xml: <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/NCT06019000</url>
    </required_header>
    <id_info>
      <org_study_id>CYR-064-01</org_study_id>
      <nct_id>NCT06019000</nct_id>
    </id_info>
    <brief_title>Study of CYR-064 Versus Placebo in Patients.</brief_title>
    <official_title>A Randomized, Double-Blinded, Placebo-Controlled Trial to Determine The Safety and Efficacy of CYR-064</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Cyrano Therapeutics, Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Cyrano Therapeutics, Inc.</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>Yes</is_fda_regulated_device>
      <is_unapproved_device>Yes</is_unapproved_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Randomized, double-blinded, placebo-controlled trial to determine the safety and efficacy of&#xD;
        CYR-064.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The purpose of this study is to determine the safety and effectiveness of CYR-064 in a&#xD;
        randomized, double-blinded, placebo-controlled trial to determine the safety and efficacy of&#xD;
        CYR064.&#xD;
  &#xD;
        The study will take approximately 32 weeks which will include a 4-week screening period to&#xD;
        evaluate if participants are right for the Study, followed by a 24-week Treatment Period, and&#xD;
        a 1 week follow up after participants have completed the Study. About 150 subjects will&#xD;
        participate in this study in about 25 research sites in the United States.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 6, 2023</start_date>
    <completion_date type="Anticipated">January 30, 2025</completion_date>
    <primary_completion_date type="Anticipated">September 30, 2024</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>The study treatment of CYR-064 is administered for a 24-week Treatment Period. Patients who meet all study criteria and have consented to participation will be randomized (1:1:1) to three parallel study arms, with two different dose strengths and a placebo group over 24 weeks.&#xD;
  CYR-064 dose 1 CYR-064 dose 2 Placebo</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <masking_description>There will be a placebo match and blinded randomization.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Primary Outcome - Safety and Tolerability</measure>
      <time_frame>Approximately 32 weeks</time_frame>
      <description>The count and percentage of patients reporting AEs, SAEs, and SUSARs will be summarized overall, by System Organ Class, Preferred Term within the System Organ Class, maximum severity, and relationship to study drug. All other safety parameters, including clinical laboratory values through blood draws, will be summarized using descriptive statistics for continuous variables and counts and percentages for categorical variables. All changes in nasal mucosal appearance will be noted.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Secondary Outcome-improvement on NRS-11 Smell-PRO</measure>
      <time_frame>Approximately 24 weeks</time_frame>
      <description>Improvement in patient reported NRS-11 Smell-PRO (scale of 0-10) in CYR-064 low dose and high dose groups as compared with placebo from Baseline to Week 24.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Secondary Outcome-improvement on NRS-11 Taste-PRO</measure>
      <time_frame>Approximately 24 weeks</time_frame>
      <description>Improvement in patient reported NRS-11 Taste-PRO (scale of 0-10) in CYR-064 low dose and high dose groups as compared with placebo from Baseline to Week 24.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Secondary Outcome-Mean Change in NRS-11 Smell-PRO</measure>
      <time_frame>Approximately 24 weeks</time_frame>
      <description>Mean Change in NRS-11 Smell-PRO from Baseline to Week 24 between CYR-064 low and high dose and placebo from Baseline to Week 24</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Secondary Outcome-Mean Change in NRS-11 Taste-PRO</measure>
      <time_frame>Approximately 24 weeks</time_frame>
      <description>Mean Change in NRS-11 Taste-PRO from Baseline to Week 24 between CYR-064 low and high dose and placebo from Baseline to Week 2</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Visual Rating Scale (VRS) scores</measure>
      <time_frame>Approximately 24 weeks</time_frame>
      <description>Change in Visual Rating Scale (VRS) scores in CYR-064 low dose and high dose groups as compared with placebo from Baseline to Week 24.&#xD;
  VRS high dose versus placebo&#xD;
  VRS low dose versus placebo&#xD;
  VRS low and high dose combined versus placebo</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">150</enrollment>
    <condition>Hyposmia</condition>
    <arm_group>
      <arm_group_label>CYR-064 dose 1</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Treatment with nasal solution of CYR-064 twice a day for 24 weeks. CYR-064 will be self-administered by patients.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>CYR-064 dose 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Treatment with nasal solution of CYR-064 twice a day for 24 weeks. CYR-064 will be self-administered by patients.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Treatment with Placebo nasal solution for 24 weeks. CYR-064 will be self-administered by patients.</description>
