<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/NCT04444284</url>
  </required_header>
  <id_info>
    <org_study_id>MV-005</org_study_id>
    <nct_id>NCT04444284</nct_id>
  </id_info>
  <brief_title>Study of the Safety and Immunogenicity of an Intranasal Vaccine for Respiratory Syncytial Virus in Seropositive Children</brief_title>
  <official_title>A Randomized, Single-Blind, Placebo-Controlled, Dose-Escalation Phase 1b Study to Evaluate the Safety and Immunogenicity of an Intranasal Live Attenuated Respiratory Syncytial Virus (RSV) Vaccine in Seropositive Young Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Meissa Vaccines, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Meissa Vaccines, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates an investigational vaccine that is designed to protect humans against&#xD;
      infection with respiratory syncytial virus (RSV) and is administered as drops in the nose.&#xD;
      Specifically, the study analyzes the safety of, and the immune response to, the vaccine when&#xD;
      administered to healthy children between the ages of 15 and 59 months who are seropositive to&#xD;
      RSV.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 9, 2020</start_date>
  <completion_date type="Actual">May 7, 2021</completion_date>
  <primary_completion_date type="Actual">May 7, 2021</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>Sequential Assignment</intervention_model>
    <intervention_model_description>The first 15 enrolled participants will be assigned to Dosage Group 1 and be randomly allocated to receive either investigational vaccine at Dosage 1 or placebo. The Safety Monitoring Committee will subsequently review Dosage Group 1 safety data through Day 14, to allow dosage escalation. The next 15 enrolled participants will be assigned to Dosage Group 2 and be randomly allocated to receive investigational vaccine at Dosage 2 or placebo. The Safety Monitoring Committee will subsequently review Dosage Group 2 safety data through Day 14, to allow dosage escalation. The final group (Dosage Group 3) will consist of up to 12 enrolled participants who will be allocated to receive investigational vaccine at Dosage 3.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>The study is single-mask in 2 of the 3 dosage groups: study participants and their parent(s)/guardian(s) will not know their child's study assignment, whereas investigators, site staff, and site pharmacists will remain unmasked.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Solicited adverse events (AEs)</measure>
    <time_frame>Immediate post-vaccination period</time_frame>
    <description>Frequency of solicited AEs will be measured, categorized by severity. Solicited AEs are predefined AEs that may occur after investigational vaccine administration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Unsolicited AEs</measure>
    <time_frame>Immediate post-vaccination period</time_frame>
    <description>Frequency of unsolicited AEs will be measured, categorized by severity. Unsolicited AEs are any untoward medical occurrences in a participant administered the investigational vaccine, regardless of causal relationship to the investigational vaccine. Unsolicited AEs can include unfavorable and unintended signs (including abnormal laboratory findings), symptoms, or diseases temporally associated with the use of the investigational vaccine.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serious adverse events (SAEs)</measure>
    <time_frame>Full study duration, an average of 6 months</time_frame>
    <description>Frequency of SAEs will be measured, categorized by vaccine-relatedness. SAEs are AEs, whether considered causally related to the investigational vaccine or not, that threaten life or result in any of the following: death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or congenital anomaly/birth defect.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Medically attended adverse events (MAEs)</measure>
    <time_frame>Full study duration, an average of 6 months</time_frame>
    <description>Frequency of MAEs will be measured, categorized by vaccine-relatedness. MAEs are AEs, whether considered causally related to the investigational vaccine or not, with unscheduled medically attended visits, such as urgent care visits, acute primary care visits, emergency department visits, or other previously unplanned visits to a medical provider. Scheduled medical visits such as routine physicals, wellness checks, 'check-ups', and vaccinations, are not considered MAEs.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in serum RSV-specific neutralizing antibody titers</measure>
    <time_frame>Baseline through Day 28, an average of six (6) weeks</time_frame>
    <description>Change in serum RSV-specific neutralizing antibody (nAb) titers will be measured per participant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum binding (RSV F-specific) antibody titers</measure>
    <time_frame>Baseline through Day 28, an average of six (6) weeks</time_frame>
