<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/NCT04430179</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY000808</org_study_id>
    <nct_id>NCT04430179</nct_id>
  </id_info>
  <brief_title>Dupilumab Severe Eosinophilic Chronic Sinusitis Without Nasal Polyposis</brief_title>
  <official_title>An Evaluation of Dupilumab in Patients With Severe Eosinophilic Chronic Sinusitis Without Nasal Polyposis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of South Florida</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of South Florida</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators will investigate the efficacy of dupilumab in patients with severe&#xD;
      eosinophilic CRSsNP who are resistant to the conventional treatment with intranasal&#xD;
      corticosteroids and have significantly extensive disease involving more than 2 sinuses&#xD;
      bilaterally in sinus CT scan and Lund-Mackay sinus (LMK) CT score &gt;=10 at baseline.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators will use high blood eosinophils (&gt;=200) as a biomarker for eosinophilic&#xD;
      CRSsNP and investigate the efficacy of dupilumab in patients with severe eosinophilic CRSsNP&#xD;
      who are resistant to the conventional treatment with intranasal corticosteroids and have&#xD;
      significantly extensive disease involving more than 2 sinuses bilaterally in sinus CT scan&#xD;
      and Lund-Mackay sinus (LMK) CT score &gt;=10 at baseline. In addition, the investigators will&#xD;
      have a prespecified enrollment goal of at least 50% of patients with type 2 inflammatory&#xD;
      diseases such as asthma, allergic rhinitis, and/or atopic dermatitis on the basis of&#xD;
      patient-reported history and will stratify subject numbers between dupilumab treatment and&#xD;
      placebo group.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 17, 2020</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">July 2023</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>
    <intervention_model_description>Active drug vs placebo</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double-blinded</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Lund-Mackay sinus computed tomography (LMK-CT) score</measure>
    <time_frame>24 weeks</time_frame>
    <description>Change in LMK-CT score in dupilumab group compared to control group. The total score ranges from 0 (normal) - 24 (more opacified): higher score indicates worse status.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in participant-reported symptoms scores of sinusitis</measure>
    <time_frame>24 weeks</time_frame>
    <description>Change in baseline in participant-reported symptoms scores of sinusitis in dupilumab group compared to control group. Morning symptoms of sinusitis will be assessed using a 0 (no symptoms) - 3 (severe symptoms) categorical scale, where a higher score indicates severe symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in visual analogue scale score for sinusitis</measure>
    <time_frame>24 weeks</time_frame>
    <description>Change in visual analogue scale score for sinusitis in dupilumab group compared to control group. the severity of sinusitis symptoms will be assessed on a 0 cm (not troublesome) - 10 cm (worst thinkable troublesome) where a higher score indicates worst thinkable troublesome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in nasal peak inspiratory flow</measure>
    <time_frame>24 weeks</time_frame>
    <description>Change in nasal peak inspiratory flow in dupilumab group compared to placebo group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in University of Pennsylvania smell identification test (UPSIT) scores</measure>
    <time_frame>24 weeks</time_frame>
    <description>Change in UPSIT scores in dupilumab group compared to placebo group. Total score ranges from 0 (anosmia)-40 (normal sense of smell), a lower score indicates severe smell loss.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first response in LMK-CT score</measure>
    <time_frame>24 weeks</time_frame>
    <description>50 percent improvement in LMK-CT score in dupilumab group compared to placebo group</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in sinonasal outcome test (SNOT-22) score</measure>
    <time_frame>24 weeks</time_frame>
