<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/NCT03232567</url>
  </required_header>
  <id_info>
    <org_study_id>ALT103-201</org_study_id>
    <nct_id>NCT03232567</nct_id>
  </id_info>
  <brief_title>Single-ascending-dose Study of the Safety and Immunogenicity of NasoVAX</brief_title>
  <official_title>Single-ascending-dose Study of the Safety and Immunogenicity of NasoVAX</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Altimmune, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Altimmune, Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 2a, randomized, double-blind, placebo-controlled trial to evaluate the safety&#xD;
      and immunogenicity of NasoVAX in healthy adults 18 to 49 years of age. Subjects will be&#xD;
      screened within 28 days of randomization (Day 1).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 2a, randomized, double-blind, placebo-controlled trial to evaluate the safety&#xD;
      and immunogenicity of NasoVAX in healthy adults 18 to 49 years of age. Subjects will be&#xD;
      screened within 28 days of randomization (Day 1). Approximately 60 subjects who meet all&#xD;
      inclusion and no exclusion criteria and provide written informed consent will be enrolled&#xD;
      into 3 sequential cohorts of 20 subjects each defined by the viral particle dose (1×10(9th),&#xD;
      1×10(10th), and 1×10(11th) vp). Within each cohort and its sentinel group, subjects will be&#xD;
      randomized in a 3:1 ratio to receive 1 intranasal dose of NasoVAX or placebo (Day 1). A&#xD;
      sentinel group of 5 subjects from each cohort will be dosed and followed through Day 8.&#xD;
      Dosing of the remainder of each cohort may proceed if no events meeting stopping criteria&#xD;
      have occurred. The SRC, consisting of the Investigator, the Medical Monitor, and a Sponsor&#xD;
      Representative, will review AE, reactogenicity, and laboratory data through Day 8 for all&#xD;
      subjects in each cohort before subjects are randomized to the next higher dose. If any event&#xD;
      meeting stopping criteria occur, the SRC will review all available safety information before&#xD;
      additional patients are dosed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 18, 2017</start_date>
  <completion_date type="Actual">June 15, 2018</completion_date>
  <primary_completion_date type="Actual">March 7, 2018</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>Sequential Assignment</intervention_model>
    <intervention_model_description>Single ascending dose study</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Treatment-Emergent Adverse Events in Participants [Safety and Tolerability]</measure>
    <time_frame>Day 1 to Day 181</time_frame>
    <description>Adverse events (AEs): counts and percentages of subjects with AEs Day 1 to day 29 and Medically attended AEs (MAEs), serious AEs (SAEs), new-onset chronic illnesses (NCIs) from Day 1 to Day 181</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Treatment-Emergent Reactogenicity Events in Participants [Safety and Tolerability]</measure>
    <time_frame>14-days after vaccination</time_frame>
    <description>Reactogenicity: counts and percentages of subjects with 'yes' to any reactogenicity event (nasal irritation, sneezing, nasal congestion, sore throat, change in smell, change in taste, change in vision, eye pain, headache, fatigue, muscle ache, nausea, vomiting, diarrhea, chills, fever)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>HAI Immune Response</measure>
    <time_frame>Day 1 to Day 181</time_frame>
    <description>Antibody level measured by hemagglutination inhibition (HAI) in serum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microneutralization Immune Response</measure>
    <time_frame>Day 1 to Day 181</time_frame>
    <description>Antibody level measured by microneutralization in serum</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Influenza</condition>
  <arm_group>
    <arm_group_label>NasoVAX low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NasoVAX administered by intranasal spray at a single dose of 1×10(9th) viral particles (vp) versus placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NasoVAX medium dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NasoVAX administered by intranasal spray at a single dose of 1×10(10th) viral particles (vp) versus placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NasoVAX high dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NasoVAX administered by intranasal spray at a single dose of 1×10(11th) viral particles (vp) versus placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Normal saline administered by intranasal spray at a single dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>NasoVAX</intervention_name>
    <description>Single ascending dose study</description>
    <arm_group_label>NasoVAX high dose</arm_group_label>
