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/NCT06029972</url>
    </required_header>
    <id_info>
      <org_study_id>GS-US-457-6411</org_study_id>
      <secondary_id>2022-501119-14</secondary_id>
      <nct_id>NCT06029972</nct_id>
    </id_info>
    <brief_title>Study of Tilpisertib Fosmecarbil in Participants With Moderately to Severely Active Ulcerative Colitis</brief_title>
    <acronym>PALEKONA</acronym>
    <official_title>A Phase 2, Double-Blinded, Randomized, Placebo-Controlled, Dose-Ranging Study Evaluating the Efficacy and Safety of GS-5290 in Participants With Moderately to Severely Active Ulcerative Colitis</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Gilead Sciences</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Gilead Sciences</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 goal of this study is to learn if tilpisertib fosmecarbil (formerly known as GS-5290) is&#xD;
        effective and safe in treating participants with moderate to severe ulcerative colitis. The&#xD;
        study will compare participants in different treatment groups treated with tilpisertib&#xD;
        fosmecarbil with participants treated with placebo.&#xD;
  &#xD;
        The primary objective of this study is to demonstrate the efficacy of tilpisertib&#xD;
        fosmecarbil, compared to placebo control, in achieving Clinical Response at Week 12.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">June 2026</completion_date>
    <primary_completion_date type="Anticipated">June 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>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Proportion of Participants Achieving Clinical Response Per Modified Mayo Clinic Score (MCS) at Week 12</measure>
      <time_frame>Week 12</time_frame>
      <description>Clinical Response is defined as a decrease from baseline of ≥ 2 points and at least 30% in 3 components of the modified Mayo Clinic Score (MCS), Stool Frequency, Rectal Bleeding, and Endoscopic Findings, in addition to a ≥ 1 point decrease from baseline in the Rectal Bleeding subscore or Rectal Bleeding subscore of ≤ 1.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Proportion of Participants Achieving Clinical Remission Per Modified Mayo Clinic Score (MCS) at Week 12</measure>
      <time_frame>Week 12</time_frame>
      <description>Clinical Remission is defined as a Stool Frequency subscore ≤ 1 and not greater than baseline, Rectal Bleeding subscore of 0, and Endoscopic Findings subscore ≤ 1 at Week 12.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of Participants Achieving Endoscopic Response at Week 12</measure>
      <time_frame>Week 12</time_frame>
      <description>Endoscopic Response is defined as an Endoscopic Findings subscore ≤ 1 at Week 12.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of Participants Achieving Histologic Endoscopic Mucosal Improvement at Week 12</measure>
      <time_frame>Week 12</time_frame>
      <description>Histologic Endoscopic Mucosal Improvement is defined as an Endoscopic Findings subscore ≤ 1 and Geboes score ≤ 3.1 (indicating neutrophil infiltration in &lt; 5% of crypts, no crypt destruction and no erosions, ulcerations, or granulation tissue).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)</measure>
      <time_frame>First dose date up to Week 52 (responders) or Week 64 (non-responders) plus 30 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities</measure>
      <time_frame>First dose date up to Week 52 (responders) or Week 64 (non-responders) plus 30 days</time_frame>
    </secondary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">176</enrollment>
    <condition>Ulcerative Colitis</condition>
    <arm_group>
      <arm_group_label>Tilpisertib Fosmecarbil Dose A</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Blinded Treatment Phase:&#xD;
  Participants will receive tilpisertib fosmecarbil Dose A for up to 12 weeks. An efficacy assessment will be performed at Week 12.&#xD;
  • Participants who achieve clinical response will receive tilpisertib fosmecarbil Dose B for up to Week 52.&#xD;
  Non-responder Treatment Phase:&#xD;
  • Participants who do not achieve clinical response at Week 12 will discontinue the Blinded Treatment Phase and have the option to enter into the Non-responder Treatment Phase. Participants will receive tilpisertib fosmecarbil Dose A for another 12 weeks. An efficacy assessment will be performed at Week 12 of the Non-responder Treatment Phase. Participants who achieved clinical response will receive tilpisertib fosmecarbil Dose B for up to Week 52. Participants who do not achieve clinical response at Non-responder Treatment Phase Week 12 will discontinue study drug.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Tilpisertib Fosmecarbil Dose B</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Blinded Treatment Phase:&#xD;
