<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/NCT02247726</url>
  </required_header>
  <id_info>
    <org_study_id>RSV-M-203</org_study_id>
    <nct_id>NCT02247726</nct_id>
  </id_info>
  <brief_title>RSV F Vaccine Maternal Immunization Study in Healthy Third-trimester Pregnant Women.</brief_title>
  <official_title>A Phase II Randomized, Observer-Blind, Placebo-Controlled, Study to Evaluate the Safety and Immunogenicity of a Respiratory Syncytial Virus (RSV) F Nanoparticle Vaccine With Aluminum, in Healthy Third-trimester Pregnant Women and to Assess the Impact of Maternal Immunization on Infant Safety Through One Year of Life</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novavax</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novavax</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety and immunogenicity of an RSV-F protein&#xD;
      nanoparticle vaccine, with aluminum, in healthy third-trimester pregnant women and to assess&#xD;
      the impact of maternal immunization on infant safety through one year of life.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">July 2016</completion_date>
  <primary_completion_date type="Actual">July 2016</primary_completion_date>
  <phase>Phase 2</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Counts and percentage of subjects with solicited injection site and systemic reactogenicity within seven days of vaccination.</measure>
    <time_frame>Day 0 to Day D+180</time_frame>
    <description>In Maternal Subjects</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Counts and percentage of subjects with unsolicited (local and systemic) adverse events (AE), unscheduled medically-attended adverse events (MAEs), and serious adverse events (SAEs) through delivery and six (6) months thereafter.</measure>
    <time_frame>Day 0 to Day D+180</time_frame>
    <description>In Maternal Subjects</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical safety laboratory assessments of select serum chemistry and hematology parameters through delivery.</measure>
    <time_frame>Screening to Day 14</time_frame>
    <description>In Maternal Subjects</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Counts and percentage of subjects with post-immunization onset of specific complications of third-trimester pregnancy and delivery</measure>
    <time_frame>Day 0 to Day 28 - 42</time_frame>
    <description>In Maternal Subjects</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Counts and percentage of term healthy infants appropriate for gestational age.</measure>
    <time_frame>Day 28 - 42</time_frame>
    <description>In Infant subjects</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neonatal SAEs (including congenital anomalies, respiratory failure, fever/infection, and neonatal death or other adverse events/complications that necessitate extended hospitalization).</measure>
    <time_frame>Birth to Day 365</time_frame>
    <description>In Infant Subjects</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Growth and development over one year</measure>
    <time_frame>Birth to Day Day 365</time_frame>
    <description>In Infant Subjects</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Counts and proportion of infants with unsolicited adverse events</measure>
    <time_frame>Birth to Day 365</time_frame>
    <description>In Infant Subjects</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Counts and proportions of infants with medically-attended RSV lower respiratory tract infection (LRTI), and age of onset of those infections.</measure>
    <time_frame>Birth to Day 365</time_frame>
    <description>In Infant Subjects</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity as assessed by serum IgG antibody titers specific fro the F-Protein antigen.</measure>
    <time_frame>Birth to Day 180</time_frame>
    <description>In Infant Subjects</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum antibody titers inhibiting binding of labeled palivizumab to RSV F protein.</measure>
    <time_frame>Birth to Day 180</time_frame>
    <description>In Infant Subjects</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum microneutralization (MN) titers against RSV/A and B.previously referenced, but based on GMT.</measure>
    <time_frame>Birth to Day 180</time_frame>
    <description>In Infant Subjects</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Counts and proportions of maternal subjects with RSV-related respiratory illness as detected by active and passive surveillance.</measure>
    <time_frame>Day 0 to Day 180</time_frame>
    <description>In Maternal Subjects</description>
  </other_outcome>
  <other_outcome>
    <measure>Counts and proportions of infants with non-medically attended RSV-related respiratory illness as detected by active and passive surveillance.</measure>
    <time_frame>Birth to Day 365</time_frame>
    <description>In Infant Subjects</description>
  </other_outcome>
  <other_outcome>
    <measure>Counts and proportions of infants with medically attended, non-RSV LRTI as assessed by multiplex real time (RT)-PCR.</measure>
    <time_frame>Birth to Day 365</time_frame>