    <arm_group_label>NasoVAX low dose</arm_group_label>
    <arm_group_label>NasoVAX medium dose</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Subjects who meet all of the following criteria may be included in the study:&#xD;
&#xD;
          1. Men and women 18 to 49 years of age, inclusive&#xD;
&#xD;
          2. Good general health status as determined by the Investigator&#xD;
&#xD;
          3. Adequate venous access for repeated phlebotomies&#xD;
&#xD;
          4. Screening laboratory results within institutional normal range or Grade 1 elevation if&#xD;
             the Investigator documents clinical insignificance. Creatine kinase or bilirubin may&#xD;
             be Grade 2 if associated with normal alanine aminotransferase (ALT) and aspartate&#xD;
             aminotransferase (AST) and the Investigator considers the result not to be clinically&#xD;
             significant due to vigorous exercise or Gilbert's syndrome&#xD;
&#xD;
          5. Negative drug and alcohol screen at Screening and predose on Day 1&#xD;
&#xD;
          6. For women who have not been surgically sterilized or have laboratory confirmation of&#xD;
             postmenopausal status, negative pregnancy test&#xD;
&#xD;
          7. Willingness to practice a highly effective method of contraception that may include,&#xD;
             but is not limited to, abstinence, sex only with persons of the same sex, monogamous&#xD;
             relationship with a postmenopausal partner, monogamous relationship with vasectomized&#xD;
             partner, vasectomy, surgical sterilization (hysterectomy, or bilateral tubal ligation,&#xD;
             salpingectomy, or oophorectomy), licensed hormonal methods, intrauterine device (IUD),&#xD;
             or consistent use of a barrier method (eg, condom, diaphragm) with spermicide for 28&#xD;
             days after the NasoVAX/placebo dose&#xD;
&#xD;
          8. Willingness to participate and comply with all aspects of the study through the entire&#xD;
             study period, including nasopharyngeal swabs and blood and urine samples&#xD;
&#xD;
          9. Provision of written informed consent&#xD;
&#xD;
        Subjects who meet any of the following criteria will be excluded from the study:&#xD;
&#xD;
          1. Pregnant, possibly pregnant, or lactating women&#xD;
&#xD;
          2. Household contacts of pregnant women, children &lt; 5 years of age, or immunocompromised&#xD;
             individuals for the period up through 2 weeks postvaccination&#xD;
&#xD;
          3. Persons who care for pregnant women, children &lt; 5 years of age, or immunocompromised&#xD;
             individuals for the period up through 2 weeks postvaccination&#xD;
&#xD;
          4. Body mass index &gt; 35.0 kg/m2&#xD;
&#xD;
          5. Positive results for HIV, hepatitis B virus, or hepatitis C virus at Screening&#xD;
&#xD;
          6. Asthma or other chronic lung disease that is greater than mild in severity.&#xD;
             Specifically excluded are participants with the any of the following events in the&#xD;
             past year:&#xD;
&#xD;
               -  Daily symptoms&#xD;
&#xD;
               -  Daily use of short acting beta 2 agonists&#xD;
&#xD;
               -  Use of inhaled steroids or theophylline&#xD;
&#xD;
               -  Use of pulse systemic steroids&#xD;
&#xD;
               -  Emergency care or hospitalization related to asthma or other chronic lung disease&#xD;
&#xD;
               -  Systemic steroids for asthma exacerbation&#xD;
&#xD;
          7. History of diabetes mellitus (gestational diabetes is allowed if treatment was not&#xD;
             required postpartum and serum glucose is currently in the normal range)&#xD;
&#xD;
          8. History of coronary artery disease, arrhythmia, or congestive heart failure&#xD;
&#xD;
          9. Clinically significant ECG abnormality as determined by the Investigator&#xD;
&#xD;
         10. Poorly controlled hypertension (systolic blood pressure &gt; 150 mmHg or diastolic blood&#xD;
             pressure &gt; 95 mmHg) at Screening or predose on Day 1&#xD;
&#xD;
         11. History of anaphylaxis or angioedema&#xD;
&#xD;
         12. Known allergy to any of the ingredients in the vaccine formulation&#xD;
&#xD;
         13. History of chronic rhinitis, nasal septal defect, cleft palate, nasal polyps, or other&#xD;
             nasal abnormality that might affect vaccine administration&#xD;
&#xD;
         14. Previous nasal surgery or nasal cauterization&#xD;
&#xD;
         15. Any symptoms of upper respiratory infection or temperature &gt; 38°C within 3 days before&#xD;
             Day 1&#xD;
&#xD;
         16. Any symptoms within 24 hours before Day 1 of upper respiratory illness of allergy&#xD;
             flare-up that, in the opinion of the Investigator, presents as nasal congestion or&#xD;
             rhinorrhea that could inhibit the proper administration of the IP&#xD;