  Participants will receive tilpisertib fosmecarbil Dose B for up to 12 weeks. An efficacy assessment will be performed at Week 12.&#xD;
  • Participants who achieve clinical response will receive tilpisertib fosmecarbil Dose B for up to Week 52.&#xD;
  Non-responder Treatment Phase:&#xD;
  • Participants who do not achieve clinical response at Week 12 will discontinue the Blinded Treatment Phase and have the option to enter into the Non-responder Treatment Phase. Participants will receive tilpisertib fosmecarbil Dose B for another 12 weeks. An efficacy assessment will be performed at Week 12 of the Non-responder Treatment Phase. Participants who achieved clinical response will receive tilpisertib fosmecarbil Dose B for up to Week 52. Participants who do not achieve clinical response at Non-responder Treatment Phase Week 12 will discontinue study drug.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Tilpisertib Fosmecarbil Dose C</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Blinded Treatment Phase:&#xD;
  Participants will receive tilpisertib fosmecarbil Dose C for up to 12 weeks. An efficacy assessment will be performed at Week 12.&#xD;
  • Participants who achieve clinical response will receive tilpisertib fosmecarbil Dose C for up to Week 52.&#xD;
  Non-responder Treatment Phase:&#xD;
  • Participants who do not achieve clinical response at Week 12 will discontinue the Blinded Treatment Phase and have the option to enter into the Non-responder Treatment Phase. Participants will receive tilpisertib fosmecarbil Dose B for another 12 weeks. An efficacy assessment will be performed at Week 12 of the Non-responder Treatment Phase. Participants who achieved clinical response will receive tilpisertib fosmecarbil Dose B for up to Week 52. Participants who do not achieve clinical response at Non-responder Treatment Phase Week 12 will discontinue study drug.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Tilpisertib Fosmecarbil Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Blinded Treatment Phase:&#xD;
  Participants will receive tilpisertib fosmecarbil placebo for up to 12 weeks. An efficacy assessment will be performed at Week 12.&#xD;
  • Participants who achieve clinical response will receive tilpisertib fosmecarbil Dose C for up to Week 52.&#xD;
  Non-responder Treatment Phase:&#xD;
  • Participants who do not achieve clinical response at Week 12 will discontinue the Blinded Treatment Phase and have the option to enter into the Non-responder Treatment Phase. Participants will receive tilpisertib fosmecarbil Dose A for another 12 weeks. An efficacy assessment will be performed at Week 12 of the Non-responder Treatment Phase. Participants who achieved Clinical Response will receive tilpisertib fosmecarbil Dose B for up to Week 52. Participants who do not achieve Clinical Response at Non-responder Treatment Phase Week 12 will discontinue study drug.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tilpisertib Fosmecarbil</intervention_name>
      <description>Tablets administered orally</description>
      <arm_group_label>Tilpisertib Fosmecarbil Dose A</arm_group_label>
      <arm_group_label>Tilpisertib Fosmecarbil Dose B</arm_group_label>
      <arm_group_label>Tilpisertib Fosmecarbil Dose C</arm_group_label>
      <arm_group_label>Tilpisertib Fosmecarbil Placebo</arm_group_label>
      <other_name>GS-5290</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Tablets administered orally</description>
      <arm_group_label>Tilpisertib Fosmecarbil Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Key Inclusion Criteria:&#xD;
  &#xD;
            -  Individuals assigned male at birth, or nonpregnant, nonlactating individuals assigned&#xD;
               female at birth, 18 to 75 years of age based on the date of the screening visit.&#xD;
  &#xD;
            -  Ulcerative colitis (UC) of at least 90-day duration before randomization confirmed by&#xD;
               endoscopy and histology at any time in the past AND a minimum disease extent of 15 cm&#xD;
               from the anal verge. Documentation of endoscopy and histology consistent with the&#xD;
               diagnosis of UC must be available in the source documents prior to the initiation of&#xD;
               screening.&#xD;
  &#xD;
            -  Moderately to severely active UC as determined during screening with a modified Mayo&#xD;
               Clinic Score based on the sum of Stool Frequency, Rectal Bleeding, and Endoscopic&#xD;
               Finding of 5 to 9 points and an endoscopic subscore of 2 to 3 (determined by central&#xD;
               reader).&#xD;
  &#xD;
            -  Previous treatment history of approved UC therapy with at least one advanced therapy&#xD;
               mechanisms of action but failure (ie, loss of response or lack of response) of no more&#xD;
               than 3 different advanced therapy mechanisms of action.&#xD;
  &#xD;