    <description>In Infant Subjects</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Respiratory Syncytial Virus Infections</condition>
  <arm_group>
    <arm_group_label>Treatment Group A</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Saline Placebo (0.5mL injection)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Group B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>RSV F vaccine with adjuvant (0.5mL injection)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline Placebo (0.5mL injection)</intervention_name>
    <arm_group_label>Treatment Group A</arm_group_label>
    <other_name>0.9% Sodium Choloride</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RSV F vaccine (0.5mL injection)</intervention_name>
    <arm_group_label>Treatment Group B</arm_group_label>
    <other_name>RSV F Protein with Aluminum adjuvant</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Pregnant women must meet all of the following criteria to be eligible to participate:&#xD;
&#xD;
          1. ≥18 and ≤40 years-of-age.&#xD;
&#xD;
          2. Singleton pregnancy of 33 to 35 weeks gestation on the day of planned vaccination.&#xD;
&#xD;
          3. Good general maternal health as demonstrated by:&#xD;
&#xD;
               -  Medical history (including history of adverse reactions to prior vaccines and&#xD;
                  allergies).&#xD;
&#xD;
               -  Physical examination including at least vital signs (blood pressure, pulse,&#xD;
                  respirations, and oral temperature); weight; height; examination of the HEENT,&#xD;
                  cardiovascular, pulmonary, gastrointestinal (abdominal), musculoskeletal,&#xD;
                  lymphatic, and dermatologic organ systems; and documentation of fetal heart&#xD;
                  tones.&#xD;
&#xD;
               -  Clinical laboratory parameters including normal blood urea nitrogen, creatinine,&#xD;
                  ALT, AST, total bilirubin, alkaline phosphatase (ALP), hemoglobin, white blood&#xD;
                  count, and platelet count; and serologic exclusion of infection with hepatitis B&#xD;
                  (HBV) and C (HCV) viruses and HIV (as required). Note that normal ranges for&#xD;
                  vital signs and clinical laboratory parameters will be based on third trimester&#xD;
                  values published in Sheffield et al. [2013] and/or reference ranges for the third&#xD;
                  trimester of pregnancy of the central laboratory.&#xD;
&#xD;
          4. Documentation that fulfills one of the following:&#xD;
&#xD;
               -  Detailed (level II) second trimester or later anatomic ultrasound with no&#xD;
                  significant anatomic or growth abnormalities identified; OR&#xD;
&#xD;
               -  Routine second trimester or later ultrasound with no significant anatomic or&#xD;
                  growth abnormalities identified, PLUS at least one of the following:&#xD;
&#xD;
                    -  Normal first trimester screening (based on ultrasound + serum analytes); or&#xD;
&#xD;
                    -  Normal cell-free fetal DNA; or&#xD;
&#xD;
                    -  Normal chorionic villus sampling (CVS) or amniocentesis; or&#xD;
&#xD;
                    -  Normal second trimester maternal serum quadruple screen; or&#xD;
&#xD;
                    -  Normal first and second trimester screening using integrated, sequential, or&#xD;
                       contingency approach; or&#xD;
&#xD;
                    -  Abnormal first or second trimester screening followed by normal CVS,&#xD;
                       amniocentesis, or cell-free fetal DNA.&#xD;
&#xD;
          5. Able to understand, and both willing and physically able to comply with study&#xD;
             procedures. This includes anticipation of reasonable geographic proximity to the study&#xD;
             clinic and adequate transportation to comply with scheduled and unscheduled study&#xD;
             follow-up visits.&#xD;
&#xD;
          6. Able and willing to provide written informed consent for themselves and infant.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Pregnant women will be excluded if there is historical, physical examination, or laboratory&#xD;
        evidence of any of the following criteria:&#xD;
&#xD;
          1. Symptomatic cardiac or pulmonary disease requiring chronic drug therapy, including&#xD;
             hypertension and asthma. Asthma will be exclusionary if the subject is receiving&#xD;
             chronic systemic glucocorticoids at any dose or inhaled glucocorticoids at any dose&#xD;
             &gt;500µg per day of beclamethasone or fluticasone, or &gt;800μg per day of budesonide.&#xD;
&#xD;
          2. Pre-pregnancy body mass index (BMI) of ≥35 or &lt;18.5.&#xD;
&#xD;
          3. Hemoglobinopathy (including known sickle trait or thalassemias, even if asymptomatic)&#xD;
             or blood dyscrasias.&#xD;
&#xD;
          4. Hepatic or renal dysfunction.&#xD;
&#xD;
          5. Established diagnosis of seizure disorder, regardless of therapy.&#xD;
&#xD;
          6. Auto-immune disease or known immunodeficiency syndrome.&#xD;
&#xD;
          7. Endocrine disorders, including (but not limited to) hyperthyroidism, untreated&#xD;
