<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02237209</url>
  </required_header>
  <id_info>
    <org_study_id>IMPAACT 2000</org_study_id>
    <secondary_id>DAIDS ES</secondary_id>
    <nct_id>NCT02237209</nct_id>
  </id_info>
  <brief_title>Safety and Immune Response to a Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccine in RSV-Seronegative Infants and Children</brief_title>
  <official_title>A Phase I Study of the Safety and Immunogenicity of Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine RSV LID ΔM2-2 in RSV-Seronegative Infants and Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institute of Allergy and Infectious Diseases (NIAID)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Respiratory syncytial virus (RSV) is a common cause of illness in infants and children around&#xD;
      the world. This study will evaluate the safety and immune response to an RSV vaccine in&#xD;
      RSV-seronegative infants and children.&#xD;
&#xD;
      This study is a companion study to CIR 291.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      RSV is the most common viral cause of serious acute lower respiratory illness (LRI) in&#xD;
      infants and children under 5 years of age in the world. RSV illness can range from mild upper&#xD;
      respiratory tract illness (URI) to severe LRI, including bronchiolitis and pneumonia. Severe&#xD;
      RSV disease in infancy may also predispose children to develop reactive airway disease during&#xD;
      childhood. The purpose of this study is to evaluate the safety and immunogenicity of an RSV&#xD;
      vaccine (RSV LID ΔM2-2) in RSV-seronegative infants and children at least 6 months and&#xD;
      through 24 months of age.&#xD;
&#xD;
      To determine study eligibility, the screening process will include a blood collection.&#xD;
      Screening may begin after the RSV season (i.e., as of April 1) and enrollment must precede&#xD;
      the RSV season (no later than October 14). At study entry, eligible participants will be&#xD;
      randomly assigned to receive one dose of either the RSV vaccine or placebo, which will be&#xD;
      delivered as nose drops. Participants will also undergo a review of medical history, clinical&#xD;
      assessment, and a nasal wash. They will then receive their assigned vaccine and will remain&#xD;
      under observation for monitoring for 30 minutes after receiving the vaccine. Additional study&#xD;
      visits will occur at Days 3, 5, 7, 10, 12, 14, 17, 19, 21, 28, and 56. These visits will&#xD;
      include clinical assessments and nasal washes; on Day 56, a blood collection will also occur.&#xD;
      On days where no study visit is scheduled (through Day 29), participants' parents or&#xD;
      guardians will report participants' temperatures and signs of illness to researchers by&#xD;
      e-mail or phone.&#xD;
&#xD;
      In October following vaccination, participants may have a pre-RSV season blood collection&#xD;
      visit. During RSV season, November through March following vaccination, researchers will&#xD;
      contact participants' parents or guardians on a weekly basis for follow-up monitoring. During&#xD;
      this time frame, participants seen by a medical provider for fever, respiratory illness, or&#xD;
      otitis media will have a study visit, which will include a nasal wash and clinical&#xD;
      assessment. In April following vaccination, participants will undergo a final blood&#xD;
      collection.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">April 2015</completion_date>
  <primary_completion_date type="Actual">April 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency of vaccine-related solicited adverse events (AEs) that occur during the acute monitoring phase of the study, the first 28 days after inoculation</measure>
    <time_frame>Measured through Day 28</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Severity of vaccine-related solicited AEs that occur during the acute monitoring phase of the study, the first 28 days after inoculation</measure>
    <time_frame>Measured through Day 28</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Frequency of vaccine-related lower respiratory illness</measure>
    <time_frame>Measured through Day 56</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of participants that develop 4-fold or greater rises in RSV-neutralizing antibody titer following vaccination</measure>
    <time_frame>Measured through Day 56</time_frame>
    <description>Antibody responses to the RSV F glycoprotein will also be assessed by enzyme-linked immunosorbent assay (ELISA).</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Respiratory Syncytial Virus Infections</condition>
  <arm_group>
    <arm_group_label>RSV LID ΔM2-2 Vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive one dose of the RSV LID ΔM2-2 vaccine at study entry, delivered as nose drops.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Vaccine</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive one dose of placebo at study entry, delivered as nose drops.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>RSV LID ΔM2-2 Vaccine</intervention_name>
