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/NCT05983471</url>
    </required_header>
    <id_info>
      <org_study_id>COSMIC-IPF</org_study_id>
      <secondary_id>SYNCD-070-22</secondary_id>
      <nct_id>NCT05983471</nct_id>
    </id_info>
    <brief_title>Efficacy and Safety of ME-015 (Suplatast Tosilate) in Cough Related to Idiopathic Pulmonary Fibrosis (COSMIC-IPF)</brief_title>
    <acronym>COSMIC-IPF</acronym>
    <official_title>A Randomized, Double-blind, Placebo-controlled, Cross-over Trial to Evaluate the Efficacy and Safety of ME-015 (Suplatast Tosilate) in Cough Related to Idiopathic Pulmonary Fibrosis</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Melius Pharma AB</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Melius Pharma AB</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Orally administered ME-015 (Suplatast Tosilate) has been available on the market as a&#xD;
        prescription drug for allergy-related conditions in Japan since 1995 with a very good safety&#xD;
        and tolerability profile.&#xD;
  &#xD;
        There is preclinical and exploratory clinical evidence suggesting that ME-015 may be&#xD;
        effective in treating cough caused by idiopathic pulmonary fibrosis (IPF-cough).&#xD;
  &#xD;
        80% of patients with idiopathic pulmonary fibrosis (IPF) are affected by a devastating dry&#xD;
        cough that is often not responsive to standard cough treatments and causes significant&#xD;
        psychological and physiological suffering as well as reduced quality of life. As of July&#xD;
        2023, there is no approved treatment for the indication of IPF-cough. There is an enormous&#xD;
        unmet clinical need for an effective, safe and well-tolerated oral treatment.&#xD;
  &#xD;
        The COSMIC-IPF Phase 2 trial is the first clinical trial assessing ME-015 for the treatment&#xD;
        of IPF-cough and aims to generate clinical proof-of-concept results regarding the safety and&#xD;
        efficacy of ME-015 in this condition.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This double-blind, cross-over, placebo-controlled clinical trial will randomize patients with&#xD;
        stable idiopathic pulmonary fibrosis (IPF) and cough related to IPF (IPF-cough) in a 1:1&#xD;
        fashion to one of two treatment sequences: active treatment followed by placebo, or placebo&#xD;
        followed by active treatment. Each 14-day active/placebo treatment phase is preceded by a&#xD;
        wash-out period. The treatment sequences are followed by an observational 7-day follow-up&#xD;
        period without medication. All subjects in the trial receive standard-of-care antifibrotic&#xD;
        treatment for IPF.&#xD;
  &#xD;
        Treatment assignment is blinded to patients, investigators, site personnel, data analysts and&#xD;
        Sponsor. The active treatment is ME-015 (Suplatast Tosilate) 200 mg t.i.d. (three times per&#xD;
        day) administered as oral capsules. The placebo treatment consists of identical capsules&#xD;
        without the active component.&#xD;
  &#xD;
        The primary efficacy endpoint is the effect on wake time cough frequency measured objectively&#xD;
        with the VitaloJak device over a 24-hour period. VitaloJak recordings are analysed using a&#xD;
        blinded, independent, central review process.&#xD;
  &#xD;
        The study is conducted as a single-country, multi-site clinical trial in India with Melius&#xD;
        Pharma AB as the Sponsor.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 2023</start_date>
    <completion_date type="Anticipated">March 2025</completion_date>
    <primary_completion_date type="Anticipated">March 2025</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>Crossover Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <masking_description>Interactive web response system (IWRS)</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Wake time cough frequency during 24 hours</measure>
      <time_frame>Change from Baseline to Day 14 in the respective treatment period</time_frame>
      <description>Measured objectively with the cough recording device VitaloJak with centralized, blinded, independent analysis</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Cough severity in the last 24 hours</measure>
      <time_frame>Change from Baseline to Day 14 in the respective treatment period</time_frame>
      <description>Visual Analogue Scale (VAS) ranging from 0 - 100 mm where higher values indicate more severe cough</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cough-related quality of life in the last 24 hours</measure>