             hypothyroidism, and glucose intolerance (e.g., diabetes mellitus type 1 or 2)&#xD;
             antedating pregnancy, or occurring during pregnancy and requiring interventions other&#xD;
             than diet for control.&#xD;
&#xD;
          8. History of major gynecologic or major abdominal surgery, including bariatric surgery.&#xD;
&#xD;
          9. Known HIV, HBV, or HCV infection, as assessed by serologic tests conducted during the&#xD;
             current pregnancy or as a procedure during the screening period of the study.&#xD;
&#xD;
         10. Primary genital herpes simplex (HSV) infection during the current pregnancy.&#xD;
&#xD;
         11. Current alcohol or drug abuse.&#xD;
&#xD;
         12. Documentation that current pregnancy results from fertility treatments, rape, or&#xD;
             incest.&#xD;
&#xD;
         13. Documentation that the infant will be a ward of the state or be released for adoption.&#xD;
&#xD;
         14. Neuro-psychiatric illness deemed likely to interfere with protocol compliance, safety&#xD;
             reporting, or receipt of pre-natal care; or requiring treatment with psychotropic&#xD;
             drugs.&#xD;
&#xD;
         15. History/presence of deep venous thrombosis or thromboembolism, or the use of&#xD;
             anticoagulants during pregnancy.&#xD;
&#xD;
         16. Untreated red blood cell allo-immunization.&#xD;
&#xD;
         17. Prior stillbirth or neonatal death, or multiple (≥3) spontaneous abortions.&#xD;
&#xD;
         18. Prior preterm delivery ≤34 weeks gestation or having ongoing intervention&#xD;
             (medical/surgical) in current pregnancy to prevent preterm birth.&#xD;
&#xD;
         19. Greater than five (5) prior deliveries.&#xD;
&#xD;
         20. Previous infant with a known genetic disorder or major congenital anomaly.&#xD;
&#xD;
         21. Receipt of investigational drugs or immune globulins (with the exception of&#xD;
             prophylactic anti-Rho D immune globulin) within six (6) months prior to the&#xD;
             administration of the study vaccine.&#xD;
&#xD;
         22. Chronic administration (defined as more than 14 continuous days) of immunosuppressants&#xD;
             or other immune-modifying drugs within 6 months prior to the administration of the&#xD;
             study vaccine. An immunosuppressant dose of glucocorticoid will be defined as a&#xD;
             systemic dose ≥10mg of prednisone per day or equivalent. The use of topical, inhaled,&#xD;
             and nasal glucocorticoids will be permitted except for the limit established in&#xD;
             exclusion criterion #1.&#xD;
&#xD;
         23. Any other physical, psychiatric or social condition which may, in the investigator's&#xD;
             opinion, increase the risks of study participation to the maternal subject or the&#xD;
             fetus/infant; or may lead to the collection of incomplete or inaccurate safety data.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Development</last_name>
    <role>Study Director</role>
    <affiliation>Novavax, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Advanced Specialty Research</name>
      <address>
        <city>Nampa</city>
        <state>Idaho</state>
        <zip>83687</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hutchinson Clinic, P.A.</name>
      <address>
        <city>Hutchinson</city>
        <state>Kansas</state>
        <zip>67502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Medical Center Research Institute</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <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>Duke University</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Magee- Womens Hospital of UPMC</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://novavax.com</url>
    <description>Novavax, Inc.</description>
  </link>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>September 16, 2014</study_first_submitted>
  <study_first_submitted_qc>September 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <disposition_first_submitted>May 30, 2017</disposition_first_submitted>
  <disposition_first_submitted_qc>May 30, 2017</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">June 6, 2017</disposition_first_posted>
  <last_update_submitted>May 25, 2022</last_update_submitted>
  <last_update_submitted_qc>May 25, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>RSV</keyword>
  <keyword>Third Trimester</keyword>
  <keyword>Maternal Immunization</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Syncytial Virus Infections</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT02247726
org study id: RSV-M-203
nct id: NCT02247726
lead sponsor: 
has dmc: Yes
The purpose of this study is to evaluate the safety and immunogenicity of an RSV-F protein
      nanoparticle vaccine, with aluminum, in healthy third-trimester pregnant women and to assess
      the impact of maternal immunization on infant safety through one year of life.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Counts and percentage of subjects with solicited injection site and systemic reactogenicity within seven days of vaccination.
