<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/NCT03296917</url>
  </required_header>
  <id_info>
    <org_study_id>PrEP-CS-002</org_study_id>
    <nct_id>NCT03296917</nct_id>
  </id_info>
  <brief_title>Study Examining PrEP-001 in Subjects With Asthma</brief_title>
  <official_title>A Phase II, Double-Blinded, Randomised, Controlled Study to Examine the Prophylactic Efficacy, Safety and Tolerability of PrEP-001 in Asthmatic Subjects Subsequently Challenged With Human Rhinovirus (HRV-16)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hvivo</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Prep Biopharm Limited</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Hvivo</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phase 2 study, to examine the prophylactic efficacy, safety and tolerability of PrEP-001 in&#xD;
      asthmatics who have been infected with the human rhinovirus (HRV16) after receiving two doses&#xD;
      of the study drug/placebo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Screening took place up to 90 days before quarantine, where volunteers were asked to complete&#xD;
      an informed consent and undergo scheduled screening assessments to determine their&#xD;
      eligibility.&#xD;
&#xD;
      Eligible volunteers were invited to test and record their respiratory symptoms and peak&#xD;
      expiratory flow (PEF), medications and any adverse events in diary cards from Day -14 to Day&#xD;
      -5.&#xD;
&#xD;
      They attended Quarantine on Day -4/-3, received the study drug/placebo intra nasally on Day&#xD;
      -2 and Day -1 and subsequently challenged with HRV16 on Day 0. Randomisation to receive study&#xD;
      drug/placebo was 1:1.&#xD;
&#xD;
      Volunteers remained in the quarantine unit for 8 days after inoculation.&#xD;
&#xD;
      PEF self-testing continued from Day 9 to Day 28.&#xD;
&#xD;
      On Day 20 (±3 days) and Day 28 (±5 days), volunteers attended follow up visits where they&#xD;
      were assessed by a study physician for well-being, on-going symptoms and adverse events.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 11, 2015</start_date>
  <completion_date type="Actual">September 2016</completion_date>
  <primary_completion_date type="Actual">September 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, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary Efficacy Endpoint: The Area Under the Curve (AUC) of total symptom score post viral challenge.</measure>
    <time_frame>Day -14 to Day 28</time_frame>
    <description>AUC of total symptom scores (upper respiratory tract (URT), lower respiratory tract (LRT) and systemic viral symptoms (SVS)). Total symptom scores (from the symptom diary card) used to calculate the AUC. The primary endpoint is only being derived from the Viral Challenge arm.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Symptom Scores: Area Under the Curve (AUC)</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>AUC of individual symptom scores (upper respiratory tract (URT), lower respiratory tract (LRT) and systemic viral symptoms (SVS)). A total symptom score is derived for each subject, separately for each assessment (symptom diary card) on each day.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Symptom Scores: Duration of symptoms</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Time (days).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Symptom Scores: Peak symptoms score</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Numerical sum of all individual composite symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Symptom Scores: Time to peak symptoms</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Time (days).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Symptom Scores: Time to resolution from peak symptoms</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Time (days).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Incidence(s) of illness and infection: viral shedding</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Number of subjects with viral shedding.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Incidence(s) of illness and infection: incidence of laboratory-confirmed Influenza illness</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The number of subjects with laboratory-confirmed influenza infection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Incidence(s) of illness and infection: laboratory confirmed Influenza A/Perth/16/2009 (H3N2) Virus infection</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The number of subjects with laboratory-confirmed influenza A/Perth/16/2009 (H3N2) Virus infection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Incidence(s) of illness and infection: HRV-like-illness</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The number of subjects with HRV-like illness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Sub-clinical infection</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The number of subjects with Sub-clinical illness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Upper respiratory tract illness</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The number of subjects with Upper respiratory tract illness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Lower respiratory tract illness</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The number of subjects with Lower respiratory tract illness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Febrile illness</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The number of subjects with Febrile illness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Systemic illness</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The number of subjects with Systemic illness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Non-sick and uninfected</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The number of subjects Non-sick and uninfected.