      <time_frame>Change from Baseline to Day 14 in the respective treatment period</time_frame>
      <description>Leicester Cough Questionnaire (LCQ) total score ranging from 3 - 23 where lower values indicate greater impairment of health status due to cough</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall patient-reported health status</measure>
      <time_frame>Change from Baseline to Day 14 in the respective treatment period</time_frame>
      <description>Global Rating of Change Scale of cough severity (range -7 to +7) and cough frequency (range -7 to +7) where 0 indicates no change, higher values above 0 indicate larger improvement, and lower values below 0 indicate increased declined</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety: Treatment-Emergent Adverse Events</measure>
      <time_frame>Number of TEAEs from Baseline to Day 14 in the respective treatment period</time_frame>
      <description>Number of patients in each treatment period (active or placebo) who experience a treatment-emergent adverse event (TEAE)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety: Serious Adverse Events</measure>
      <time_frame>Number of SAEs from Baseline to Day 14 in the respective treatment period</time_frame>
      <description>Number of patients in each treatment period (active or placebo) who experience a serious adverse event (SAE)</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Idiopathic Pulmonary Fibrosis</condition>
    <condition>Cough</condition>
    <arm_group>
      <arm_group_label>ME-015 (Suplatast Tosilate)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>ME-015 (Suplatast Tosilate) 2 x 100 mg capsule t.i.d. (three times per day), for 2 weeks</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Identical placebo capsules 2 x t.i.d. (three times per day), for 2 weeks</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>ME-015 (Suplatast Tosilate)</intervention_name>
      <description>Oral capsule form, 200 mg t.i.d. (total 600 mg per 24 hours)</description>
      <arm_group_label>ME-015 (Suplatast Tosilate)</arm_group_label>
      <other_name>Suplatast</other_name>
      <other_name>Suplatast Tosilate</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Identical placebo</intervention_name>
      <description>Without active component</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Diagnosis of idiopathic pulmonary fibrosis (IPF) according to the 2018 American&#xD;
               Thoracic Society (ATS) guidelines, confirmed by high-resolution computed tomography&#xD;
               (HRCT) chest scan taken within &lt; 2 years&#xD;
  &#xD;
            -  Age ≥ 18 years&#xD;
  &#xD;
            -  Cough attributed to IPF unresponsive to standard anti-tussive treatment and present&#xD;
               for &gt; 8 weeks&#xD;
  &#xD;
            -  Arithmetic mean of ≥ 10 coughs/hour during waking hours&#xD;
  &#xD;
            -  Ability to read, comprehend, and complete the informed consent form (ICF) and all&#xD;
               questionnaires in the study without help&#xD;
  &#xD;
            -  Cough severity score of ≥ 40 mm on a 0-to-100 mm Visual Analogue Scale (VAS)&#xD;
  &#xD;
            -  Life expectancy &gt; 6 months&#xD;
  &#xD;
            -  Stable medical condition: stable treatment for &gt; 12 weeks and absence of acute&#xD;
               exacerbations for &gt; 4 weeks&#xD;
  &#xD;
            -  Antifibrotics pirfenidone and nintedanib are allowed if the patient has been on a&#xD;
               stable dose for ≥ 12 weeks and remains on a stable dose throughout the study&#xD;
  &#xD;
            -  Forced vital capacity (FVC) ≥ 40% predicted&#xD;
  &#xD;
            -  Ratio between forced expiratory volume in one second and forced vital capacity (FEV1 /&#xD;
               FVC) ≥ 65%&#xD;
  &#xD;
            -  Women of childbearing potential must agree to use a highly effective method of&#xD;
               contraception&#xD;
  &#xD;
            -  Male partner must agree to use a condom during the study, unless they had a vasectomy&#xD;
               &gt; 6 months prior to first study drug administration&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Likely need for lung transplantation in next 12 months&#xD;
  &#xD;
            -  Permanent long-term oxygen therapy&#xD;
  &#xD;
            -  Use of high-dose corticosteroids or cytotoxic medications&#xD;
  &#xD;