    <description>Change in 22-item SNOT-22 test score in dupilumab group compared to placebo group. The total score may range from 0 (no problem)-110 (worst quality of life), higher scores represent the worst quality of life; minimal clinically important change ≥ 8.90.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in biomarkers concentrations in nasal secretion measured by enzyme-linked immunosorbent assay (ELISA)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Change in biomarkers concentrations in nasal secretion in dupilumab group compared to placebo group. ELISA will be done to measure biomarkers concentrations (pg/mL): ECP, IL-4, IL-5, IL-13, periostin, eotaxin-3, TARC, and IgE</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Severe Eosinophilic Chronic Sinusitis Without Nasal Polyposis</condition>
  <arm_group>
    <arm_group_label>Active drug</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dupilumab 300 mg every other week for 24 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dupilumab 300 MG/2 ML Subcutaneous Solution [DUPIXENT]</intervention_name>
    <description>300 mg every other week for 24 weeks</description>
    <arm_group_label>Active drug</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>No active drug</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 or older&#xD;
&#xD;
          -  LMK-CT score ≥ 10 (out of maximum of 24) at screening.&#xD;
&#xD;
          -  Bilateral sinusitis with at least more than 2 sinus involvement despite completion of&#xD;
             a prior intranasal corticosteroid (INCS) treatment for at least 8 weeks prior to&#xD;
             screening&#xD;
&#xD;
          -  Presence of at least two of the following symptoms prior to screening:&#xD;
&#xD;
          -  Nasal blockage/obstruction/congestion&#xD;
&#xD;
          -  Nasal discharge (anterior/posterior nasal drip)&#xD;
&#xD;
          -  Facial pain/pressure&#xD;
&#xD;
          -  Reduction or loss of smell&#xD;
&#xD;
          -  Must have Eosinophilic CRSsNP (blood eos ≥ 200) within 6 months prior to screening&#xD;
&#xD;
          -  Able and willing to undergo regular intervention as well as evaluation per study&#xD;
             protocol&#xD;
&#xD;
          -  Must agree not to participate in a clinical study involving another investigational&#xD;
             drug or device throughout the duration of this study&#xD;
&#xD;
          -  Must be competent to understand the information given in IRB approved ICF and must&#xD;
             sign the form prior to the initiation of any study procedure&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt; 18&#xD;
&#xD;
          -  With CRS with nasal polyps&#xD;
&#xD;
          -  Treated in any clinical trial of dupilumab&#xD;
&#xD;
          -  Has taken:&#xD;
&#xD;
               1. Biologic therapy/systemic immunosuppressant to treat inflammatory disease or&#xD;
                  autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel disease, primary&#xD;
                  biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis, etc) within&#xD;
                  2 months before screening or 5 half-lives, whichever is longer&#xD;
&#xD;
               2. An experimental monoclonal antibody within five half-lives or within 6 months&#xD;
                  before screening if the half-life is unknown&#xD;
&#xD;
               3. Anti-immunoglobulin E (IgE) therapy (omalizumab) within 130 days prior to&#xD;
                  screening&#xD;
&#xD;
               4. Leukotriene antagonists/modifiers unless patient is on a continuous treatment for&#xD;
                  at least 30 days prior to screening&#xD;
&#xD;
               5. Initiation of allergen immunotherapy within 3 months prior to screening or a plan&#xD;
                  to begin therapy or change its dose during the run-in period or the randomized&#xD;
                  treatment period&#xD;
&#xD;
          -  Have had a sino-nasal surgery changing the lateral wall structure of the nose making&#xD;
             impossible the evaluation of NPS&#xD;
&#xD;
          -  Patients with conditions/concomitant diseases making them non-evaluable at screening&#xD;
             or for the primary efficacy endpoint such as:&#xD;
&#xD;
               1. Antrochoanal polyps&#xD;
&#xD;