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Viral replication, as measured by tissue culture assay</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The number of subjects with viral replication.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Seroconversion</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The number of subjects with seroconversion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Viral Load Parameters: Area under the curve (AUC) of viral load, as measured by nasopharyngeal swab RT-qPCR</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Viral load data supplied in Log10 Copies/mL. These values used to calculate the Area Under the Curve (AUC) for each subject.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Duration of virus shedding, as measured by nasal wash RT-qPCR</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Time (days).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Peak virus shedding, as measured by nasal wash RT-qPCR</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The highest observed RT-qPCR viral load value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Viral Load Parameters: Time to peak viral shedding, as measured by nasal wash RT-qPCR</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Time (days).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Time to resolution from peak viral shedding, as measured by nasal wash RT-qPCR.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Time (days).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Area under the curve (AUC) of viral load, as measured by nasal wash TCID50.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Tissue culture viral load data supplied in log10 TCID50/mL. These values used to calculate the Area Under the Curve (AUC) for each subject.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Duration of virus shedding, as measured by nasal wash TCID50.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Time (days).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Peak virus shedding, as measured by nasal wash TCID50.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The highest observed RT-qPCR viral load value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Time to peak viral shedding, as measured by nasal wash TCID50.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Time (days).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Total weight of nasal discharge produced post Viral Challenge to Quarantine discharge.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Weight (grams).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Change in lung function compared to pre-Challenge.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Peak Expiratory Flow (L/min) and FEV1 (L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Change in Asthma Control Questionnaire (ACQ) score compared to pre-Challenge.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>ACQ score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoint: Change in Fractional exhaled nitric oxide (FeNO) compared to pre-Challenge.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>FeNO (ppb).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Exploratory Efficacy Analysis: Proportion (on any occasion) of subjects with Grade 2 or worse symptoms at any day post-Viral Challenge.</measure>
    <time_frame>Day -14 to Day 28</time_frame>
    <description>Number of subjects with Grade 2 or higher symptoms at any day post-Viral Challenge.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory Efficacy Analysis: Proportion of subjects with Grade 2 or worse symptoms at each day post-Viral Challenge.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Number of subjects with symptoms at Grade 2 or higher, at each day post-Viral Challenge.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory Efficacy Analysis: Duration of Grade 2 or worse symptoms (post-Viral Challenge).</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Time (days).</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory Efficacy Analysis: Proportion of subjects with any clinical symptoms (i.e., with Grade ≥ 1) (post-Viral Challenge).</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The proportion of subjects with symptoms grade 1 or higher.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory Efficacy Analysis: Proportion of subjects with Grade ≥1 symptom score for upper respiratory tract (URT) symptoms (post-Viral Challenge).</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The proportion of subjects with upper respiratory tract symptoms.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory Efficacy Analysis: Proportion of subjects with Grade ≥1 symptom score for lower respiratory tract (LRT) symptoms (post-Viral Challenge).</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The proportion of subjects with lower respiratory tract symptoms.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory Efficacy Analysis: Proportion of subjects with Grade ≥1 symptom score for systemic symptoms (post-Viral Challenge).</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The proportion of subjects with systemic symptoms.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory Efficacy Analysis: Time to peak for each reported and any symptoms (post-Viral Challenge).</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Time (days).