1 through Day 113)
  • Geometric Mean Titer (GMT) of Nasal Secretory Immunoglobulin A (sIgA) Responses Directed Against the H3N2 QIV-like Virus A/North Carolina/04/2016 Normalized to Total sIgA(Day 1 through Day 113)
  • Geometric Mean Titer (GMT) of Nasal Secretory Immunoglobulin A (sIgA) Responses Directed Against the H3N2 QIV-like Virus A/Kansas/14/2017 Normalized to Total sIgA(Day 1 through Day 113)
  • Geometric Mean Fold Rise (GMFR) of Nasal Secretory Immunoglobulin A (sIgA) Responses Directed Against the H3N2 M2SR-like Virus A/Brisbane/10/2007 Normalized to Total sIgA(Day 8 through Day 113)
  • Frequency of Conserved Internal Viral Protein-specific Spot Forming Cells(Day 1 through Day 113)
  • Frequency of Influenza H3 HA-specific Spot Forming Cells for the H3N2 QIV-like Virus A/Singapore/INFIMH-16-0019/2016(Day 1 through Day 113)
  • Geometric Mean Fold Rise (GMFR) of Nasal Secretory Immunoglobulin A (sIgA) Responses Directed Against the H3N2 M2SR-like Virus A/Brisbane/10/2007(Day 8 through Day 113)
  • Frequency of Influenza H3 HA-specific Spot Forming Cells for the H3N2 M2SR-like Virus A/Brisbane/10/2007(Day 1 through Day 113)
  • Frequency of Influenza H3 HA-specific Spot Forming Cells for the H3N2 QIV-like Virus A/Kansas/14/2017(Day 1 through Day 113)
  • Geometric Mean Fold Rise (GMFR) of Nasal Secretory Immunoglobulin A (sIgA) Responses Directed Against the H3N2 QIV-like Virus A/North Carolina/04/2016(Day 8 through Day 113)
  • Geometric Mean Fold Rise (GMFR) of Nasal Secretory Immunoglobulin A (sIgA) Responses Directed Against the H3N2 QIV-like Virus A/Kansas/14/2017(Day 8 through Day 113)
  • Geometric Mean Fold Rise (GMFR) of Nasal Secretory Immunoglobulin A (sIgA) Responses Directed Against the H3N2 QIV-like Virus A/Kansas/14/2017 Normalized to Total sIgA(Day 8 through Day 113)
  • Geometric Mean Titer (GMT) of Nasal Secretory Immunoglobulin A (sIgA) Responses Directed Against the H3N2 QIV-like Virus A/Singapore/INFIMH-16-0019/2016(Day 1 through Day 113)
  • Geometric Mean Titer (GMT) of Nasal Secretory Immunoglobulin A (sIgA) Responses Directed Against the H3N2 QIV-like Virus A/Kansas/14/2017(Day 1 through Day 113)
  • Geometric Mean Titer (GMT) of Nasal Secretory Immunoglobulin A (sIgA) Responses Directed Against the H3N2 QIV-like Virus A/North Carolina/04/2016(Day 1 through Day 113)
  • Geometric Mean Titer (GMT) of Nasal Secretory Immunoglobulin A (sIgA) Responses Directed Against the H3N2 QIV-like Virus A/Singapore/INFIMH-16-0019/2016 Normalized to Total sIgA(Day 1 through Day 113)
  • Hemagglutination Inhibition (HAI) Antibody Geometric Mean Fold Rise (GMFR) to the H3N2 QIV-like Virus A/North Carolina/04/2016(Day 8 through Day 113)
  • Hemagglutination Inhibition (HAI) Antibody Geometric Mean Fold Rise (GMFR) to the H3N2 QIV-like Virus A/Singapore/INFIMH-16-0019/2016(Day 8 through Day 113)
  • Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMTs) to the H3N2 M2SR-like Virus A/Brisbane/10/2007(Day 1 through Day 113)
  • Neutralizing Antibody Geometric Mean Fold Rise (GMFR) to the H3N2 QIV-like Virus A/North Carolina/04/2016(Day 8 through Day 113)
  • Geometric Mean Fold Rise (GMFR) of Nasal Secretory Immunoglobulin A (sIgA) Responses Directed Against the H3N2 QIV-like Virus A/North Carolina/04/2016 Normalized to Total sIgA(Day 8 through Day 113)
  • Geometric Mean Fold Rise (GMFR) of Nasal Secretory Immunoglobulin A (sIgA) Responses Directed Against the H3N2 QIV-like Virus A/Singapore/INFIMH-16-0019/2016(Day 8 through Day 113)
  • Geometric Mean Fold Rise (GMFR) of Nasal Secretory Immunoglobulin A (sIgA) Responses Directed Against the H3N2 QIV-like Virus A/Singapore/INFIMH-16-0019/2016 Normalized to Total sIgA(Day 8 through Day 113)
  • Geometric Mean Titer (GMT) of Nasal Secretory Immunoglobulin A (sIgA) Responses Directed Against the H3N2 M2SR-like Virus A/Brisbane/10/2007 Normalized to Total sIgA(Day 1 through Day 113)
  • Hemagglutination Inhibition (HAI) Antibody Geometric Mean Fold Rise (GMFR) to the H3N2 QIV-like Virus A/Kansas/14/2017(Day 8 through Day 113)
  • Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMTs) to the H3N2 QIV-like Virus A/North Carolina/04/2016(Day 1 through Day 113)