    <description>10^5.0 plaque forming units (PFU); 0.5 mL dose delivered as nose drops (approximately 0.25 mL per nostril)</description>
    <arm_group_label>RSV LID ΔM2-2 Vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo Vaccine</intervention_name>
    <description>0.5 mL dose delivered as nose drops (approximately 0.25 mL per nostril)</description>
    <arm_group_label>Placebo Vaccine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant is at least 6 months (defined as at least 180 days) of age at the time of&#xD;
             screening and less than 25 months (defined as less than 750 days) of age&#xD;
&#xD;
          -  Participant is in good health based on review of the medical record, history, and&#xD;
             physical examination, without evidence of chronic disease. Note: any questions&#xD;
             regarding interpretation of this criterion should be forwarded to the team.&#xD;
&#xD;
          -  Parents/guardians demonstrate their understanding of the study, sign the informed&#xD;
             consent, and agree to administration of study product following a detailed explanation&#xD;
             of the study&#xD;
&#xD;
          -  Seronegative for RSV antibody, defined as a serum RSV-neutralizing antibody titer less&#xD;
             than 1:40 at screening obtained no more than 42 days prior to scheduled inoculation&#xD;
&#xD;
          -  Has a current height and weight above the 5th percentile for age&#xD;
&#xD;
          -  Participant has received routine immunizations appropriate for age. Prior vaccines&#xD;
             were administered at least:&#xD;
&#xD;
               -  2 weeks prior to enrollment for inactivated and subunit vaccines and rotavirus&#xD;
                  vaccine, and&#xD;
&#xD;
               -  4 weeks prior to enrollment for all other live vaccines.&#xD;
&#xD;
          -  Participant is expected to be available for the duration of the study&#xD;
&#xD;
          -  If born to an HIV-infected woman, participant must be non-breastfeeding with&#xD;
             documentation of two negative HIV nucleic acid (RNA or DNA) tests with both collected&#xD;
             when at least 1 month of age and at least one collected when at least 4 months of age,&#xD;
             and no positive HIV nucleic acid (RNA or DNA) test; or two negative HIV antibody&#xD;
             tests, both collected at less than or equal to 6 months of age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known or suspected HIV infection or impairment of immunological functions&#xD;
&#xD;
          -  Receipt of immunosuppressive therapy, including any systemic corticosteroids within 30&#xD;
             days of enrollment. Note: Cutaneous (topical) steroid treatment is not an exclusion.&#xD;
&#xD;
          -  Bone marrow/solid organ transplant recipient&#xD;
&#xD;
          -  Major congenital malformations (such as congenital cleft palate) or cytogenetic&#xD;
             abnormalities&#xD;
&#xD;
          -  Previous receipt of a licensed or investigational RSV vaccine (or placebo) or previous&#xD;
             receipt of or planned administration of any anti-RSV product (such as ribavirin or RSV&#xD;
             IG)&#xD;
&#xD;
          -  Previous vaccine-associated anaphylactic or other severe adverse vaccine reaction&#xD;
&#xD;
          -  Known hypersensitivity to any study product component&#xD;
&#xD;
          -  Heart disease. Note: Participants with cardiac abnormalities documented to be&#xD;
             clinically insignificant and requiring no treatment may be enrolled.&#xD;
&#xD;
          -  Lung disease, including any history of wheezing or reactive airway disease&#xD;
&#xD;
          -  Member of a household that contains, or will contain, an infant who is less than 6&#xD;
             months of age at the enrollment date through Day 28&#xD;
&#xD;
          -  Member of a household that contains another child who is, or is scheduled to be,&#xD;
             enrolled in IMPAACT 2000, and there has been or will be an overlap in residency during&#xD;
             that other child's participation in the study's Acute Phase (Days 0 to 28)&#xD;
&#xD;
          -  Member of a household that contains an immunocompromised individual, including, but&#xD;
             not limited to:&#xD;
&#xD;
               -  a person who is greater than or equal to 5 years of age with HIV-related&#xD;
                  immunodeficiency, defined as having a most recent CD4 T lymphocyte cell count&#xD;
                  less than 300/mcL. CD4 T lymphocyte count must have been measured within 6 months&#xD;
                  prior to enrollment; or&#xD;
&#xD;
               -  a person less than 5 years of age with HIV-related immunodeficiency, defined as&#xD;
                  having a most recent CD4 T lymphocyte cell percentage less than 15. CD4 T&#xD;
                  lymphocyte percentage must have been measured within the 6 months prior to&#xD;
                  enrollment; or&#xD;
&#xD;
               -  a person who has received chemotherapy within the 12 months prior to enrollment.&#xD;
&#xD;