</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory Efficacy Analysis: Proportion of subjects with pyrexia.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The proportion of subjects with pyrexia.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory Efficacy Analysis: Duration of pyrexia.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Time (hours).</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory Efficacy Analysis: Tympanic temperature.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Changes in tympanic temperature over time (post Viral Challenge) (degrees Celcius)</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory Efficacy Analysis: Area under the curve (AUC) of symptom scores using the 13-item symptom diary card (total, URT, LRT and SVS), Day 1 (assessment 1) to Day 8.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>AUC of individual symptom scores.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory Efficacy Analysis: Proportion of subjects with Lab-confirmed Clinical Symptoms of URTI.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The number of subjects with lab-confirmed clinical symptoms of URTI.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory Efficacy Analysis: Proportion of subjects with Lab-confirmed Clinical Symptoms of LRTI.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The number of subjects with lab-confirmed clinical symptoms of LRTI.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory Efficacy Analysis: Proportion of subjects with Lab-confirmed Clinical Symptoms of Systemic Illness (SI).</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>The number of subjects with lab-confirmed clinical symptoms of SI.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory Efficacy Analysis: Overall total symptom score, Day 1 (assessment 1) to Day 8, using the 10-item symptom diary card.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Total symptom score.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory Efficacy Analysis: Overall symptom scores (URT, LRT SVS), Day 1 (assessment 1) to Day 8, using the 10-item symptom diary card.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Total symptom score.</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety endpoint: Treatment-emergent Adverse Events (TEAE).</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Incidence of treatment-emergent AEs (TEAE), overall, and by severity and causality (analysed descriptively).</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety endpoint: Clinical laboratory parameters.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Absolute values and change from baseline in routine clinical laboratory parameters by timepoint (analysed descriptively). Includes haematology, biochemistry, coagulation, cardiac enzymes, thyroid function tests and urinalysis parameters.</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety endpoint: Vital signs.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Absolute values and change from baseline in vital signs parameters by timepoint (analysed descriptively); systolic blood pressure (SBP) (mmHg), diastolic blood pressure (DBP) (mmHg), respiratory rate (RR) (breaths per minute), heart rate (HR) (beats per minute) and SpO2 (%).</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety endpoint: Physical Examination.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Physical examination findings (analysed descriptively).</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety endpoint: Spirometry.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Absolute and changes from baseline for FEV1 [absolute] (L), FEV1 [% predicted] (%), FVC [absolute] (L), FVC [% predicted] (%), FEV1/FVC ratio [absolute], FEV1/FVC ratio [% predicted] (%), maximum mid expiratory flow (MMEF) [absolute] (L/sec) and MMEF [% predicted]). The lung function parameter Peak Expiratory Flow [L/min] will also be summarised (analysed descriptively).</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety endpoint: ECGs.</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>12-lead electrocardiogram (ECG) findings (analysed descriptively).</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety endpoint: Asthma Exacerbations (Number)</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Number and percentage of subjects experiencing any asthma exacerbations.</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety endpoint: Duration of each asthma exacerbation</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Time (days)</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety endpoint: Time to first asthma exacerbation</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Time (days)</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety endpoint: Subjects requiring treatment for asthma exacerbation</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Number of subjects requiring oral or parenteral steroids as treatment for their exacerbation.</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety endpoint: Subjects requiring hospitalisation for asthma exacerbation</measure>
    <time_frame>Day -4 to Day 28</time_frame>
    <description>Number of subjects requiring hospitalisation for their exacerbation.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>IMP - PrEP-001</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In Viral Challenge arm cohort:&#xD;
A nasal dose of 6400 μg PrEP-001 equally divided over both nostrils on 2 consecutive days (Day -2 and Day -1).&#xD;
In the Safety arm's first dose cohort:&#xD;
A nasal dose of 6400 μg PrEP-001 equally divided over both nostrils on 2 consecutive days (Day -2 and Day -1).&#xD;
