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Study of Tilpisertib Fosmecarbil in Participants With Moderately to Severely Active Ulcerative Colitis (PALEKONA)

Primary Purpose

Ulcerative Colitis

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Tilpisertib Fosmecarbil
Placebo
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ulcerative Colitis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria: Individuals assigned male at birth, or nonpregnant, nonlactating individuals assigned female at birth, 18 to 75 years of age based on the date of the screening visit. Ulcerative colitis (UC) of at least 90-day duration before randomization confirmed by endoscopy and histology at any time in the past AND a minimum disease extent of 15 cm from the anal verge. Documentation of endoscopy and histology consistent with the diagnosis of UC must be available in the source documents prior to the initiation of screening. Moderately to severely active UC as determined during screening with a modified Mayo Clinic Score based on the sum of Stool Frequency, Rectal Bleeding, and Endoscopic Finding of 5 to 9 points and an endoscopic subscore of 2 to 3 (determined by central reader). Previous treatment history of approved UC therapy with at least one advanced therapy mechanisms of action but failure (ie, loss of response or lack of response) of no more than 3 different advanced therapy mechanisms of action. Documentation of a surveillance colonoscopy in the 24 months prior to screening in individuals who have a history of UC for 8 or more years. Key Exclusion Criteria: Current diagnosis of Crohn's Disease (CD) or diagnosis of indeterminate colitis due to an enteric pathogen, lymphocytic or collagenous colitis. Individuals with disease limited to the rectum (ulcerative proctitis) during screening endoscopy. Requirement for ongoing therapy with or prior use of any prohibited medications. Active clinically significant infection, or any infection requiring hospitalization or treatment with intravenous anti-infectives within 8 weeks. of randomization; or any infection requiring oral anti-infective therapy within 6 weeks of randomization. History of opportunistic infection. Current diagnosis of acute severe colitis, fulminant colitis, or toxic megacolon. Note: Other protocol-defined Inclusion/Exclusion criteria may apply.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Experimental

    Experimental

    Placebo Comparator

    Arm Label

    Tilpisertib Fosmecarbil Dose A

    Tilpisertib Fosmecarbil Dose B

    Tilpisertib Fosmecarbil Dose C

    Tilpisertib Fosmecarbil Placebo

    Arm 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.

    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.

    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.

    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.

    Outcomes

    Primary Outcome Measures

    Proportion of Participants Achieving Clinical Response Per Modified Mayo Clinic Score at Week 12
    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, 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. The modified Mayo Clinic Score is a scoring system for assessment of UC activity and is composed of subscores from endoscopy (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]), rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), and stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 or more stools more than normal). Total score for modified Mayo Clinic Score ranges from 0 to 9 (sum of all subscores), with higher scores indicating higher disease activity.

    Secondary Outcome Measures

    Proportion of Participants Achieving Clinical Remission Per Modified Mayo Clinic Score at Week 12
    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. The modified Mayo Clinic Score is a scoring system for assessment of UC activity and is composed of subscores from endoscopy (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]), rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 or more stools more than normal). Total score for modified Mayo Clinic Score ranges from 0 to 9 (sum of all subscores), with higher scores indicating higher disease activity.
    Proportion of Participants Achieving Endoscopic Response at Week 12
    Endoscopic Response is defined as an Endoscopic Findings subscore ≤ 1 at Week 12. Endoscopic subscore is a part of the modified Mayo Clinic Score which is a scoring system for assessment of UC activity. Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease, 1 = mild disease (erythema, decreased vascular pattern), 2 = moderate disease (marked erythema, lack of vascular pattern, friability, erosions), and 3 = severe disease (spontaneous bleeding, ulceration). Higher scores indicate higher disease activity.
    Proportion of Participants Achieving Histologic Endoscopic Mucosal Improvement at Week 12
    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). Endoscopic subscore is a part of the modified Mayo Clinic Score which is a scoring system for assessment of UC activity. Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease, 1 = mild disease (erythema, decreased vascular pattern), 2 = moderate disease (marked erythema, lack of vascular pattern, friability, erosions), and 3 = severe disease (spontaneous bleeding, ulceration). Geboes histologic remission is assessed using the Geboes histologic scores to identify histologic changes in ulcerative colitis. Possible scores are graded as Grade 0 to Grade 5, with higher grade representing higher levels of disease activity.
    Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
    Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities

    Full Information

    First Posted
    September 1, 2023
    Last Updated
    October 10, 2023
    Sponsor
    Gilead Sciences
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06029972
    Brief Title
    Study of Tilpisertib Fosmecarbil in Participants With Moderately to Severely Active Ulcerative Colitis
    Acronym
    PALEKONA
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 2023 (Anticipated)
    Primary Completion Date
    June 2025 (Anticipated)
    Study Completion Date
    June 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Gilead Sciences