               -  Verbal report of CD4 T cell lymphocyte is sufficient documentation if the&#xD;
                  parent/guardian is confident of history.&#xD;
&#xD;
          -  Attends a daycare facility and shares a room with infants less than 6 months of age,&#xD;
             and parent/guardian is unable or unwilling to suspend daycare for 28 days following&#xD;
             inoculation.&#xD;
&#xD;
          -  Any of the following events at the time of enrollment:&#xD;
&#xD;
               -  fever (rectal temperature of greater than or equal to 100.4°F [38°C]), or&#xD;
&#xD;
               -  upper respiratory signs or symptoms (rhinorrhea, cough, or pharyngitis), or&#xD;
&#xD;
               -  nasal congestion significant enough to interfere with successful inoculation, or&#xD;
&#xD;
               -  otitis media.&#xD;
&#xD;
          -  Receipt of the following prior to enrollment:&#xD;
&#xD;
               -  any killed vaccine or live-attenuated rotavirus vaccine within the 14 days prior,&#xD;
                  or&#xD;
&#xD;
               -  any live vaccine, other than rotavirus vaccine, within the 28 days prior, or&#xD;
&#xD;
               -  another investigational vaccine or investigational drug within 28 days prior.&#xD;
&#xD;
          -  Scheduled administration of the following after planned inoculation:&#xD;
&#xD;
               -  killed vaccine within the 14 days after, or&#xD;
&#xD;
               -  any live vaccine other than rotavirus in the 28 days after, or&#xD;
&#xD;
               -  another investigational vaccine or drug in the 28 days after.&#xD;
&#xD;
          -  Receipt of immunoglobulin, any antibody products, or any blood products&#xD;
&#xD;
          -  Receipt of any of the following medications within 3 days of study enrollment:&#xD;
&#xD;
               -  systemic antibacterial, antiviral, antifungal, antiparasitic, or antituberculous&#xD;
                  agents, whether for treatment or prophylaxis, or&#xD;
&#xD;
               -  intranasal medications, or&#xD;
&#xD;
               -  other prescription medication except as listed below. Permitted concomitant&#xD;
                  medications (prescription or non-prescription) include nutritional supplements,&#xD;
                  medications for gastroesophageal reflux, eye drops, and topical medications,&#xD;
                  including (but not limited to) cutaneous (topical) steroids, topical antibiotics,&#xD;
                  and topical antifungal agents.&#xD;
&#xD;
          -  Receipt of salicylate (aspirin) or salicylate-containing products within the past&#xD;
             month&#xD;
&#xD;
          -  Born at less than 37 weeks gestation and less than 1 year of age at the time of&#xD;
             enrollment&#xD;
&#xD;
          -  Meets criteria for failure to thrive within the 6 months prior to enrollment: a&#xD;
             decline in height or weight growth that has crossed two major growth percentiles&#xD;
             (e.g., from above the 75th to below the 25th) in an interval of less than 6 months&#xD;
&#xD;
          -  Suspected or documented developmental disorder, delay, or other developmental problem&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>24 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Elizabeth McFarland, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Children's Hospital Colorado</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Usc La Nichd Crs</name>
      <address>
        <city>Alhambra</city>
        <state>California</state>
        <zip>91803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, UC San Diego CRS</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093-0672</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Univ. of Colorado Denver NICHD CRS</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush Univ. Cook County Hosp. Chicago NICHD CRS</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ann &amp; Robert H. Lurie Children's Hospital of Chicago (LCH) CRS</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60614-3393</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University Center for Immunization Research</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Jude Children's Research Hospital CRS</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105-3678</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2015</verification_date>
  <study_first_submitted>September 9, 2014</study_first_submitted>
  <study_first_submitted_qc>September 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2014</study_first_posted>
  <last_update_submitted>October 7, 2015</last_update_submitted>
  <last_update_submitted_qc>October 7, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 8, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Syncytial Virus Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02237209
org study id: IMPAACT 2000
secondary id: DAIDS ES
nct id: NCT02237209
lead sponsor: 
has dmc: Yes
Respiratory syncytial virus (RSV) is a common cause of illness in infants and children around
      the world. This study will evaluate the safety and immune response to an RSV vaccine in
      RSV-seronegative infants and children.