Then assuming no significant safety issues with the lower dose (as determined by blinded review by the DSMB team), the Safety arm's second dose cohort will consist of:&#xD;
A nasal dose of 12800 μg PrEP-001 equally divided over both nostrils on 2 consecutive days (Day -2 and Day -1)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo - G-004</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>In the Viral Challenge arm and each Safety Arm cohort:&#xD;
A nasal dose of placebo equally divided over both nostrils on 2 consecutive days (Day -2 and Day -1).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PrEP-001</intervention_name>
    <description>A spray dried powder for intranasal administration formulated from an aqueous mixture of pre-gelatinized waxy maize starch and the drug substance delivered using a single dose nasal powder device.</description>
    <arm_group_label>IMP - PrEP-001</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>G-004</intervention_name>
    <description>A spray dried pre-gelatinized waxy maize starch powder (G-001) in the single dose nasal powder device</description>
    <arm_group_label>Placebo - G-004</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged 18 to 55 years on the day of first dosing with IMP.&#xD;
&#xD;
          -  Physician diagnosed asthma for at least 6 months prior to Screening and using&#xD;
             treatment equivalent up to and including Global Initiative for Asthma (GINA) Stage 3.&#xD;
&#xD;
          -  In good health with no history of major medical conditions (other than asthma) that&#xD;
             will interfere with subject safety, as defined by medical history, physical&#xD;
             examination, and routine laboratory tests as determined by the Investigator at a&#xD;
             screening evaluation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any ex-smoker or smoker with a history of more than 10 pack-years.&#xD;
&#xD;
          -  History of life-threatening asthma, Diagnosis of COPD as defined by the current Global&#xD;
             Initiative for Chronic Obstructive Lung Disease (GOLD) 2014 guidelines.&#xD;
&#xD;
          -  Any history or evidence of any clinically significant medical and psychiatric&#xD;
             conditions&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John Efthimiou</last_name>
    <role>Study Chair</role>
    <affiliation>Sponsor's Representative</affiliation>
  </overall_official>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>June 13, 2017</study_first_submitted>
  <study_first_submitted_qc>September 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 29, 2017</study_first_posted>
  <last_update_submitted>September 25, 2017</last_update_submitted>
  <last_update_submitted_qc>September 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 29, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
  </condition_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/NCT03296917
org study id: PrEP-CS-002
nct id: NCT03296917
lead sponsor: 
collaborator: 
has dmc: No
Phase 2 study, to examine the prophylactic efficacy, safety and tolerability of PrEP-001 in
      asthmatics who have been infected with the human rhinovirus (HRV16) after receiving two doses
      of the study drug/placebo.
Screening took place up to 90 days before quarantine, where volunteers were asked to complete
      an informed consent and undergo scheduled screening assessments to determine their
      eligibility.

      Eligible volunteers were invited to test and record their respiratory symptoms and peak
      expiratory flow (PEF), medications and any adverse events in diary cards from Day -14 to Day
      -5.

      They attended Quarantine on Day -4/-3, received the study drug/placebo intra nasally on Day
      -2 and Day -1 and subsequently challenged with HRV16 on Day 0. Randomisation to receive study
      drug/placebo was 1:1.

      Volunteers remained in the quarantine unit for 8 days after inoculation.

      PEF self-testing continued from Day 9 to Day 28.

      On Day 20 (±3 days) and Day 28 (±5 days), volunteers attended follow up visits where they
      were assessed by a study physician for well-being, on-going symptoms and adverse events.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Investigator)
measure: Primary Efficacy Endpoint: The Area Under the Curve (AUC) of total symptom score post viral challenge.
time frame: Day -14 to Day 28
description: AUC of total symptom scores (upper respiratory tract (URT), lower respiratory tract (LRT) and systemic viral symptoms (SVS)). Total symptom scores (from the symptom diary card) used to calculate the AUC. The primary endpoint is only being derived from the Viral Challenge arm.
measure: Secondary Efficacy Endpoint: Symptom Scores: Area Under the Curve (AUC)
time frame: Day -4 to Day 28
description: AUC of individual symptom scores (upper respiratory tract (URT), lower respiratory tract (LRT) and systemic viral symptoms (SVS)). A total symptom score is derived for each subject, separately for each assessment (symptom diary card) on each day.
measure: Secondary Efficacy Endpoint: Symptom Scores: Duration of symptoms
time frame: Day -4 to Day 28
description: Time (days).
measure: Secondary Efficacy Endpoint: Symptom Scores: Peak symptoms score
time frame: Day -4 to Day 28
description: Numerical sum of all individual composite symptoms.
measure: Secondary Efficacy Endpoint: Symptom Scores: Time to peak symptoms
time frame: Day -4 to Day 28
description: Time (days).
measure: Secondary Efficacy Endpoint: Symptom Scores: Time to resolution from peak symptoms
time frame: Day -4 to Day 28
description: Time (days).