               2. Nasal septal deviation that would occlude at least one nostril&#xD;
&#xD;
               3. Acute sinusitis, nasal infection or upper respiratory infection at screening&#xD;
&#xD;
               4. Ongoing rhinitis medicamentosa&#xD;
&#xD;
               5. Allergic granulomatous angiitis (Churg-Strauss syndrome), granulomatosis with&#xD;
                  polyangiitis (Wegener's granulomatosis), Young's syndrome, Kartagener's syndrome&#xD;
                  or other dyskinetic ciliary syndromes, concomitant cystic fibrosis&#xD;
&#xD;
               6. Radiologic suspicion, or confirmed invasive or expansive fungal rhinosinusitis&#xD;
&#xD;
          -  With co-morbid asthma are excluded if forced expiratory volume (FEV1) is 50% (of&#xD;
             predicted normal) or less&#xD;
&#xD;
          -  With known active bacterial, viral, fungal, mycobacterial infection, or other&#xD;
             infection or any major episode of infection that required hospitalization or treatment&#xD;
             with IV antibiotics within 30 days of screening or during screening or oral&#xD;
             antibiotics within 14 days prior to screening. Fungal infection of nail beds is&#xD;
             allowed&#xD;
&#xD;
          -  Have human immunodeficiency virus/acquired immune deficiency syndrome&#xD;
&#xD;
          -  Have acute or chronic hepatitis B/hepatitis C infection&#xD;
&#xD;
          -  History of an opportunistic infection (eg, pneumocystis carinii, cryptococcal&#xD;
             meningitis, progressive multifocal leukoencephalopathy) or serious bacterial, viral,&#xD;
             or fungal infections (eg, disseminated herpes simplex, disseminated herpes zoster) and&#xD;
             requiring IV medication(s) ≤ 3 weeks prior to randomization&#xD;
&#xD;
          -  History of or currently active primary or secondary immunodeficiency&#xD;
&#xD;
          -  History of cancer within the last 5 years, including solid tumors and hematological&#xD;
             malignancies (except basal cell and in situ squamous cell carcinomas of the skin that&#xD;
             have been excised and resolved) or colonic mucosal dysplasia&#xD;
&#xD;
          -  History of lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative&#xD;
             disorder, or multiple myeloma&#xD;
&#xD;
          -  History of alcohol or drug abuse within 1 year prior to randomization&#xD;
&#xD;
          -  Receipt of live vaccine within 4 weeks prior to randomization&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  Participation in another clinical study or treatment with an investigational drug or&#xD;
             device&#xD;
&#xD;
          -  Serious or active medical or psychiatric condition which, in the opinion of the&#xD;
             Investigator, may interfere with treatment, assessment, or compliance with the&#xD;
             protocol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Seong Cho, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of South Florida</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Thanh Q Tran, MPH</last_name>
    <phone>813-844-8544</phone>
    <email>tqtran@usf.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Catherine Smith</last_name>
    <phone>813-631-4024</phone>
    <phone_ext>207</phone_ext>
    <email>catherinesmith@usf.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of South Florida Asthma, Allergy and Immunology</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33613</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Catherine Smith</last_name>
      <phone>813-631-4024</phone>
      <phone_ext>207</phone_ext>
      <email>catherinesmith@usf.edu</email>
    </contact>
    <contact_backup>
      <last_name>Tiffani Kaage</last_name>
      <phone>813-631-4024</phone>
      <phone_ext>200</phone_ext>