  • Geometric Mean Titer (GMT) of Nasal Secretory Immunoglobulin A (sIgA) Responses Directed Against the H3N2 M2SR-like Virus A/Brisbane/10/2007(Day 1 through Day 113)
  • Hemagglutination Inhibition (HAI) Antibody Geometric Mean Fold Rise (GMFR) to the H3N2 M2SR-like Virus A/Brisbane/10/2007(Day 8 through Day 113)
  • Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMTs) to the H3N2 QIV-like Virus A/Kansas/14/2017(Day 1 through Day 113)
  • Neutralizing Antibody Geometric Mean Fold Rise (GMFR) to the H3N2 QIV-like Virus A/Kansas/14/2017(Day 8 through Day 113)
  • Neutralizing Antibody Geometric Mean Titers (GMTs) to the H3N2 M2SR-like Virus A/Brisbane/10/2007(Day 1 through Day 113)
  • Neutralizing Antibody Geometric Mean Titers (GMTs) to the H3N2 QIV-like Virus A/Kansas/14/2017(Day 1 through Day 113)
  • Percentage of Participants Achieving a Serum Neutralizing Antibody Titer of >= 1:40 Against the H3N2 M2SR-like Virus A/Brisbane/10/2007(Day 1 through Day 113)
  • Percentage of Participants Achieving a Serum Neutralizing Antibody Titer of >= 1:40 Against the H3N2 QIV-like Virus A/Singapore/INFIMH-16-0019/2016(Day 1 through Day 113)
  • Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMTs) to the H3N2 QIV-like Virus A/Singapore/INFIMH-16-0019/2016(Day 1 through Day 113)
  • Neutralizing Antibody Geometric Mean Fold Rise (GMFR) to the H3N2 M2SR-like Virus A/Brisbane/10/2007(Day 8 through Day 113)
  • Neutralizing Antibody Geometric Mean Fold Rise (GMFR) to the H3N2 QIV-like Virus A/Singapore/INFIMH-16-0019/2016(Day 8 through Day 113)
  • Neutralizing Antibody Geometric Mean Titers (GMTs) to the H3N2 QIV-like Virus A/North Carolina/04/2016(Day 1 through Day 113)
  • Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Antibody Seroconversion Against the H3N2 M2SR-like Virus A/Brisbane/10/2007(Day 8 through Day 113)
  • Neutralizing Antibody Geometric Mean Titers (GMTs) to the H3N2 QIV-like Virus A/Singapore/INFIMH-16-0019/2016(Day 1 through Day 113)
  • Percentage of Participants Achieving a Serum Hemagglutination Inhibition (HAI) Antibody Titer of >= 1:40 Against the H3N2 QIV-like Virus A/North Carolina/04/2016(Day 1 through Day 113)
  • Percentage of Participants Achieving a Serum Hemagglutination Inhibition (HAI) Antibody Titer of >= 1:40 Against the H3N2 M2SR-like Virus A/Brisbane/10/2007(Day 1 through Day 113)
  • Percentage of Participants Achieving a Serum Hemagglutination Inhibition (HAI) Antibody Titer of >= 1:40 Against the H3N2 QIV-like Virus A/Singapore/INFIMH-16-0019/2016(Day 1 through Day 113)
  • Percentage of Participants Achieving a Serum Hemagglutination Inhibition (HAI) Antibody Titer of >= 1:40 Against the H3N2 QIV-like Virus A/Kansas/14/2017(Day 1 through Day 113)
  • Percentage of Participants Achieving a Serum Neutralizing Antibody Titer of >= 1:40 Against the H3N2 QIV-like Virus A/Kansas/14/2017(Day 1 through Day 113)
  • Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Antibody Seroconversion Against the H3N2 QIV-like Virus A/Singapore/INFIMH-16-0019/2016(Day 8 through Day 113)
  • Percentage of Participants Achieving Neutralizing Antibody Seroconversion Against the H3N2 QIV-like Virus A/Singapore/INFIMH-16-0019/2016(Day 8 through Day 113)
  • Percentage of Participants Achieving a Serum Neutralizing Antibody Titer of >= 1:40 Against the H3N2 QIV-like Virus A/North Carolina/04/2016(Day 1 through Day 113)
  • Percentage of Participants Achieving Neutralizing Antibody Seroconversion Against the H3N2 QIV-like Virus A/Kansas/14/2017(Day 8 through Day 113)
  • Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Antibody Seroconversion Against the H3N2 QIV-like Virus A/North Carolina/04/2016(Day 8 through Day 113)
  • Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Antibody Seroconversion Against the H3N2 QIV-like Virus A/Kansas/14/2017(Day 8 through Day 113)
  • Percentage of Participants Achieving Neutralizing Antibody Seroconversion Against the H3N2 QIV-like Virus A/North Carolina/04/2016(Day 8 through Day 113)
  • Percentage of Participants Achieving Neutralizing Antibody Seroconversion Against the H3N2 M2SR-like Virus A/Brisbane/10/2007(Day 8 through Day 113)

研究者

申办方类型
Nih
责任方
Sponsor

研究点 (2)

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