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: viral shedding
time frame: Day -4 to Day 28
description: Number of subjects with viral shedding.
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: incidence of laboratory-confirmed Influenza illness
time frame: Day -4 to Day 28
description: The number of subjects with laboratory-confirmed influenza infection.
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: laboratory confirmed Influenza A/Perth/16/2009 (H3N2) Virus infection
time frame: Day -4 to Day 28
description: The number of subjects with laboratory-confirmed influenza A/Perth/16/2009 (H3N2) Virus infection.
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: HRV-like-illness
time frame: Day -4 to Day 28
description: The number of subjects with HRV-like illness.
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Sub-clinical infection
time frame: Day -4 to Day 28
description: The number of subjects with Sub-clinical illness.
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Upper respiratory tract illness
time frame: Day -4 to Day 28
description: The number of subjects with Upper respiratory tract illness.
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Lower respiratory tract illness
time frame: Day -4 to Day 28
description: The number of subjects with Lower respiratory tract illness.
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Febrile illness
time frame: Day -4 to Day 28
description: The number of subjects with Febrile illness.
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Systemic illness
time frame: Day -4 to Day 28
description: The number of subjects with Systemic illness.
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Non-sick and uninfected
time frame: Day -4 to Day 28
description: The number of subjects Non-sick and uninfected.
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Viral replication, as measured by tissue culture assay
time frame: Day -4 to Day 28
description: The number of subjects with viral replication.
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Seroconversion
time frame: Day -4 to Day 28
description: The number of subjects with seroconversion.
measure: Secondary Efficacy Endpoint: Viral Load Parameters: Area under the curve (AUC) of viral load, as measured by nasopharyngeal swab RT-qPCR
time frame: Day -4 to Day 28
description: Viral load data supplied in Log10 Copies/mL. These values used to calculate the Area Under the Curve (AUC) for each subject.
measure: Secondary Efficacy Endpoint: Duration of virus shedding, as measured by nasal wash RT-qPCR
time frame: Day -4 to Day 28
description: Time (days).
measure: Secondary Efficacy Endpoint: Peak virus shedding, as measured by nasal wash RT-qPCR
time frame: Day -4 to Day 28
description: The highest observed RT-qPCR viral load value.
measure: Secondary Efficacy Endpoint: Viral Load Parameters: Time to peak viral shedding, as measured by nasal wash RT-qPCR
time frame: Day -4 to Day 28
description: Time (days).
measure: Secondary Efficacy Endpoint: Time to resolution from peak viral shedding, as measured by nasal wash RT-qPCR.
time frame: Day -4 to Day 28
description: Time (days).
measure: Secondary Efficacy Endpoint: Area under the curve (AUC) of viral load, as measured by nasal wash TCID50.
time frame: Day -4 to Day 28
description: Tissue culture viral load data supplied in log10 TCID50/mL. These values used to calculate the Area Under the Curve (AUC) for each subject.
measure: Secondary Efficacy Endpoint: Duration of virus shedding, as measured by nasal wash TCID50.
time frame: Day -4 to Day 28
description: Time (days).
measure: Secondary Efficacy Endpoint: Peak virus shedding, as measured by nasal wash TCID50.
time frame: Day -4 to Day 28
description: The highest observed RT-qPCR viral load value.
measure: Secondary Efficacy Endpoint: Time to peak viral shedding, as measured by nasal wash TCID50.
time frame: Day -4 to Day 28
description: Time (days).
measure: Secondary Efficacy Endpoint: Total weight of nasal discharge produced post Viral Challenge to Quarantine discharge.
time frame: Day -4 to Day 28
description: Weight (grams).
measure: Secondary Efficacy Endpoint: Change in lung function compared to pre-Challenge.
time frame: Day -4 to Day 28
description: Peak Expiratory Flow (L/min) and FEV1 (L)
measure: Secondary Efficacy Endpoint: Change in Asthma Control Questionnaire (ACQ) score compared to pre-Challenge.
time frame: Day -4 to Day 28
description: ACQ score.