      <email>tiffanik@usf.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Seong Cho, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Richard F Lockey, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Thomas B Casale, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Dennis K Ledford, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Amber N Pepper, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Nicholas Kolinsky, DO</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>David Gubernick, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Stephanie Hudey, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Natalie Diaz-Cabrera, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Donya Imanirad, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Walaa Hamadi, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Leah Ishmael, DO</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Silpa Taunk, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sonia Mathew, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Kim DY, Lee SH, Carter RG, Kato A, Schleimer RP, Cho SH. A Recently Established Murine Model of Nasal Polyps Demonstrates Activation of B Cells, as Occurs in Human Nasal Polyps. Am J Respir Cell Mol Biol. 2016 Aug;55(2):170-5. doi: 10.1165/rcmb.2016-0002RC.</citation>
    <PMID>27163839</PMID>
  </reference>
  <reference>
    <citation>Tokunaga T, Sakashita M, Haruna T, Asaka D, Takeno S, Ikeda H, Nakayama T, Seki N, Ito S, Murata J, Sakuma Y, Yoshida N, Terada T, Morikura I, Sakaida H, Kondo K, Teraguchi K, Okano M, Otori N, Yoshikawa M, Hirakawa K, Haruna S, Himi T, Ikeda K, Ishitoya J, Iino Y, Kawata R, Kawauchi H, Kobayashi M, Yamasoba T, Miwa T, Urashima M, Tamari M, Noguchi E, Ninomiya T, Imoto Y, Morikawa T, Tomita K, Takabayashi T, Fujieda S. Novel scoring system and algorithm for classifying chronic rhinosinusitis: the JESREC Study. Allergy. 2015 Aug;70(8):995-1003. doi: 10.1111/all.12644. Epub 2015 May 26.</citation>
    <PMID>25945591</PMID>
  </reference>
  <reference>
    <citation>Hu Y, Cao PP, Liang GT, Cui YH, Liu Z. Diagnostic significance of blood eosinophil count in eosinophilic chronic rhinosinusitis with nasal polyps in Chinese adults. Laryngoscope. 2012 Mar;122(3):498-503. doi: 10.1002/lary.22507. Epub 2012 Jan 17.</citation>
    <PMID>22252861</PMID>
  </reference>
  <reference>
    <citation>Ho J, Hamizan AW, Alvarado R, Rimmer J, Sewell WA, Harvey RJ. Systemic Predictors of Eosinophilic Chronic Rhinosinusitis. Am J Rhinol Allergy. 2018 Jul;32(4):252-257. doi: 10.1177/1945892418779451. Epub 2018 Jun 4.</citation>
    <PMID>29862828</PMID>
  </reference>
  <reference>
    <citation>Thwaites RS, Gunawardana NC, Broich V, Mann EH, Ahnstrom J, Campbell GA, Lindsley S, Singh N, Tunstall T, Lane DA, Openshaw PJ, Hawrylowicz CM, Hansel TT. Biphasic activation of complement and fibrinolysis during the human nasal allergic response. J Allergy Clin Immunol. 2018 May;141(5):1892-1895.e6. doi: 10.1016/j.jaci.2018.01.022. Epub 2018 Feb 7. No abstract available.</citation>
    <PMID>29427640</PMID>
  </reference>
  <reference>
    <citation>Hopkins C, Browne JP, Slack R, Lund VJ, Topham J, Reeves BC, Copley LP, Brown P, van der Meulen JH. Complications of surgery for nasal polyposis and chronic rhinosinusitis: the results of a national audit in England and Wales. Laryngoscope. 2006 Aug;116(8):1494-9. doi: 10.1097/01.mlg.0000230399.24306.50.</citation>
    <PMID>16885760</PMID>
  </reference>
  <reference>
    <citation>Gevaert P, Lang-Loidolt D, Lackner A, Stammberger H, Staudinger H, Van Zele T, Holtappels G, Tavernier J, van Cauwenberge P, Bachert C. Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps. J Allergy Clin Immunol. 2006 Nov;118(5):1133-41. doi: 10.1016/j.jaci.2006.05.031. Epub 2006 Sep 26.</citation>
    <PMID>17088140</PMID>
  </reference>
  <reference>
    <citation>Gevaert P, Calus L, Van Zele T, Blomme K, De Ruyck N, Bauters W, Hellings P, Brusselle G, De Bacquer D, van Cauwenberge P, Bachert C. Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol. 2013 Jan;131(1):110-6.e1. doi: 10.1016/j.jaci.2012.07.047. Epub 2012 Sep 27.</citation>
    <PMID>23021878</PMID>
  </reference>
  <reference>
    <citation>Gevaert P, Van Bruaene N, Cattaert T, Van Steen K, Van Zele T, Acke F, De Ruyck N, Blomme K, Sousa AR, Marshall RP, Bachert C. Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis. J Allergy Clin Immunol. 2011 Nov;128(5):989-95.e1-8. doi: 10.1016/j.jaci.2011.07.056. Epub 2011 Sep 28.</citation>
    <PMID>21958585</PMID>
  </reference>
  <results_reference>
    <citation>Benjamin MR, Stevens WW, Li N, Bose S, Grammer LC, Kern RC, Tan BK, Conley DB, Smith SS, Welch KC, Schleimer RP, Peters AT. Clinical Characteristics of Patients with Chronic Rhinosinusitis without Nasal Polyps in an Academic Setting. J Allergy Clin Immunol Pract. 2019 Mar;7(3):1010-1016. doi: 10.1016/j.jaip.2018.10.014. Epub 2018 Oct 25.</citation>