    </arm_group>
    <intervention>
      <intervention_type>Combination Product</intervention_type>
      <intervention_name>CYR-064</intervention_name>
      <description>CYR-064 is a nasal solution.</description>
      <arm_group_label>CYR-064 dose 1</arm_group_label>
      <arm_group_label>CYR-064 dose 2</arm_group_label>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Able to provide written informed consent.&#xD;
  &#xD;
            -  Male or female 18-65 years of age.&#xD;
  &#xD;
            -  Endoscopy of the nasal cavity showing no structural or pathologic issues leading to&#xD;
               hyposmia (nasal polyps, sinusitis, infection, etc.) that in the opinion of the&#xD;
               Investigator, believes would hinder the delivery of study drug to the olfactory&#xD;
               receptors.&#xD;
  &#xD;
            -  CT scan of the nasal cavity after the onset of hyposmia (within prior 2 years) prior&#xD;
               to Baseline showing no structural or pathologic issue leading to hyposmia that in the&#xD;
               opinion of the Investigator, believes would hinder the delivery of study drug to the&#xD;
               olfactory receptors.&#xD;
  &#xD;
            -  Willing and able to self-administer the study drug, follow the study drug&#xD;
               administration instructions, comply with study procedures, and participate in the&#xD;
               scheduled study visits specified in this protocol.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  History of traumatic brain injury, Parkinson's disease, early dementia, Alzheimer's&#xD;
               disease, or any other condition in which hyposmia is not expected to improve in the&#xD;
               opinion of the Investigator, such as history of congenital or idiopathic hyposmia or a&#xD;
               surgical procedure that led to hyposmia.&#xD;
  &#xD;
            -  History of surgery that led to hyposmia.&#xD;
  &#xD;
            -  Concomitant Medical Conditions&#xD;
  &#xD;
            -  Current symptoms or signs of an acute respiratory viral illness at Screening or&#xD;
               Baseline.&#xD;
  &#xD;
            -  Chronic viral infection or immunodeficiency condition (e.g., medical history of human&#xD;
               immunodeficiency virus) based on medical records.&#xD;
  &#xD;
            -  Any active malignancy.&#xD;
  &#xD;
            -  Any concomitant medical condition that in the opinion of the Investigator, compromises&#xD;
               patient safety or compliance with the study protocol or collected data.&#xD;
  &#xD;
            -  History of moderate to severe Substance Use Disorder within the past 3 years as&#xD;
               assessed by the Investigator.&#xD;
  &#xD;
            -  History of persistent chronic sinusitis without polyps or chronic sinusitis with&#xD;
               polyps.&#xD;
  &#xD;
            -  Use or planned use of tobacco or nicotine-containing products, including smoking,&#xD;
               smokeless tobacco, e-cigarettes, or nicotine replacement products within 3 months&#xD;
               prior to Screening through EOS.&#xD;
  &#xD;
            -  Unwilling or unable to discontinue current or planned use of over the counter or&#xD;
               prescription medication administered intranasally, with the exception of nasal saline.&#xD;
  &#xD;
            -  Use or planned use of another investigational drug within 4 weeks prior to Screening&#xD;
               through Follow-Up.&#xD;
  &#xD;
            -  Receiving any concomitant medication/therapy that would, in the opinion of the&#xD;
               Investigator, compromise patient safety or compliance with the study protocol or&#xD;
               collected data.&#xD;
  &#xD;
            -  General Exclusions Any female who is pregnant, planning to become pregnant during the&#xD;
               study, or who is lactating.&#xD;
  &#xD;
          Vulnerable patients. Any condition or abnormality (including clinical laboratory, physical&#xD;
          examination, or vital sign abnormalities), current or past, that, in the opinion of the&#xD;
          Investigator, would compromise the efficacy evaluation, safety of the patient, or would&#xD;
          interfere with or complicate study procedures or assessments.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <reference>
      <citation>Henkin RI. Growth Factors in Olfaction. In: Preedy VR, editor. Handbook of Growth and Growth Monitoring in Health and Disease. New York, NY: Springer New York; 2012. p. 1417-36.</citation>
    </reference>
    <reference>
      <citation>Henkin RI, Abdelmeguid M. Improved Smell and Taste Dysfunction with Intranasal Theophylline. Am J Otolaryngol Head Neck Surg. 2019;2(9):1070.</citation>
    </reference>
    <results_reference>
      <citation>Henkin RI, Levy LM, Fordyce A. Taste and smell function in chronic disease: a review of clinical and biochemical evaluations of taste and smell dysfunction in over 5000 patients at The Taste and Smell Clinic in Washington, DC. Am J Otolaryngol. 2013 Sep-Oct;34(5):477-89. doi: 10.1016/j.amjoto.2013.04.006. Epub 2013 Jun 2.</citation>