measure: Secondary Efficacy Endpoint: Change in Fractional exhaled nitric oxide (FeNO) compared to pre-Challenge.
time frame: Day -4 to Day 28
description: FeNO (ppb).
measure: Exploratory Efficacy Analysis: Proportion (on any occasion) of subjects with Grade 2 or worse symptoms at any day post-Viral Challenge.
time frame: Day -14 to Day 28
description: Number of subjects with Grade 2 or higher symptoms at any day post-Viral Challenge.
measure: Exploratory Efficacy Analysis: Proportion of subjects with Grade 2 or worse symptoms at each day post-Viral Challenge.
time frame: Day -4 to Day 28
description: Number of subjects with symptoms at Grade 2 or higher, at each day post-Viral Challenge.
measure: Exploratory Efficacy Analysis: Duration of Grade 2 or worse symptoms (post-Viral Challenge).
time frame: Day -4 to Day 28
description: Time (days).
measure: Exploratory Efficacy Analysis: Proportion of subjects with any clinical symptoms (i.e., with Grade ≥ 1) (post-Viral Challenge).
time frame: Day -4 to Day 28
description: The proportion of subjects with symptoms grade 1 or higher.
measure: Exploratory Efficacy Analysis: Proportion of subjects with Grade ≥1 symptom score for upper respiratory tract (URT) symptoms (post-Viral Challenge).
time frame: Day -4 to Day 28
description: The proportion of subjects with upper respiratory tract symptoms.
measure: Exploratory Efficacy Analysis: Proportion of subjects with Grade ≥1 symptom score for lower respiratory tract (LRT) symptoms (post-Viral Challenge).
time frame: Day -4 to Day 28
description: The proportion of subjects with lower respiratory tract symptoms.
measure: Exploratory Efficacy Analysis: Proportion of subjects with Grade ≥1 symptom score for systemic symptoms (post-Viral Challenge).
time frame: Day -4 to Day 28
description: The proportion of subjects with systemic symptoms.
measure: Exploratory Efficacy Analysis: Time to peak for each reported and any symptoms (post-Viral Challenge).
time frame: Day -4 to Day 28
description: Time (days).
measure: Exploratory Efficacy Analysis: Proportion of subjects with pyrexia.
time frame: Day -4 to Day 28
description: The proportion of subjects with pyrexia.
measure: Exploratory Efficacy Analysis: Duration of pyrexia.
time frame: Day -4 to Day 28
description: Time (hours).
measure: Exploratory Efficacy Analysis: Tympanic temperature.
time frame: Day -4 to Day 28
description: Changes in tympanic temperature over time (post Viral Challenge) (degrees Celcius)
measure: Exploratory Efficacy Analysis: Area under the curve (AUC) of symptom scores using the 13-item symptom diary card (total, URT, LRT and SVS), Day 1 (assessment 1) to Day 8.
time frame: Day -4 to Day 28
description: AUC of individual symptom scores.
measure: Exploratory Efficacy Analysis: Proportion of subjects with Lab-confirmed Clinical Symptoms of URTI.
time frame: Day -4 to Day 28
description: The number of subjects with lab-confirmed clinical symptoms of URTI.
measure: Exploratory Efficacy Analysis: Proportion of subjects with Lab-confirmed Clinical Symptoms of LRTI.
time frame: Day -4 to Day 28
description: The number of subjects with lab-confirmed clinical symptoms of LRTI.
measure: Exploratory Efficacy Analysis: Proportion of subjects with Lab-confirmed Clinical Symptoms of Systemic Illness (SI).
time frame: Day -4 to Day 28
description: The number of subjects with lab-confirmed clinical symptoms of SI.
measure: Exploratory Efficacy Analysis: Overall total symptom score, Day 1 (assessment 1) to Day 8, using the 10-item symptom diary card.
time frame: Day -4 to Day 28
description: Total symptom score.
measure: Exploratory Efficacy Analysis: Overall symptom scores (URT, LRT SVS), Day 1 (assessment 1) to Day 8, using the 10-item symptom diary card.
time frame: Day -4 to Day 28
description: Total symptom score.