    <PMID>30368005</PMID>
  </results_reference>
  <results_reference>
    <citation>Wang X, Zhang N, Bo M, Holtappels G, Zheng M, Lou H, Wang H, Zhang L, Bachert C. Diversity of TH cytokine profiles in patients with chronic rhinosinusitis: A multicenter study in Europe, Asia, and Oceania. J Allergy Clin Immunol. 2016 Nov;138(5):1344-1353. doi: 10.1016/j.jaci.2016.05.041. Epub 2016 Jul 15.</citation>
    <PMID>27544740</PMID>
  </results_reference>
  <results_reference>
    <citation>Stevens WW, Peters AT, Tan BK, Klingler AI, Poposki JA, Hulse KE, Grammer LC, Welch KC, Smith SS, Conley DB, Kern RC, Schleimer RP, Kato A. Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis. J Allergy Clin Immunol Pract. 2019 Nov-Dec;7(8):2812-2820.e3. doi: 10.1016/j.jaip.2019.05.009. Epub 2019 May 22.</citation>
    <PMID>31128376</PMID>
  </results_reference>
  <results_reference>
    <citation>Han DH, Kim SW, Cho SH, Kim DY, Lee CH, Kim SS, Rhee CS. Predictors of bronchial hyperresponsiveness in chronic rhinosinusitis with nasal polyp. Allergy. 2009 Jan;64(1):118-22. doi: 10.1111/j.1398-9995.2008.01841.x. Epub 2008 Dec 17.</citation>
    <PMID>19120071</PMID>
  </results_reference>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>April 13, 2020</study_first_submitted>
  <study_first_submitted_qc>June 11, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 12, 2020</study_first_posted>
  <last_update_submitted>November 14, 2022</last_update_submitted>
  <last_update_submitted_qc>November 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 15, 2022</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>Sinusitis</mesh_term>
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Nasopharyngeal Neoplasms</mesh_term>
    <mesh_term>Nasal Polyps</mesh_term>
    <mesh_term>Chronic Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04430179
org study id: STUDY000808
nct id: NCT04430179
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The investigators will investigate the efficacy of dupilumab in patients with severe
      eosinophilic CRSsNP who are resistant to the conventional treatment with intranasal
      corticosteroids and have significantly extensive disease involving more than 2 sinuses
      bilaterally in sinus CT scan and Lund-Mackay sinus (LMK) CT score >=10 at baseline.
The investigators will use high blood eosinophils (>=200) as a biomarker for eosinophilic
      CRSsNP and investigate the efficacy of dupilumab in patients with severe eosinophilic CRSsNP
      who are resistant to the conventional treatment with intranasal corticosteroids and have
      significantly extensive disease involving more than 2 sinuses bilaterally in sinus CT scan
      and Lund-Mackay sinus (LMK) CT score >=10 at baseline. In addition, the investigators will
      have a prespecified enrollment goal of at least 50% of patients with type 2 inflammatory
      diseases such as asthma, allergic rhinitis, and/or atopic dermatitis on the basis of
      patient-reported history and will stratify subject numbers between dupilumab treatment and
      placebo group.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Active drug vs placebo
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double-blinded
measure: Change in Lund-Mackay sinus computed tomography (LMK-CT) score
time frame: 24 weeks
description: Change in LMK-CT score in dupilumab group compared to control group. The total score ranges from 0 (normal) - 24 (more opacified): higher score indicates worse status.
measure: Change in participant-reported symptoms scores of sinusitis
time frame: 24 weeks
description: Change in baseline in participant-reported symptoms scores of sinusitis in dupilumab group compared to control group. Morning symptoms of sinusitis will be assessed using a 0 (no symptoms) - 3 (severe symptoms) categorical scale, where a higher score indicates severe symptoms.
measure: Change in visual analogue scale score for sinusitis
time frame: 24 weeks
description: Change in visual analogue scale score for sinusitis in dupilumab group compared to control group. the severity of sinusitis symptoms will be assessed on a 0 cm (not troublesome) - 10 cm (worst thinkable troublesome) where a higher score indicates worst thinkable troublesome.