            -  History of unstable or deteriorating cardiac or pulmonary disease in the preceding 6&#xD;
               months&#xD;
  &#xD;
            -  Current smoking, vaping, or tobacco chewing&#xD;
  &#xD;
            -  Treatment with an angiotensin-converting enzyme (ACE) inhibitor or sitagliptin started&#xD;
               in the last 12 weeks&#xD;
  &#xD;
            -  Suspected acute infection, including COVID-19 or influenza or any upper respiratory&#xD;
               tract infection&#xD;
  &#xD;
            -  History of malignancy within the last 2 years&#xD;
  &#xD;
            -  History of drug/alcohol dependency/abuse within the last 2 years&#xD;
  &#xD;
            -  Recent history of stroke or transient ischemic attack&#xD;
  &#xD;
            -  Blood pressure &gt; 160/90 mmHg&#xD;
  &#xD;
            -  Pregnant/lactating women&#xD;
  &#xD;
            -  Exposure to an investigational drug or biologic within the last 2 months&#xD;
  &#xD;
            -  Blood donation within the last 56 days or plasma donation within the last 7 days&#xD;
  &#xD;
            -  Body Mass Index &lt; 18 kg/m2 or ≥ 40 kg/m2&#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_contact>
      <last_name>Christoph Nowak, MD, PhD, Dipl-Psych</last_name>
      <phone>+46739806535</phone>
      <email>chris.nowak@meliuspharma.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Aditya Multi Specialty Hospital</name>
        <address>
          <city>Guntur</city>
          <state>Andhra Pradesh</state>
          <country>India</country>
        </address>
      </facility>
      <contact>
        <last_name>Goli M Venkata Kasiram, MD</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Hindusthan Hospital</name>
        <address>
          <city>Chennai</city>
          <state>Tamil Nadu</state>
          <country>India</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Government Chest Hospital</name>
        <address>
          <city>Hyderabad</city>
          <state>Telangana</state>
          <country>India</country>
        </address>
      </facility>
      <contact>
        <last_name>Karthik Velimala, MD</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Health Point Hospital</name>
        <address>
          <city>Kolkata</city>
          <state>West Bengal</state>
          <country>India</country>
        </address>
      </facility>
      <contact>
        <last_name>Amitabha Sengupta, MD</last_name>
      </contact>
    </location>
    <location_countries>
      <country>India</country>
    </location_countries>
    <link>
      <url>https://www.meliuspharma.com/</url>
      <description>Sponsor website</description>
    </link>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 24, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 1, 2023</last_update_submitted>
    <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 9, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>IPF-cough</keyword>
    <keyword>IPF cough</keyword>
    <keyword>Idiopathic Pulmonary Fibrosis</keyword>
    <keyword>Chronic cough</keyword>
    <keyword>Suplatast</keyword>
    <keyword>Melius</keyword>
    <keyword>Refractory cough</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Pulmonary Fibrosis</mesh_term>
      <mesh_term>Cough</mesh_term>
      <mesh_term>Idiopathic Pulmonary Fibrosis</mesh_term>
      <mesh_term>Fibrosis</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Suplatast tosilate</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </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/NCT05983471
  org study id: COSMIC-IPF
  secondary id: SYNCD-070-22
  nct id: NCT05983471
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  Orally administered ME-015 (Suplatast Tosilate) has been available on the market as a
        prescription drug for allergy-related conditions in Japan since 1995 with a very good safety
        and tolerability profile.
  
        There is preclinical and exploratory clinical evidence suggesting that ME-015 may be
        effective in treating cough caused by idiopathic pulmonary fibrosis (IPF-cough).
  
        80% of patients with idiopathic pulmonary fibrosis (IPF) are affected by a devastating dry
        cough that is often not responsive to standard cough treatments and causes significant
        psychological and physiological suffering as well as reduced quality of life. As of July
        2023, there is no approved treatment for the indication of IPF-cough. There is an enormous
        unmet clinical need for an effective, safe and well-tolerated oral treatment.