    <description>Change in serum binding (RSV F-specific) antibody titers will be measured per participant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in nasal mucosal binding (RSV F-specific) antibody titers</measure>
    <time_frame>Baseline through Day 28, an average of six (6) weeks</time_frame>
    <description>Change in mucosal binding (RSV F-specific) antibody titers will be measured per participant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Potential vaccine virus shedding: frequency</measure>
    <time_frame>Baseline through Day 28, an average of four (4) weeks</time_frame>
    <description>Frequency of any post-vaccination shedding of vaccine virus (as detected by viral culture) will be measured per dosage group and overall.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Potential vaccine virus shedding: magnitude</measure>
    <time_frame>Baseline through Day 28, an average of four (4) weeks</time_frame>
    <description>If post-vaccination shedding of vaccine virus is detected by culture, peak viral titer (measured in plaque forming units, PFU) will be measured per dosage group and overall.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Potential vaccine virus shedding: duration</measure>
    <time_frame>Baseline through Day 28, an average of four (4) weeks</time_frame>
    <description>If post-vaccination shedding of vaccine virus is detected by culture, duration of shedding (in days) will be measured per dosage group and overall.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Respiratory Syncytial Virus Infections</condition>
  <arm_group>
    <arm_group_label>Dosage Group 1: RSV Vaccine Dosage 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this arm will receive a single intranasal dose of the investigational RSV vaccine at Dosage 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dosage Group 1: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants in this arm will receive a single intranasal dose of placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dosage Group 2: RSV Vaccine Dosage 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this arm will receive a single intranasal dose of the investigational RSV vaccine at Dosage 2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dosage Group 2: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants in this arm will receive a single intranasal dose of placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dosage Group 3: RSV Vaccine Dosage 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this arm will receive a single intranasal dose of the investigational RSV vaccine at Dosage 3.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Investigational RSV vaccine MV-012-968 (Dosage 1)</intervention_name>
    <description>Single dose administered intranasally on Day 1</description>
    <arm_group_label>Dosage Group 1: RSV Vaccine Dosage 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Investigational RSV vaccine MV-012-968 (Dosage 2)</intervention_name>
    <description>Single dose administered intranasally on Day 1</description>
    <arm_group_label>Dosage Group 2: RSV Vaccine Dosage 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Single dose administered intranasally on Day 1</description>
    <arm_group_label>Dosage Group 1: Placebo</arm_group_label>
    <arm_group_label>Dosage Group 2: Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Investigational RSV vaccine MV-012-968 (Dosage 3)</intervention_name>
    <description>Single dose administered intranasally on Day 1</description>
    <arm_group_label>Dosage Group 3: RSV Vaccine Dosage 3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          1. Children aged 15-59 months&#xD;
&#xD;
          2. Good health based on history, physical examination and medical record review, without&#xD;
             evidence or suspicion of chronic disease&#xD;
&#xD;
          3. Seropositive to RSV, as defined by serum neutralizing antibody titer above the&#xD;
             threshold described in the study Analytical Plan&#xD;
&#xD;
          4. Written informed consent provided by parent(s)/guardian(s)&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          1. Known or suspected chronic illness, particularly cardiopulmonary (including asthma or&#xD;
             reactive airways disease), metabolic, hepatic, renal, or infectious (including&#xD;
             recurrent or chronic sinusitis)&#xD;
&#xD;
          2. Known or suspected immunodeficiency&#xD;
&#xD;
          3. Household or close contact with anyone ≤ 6 months of age or with immunocompromised&#xD;
             individual(s)&#xD;
&#xD;
          4. Nasal obstruction (including due to anatomic/structural causes, acute or chronic&#xD;
             rhinosinusitis, or other causes)&#xD;
&#xD;
          5. Receipt of immunoglobulins, monoclonal antibodies and/or any blood products, or&#xD;
             ribavirin within 3 months prior to study inoculation, or planned during study period&#xD;
&#xD;
          6. Receipt of an investigational RSV vaccine at any time&#xD;
&#xD;
          7. Any other condition that, in the judgment of the investigator, would be a risk to&#xD;