time frame: Day 0 to Day D+180
description: In Maternal Subjects
measure: Counts and percentage of subjects with unsolicited (local and systemic) adverse events (AE), unscheduled medically-attended adverse events (MAEs), and serious adverse events (SAEs) through delivery and six (6) months thereafter.
time frame: Day 0 to Day D+180
description: In Maternal Subjects
measure: Clinical safety laboratory assessments of select serum chemistry and hematology parameters through delivery.
time frame: Screening to Day 14
description: In Maternal Subjects
measure: Counts and percentage of subjects with post-immunization onset of specific complications of third-trimester pregnancy and delivery
time frame: Day 0 to Day 28 - 42
description: In Maternal Subjects
measure: Counts and percentage of term healthy infants appropriate for gestational age.
time frame: Day 28 - 42
description: In Infant subjects
measure: Neonatal SAEs (including congenital anomalies, respiratory failure, fever/infection, and neonatal death or other adverse events/complications that necessitate extended hospitalization).
time frame: Birth to Day 365
description: In Infant Subjects
measure: Growth and development over one year
time frame: Birth to Day Day 365
description: In Infant Subjects
measure: Counts and proportion of infants with unsolicited adverse events
time frame: Birth to Day 365
description: In Infant Subjects
measure: Counts and proportions of infants with medically-attended RSV lower respiratory tract infection (LRTI), and age of onset of those infections.
time frame: Birth to Day 365
description: In Infant Subjects
measure: Immunogenicity as assessed by serum IgG antibody titers specific fro the F-Protein antigen.
time frame: Birth to Day 180
description: In Infant Subjects
measure: Serum antibody titers inhibiting binding of labeled palivizumab to RSV F protein.
time frame: Birth to Day 180
description: In Infant Subjects
measure: Serum microneutralization (MN) titers against RSV/A and B.previously referenced, but based on GMT.
time frame: Birth to Day 180
description: In Infant Subjects
measure: Counts and proportions of maternal subjects with RSV-related respiratory illness as detected by active and passive surveillance.
time frame: Day 0 to Day 180
description: In Maternal Subjects
measure: Counts and proportions of infants with non-medically attended RSV-related respiratory illness as detected by active and passive surveillance.
time frame: Birth to Day 365
description: In Infant Subjects
measure: Counts and proportions of infants with medically attended, non-RSV LRTI as assessed by multiplex real time (RT)-PCR.
time frame: Birth to Day 365
description: In Infant Subjects
arm group label: Treatment Group A
arm group type: Placebo Comparator
description: Saline Placebo (0.5mL injection)
arm group label: Treatment Group B
arm group type: Experimental
description: RSV F vaccine with adjuvant (0.5mL injection)
intervention type: Drug
intervention name: Saline Placebo (0.5mL injection)
arm group label: Treatment Group A
other name: 0.9% Sodium Choloride
intervention type: Drug
intervention name: RSV F vaccine (0.5mL injection)
arm group label: Treatment Group B
other name: RSV F Protein with Aluminum adjuvant
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Clinical Development
role: Study Director
affiliation: Novavax, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://novavax.com
description: Novavax, Inc.
responsible party type: Sponsor
mesh term: Respiratory Syncytial Virus Infections