  
        The COSMIC-IPF Phase 2 trial is the first clinical trial assessing ME-015 for the treatment
        of IPF-cough and aims to generate clinical proof-of-concept results regarding the safety and
        efficacy of ME-015 in this condition.
  This double-blind, cross-over, placebo-controlled clinical trial will randomize patients with
        stable idiopathic pulmonary fibrosis (IPF) and cough related to IPF (IPF-cough) in a 1:1
        fashion to one of two treatment sequences: active treatment followed by placebo, or placebo
        followed by active treatment. Each 14-day active/placebo treatment phase is preceded by a
        wash-out period. The treatment sequences are followed by an observational 7-day follow-up
        period without medication. All subjects in the trial receive standard-of-care antifibrotic
        treatment for IPF.
  
        Treatment assignment is blinded to patients, investigators, site personnel, data analysts and
        Sponsor. The active treatment is ME-015 (Suplatast Tosilate) 200 mg t.i.d. (three times per
        day) administered as oral capsules. The placebo treatment consists of identical capsules
        without the active component.
  
        The primary efficacy endpoint is the effect on wake time cough frequency measured objectively
        with the VitaloJak device over a 24-hour period. VitaloJak recordings are analysed using a
        blinded, independent, central review process.
  
        The study is conducted as a single-country, multi-site clinical trial in India with Melius
        Pharma AB as the Sponsor.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  masking description: Interactive web response system (IWRS)
  measure: Wake time cough frequency during 24 hours
  time frame: Change from Baseline to Day 14 in the respective treatment period
  description: Measured objectively with the cough recording device VitaloJak with centralized, blinded, independent analysis
  measure: Cough severity in the last 24 hours
  time frame: Change from Baseline to Day 14 in the respective treatment period
  description: Visual Analogue Scale (VAS) ranging from 0 - 100 mm where higher values indicate more severe cough
  measure: Cough-related quality of life in the last 24 hours
  time frame: Change from Baseline to Day 14 in the respective treatment period
  description: Leicester Cough Questionnaire (LCQ) total score ranging from 3 - 23 where lower values indicate greater impairment of health status due to cough
  measure: Overall patient-reported health status
  time frame: Change from Baseline to Day 14 in the respective treatment period
  description: Global Rating of Change Scale of cough severity (range -7 to +7) and cough frequency (range -7 to +7) where 0 indicates no change, higher values above 0 indicate larger improvement, and lower values below 0 indicate increased declined
  measure: Safety: Treatment-Emergent Adverse Events
  time frame: Number of TEAEs from Baseline to Day 14 in the respective treatment period
  description: Number of patients in each treatment period (active or placebo) who experience a treatment-emergent adverse event (TEAE)
  measure: Safety: Serious Adverse Events
  time frame: Number of SAEs from Baseline to Day 14 in the respective treatment period
  description: Number of patients in each treatment period (active or placebo) who experience a serious adverse event (SAE)
  arm group label: ME-015 (Suplatast Tosilate)
  arm group type: Experimental
  description: ME-015 (Suplatast Tosilate) 2 x 100 mg capsule t.i.d. (three times per day), for 2 weeks
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Identical placebo capsules 2 x t.i.d. (three times per day), for 2 weeks
  intervention type: Drug
  intervention name: ME-015 (Suplatast Tosilate)
  description: Oral capsule form, 200 mg t.i.d. (total 600 mg per 24 hours)
  arm group label: ME-015 (Suplatast Tosilate)
  other name: Suplatast
  other name: Suplatast Tosilate
  intervention type: Other
  intervention name: Identical placebo
  description: Without active component
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Christoph Nowak, MD, PhD, Dipl-Psych
  phone: +46739806535
  email: chris.nowak@meliuspharma.com
  facility: 
  contact: 
  facility: 
  facility: 
  contact: 
  facility: 
  contact: 
  country: India
  url: https://www.meliuspharma.com/
  description: Sponsor website
  responsible party type: Sponsor
  mesh term: Pulmonary Fibrosis
  mesh term: Cough
  mesh term: Idiopathic Pulmonary Fibrosis
  mesh term: Fibrosis
  mesh term: Suplatast tosilate
  sharing ipd: No