             participant's safety and/or may interfere with study procedures or interpretation of&#xD;
             results&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>15 Months</minimum_age>
    <maximum_age>59 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Oliver Medzihradsky, MD MPH MS</last_name>
    <role>Study Director</role>
    <affiliation>Meissa Vaccines, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Meridian Clinical Research</name>
      <address>
        <city>Norfolk</city>
        <state>Nebraska</state>
        <zip>68701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Meridian Clinical Research</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68134</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Stobart CC, Rostad CA, Ke Z, Dillard RS, Hampton CM, Strauss JD, Yi H, Hotard AL, Meng J, Pickles RJ, Sakamoto K, Lee S, Currier MG, Moin SM, Graham BS, Boukhvalova MS, Gilbert BE, Blanco JC, Piedra PA, Wright ER, Moore ML. A live RSV vaccine with engineered thermostability is immunogenic in cotton rats despite high attenuation. Nat Commun. 2016 Dec 21;7:13916. doi: 10.1038/ncomms13916.</citation>
    <PMID>28000669</PMID>
  </results_reference>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>June 12, 2020</study_first_submitted>
  <study_first_submitted_qc>June 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>June 26, 2021</last_update_submitted>
  <last_update_submitted_qc>June 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 29, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Live attenuated vaccine</keyword>
  <keyword>Safety</keyword>
  <keyword>Immunogenicity</keyword>
  <keyword>Phase 1 clinical trial</keyword>
  <keyword>Pediatric</keyword>
  <keyword>Seropositive</keyword>
  <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/NCT04444284
org study id: MV-005
nct id: NCT04444284
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study evaluates an investigational vaccine that is designed to protect humans against
      infection with respiratory syncytial virus (RSV) and is administered as drops in the nose.
      Specifically, the study analyzes the safety of, and the immune response to, the vaccine when
      administered to healthy children between the ages of 15 and 59 months who are seropositive to
      RSV.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: The first 15 enrolled participants will be assigned to Dosage Group 1 and be randomly allocated to receive either investigational vaccine at Dosage 1 or placebo. The Safety Monitoring Committee will subsequently review Dosage Group 1 safety data through Day 14, to allow dosage escalation. The next 15 enrolled participants will be assigned to Dosage Group 2 and be randomly allocated to receive investigational vaccine at Dosage 2 or placebo. The Safety Monitoring Committee will subsequently review Dosage Group 2 safety data through Day 14, to allow dosage escalation. The final group (Dosage Group 3) will consist of up to 12 enrolled participants who will be allocated to receive investigational vaccine at Dosage 3.
primary purpose: Prevention
masking: Single (Participant)
masking description: The study is single-mask in 2 of the 3 dosage groups: study participants and their parent(s)/guardian(s) will not know their child's study assignment, whereas investigators, site staff, and site pharmacists will remain unmasked.
measure: Solicited adverse events (AEs)
time frame: Immediate post-vaccination period
description: Frequency of solicited AEs will be measured, categorized by severity. Solicited AEs are predefined AEs that may occur after investigational vaccine administration
measure: Unsolicited AEs
time frame: Immediate post-vaccination period
description: Frequency of unsolicited AEs will be measured, categorized by severity. Unsolicited AEs are any untoward medical occurrences in a participant administered the investigational vaccine, regardless of causal relationship to the investigational vaccine. Unsolicited AEs can include unfavorable and unintended signs (including abnormal laboratory findings), symptoms, or diseases temporally associated with the use of the investigational vaccine.
measure: Serious adverse events (SAEs)
time frame: Full study duration, an average of 6 months
description: Frequency of SAEs will be measured, categorized by vaccine-relatedness. SAEs are AEs, whether considered causally related to the investigational vaccine or not, that threaten life or result in any of the following: death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or congenital anomaly/birth defect.
measure: Medically attended adverse events (MAEs)
time frame: Full study duration, an average of 6 months
description: Frequency of MAEs will be measured, categorized by vaccine-relatedness. MAEs are AEs, whether considered causally related to the investigational vaccine or not, with unscheduled medically attended visits, such as urgent care visits, acute primary care visits, emergency department visits, or other previously unplanned visits to a medical provider. Scheduled medical visits such as routine physicals, wellness checks, 'check-ups', and vaccinations, are not considered MAEs.