      This study is a companion study to CIR 291.
RSV is the most common viral cause of serious acute lower respiratory illness (LRI) in
      infants and children under 5 years of age in the world. RSV illness can range from mild upper
      respiratory tract illness (URI) to severe LRI, including bronchiolitis and pneumonia. Severe
      RSV disease in infancy may also predispose children to develop reactive airway disease during
      childhood. The purpose of this study is to evaluate the safety and immunogenicity of an RSV
      vaccine (RSV LID ΔM2-2) in RSV-seronegative infants and children at least 6 months and
      through 24 months of age.

      To determine study eligibility, the screening process will include a blood collection.
      Screening may begin after the RSV season (i.e., as of April 1) and enrollment must precede
      the RSV season (no later than October 14). At study entry, eligible participants will be
      randomly assigned to receive one dose of either the RSV vaccine or placebo, which will be
      delivered as nose drops. Participants will also undergo a review of medical history, clinical
      assessment, and a nasal wash. They will then receive their assigned vaccine and will remain
      under observation for monitoring for 30 minutes after receiving the vaccine. Additional study
      visits will occur at Days 3, 5, 7, 10, 12, 14, 17, 19, 21, 28, and 56. These visits will
      include clinical assessments and nasal washes; on Day 56, a blood collection will also occur.
      On days where no study visit is scheduled (through Day 29), participants' parents or
      guardians will report participants' temperatures and signs of illness to researchers by
      e-mail or phone.

      In October following vaccination, participants may have a pre-RSV season blood collection
      visit. During RSV season, November through March following vaccination, researchers will
      contact participants' parents or guardians on a weekly basis for follow-up monitoring. During
      this time frame, participants seen by a medical provider for fever, respiratory illness, or
      otitis media will have a study visit, which will include a nasal wash and clinical
      assessment. In April following vaccination, participants will undergo a final blood
      collection.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Frequency of vaccine-related solicited adverse events (AEs) that occur during the acute monitoring phase of the study, the first 28 days after inoculation
time frame: Measured through Day 28
measure: Severity of vaccine-related solicited AEs that occur during the acute monitoring phase of the study, the first 28 days after inoculation
time frame: Measured through Day 28
measure: Frequency of vaccine-related lower respiratory illness
time frame: Measured through Day 56
measure: Proportion of participants that develop 4-fold or greater rises in RSV-neutralizing antibody titer following vaccination
time frame: Measured through Day 56
description: Antibody responses to the RSV F glycoprotein will also be assessed by enzyme-linked immunosorbent assay (ELISA).
arm group label: RSV LID ΔM2-2 Vaccine
arm group type: Experimental
description: Participants will receive one dose of the RSV LID ΔM2-2 vaccine at study entry, delivered as nose drops.
arm group label: Placebo Vaccine
arm group type: Placebo Comparator
description: Participants will receive one dose of placebo at study entry, delivered as nose drops.
intervention type: Biological
intervention name: RSV LID ΔM2-2 Vaccine
description: 10^5.0 plaque forming units (PFU); 0.5 mL dose delivered as nose drops (approximately 0.25 mL per nostril)
arm group label: RSV LID ΔM2-2 Vaccine
intervention type: Biological
intervention name: Placebo Vaccine
description: 0.5 mL dose delivered as nose drops (approximately 0.25 mL per nostril)
arm group label: Placebo Vaccine
criteria: 
gender: All
minimum age: 6 Months
maximum age: 24 Months
healthy volunteers: Accepts Healthy Volunteers
last name: Elizabeth McFarland, MD
role: Study Chair
affiliation: Children's Hospital Colorado
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Respiratory Syncytial Virus Infections
mesh term: Vaccines