&#xD;
         17. Known or suspected malignancy, excluding non-melanoma skin cancers and other early&#xD;
             stage surgically excised malignancies that the Investigator considers to be&#xD;
             exceedingly unlikely to recur&#xD;
&#xD;
         18. Immunocompromised individuals, including those who have used corticosteroids&#xD;
             (including intranasal steroids), alkylating drugs, antimetabolites, radiation,&#xD;
             immune-modulating biologics, or other immunomodulating therapies within 90 days before&#xD;
             Day 1 or those who plan use during the study period&#xD;
&#xD;
         19. Use of statin medication within 30 days before Day 1 (see list in Section 6.8.1)&#xD;
&#xD;
         20. Receipt of intranasal medications (including over-the-counter medications) within 30&#xD;
             days before Day 1&#xD;
&#xD;
         21. Receipt of any investigational product (IP) within 30 days before Day 1&#xD;
&#xD;
         22. Receipt of any vaccine within 30 days before Day 1&#xD;
&#xD;
         23. Receipt of intranasal vaccine within 90 days before Day 1&#xD;
&#xD;
         24. Receipt of any influenza vaccine within 6 months before Day 1&#xD;
&#xD;
         25. Any change in medication for a chronic medical condition within 30 days before Day 1&#xD;
&#xD;
         26. Past regular use or current use of intranasal illicit drugs&#xD;
&#xD;
         27. Smoking of any type (eg, cigarettes, electronic cigarettes, marijuana) or use of any&#xD;
             tobacco product within 30 days before Day 1&#xD;
&#xD;
         28. Any medical, psychiatric, or social condition or occupational or other responsibility&#xD;
             that in the judgment of the Investigator would interfere with or serve as a&#xD;
             contraindication to protocol adherence, assessment of safety (including&#xD;
             reactogenicity), or a subject's ability to give informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>49 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stephen Bart, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Optimal Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Optimal Health Research</name>
      <address>
        <city>Rockville</city>
        <state>Maryland</state>
        <zip>20850</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>July 24, 2017</study_first_submitted>
  <study_first_submitted_qc>July 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2017</study_first_posted>
  <results_first_submitted>February 26, 2019</results_first_submitted>
  <results_first_submitted_qc>March 19, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">April 11, 2019</results_first_posted>
  <last_update_submitted>March 19, 2019</last_update_submitted>
  <last_update_submitted_qc>March 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 5, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/67/NCT03232567/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 7, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/67/NCT03232567/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Phase 2a, randomized, double-blind, placebo-controlled trial to evaluate the safety and immunogenicity of NasoVAX in healthy adults 18 to 49 years of age. Subjects were screened within 28 days of randomization.</recruitment_details>
      <pre_assignment_details>60 subjects who met all inclusion and no exclusion criteria and provided written informed consent were enrolled into 3 sequential cohorts of 20 subjects each defined by the vaccine dose (1×10^9, 1×10^10,1×10^11 vp). Within each cohort and its sentinel group, subjects were randomized in a 3:1 ratio to receive 1 intranasal dose of NasoVAX or placebo</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>NasoVAX Low Dose</title>
          <description>NasoVAX administered by intranasal spray at a single dose of 1×10^9 viral particles (vp)</description>
        </group>
        <group group_id="P2">
          <title>NasoVAX Medium Dose</title>
          <description>NasoVAX administered by intranasal spray at a single dose of 1×10^10 viral particles (vp)</description>
        </group>
        <group group_id="P3">
          <title>NasoVAX High Dose</title>
          <description>NasoVAX administered by intranasal spray at a single dose of 1×10^11 viral particles (vp)</description>
        </group>
        <group group_id="P4">
          <title>Placebo</title>
          <description>Normal saline administered by intranasal spray at a single dose</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
                <participants group_id="P3" count="15"/>
                <participants group_id="P4" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="15"/>
                <participants group_id="P4" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>NasoVAX Low Dose</title>