measure: Change in serum RSV-specific neutralizing antibody titers
time frame: Baseline through Day 28, an average of six (6) weeks
description: Change in serum RSV-specific neutralizing antibody (nAb) titers will be measured per participant.
measure: Change in serum binding (RSV F-specific) antibody titers
time frame: Baseline through Day 28, an average of six (6) weeks
description: Change in serum binding (RSV F-specific) antibody titers will be measured per participant.
measure: Change in nasal mucosal binding (RSV F-specific) antibody titers
time frame: Baseline through Day 28, an average of six (6) weeks
description: Change in mucosal binding (RSV F-specific) antibody titers will be measured per participant.
measure: Potential vaccine virus shedding: frequency
time frame: Baseline through Day 28, an average of four (4) weeks
description: Frequency of any post-vaccination shedding of vaccine virus (as detected by viral culture) will be measured per dosage group and overall.
measure: Potential vaccine virus shedding: magnitude
time frame: Baseline through Day 28, an average of four (4) weeks
description: If post-vaccination shedding of vaccine virus is detected by culture, peak viral titer (measured in plaque forming units, PFU) will be measured per dosage group and overall.
measure: Potential vaccine virus shedding: duration
time frame: Baseline through Day 28, an average of four (4) weeks
description: If post-vaccination shedding of vaccine virus is detected by culture, duration of shedding (in days) will be measured per dosage group and overall.
arm group label: Dosage Group 1: RSV Vaccine Dosage 1
arm group type: Experimental
description: Participants in this arm will receive a single intranasal dose of the investigational RSV vaccine at Dosage 1.
arm group label: Dosage Group 1: Placebo
arm group type: Placebo Comparator
description: Participants in this arm will receive a single intranasal dose of placebo.
arm group label: Dosage Group 2: RSV Vaccine Dosage 2
arm group type: Experimental
description: Participants in this arm will receive a single intranasal dose of the investigational RSV vaccine at Dosage 2.
arm group label: Dosage Group 2: Placebo
arm group type: Placebo Comparator
description: Participants in this arm will receive a single intranasal dose of placebo.
arm group label: Dosage Group 3: RSV Vaccine Dosage 3
arm group type: Experimental
description: Participants in this arm will receive a single intranasal dose of the investigational RSV vaccine at Dosage 3.
intervention type: Biological
intervention name: Investigational RSV vaccine MV-012-968 (Dosage 1)
description: Single dose administered intranasally on Day 1
arm group label: Dosage Group 1: RSV Vaccine Dosage 1
intervention type: Biological
intervention name: Investigational RSV vaccine MV-012-968 (Dosage 2)
description: Single dose administered intranasally on Day 1
arm group label: Dosage Group 2: RSV Vaccine Dosage 2
intervention type: Other
intervention name: Placebo
description: Single dose administered intranasally on Day 1
arm group label: Dosage Group 1: Placebo
arm group label: Dosage Group 2: Placebo
intervention type: Biological
intervention name: Investigational RSV vaccine MV-012-968 (Dosage 3)
description: Single dose administered intranasally on Day 1
arm group label: Dosage Group 3: RSV Vaccine Dosage 3
criteria: 
gender: All
minimum age: 15 Months
maximum age: 59 Months
healthy volunteers: Accepts Healthy Volunteers
last name: Oliver Medzihradsky, MD MPH MS
role: Study Director
affiliation: Meissa Vaccines, Inc.
facility: 
facility: 
facility: 
country: United States
citation: Stobart CC, Rostad CA, Ke Z, Dillard RS, Hampton CM, Strauss JD, Yi H, Hotard AL, Meng J, Pickles RJ, Sakamoto K, Lee S, Currier MG, Moin SM, Graham BS, Boukhvalova MS, Gilbert BE, Blanco JC, Piedra PA, Wright ER, Moore ML. A live RSV vaccine with engineered thermostability is immunogenic in cotton rats despite high attenuation. Nat Commun. 2016 Dec 21;7:13916. doi: 10.1038/ncomms13916.
PMID: 28000669
responsible party type: Sponsor
mesh term: Respiratory Syncytial Virus Infections
mesh term: Vaccines