measure: Change in nasal peak inspiratory flow
time frame: 24 weeks
description: Change in nasal peak inspiratory flow in dupilumab group compared to placebo group.
measure: Change in University of Pennsylvania smell identification test (UPSIT) scores
time frame: 24 weeks
description: Change in UPSIT scores in dupilumab group compared to placebo group. Total score ranges from 0 (anosmia)-40 (normal sense of smell), a lower score indicates severe smell loss.
measure: Time to first response in LMK-CT score
time frame: 24 weeks
description: 50 percent improvement in LMK-CT score in dupilumab group compared to placebo group
measure: Change in sinonasal outcome test (SNOT-22) score
time frame: 24 weeks
description: Change in 22-item SNOT-22 test score in dupilumab group compared to placebo group. The total score may range from 0 (no problem)-110 (worst quality of life), higher scores represent the worst quality of life; minimal clinically important change ≥ 8.90.
measure: Change in biomarkers concentrations in nasal secretion measured by enzyme-linked immunosorbent assay (ELISA)
time frame: 24 weeks
description: Change in biomarkers concentrations in nasal secretion in dupilumab group compared to placebo group. ELISA will be done to measure biomarkers concentrations (pg/mL): ECP, IL-4, IL-5, IL-13, periostin, eotaxin-3, TARC, and IgE
arm group label: Active drug
arm group type: Active Comparator
description: Dupilumab 300 mg every other week for 24 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
intervention type: Drug
intervention name: Dupilumab 300 MG/2 ML Subcutaneous Solution [DUPIXENT]
description: 300 mg every other week for 24 weeks
arm group label: Active drug
intervention type: Other
intervention name: Placebo
description: No active drug
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Seong Cho, MD
role: Principal Investigator
affiliation: University of South Florida
last name: Thanh Q Tran, MPH
phone: 813-844-8544
email: tqtran@usf.edu
last name: Catherine Smith
phone: 813-631-4024
phone ext: 207
email: catherinesmith@usf.edu
facility: 
status: Recruiting
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country: United States
citation: Kim DY, Lee SH, Carter RG, Kato A, Schleimer RP, Cho SH. A Recently Established Murine Model of Nasal Polyps Demonstrates Activation of B Cells, as Occurs in Human Nasal Polyps. Am J Respir Cell Mol Biol. 2016 Aug;55(2):170-5. doi: 10.1165/rcmb.2016-0002RC.
PMID: 27163839
citation: Tokunaga T, Sakashita M, Haruna T, Asaka D, Takeno S, Ikeda H, Nakayama T, Seki N, Ito S, Murata J, Sakuma Y, Yoshida N, Terada T, Morikura I, Sakaida H, Kondo K, Teraguchi K, Okano M, Otori N, Yoshikawa M, Hirakawa K, Haruna S, Himi T, Ikeda K, Ishitoya J, Iino Y, Kawata R, Kawauchi H, Kobayashi M, Yamasoba T, Miwa T, Urashima M, Tamari M, Noguchi E, Ninomiya T, Imoto Y, Morikawa T, Tomita K, Takabayashi T, Fujieda S. Novel scoring system and algorithm for classifying chronic rhinosinusitis: the JESREC Study. Allergy. 2015 Aug;70(8):995-1003. doi: 10.1111/all.12644. Epub 2015 May 26.
PMID: 25945591
citation: Hu Y, Cao PP, Liang GT, Cui YH, Liu Z. Diagnostic significance of blood eosinophil count in eosinophilic chronic rhinosinusitis with nasal polyps in Chinese adults. Laryngoscope. 2012 Mar;122(3):498-503. doi: 10.1002/lary.22507. Epub 2012 Jan 17.
PMID: 22252861
citation: Ho J, Hamizan AW, Alvarado R, Rimmer J, Sewell WA, Harvey RJ. Systemic Predictors of Eosinophilic Chronic Rhinosinusitis. Am J Rhinol Allergy. 2018 Jul;32(4):252-257. doi: 10.1177/1945892418779451. Epub 2018 Jun 4.