          <description>NasoVAX administered by intranasal spray at a single dose of 1×10^9viral particles (vp)</description>
        </group>
        <group group_id="B2">
          <title>NasoVAX Medium Dose</title>
          <description>NasoVAX administered by intranasal spray at a single dose of 1×10^10 viral particles (vp)</description>
        </group>
        <group group_id="B3">
          <title>NasoVAX High Dose</title>
          <description>NasoVAX administered by intranasal spray at a single dose of 1×10^11 viral particles (vp)</description>
        </group>
        <group group_id="B4">
          <title>Placebo</title>
          <description>Normal saline administered by intranasal spray at a single dose</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="15"/>
            <count group_id="B2" value="15"/>
            <count group_id="B3" value="15"/>
            <count group_id="B4" value="15"/>
            <count group_id="B5" value="60"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Age</title>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="15"/>
                    <measurement group_id="B5" value="60"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30.1" lower_limit="19" upper_limit="47"/>
                    <measurement group_id="B2" value="31.6" lower_limit="18" upper_limit="46"/>
                    <measurement group_id="B3" value="32.6" lower_limit="21" upper_limit="48"/>
                    <measurement group_id="B4" value="29.3" lower_limit="20" upper_limit="45"/>
                    <measurement group_id="B5" value="30.9" lower_limit="18" upper_limit="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="13"/>
                    <measurement group_id="B4" value="15"/>
                    <measurement group_id="B5" value="51"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Treatment-Emergent Adverse Events in Participants [Safety and Tolerability]</title>
        <description>Adverse events (AEs): counts and percentages of subjects with AEs Day 1 to day 29 and Medically attended AEs (MAEs), serious AEs (SAEs), new-onset chronic illnesses (NCIs) from Day 1 to Day 181</description>
        <time_frame>Day 1 to Day 181</time_frame>
        <population>All ALT-103-201 and ALT-FLZ-401 subjects who provide informed consent, are randomized, and receive at least 1 vaccination. The Safety Population will be used for all safety analyses and will be analyzed according to the treatment received.</population>
        <group_list>
          <group group_id="O1">
            <title>NasoVAX Low Dose</title>
            <description>NasoVAX administered by intranasal spray at a single dose of 1×10^9 viral particles (vp) versus placebo&#xD;
NasoVAX: Single ascending dose study</description>
          </group>
          <group group_id="O2">
            <title>NasoVAX Medium Dose</title>
            <description>NasoVAX administered by intranasal spray at a single dose of 1×10^10 viral particles (vp) versus placebo&#xD;
NasoVAX: Single ascending dose study</description>
          </group>
          <group group_id="O3">
            <title>NasoVAX High Dose</title>
            <description>NasoVAX administered by intranasal spray at a single dose of 1×10^11 viral particles (vp) versus placebo&#xD;
NasoVAX: Single ascending dose study</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Normal saline administered by intranasal spray at a single dose</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Treatment-Emergent Adverse Events in Participants [Safety and Tolerability]</title>
          <description>Adverse events (AEs): counts and percentages of subjects with AEs Day 1 to day 29 and Medically attended AEs (MAEs), serious AEs (SAEs), new-onset chronic illnesses (NCIs) from Day 1 to Day 181</description>
          <population>All ALT-103-201 and ALT-FLZ-401 subjects who provide informed consent, are randomized, and receive at least 1 vaccination. The Safety Population will be used for all safety analyses and will be analyzed according to the treatment received.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
                <count group_id="O4" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="10"/>
                    <measurement group_id="O4" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IP Related TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IP Related SAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3 or 4 TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE Leading to Withdrawal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Treatment-Emergent Reactogenicity Events in Participants [Safety and Tolerability]</title>
        <description>Reactogenicity: counts and percentages of subjects with 'yes' to any reactogenicity event (nasal irritation, sneezing, nasal congestion, sore throat, change in smell, change in taste, change in vision, eye pain, headache, fatigue, muscle ache, nausea, vomiting, diarrhea, chills, fever)</description>