            -  Documentation of a surveillance colonoscopy in the 24 months prior to screening in&#xD;
               individuals who have a history of UC for 8 or more years.&#xD;
  &#xD;
          Key Exclusion Criteria:&#xD;
  &#xD;
            -  Current diagnosis of Crohn's Disease (CD) or diagnosis of indeterminate colitis due to&#xD;
               an enteric pathogen, lymphocytic or collagenous colitis.&#xD;
  &#xD;
            -  Individuals with disease limited to the rectum (ulcerative proctitis) during screening&#xD;
               endoscopy.&#xD;
  &#xD;
            -  Requirement for ongoing therapy with or prior use of any prohibited medications.&#xD;
  &#xD;
            -  Active clinically significant infection, or any infection requiring hospitalization or&#xD;
               treatment with intravenous anti-infectives within 8 weeks.&#xD;
  &#xD;
          of randomization; or any infection requiring oral anti-infective therapy within 6 weeks of&#xD;
          randomization.&#xD;
  &#xD;
            -  History of opportunistic infection.&#xD;
  &#xD;
            -  Current diagnosis of acute severe colitis, fulminant colitis, or toxic megacolon.&#xD;
  &#xD;
          Note: Other protocol-defined Inclusion/Exclusion criteria may apply.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Gilead Study Director</last_name>
      <role>Study Director</role>
      <affiliation>Gilead Sciences</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Gilead Clinical Study Information Center</last_name>
      <phone>1-833-445-3230 (GILEAD-0)</phone>
      <email>GileadClinicalTrials@gilead.com</email>
    </overall_contact>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 1, 2023</study_first_submitted>
    <study_first_submitted_qc>September 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 8, 2023</study_first_posted>
    <last_update_submitted>September 1, 2023</last_update_submitted>
    <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 8, 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>Colitis</mesh_term>
      <mesh_term>Colitis, Ulcerative</mesh_term>
      <mesh_term>Ulcer</mesh_term>
    </condition_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/NCT06029972
  org study id: GS-US-457-6411
  secondary id: 2022-501119-14
  nct id: NCT06029972
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  The goal of this study is to learn if tilpisertib fosmecarbil (formerly known as GS-5290) is
        effective and safe in treating participants with moderate to severe ulcerative colitis. The
        study will compare participants in different treatment groups treated with tilpisertib
        fosmecarbil with participants treated with placebo.
  
        The primary objective of this study is to demonstrate the efficacy of tilpisertib
        fosmecarbil, compared to placebo control, in achieving Clinical Response at Week 12.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  measure: Proportion of Participants Achieving Clinical Response Per Modified Mayo Clinic Score (MCS) at Week 12
  time frame: Week 12
  description: Clinical Response is defined as a decrease from baseline of ≥ 2 points and at least 30% in 3 components of the modified Mayo Clinic Score (MCS), Stool Frequency, Rectal Bleeding, and Endoscopic Findings, in addition to a ≥ 1 point decrease from baseline in the Rectal Bleeding subscore or Rectal Bleeding subscore of ≤ 1.
  measure: Proportion of Participants Achieving Clinical Remission Per Modified Mayo Clinic Score (MCS) at Week 12
  time frame: Week 12
  description: Clinical Remission is defined as a Stool Frequency subscore ≤ 1 and not greater than baseline, Rectal Bleeding subscore of 0, and Endoscopic Findings subscore ≤ 1 at Week 12.
  measure: Proportion of Participants Achieving Endoscopic Response at Week 12
  time frame: Week 12
  description: Endoscopic Response is defined as an Endoscopic Findings subscore ≤ 1 at Week 12.
  measure: Proportion of Participants Achieving Histologic Endoscopic Mucosal Improvement at Week 12
  time frame: Week 12
  description: Histologic Endoscopic Mucosal Improvement is defined as an Endoscopic Findings subscore ≤ 1 and Geboes score ≤ 3.1 (indicating neutrophil infiltration in < 5% of crypts, no crypt destruction and no erosions, ulcerations, or granulation tissue).
  measure: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
  time frame: First dose date up to Week 52 (responders) or Week 64 (non-responders) plus 30 days
  measure: Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities
  time frame: First dose date up to Week 52 (responders) or Week 64 (non-responders) plus 30 days
  arm group label: Tilpisertib Fosmecarbil Dose A
  arm group type: Experimental
  description: Blinded Treatment Phase:
  Participants will receive tilpisertib fosmecarbil Dose A for up to 12 weeks. An efficacy assessment will be performed at Week 12.