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Ulcerative Colitis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    176 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Tilpisertib Fosmecarbil Dose A
    Arm Type
    Experimental
    Arm 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 Title
    Tilpisertib Fosmecarbil Dose B
    Arm Type
    Experimental
    Arm 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 Title
    Tilpisertib Fosmecarbil Dose C
    Arm Type
    Experimental
    Arm 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 Title
    Tilpisertib Fosmecarbil Placebo
    Arm Type
    Placebo Comparator
    Arm 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(s)
    Tilpisertib Fosmecarbil
    Other Intervention Name(s)
    GS-5290
    Intervention Description
    Tablets administered orally
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Tablets administered orally
    Primary Outcome Measure Information:
    Title
    Proportion of Participants Achieving Clinical Response Per Modified Mayo Clinic Score at 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, 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. The modified Mayo Clinic Score is a scoring system for assessment of UC activity and is composed of subscores from endoscopy (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]), rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), and stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 or more stools more than normal). Total score for modified Mayo Clinic Score ranges from 0 to 9 (sum of all subscores), with higher scores indicating higher disease activity.
    Time Frame
    Week 12
    Secondary Outcome Measure Information:
    Title
    Proportion of Participants Achieving Clinical Remission Per Modified Mayo Clinic Score at 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. The modified Mayo Clinic Score is a scoring system for assessment of UC activity and is composed of subscores from endoscopy (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]), rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 or more stools more than normal). Total score for modified Mayo Clinic Score ranges from 0 to 9 (sum of all subscores), with higher scores indicating higher disease activity.
    Time Frame
    Week 12
    Title
    Proportion of Participants Achieving Endoscopic Response at Week 12
    Description
    Endoscopic Response is defined as an Endoscopic Findings subscore ≤ 1 at Week 12. Endoscopic subscore is a part of the modified Mayo Clinic Score which is a scoring system for assessment of UC activity. Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease, 1 = mild disease (erythema, decreased vascular pattern), 2 = moderate disease (marked erythema, lack of vascular pattern, friability, erosions), and 3 = severe disease (spontaneous bleeding, ulceration). Higher scores indicate higher disease activity.
    Time Frame
    Week 12
    Title
    Proportion of Participants Achieving Histologic Endoscopic Mucosal Improvement at 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). Endoscopic subscore is a part of the modified Mayo Clinic Score which is a scoring system for assessment of UC activity. Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease, 1 = mild disease (erythema, decreased vascular pattern), 2 = moderate disease (marked erythema, lack of vascular pattern, friability, erosions), and 3 = severe disease (spontaneous bleeding, ulceration). Geboes histologic remission is assessed using the Geboes histologic scores to identify histologic changes in ulcerative colitis. Possible scores are graded as Grade 0 to Grade 5, with higher grade representing higher levels of disease activity.
    Time Frame
    Week 12
    Title
    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
    Title
    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

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Key Inclusion Criteria: Individuals assigned male at birth, or nonpregnant, nonlactating individuals assigned female at birth, 18 to 75 years of age based on the date of the screening visit. Ulcerative colitis (UC) of at least 90-day duration before randomization confirmed by endoscopy and histology at any time in the past AND a minimum disease extent of 15 cm from the anal verge. Documentation of endoscopy and histology consistent with the diagnosis of UC must be available in the source documents prior to the initiation of screening. Moderately to severely active UC as determined during screening with a modified Mayo Clinic Score based on the sum of Stool Frequency, Rectal Bleeding, and Endoscopic Finding of 5 to 9 points and an endoscopic subscore of 2 to 3 (determined by central reader). Previous treatment history of approved UC therapy with at least one advanced therapy mechanisms of action but failure (ie, loss of response or lack of response) of no more than 3 different advanced therapy mechanisms of action. Documentation of a surveillance colonoscopy in the 24 months prior to screening in individuals who have a history of UC for 8 or more years. Key Exclusion Criteria: Current diagnosis of Crohn's Disease (CD) or diagnosis of indeterminate colitis due to an enteric pathogen, lymphocytic or collagenous colitis. Individuals with disease limited to the rectum (ulcerative proctitis) during screening endoscopy. Requirement for ongoing therapy with or prior use of any prohibited medications. Active clinically significant infection, or any infection requiring hospitalization or treatment with intravenous anti-infectives within 8 weeks. of randomization; or any infection requiring oral anti-infective therapy within 6 weeks of randomization. History of opportunistic infection. Current diagnosis of acute severe colitis, fulminant colitis, or toxic megacolon. Note: Other protocol-defined Inclusion/Exclusion criteria may apply.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Gilead Clinical Study Information Center
    Phone
    1-833-445-3230 (GILEAD-0)
    Email
    GileadClinicalTrials@gilead.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Gilead Study Director
    Organizational Affiliation
    Gilead Sciences
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Links:
    URL
    https://www.gileadclinicaltrials.com/study?nctid=NCT06029972
    Description
    Related Info

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    Study of Tilpisertib Fosmecarbil in Participants With Moderately to Severely Active Ulcerative Colitis

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