        <time_frame>14-days after vaccination</time_frame>
        <population>All ALT-103-201 and ALT-FLZ-401 subjects who provide informed consent, are randomized, and receive at least 1 vaccination. The Safety Population will be used for all safety analyses and will be analyzed according to the treatment received.</population>
        <group_list>
          <group group_id="O1">
            <title>NasoVAX Low Dose</title>
            <description>NasoVAX administered by intranasal spray at a single dose of 1×10^9 viral particles (vp) versus placebo&#xD;
NasoVAX: Single ascending dose study</description>
          </group>
          <group group_id="O2">
            <title>NasoVAX Medium Dose</title>
            <description>NasoVAX administered by intranasal spray at a single dose of 1×10^10 viral particles (vp) versus placebo&#xD;
NasoVAX: Single ascending dose study</description>
          </group>
          <group group_id="O3">
            <title>NasoVAX High Dose</title>
            <description>NasoVAX administered by intranasal spray at a single dose of 1×10^11 viral particles (vp) versus placebo&#xD;
NasoVAX: Single ascending dose study</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Normal saline administered by intranasal spray at a single dose</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Treatment-Emergent Reactogenicity Events in Participants [Safety and Tolerability]</title>
          <description>Reactogenicity: counts and percentages of subjects with 'yes' to any reactogenicity event (nasal irritation, sneezing, nasal congestion, sore throat, change in smell, change in taste, change in vision, eye pain, headache, fatigue, muscle ache, nausea, vomiting, diarrhea, chills, fever)</description>
          <population>All ALT-103-201 and ALT-FLZ-401 subjects who provide informed consent, are randomized, and receive at least 1 vaccination. The Safety Population will be used for all safety analyses and will be analyzed according to the treatment received.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
                <count group_id="O4" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any local event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="6"/>
                    <measurement group_id="O4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any systemic event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="11"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>HAI Immune Response</title>
        <description>Antibody level measured by hemagglutination inhibition (HAI) in serum</description>
        <time_frame>Day 1 to Day 181</time_frame>
        <population>All subjects in the Safety Population that received the assigned dose of the test article, have HAI assay results on Days 1 and 29 and had no major protocol deviations affecting the primary immunogenicity outcomes prior to database lock. Per Protocol primary population for immunogenicity analyses was analyzed as randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>NasoVAX Low Dose</title>
            <description>NasoVAX administered by intranasal spray at a single dose of 1×10^9 viral particles (vp) versus placebo&#xD;
NasoVAX: Single ascending dose study</description>
          </group>
          <group group_id="O2">
            <title>NasoVAX Medium Dose</title>
            <description>NasoVAX administered by intranasal spray at a single dose of 1×10^10 viral particles (vp) versus placebo&#xD;
NasoVAX: Single ascending dose study</description>
          </group>
          <group group_id="O3">
            <title>NasoVAX High Dose</title>
            <description>NasoVAX administered by intranasal spray at a single dose of 1×10^11 viral particles (vp) versus placebo&#xD;
NasoVAX: Single ascending dose study</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Normal saline administered by intranasal spray at a single dose</description>
          </group>
        </group_list>
        <measure>
          <title>HAI Immune Response</title>
          <description>Antibody level measured by hemagglutination inhibition (HAI) in serum</description>
          <population>All subjects in the Safety Population that received the assigned dose of the test article, have HAI assay results on Days 1 and 29 and had no major protocol deviations affecting the primary immunogenicity outcomes prior to database lock. Per Protocol primary population for immunogenicity analyses was analyzed as randomized.</population>
          <units>GMT</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
                <count group_id="O4" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83.8" lower_limit="42.1" upper_limit="166.7"/>
                    <measurement group_id="O2" value="160" lower_limit="94.8" upper_limit="270"/>
                    <measurement group_id="O3" value="152.8" lower_limit="93.5" upper_limit="249.7"/>