  • Participants who achieve clinical response will receive tilpisertib fosmecarbil Dose B for up to Week 52.
  Non-responder Treatment Phase:
  • Participants who do not achieve clinical response at Week 12 will discontinue the Blinded Treatment Phase and have the option to enter into the Non-responder Treatment Phase. Participants will receive tilpisertib fosmecarbil Dose A for another 12 weeks. An efficacy assessment will be performed at Week 12 of the Non-responder Treatment Phase. Participants who achieved clinical response will receive tilpisertib fosmecarbil Dose B for up to Week 52. Participants who do not achieve clinical response at Non-responder Treatment Phase Week 12 will discontinue study drug.
  arm group label: Tilpisertib Fosmecarbil Dose B
  arm group type: Experimental
  description: Blinded Treatment Phase:
  Participants will receive tilpisertib fosmecarbil Dose B for up to 12 weeks. An efficacy assessment will be performed at Week 12.
  • Participants who achieve clinical response will receive tilpisertib fosmecarbil Dose B for up to Week 52.
  Non-responder Treatment Phase:
  • Participants who do not achieve clinical response at Week 12 will discontinue the Blinded Treatment Phase and have the option to enter into the Non-responder Treatment Phase. Participants will receive tilpisertib fosmecarbil Dose B for another 12 weeks. An efficacy assessment will be performed at Week 12 of the Non-responder Treatment Phase. Participants who achieved clinical response will receive tilpisertib fosmecarbil Dose B for up to Week 52. Participants who do not achieve clinical response at Non-responder Treatment Phase Week 12 will discontinue study drug.
  arm group label: Tilpisertib Fosmecarbil Dose C
  arm group type: Experimental
  description: Blinded Treatment Phase:
  Participants will receive tilpisertib fosmecarbil Dose C for up to 12 weeks. An efficacy assessment will be performed at Week 12.
  • Participants who achieve clinical response will receive tilpisertib fosmecarbil Dose C for up to Week 52.
  Non-responder Treatment Phase:
  • Participants who do not achieve clinical response at Week 12 will discontinue the Blinded Treatment Phase and have the option to enter into the Non-responder Treatment Phase. Participants will receive tilpisertib fosmecarbil Dose B for another 12 weeks. An efficacy assessment will be performed at Week 12 of the Non-responder Treatment Phase. Participants who achieved clinical response will receive tilpisertib fosmecarbil Dose B for up to Week 52. Participants who do not achieve clinical response at Non-responder Treatment Phase Week 12 will discontinue study drug.
  arm group label: Tilpisertib Fosmecarbil Placebo
  arm group type: Placebo Comparator
  description: Blinded Treatment Phase:
  Participants will receive tilpisertib fosmecarbil placebo for up to 12 weeks. An efficacy assessment will be performed at Week 12.
  • Participants who achieve clinical response will receive tilpisertib fosmecarbil Dose C for up to Week 52.
  Non-responder Treatment Phase:
  • Participants who do not achieve clinical response at Week 12 will discontinue the Blinded Treatment Phase and have the option to enter into the Non-responder Treatment Phase. Participants will receive tilpisertib fosmecarbil Dose A for another 12 weeks. An efficacy assessment will be performed at Week 12 of the Non-responder Treatment Phase. Participants who achieved Clinical Response will receive tilpisertib fosmecarbil Dose B for up to Week 52. Participants who do not achieve Clinical Response at Non-responder Treatment Phase Week 12 will discontinue study drug.
  intervention type: Drug
  intervention name: Tilpisertib Fosmecarbil
  description: Tablets administered orally
  arm group label: Tilpisertib Fosmecarbil Dose A
  arm group label: Tilpisertib Fosmecarbil Dose B
  arm group label: Tilpisertib Fosmecarbil Dose C
  arm group label: Tilpisertib Fosmecarbil Placebo
  other name: GS-5290
  intervention type: Drug
  intervention name: Placebo
  description: Tablets administered orally
  arm group label: Tilpisertib Fosmecarbil Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Gilead Study Director
  role: Study Director
  affiliation: Gilead Sciences
  last name: Gilead Clinical Study Information Center
  phone: 1-833-445-3230 (GILEAD-0)
  email: GileadClinicalTrials@gilead.com
  responsible party type: Sponsor
  mesh term: Colitis
  mesh term: Colitis, Ulcerative
  mesh term: Ulcer
  sharing ipd: No