PMID: 29862828
citation: Thwaites RS, Gunawardana NC, Broich V, Mann EH, Ahnstrom J, Campbell GA, Lindsley S, Singh N, Tunstall T, Lane DA, Openshaw PJ, Hawrylowicz CM, Hansel TT. Biphasic activation of complement and fibrinolysis during the human nasal allergic response. J Allergy Clin Immunol. 2018 May;141(5):1892-1895.e6. doi: 10.1016/j.jaci.2018.01.022. Epub 2018 Feb 7. No abstract available.
PMID: 29427640
citation: Hopkins C, Browne JP, Slack R, Lund VJ, Topham J, Reeves BC, Copley LP, Brown P, van der Meulen JH. Complications of surgery for nasal polyposis and chronic rhinosinusitis: the results of a national audit in England and Wales. Laryngoscope. 2006 Aug;116(8):1494-9. doi: 10.1097/01.mlg.0000230399.24306.50.
PMID: 16885760
citation: Gevaert P, Lang-Loidolt D, Lackner A, Stammberger H, Staudinger H, Van Zele T, Holtappels G, Tavernier J, van Cauwenberge P, Bachert C. Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps. J Allergy Clin Immunol. 2006 Nov;118(5):1133-41. doi: 10.1016/j.jaci.2006.05.031. Epub 2006 Sep 26.
PMID: 17088140
citation: Gevaert P, Calus L, Van Zele T, Blomme K, De Ruyck N, Bauters W, Hellings P, Brusselle G, De Bacquer D, van Cauwenberge P, Bachert C. Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol. 2013 Jan;131(1):110-6.e1. doi: 10.1016/j.jaci.2012.07.047. Epub 2012 Sep 27.
PMID: 23021878
citation: Gevaert P, Van Bruaene N, Cattaert T, Van Steen K, Van Zele T, Acke F, De Ruyck N, Blomme K, Sousa AR, Marshall RP, Bachert C. Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis. J Allergy Clin Immunol. 2011 Nov;128(5):989-95.e1-8. doi: 10.1016/j.jaci.2011.07.056. Epub 2011 Sep 28.
PMID: 21958585
citation: Benjamin MR, Stevens WW, Li N, Bose S, Grammer LC, Kern RC, Tan BK, Conley DB, Smith SS, Welch KC, Schleimer RP, Peters AT. Clinical Characteristics of Patients with Chronic Rhinosinusitis without Nasal Polyps in an Academic Setting. J Allergy Clin Immunol Pract. 2019 Mar;7(3):1010-1016. doi: 10.1016/j.jaip.2018.10.014. Epub 2018 Oct 25.
PMID: 30368005
citation: Wang X, Zhang N, Bo M, Holtappels G, Zheng M, Lou H, Wang H, Zhang L, Bachert C. Diversity of TH cytokine profiles in patients with chronic rhinosinusitis: A multicenter study in Europe, Asia, and Oceania. J Allergy Clin Immunol. 2016 Nov;138(5):1344-1353. doi: 10.1016/j.jaci.2016.05.041. Epub 2016 Jul 15.
PMID: 27544740
citation: Stevens WW, Peters AT, Tan BK, Klingler AI, Poposki JA, Hulse KE, Grammer LC, Welch KC, Smith SS, Conley DB, Kern RC, Schleimer RP, Kato A. Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis. J Allergy Clin Immunol Pract. 2019 Nov-Dec;7(8):2812-2820.e3. doi: 10.1016/j.jaip.2019.05.009. Epub 2019 May 22.
PMID: 31128376
citation: Han DH, Kim SW, Cho SH, Kim DY, Lee CH, Kim SS, Rhee CS. Predictors of bronchial hyperresponsiveness in chronic rhinosinusitis with nasal polyp. Allergy. 2009 Jan;64(1):118-22. doi: 10.1111/j.1398-9995.2008.01841.x. Epub 2008 Dec 17.
PMID: 19120071
responsible party type: Sponsor
mesh term: Sinusitis
mesh term: Colorectal Neoplasms
mesh term: Nasopharyngeal Neoplasms
mesh term: Nasal Polyps
mesh term: Chronic Disease
mesh term: Antibodies, Monoclonal
sharing ipd: No