measure: Safety endpoint: Treatment-emergent Adverse Events (TEAE).
time frame: Day -4 to Day 28
description: Incidence of treatment-emergent AEs (TEAE), overall, and by severity and causality (analysed descriptively).
measure: Safety endpoint: Clinical laboratory parameters.
time frame: Day -4 to Day 28
description: Absolute values and change from baseline in routine clinical laboratory parameters by timepoint (analysed descriptively). Includes haematology, biochemistry, coagulation, cardiac enzymes, thyroid function tests and urinalysis parameters.
measure: Safety endpoint: Vital signs.
time frame: Day -4 to Day 28
description: Absolute values and change from baseline in vital signs parameters by timepoint (analysed descriptively); systolic blood pressure (SBP) (mmHg), diastolic blood pressure (DBP) (mmHg), respiratory rate (RR) (breaths per minute), heart rate (HR) (beats per minute) and SpO2 (%).
measure: Safety endpoint: Physical Examination.
time frame: Day -4 to Day 28
description: Physical examination findings (analysed descriptively).
measure: Safety endpoint: Spirometry.
time frame: Day -4 to Day 28
description: Absolute and changes from baseline for FEV1 [absolute] (L), FEV1 [% predicted] (%), FVC [absolute] (L), FVC [% predicted] (%), FEV1/FVC ratio [absolute], FEV1/FVC ratio [% predicted] (%), maximum mid expiratory flow (MMEF) [absolute] (L/sec) and MMEF [% predicted]). The lung function parameter Peak Expiratory Flow [L/min] will also be summarised (analysed descriptively).
measure: Safety endpoint: ECGs.
time frame: Day -4 to Day 28
description: 12-lead electrocardiogram (ECG) findings (analysed descriptively).
measure: Safety endpoint: Asthma Exacerbations (Number)
time frame: Day -4 to Day 28
description: Number and percentage of subjects experiencing any asthma exacerbations.
measure: Safety endpoint: Duration of each asthma exacerbation
time frame: Day -4 to Day 28
description: Time (days)
measure: Safety endpoint: Time to first asthma exacerbation
time frame: Day -4 to Day 28
description: Time (days)
measure: Safety endpoint: Subjects requiring treatment for asthma exacerbation
time frame: Day -4 to Day 28
description: Number of subjects requiring oral or parenteral steroids as treatment for their exacerbation.
measure: Safety endpoint: Subjects requiring hospitalisation for asthma exacerbation
time frame: Day -4 to Day 28
description: Number of subjects requiring hospitalisation for their exacerbation.
arm group label: IMP - PrEP-001
arm group type: Experimental
description: In Viral Challenge arm cohort:
A nasal dose of 6400 μg PrEP-001 equally divided over both nostrils on 2 consecutive days (Day -2 and Day -1).
In the Safety arm's first dose cohort:
A nasal dose of 6400 μg PrEP-001 equally divided over both nostrils on 2 consecutive days (Day -2 and Day -1).
Then assuming no significant safety issues with the lower dose (as determined by blinded review by the DSMB team), the Safety arm's second dose cohort will consist of:
A nasal dose of 12800 μg PrEP-001 equally divided over both nostrils on 2 consecutive days (Day -2 and Day -1)
arm group label: Placebo - G-004
arm group type: Placebo Comparator
description: In the Viral Challenge arm and each Safety Arm cohort:
A nasal dose of placebo equally divided over both nostrils on 2 consecutive days (Day -2 and Day -1).
intervention type: Drug
intervention name: PrEP-001
description: A spray dried powder for intranasal administration formulated from an aqueous mixture of pre-gelatinized waxy maize starch and the drug substance delivered using a single dose nasal powder device.
arm group label: IMP - PrEP-001
intervention type: Drug
intervention name: G-004
description: A spray dried pre-gelatinized waxy maize starch powder (G-001) in the single dose nasal powder device
arm group label: Placebo - G-004
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: John Efthimiou
role: Study Chair
affiliation: Sponsor's Representative
responsible party type: Sponsor
mesh term: Asthma