      <PMID>23731850</PMID>
    </results_reference>
    <results_reference>
      <citation>Henkin RI. Comparative monitoring of oral theophylline treatment in blood serum, saliva, and nasal mucus. Ther Drug Monit. 2012 Apr;34(2):217-21. doi: 10.1097/FTD.0b013e3182492a20.</citation>
      <PMID>22377744</PMID>
    </results_reference>
    <results_reference>
      <citation>Henkin RI, Hosein S, Stateman WA, Knoppel AB, Abdelmeguid M. Improved smell function with increased nasal mucus sonic hedgehog in hyposmic patients after treatment with oral theophylline. Am J Otolaryngol. 2017 Mar-Apr;38(2):143-147. doi: 10.1016/j.amjoto.2016.11.010. Epub 2016 Nov 23.</citation>
      <PMID>27923495</PMID>
    </results_reference>
    <results_reference>
      <citation>Henkin RI, Schultz M, Minnick-Poppe L. Intranasal theophylline treatment of hyposmia and hypogeusia: a pilot study. Arch Otolaryngol Head Neck Surg. 2012 Nov;138(11):1064-70. doi: 10.1001/2013.jamaoto.342.</citation>
      <PMID>23165381</PMID>
    </results_reference>
    <results_reference>
      <citation>Henkin RI, Velicu I. cAMP and cGMP in nasal mucus related to severity of smell loss in patients with smell dysfunction. Clin Invest Med. 2008;31(2):E78-84. doi: 10.25011/cim.v31i2.3367.</citation>
      <PMID>18377764</PMID>
    </results_reference>
    <results_reference>
      <citation>Henkin RI, Velicu I, Schmidt L. An open-label controlled trial of theophylline for treatment of patients with hyposmia. Am J Med Sci. 2009 Jun;337(6):396-406. doi: 10.1097/MAJ.0b013e3181914a97.</citation>
      <PMID>19359985</PMID>
    </results_reference>
    <results_reference>
      <citation>Henkin RI, Velicu I, Schmidt L. Relative resistance to oral theophylline treatment in patients with hyposmia manifested by decreased secretion of nasal mucus cyclic nucleotides. Am J Med Sci. 2011 Jan;341(1):17-22. doi: 10.1097/MAJ.0b013e3181f1fdc8.</citation>
      <PMID>21191261</PMID>
    </results_reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>May 11, 2023</study_first_submitted>
    <study_first_submitted_qc>August 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 31, 2023</study_first_posted>
    <last_update_submitted>August 24, 2023</last_update_submitted>
    <last_update_submitted_qc>August 24, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 31, 2023</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>Anosmia</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>Descriptive statistics</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06019000
  org study id: CYR-064-01
  nct id: NCT06019000
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: Yes
  is unapproved device: Yes
  Randomized, double-blinded, placebo-controlled trial to determine the safety and efficacy of
        CYR-064.
  The purpose of this study is to determine the safety and effectiveness of CYR-064 in a
        randomized, double-blinded, placebo-controlled trial to determine the safety and efficacy of
        CYR064.
  
        The study will take approximately 32 weeks which will include a 4-week screening period to
        evaluate if participants are right for the Study, followed by a 24-week Treatment Period, and
        a 1 week follow up after participants have completed the Study. About 150 subjects will
        participate in this study in about 25 research sites in the United States.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: The study treatment of CYR-064 is administered for a 24-week Treatment Period. Patients who meet all study criteria and have consented to participation will be randomized (1:1:1) to three parallel study arms, with two different dose strengths and a placebo group over 24 weeks.
  CYR-064 dose 1 CYR-064 dose 2 Placebo
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  masking description: There will be a placebo match and blinded randomization.
  measure: Primary Outcome - Safety and Tolerability
  time frame: Approximately 32 weeks
  description: The count and percentage of patients reporting AEs, SAEs, and SUSARs will be summarized overall, by System Organ Class, Preferred Term within the System Organ Class, maximum severity, and relationship to study drug. All other safety parameters, including clinical laboratory values through blood draws, will be summarized using descriptive statistics for continuous variables and counts and percentages for categorical variables. All changes in nasal mucosal appearance will be noted.
  measure: Secondary Outcome-improvement on NRS-11 Smell-PRO
  time frame: Approximately 24 weeks
  description: Improvement in patient reported NRS-11 Smell-PRO (scale of 0-10) in CYR-064 low dose and high dose groups as compared with placebo from Baseline to Week 24.
  measure: Secondary Outcome-improvement on NRS-11 Taste-PRO
  time frame: Approximately 24 weeks
  description: Improvement in patient reported NRS-11 Taste-PRO (scale of 0-10) in CYR-064 low dose and high dose groups as compared with placebo from Baseline to Week 24.