                    <measurement group_id="O4" value="27.6" lower_limit="13.5" upper_limit="56.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Microneutralization Immune Response</title>
        <description>Antibody level measured by microneutralization in serum</description>
        <time_frame>Day 1 to Day 181</time_frame>
        <population>All subjects in the Safety Population that received the assigned dose of the test article, have HAI assay results on Days 1 and 29 and had no major protocol deviations affecting the primary immunogenicity outcomes prior to database lock. Per Protocol primary population for immunogenicity analyses was analyzed as randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>NasoVAX Low Dose</title>
            <description>NasoVAX administered by intranasal spray at a single dose of 1×10^9 viral particles (vp) versus placebo&#xD;
NasoVAX: Single ascending dose study</description>
          </group>
          <group group_id="O2">
            <title>NasoVAX Medium Dose</title>
            <description>NasoVAX administered by intranasal spray at a single dose of 1×10^10 viral particles (vp) versus placebo&#xD;
NasoVAX: Single ascending dose study</description>
          </group>
          <group group_id="O3">
            <title>NasoVAX High Dose</title>
            <description>NasoVAX administered by intranasal spray at a single dose of 1×10^11 viral particles (vp) versus placebo&#xD;
NasoVAX: Single ascending dose study</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Normal saline administered by intranasal spray at a single dose</description>
          </group>
        </group_list>
        <measure>
          <title>Microneutralization Immune Response</title>
          <description>Antibody level measured by microneutralization in serum</description>
          <population>All subjects in the Safety Population that received the assigned dose of the test article, have HAI assay results on Days 1 and 29 and had no major protocol deviations affecting the primary immunogenicity outcomes prior to database lock. Per Protocol primary population for immunogenicity analyses was analyzed as randomized.</population>
          <units>GMT</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
                <count group_id="O4" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83.8" lower_limit="42.1" upper_limit="166.7"/>
                    <measurement group_id="O2" value="160." lower_limit="94.8" upper_limit="270"/>
                    <measurement group_id="O3" value="152.8" lower_limit="93.5" upper_limit="249.7"/>
                    <measurement group_id="O4" value="27.6" lower_limit="13.5" upper_limit="56.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>AEs Day 1 to day 29 Medically attended AEs (MAEs), serious AEs (SAEs), new-onset chronic illnesses (NCIs) from Day 1 to Day 181</time_frame>
      <desc>Adverse events (AEs): counts and percentages of subjects with AEs Day 1 to day 29 and Medically attended AEs (MAEs), serious AEs (SAEs), new-onset chronic illnesses (NCIs) from Day 1 to Day 181</desc>
      <group_list>
        <group group_id="E1">
          <title>NasoVAX Low Dose</title>
          <description>NasoVAX administered by intranasal spray at a single dose of 1×10(9th) viral particles (vp) versus placebo&#xD;
NasoVAX: Single ascending dose study</description>
        </group>
        <group group_id="E2">
          <title>NasoVAX Medium Dose</title>
          <description>NasoVAX administered by intranasal spray at a single dose of 1×10(10th) viral particles (vp) versus placebo&#xD;
NasoVAX: Single ascending dose study</description>
        </group>
        <group group_id="E3">
          <title>NasoVAX High Dose</title>
          <description>NasoVAX administered by intranasal spray at a single dose of 1×10(11th) viral particles (vp) versus placebo&#xD;
NasoVAX: Single ascending dose study</description>
        </group>
        <group group_id="E4">
          <title>Placebo</title>
          <description>Normal saline administered</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="15" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Any treatment emergent adverse event</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="15" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Stephanie Holland, Clinical Project Manager</name_or_title>
      <organization>Altimmune</organization>
      <phone>240-654-1450 ext 40</phone>
      <email>sholland@altimmune.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03232567
org study id: ALT103-201
nct id: NCT03232567
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 2a, randomized, double-blind, placebo-controlled trial to evaluate the safety
      and immunogenicity of NasoVAX in healthy adults 18 to 49 years of age. Subjects will be
      screened within 28 days of randomization (Day 1).