  measure: Secondary Outcome-Mean Change in NRS-11 Smell-PRO
  time frame: Approximately 24 weeks
  description: Mean Change in NRS-11 Smell-PRO from Baseline to Week 24 between CYR-064 low and high dose and placebo from Baseline to Week 24
  measure: Secondary Outcome-Mean Change in NRS-11 Taste-PRO
  time frame: Approximately 24 weeks
  description: Mean Change in NRS-11 Taste-PRO from Baseline to Week 24 between CYR-064 low and high dose and placebo from Baseline to Week 2
  measure: Change in Visual Rating Scale (VRS) scores
  time frame: Approximately 24 weeks
  description: Change in Visual Rating Scale (VRS) scores in CYR-064 low dose and high dose groups as compared with placebo from Baseline to Week 24.
  VRS high dose versus placebo
  VRS low dose versus placebo
  VRS low and high dose combined versus placebo
  arm group label: CYR-064 dose 1
  arm group type: Active Comparator
  description: Treatment with nasal solution of CYR-064 twice a day for 24 weeks. CYR-064 will be self-administered by patients.
  arm group label: CYR-064 dose 2
  arm group type: Experimental
  description: Treatment with nasal solution of CYR-064 twice a day for 24 weeks. CYR-064 will be self-administered by patients.
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Treatment with Placebo nasal solution for 24 weeks. CYR-064 will be self-administered by patients.
  intervention type: Combination Product
  intervention name: CYR-064
  description: CYR-064 is a nasal solution.
  arm group label: CYR-064 dose 1
  arm group label: CYR-064 dose 2
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: Accepts Healthy Volunteers
  citation: Henkin RI. Growth Factors in Olfaction. In: Preedy VR, editor. Handbook of Growth and Growth Monitoring in Health and Disease. New York, NY: Springer New York; 2012. p. 1417-36.
  citation: Henkin RI, Abdelmeguid M. Improved Smell and Taste Dysfunction with Intranasal Theophylline. Am J Otolaryngol Head Neck Surg. 2019;2(9):1070.
  citation: Henkin RI, Levy LM, Fordyce A. Taste and smell function in chronic disease: a review of clinical and biochemical evaluations of taste and smell dysfunction in over 5000 patients at The Taste and Smell Clinic in Washington, DC. Am J Otolaryngol. 2013 Sep-Oct;34(5):477-89. doi: 10.1016/j.amjoto.2013.04.006. Epub 2013 Jun 2.
  PMID: 23731850
  citation: Henkin RI. Comparative monitoring of oral theophylline treatment in blood serum, saliva, and nasal mucus. Ther Drug Monit. 2012 Apr;34(2):217-21. doi: 10.1097/FTD.0b013e3182492a20.
  PMID: 22377744
  citation: Henkin RI, Hosein S, Stateman WA, Knoppel AB, Abdelmeguid M. Improved smell function with increased nasal mucus sonic hedgehog in hyposmic patients after treatment with oral theophylline. Am J Otolaryngol. 2017 Mar-Apr;38(2):143-147. doi: 10.1016/j.amjoto.2016.11.010. Epub 2016 Nov 23.
  PMID: 27923495
  citation: Henkin RI, Schultz M, Minnick-Poppe L. Intranasal theophylline treatment of hyposmia and hypogeusia: a pilot study. Arch Otolaryngol Head Neck Surg. 2012 Nov;138(11):1064-70. doi: 10.1001/2013.jamaoto.342.
  PMID: 23165381
  citation: Henkin RI, Velicu I. cAMP and cGMP in nasal mucus related to severity of smell loss in patients with smell dysfunction. Clin Invest Med. 2008;31(2):E78-84. doi: 10.25011/cim.v31i2.3367.
  PMID: 18377764
  citation: Henkin RI, Velicu I, Schmidt L. An open-label controlled trial of theophylline for treatment of patients with hyposmia. Am J Med Sci. 2009 Jun;337(6):396-406. doi: 10.1097/MAJ.0b013e3181914a97.
  PMID: 19359985
  citation: Henkin RI, Velicu I, Schmidt L. Relative resistance to oral theophylline treatment in patients with hyposmia manifested by decreased secretion of nasal mucus cyclic nucleotides. Am J Med Sci. 2011 Jan;341(1):17-22. doi: 10.1097/MAJ.0b013e3181f1fdc8.
  PMID: 21191261
  responsible party type: Sponsor
  mesh term: Anosmia
  sharing ipd: No
  ipd description: Descriptive statistics