This is a Phase 2a, randomized, double-blind, placebo-controlled trial to evaluate the safety
      and immunogenicity of NasoVAX in healthy adults 18 to 49 years of age. Subjects will be
      screened within 28 days of randomization (Day 1). Approximately 60 subjects who meet all
      inclusion and no exclusion criteria and provide written informed consent will be enrolled
      into 3 sequential cohorts of 20 subjects each defined by the viral particle dose (1×10(9th),
      1×10(10th), and 1×10(11th) vp). Within each cohort and its sentinel group, subjects will be
      randomized in a 3:1 ratio to receive 1 intranasal dose of NasoVAX or placebo (Day 1). A
      sentinel group of 5 subjects from each cohort will be dosed and followed through Day 8.
      Dosing of the remainder of each cohort may proceed if no events meeting stopping criteria
      have occurred. The SRC, consisting of the Investigator, the Medical Monitor, and a Sponsor
      Representative, will review AE, reactogenicity, and laboratory data through Day 8 for all
      subjects in each cohort before subjects are randomized to the next higher dose. If any event
      meeting stopping criteria occur, the SRC will review all available safety information before
      additional patients are dosed.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: Single ascending dose study
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Investigator)
measure: Number of Treatment-Emergent Adverse Events in Participants [Safety and Tolerability]
time frame: Day 1 to Day 181
description: Adverse events (AEs): counts and percentages of subjects with AEs Day 1 to day 29 and Medically attended AEs (MAEs), serious AEs (SAEs), new-onset chronic illnesses (NCIs) from Day 1 to Day 181
measure: Number of Treatment-Emergent Reactogenicity Events in Participants [Safety and Tolerability]
time frame: 14-days after vaccination
description: Reactogenicity: counts and percentages of subjects with 'yes' to any reactogenicity event (nasal irritation, sneezing, nasal congestion, sore throat, change in smell, change in taste, change in vision, eye pain, headache, fatigue, muscle ache, nausea, vomiting, diarrhea, chills, fever)
measure: HAI Immune Response
time frame: Day 1 to Day 181
description: Antibody level measured by hemagglutination inhibition (HAI) in serum
measure: Microneutralization Immune Response
time frame: Day 1 to Day 181
description: Antibody level measured by microneutralization in serum
arm group label: NasoVAX low dose
arm group type: Experimental
description: NasoVAX administered by intranasal spray at a single dose of 1×10(9th) viral particles (vp) versus placebo
arm group label: NasoVAX medium dose
arm group type: Experimental
description: NasoVAX administered by intranasal spray at a single dose of 1×10(10th) viral particles (vp) versus placebo
arm group label: NasoVAX high dose
arm group type: Experimental
description: NasoVAX administered by intranasal spray at a single dose of 1×10(11th) viral particles (vp) versus placebo
arm group label: Placebo
arm group type: Placebo Comparator
description: Normal saline administered by intranasal spray at a single dose
intervention type: Biological
intervention name: NasoVAX
description: Single ascending dose study
arm group label: NasoVAX high dose
arm group label: NasoVAX low dose
arm group label: NasoVAX medium dose
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 49 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Stephen Bart, MD
role: Principal Investigator
affiliation: Optimal Research
facility: 
country: United States
responsible party type: Sponsor
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 