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Efficacy & Safety of TD-1473 in Ulcerative Colitis (RHEA)

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ClinicalTrials.gov Identifier: NCT03758443
Recruitment Status : Recruiting
First Posted : November 29, 2018
Last Update Posted : December 10, 2019
Sponsor:
Information provided by (Responsible Party):
Theravance Biopharma

Brief Summary:
A Phase 2b/3 set of studies to evaluate the efficacy and safety of induction and maintenance therapy with TD-1473 in subjects with moderately-to-severely active ulcerative colitis with up to 60 weeks of treatment.

Condition or disease Intervention/treatment Phase
Ulcerative Colitis (UC) Drug: TD-1473 Dose A Drug: TD-1473 Dose B Drug: TD-1473 Dose C Drug: Placebo Phase 2 Phase 3

Detailed Description:

This protocol consists of 3 separate studies: an 8-week Phase 2b dose-finding induction study, an 8-week dose-confirming Phase 3 induction study, and a 44-week Phase 3 maintenance study. Subjects who respond to induction will enter the maintenance study; those who do not will receive TD-1473 during extended induction. The safety and efficacy data of the Phase 2b study will be analyzed to select the induction and maintenance dose regimens for the confirmatory Phase 3 studies. Participants who have disease relapse or complete the maintenance study may be eligible to enter a separate long-term safety study. Efficacy, pharmacokinetic, biomarkers, and safety will be evaluated in all 3 studies.

240 subjects are planned for the Phase 2b and 640 subjects are planned for the Phase 3.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 880 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Integrated and Adaptive Design
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2b/3 Multi-Center, Randomized, Double-Blind, Multi-Dose, Placebo-Controlled, Parallel-Group Set of Studies to Evaluate the Efficacy and Safety of Induction and Maintenance Therapy With TD-1473 in Subjects With Moderately-to-Severely Active Ulcerative Colitis
Actual Study Start Date : March 11, 2019
Estimated Primary Completion Date : June 2025
Estimated Study Completion Date : July 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Active Treatment TD-1473 Dose A
Participants will be randomized to receive an oral daily dose of TD-1473. Responders will be re-randomized into the Phase 3 Maintenance portion of the study. Non-responders may participate in an extended induction.
Drug: TD-1473 Dose A
See Arm description

Experimental: Active Treatment TD-1473 Dose B
Participants will be randomized to receive an oral daily dose of TD-1473. Responders will be re-randomized into the Phase 3 Maintenance portion of the study. Non-responders may participate in an extended induction.
Drug: TD-1473 Dose B
See Arm description

Experimental: Active Treatment TD-1473 Dose C
Participants will be randomized to receive an oral daily dose of TD-1473. Responders will be re-randomized into the Phase 3 Maintenance portion of the study. Non-responders may participate in an extended induction.
Drug: TD-1473 Dose C
See Arm description

Placebo Comparator: Placebo
Participants will be randomized to receive an oral daily dose of placebo. Participants who received Placebo (and were non-responders) may move to an extended induction. Subjects who are on placebo will be assigned to active TD-1473 for the extended induction (they will be blinded to dose).
Drug: Placebo
See Arm description




Primary Outcome Measures :
  1. Phase 2b Induction: Change from baseline in total Mayo score (tMS) at Week 8 [ Time Frame: Baseline to Week 8 ]
    Total Mayo Score (tMS) is calculated as the sum of four components: rectal bleeding (0-3), stool frequency (0-3), physician's global assessment (0-3) and Mayo endoscopic subscore (0-3). tMS is reported as a 0-12 point score with 12 reflecting the highest severity.

  2. Phase 3 Induction: Clinical remission by adapted Mayo score components at Week 8 [ Time Frame: Week 8 ]

    Clinical remission by Adapted Mayo score is defined based on Adapted Mayo score components within specific ranges: stool frequency score of 0 or 1, a rectal bleeding subscore of 0 and a Mayo endoscopy subscore of 0 or 1.

    The Adapted Mayo score is the sum of three components: rectal bleeding, stool frequency, and Mayo endoscopic subscore, each measured on a scale of 0-3.


  3. Phase 3 Maintenance: Clinical remission by adapted Mayo score components at Maintenance (m) Week 44 [ Time Frame: (maintenance Week) mWeek 44 ]

    Clinical remission by Adapted Mayo score is defined based on Adapted Mayo score components within specific ranges: stool frequency score of 0 or 1, a rectal bleeding subscore of 0 and a Mayo endoscopy subscore of 0 or 1.

    The Adapted Mayo score is the sum of three components: rectal bleeding, stool frequency, and Mayo endoscopic subscore, each measured on a scale of 0-3.



Secondary Outcome Measures :
  1. Clinical remission by adapted Mayo Score Components at Week 8 [ Time Frame: Week 8 ]

    Clinical remission by Adapted Mayo score is defined based on Adapted Mayo score components within specific ranges: stool frequency score of 0 or 1, a rectal bleeding subscore of 0 and a Mayo endoscopy subscore of 0 or 1.

    The Adapted Mayo score is the sum of three components: rectal bleeding, stool frequency, and Mayo endoscopic subscore, each measured on a scale of 0-3.


  2. Endoscopic healing at Week 8 [ Time Frame: Week 8 ]

    Endoscopic Healing is defined as an Endoscopic subscore ≤ 1.

    Endoscopic subscore is measured using scale of 0-3, where higher numbers reflect greater severity.


  3. Symptomatic remission at Week 8 [ Time Frame: Week 8 ]

    Symptomatic remission is defined as stool frequency score ≤ 1 and a rectal bleeding subscore of 0.

    Stool frequency score and rectal bleeding score are each measured using scale of 0-3, where higher numbers reflect greater severity.


  4. Clinical response by Adapted Mayo score (aMS response) at Week 8 [ Time Frame: Baseline to Week 8 ]

    Clinical response is defined by Adapted Mayo score reduction ≥ 2 and ≥ 30%, with a reduction in the rectal bleeding subscore ≥ 1 or an absolute subscore ≤1.

    The Adapted Mayo score is the sum of three components: rectal bleeding, stool frequency, and Mayo endoscopic subscore, each measured on a scale of 0-3.


  5. Mucosal healing at Week 8 [ Time Frame: Week 8 ]

    Mucosal healing is defined as Mayo endoscopic score ≤ 1 and achieving histologic healing

    Mayo endoscopic subscore is measured using scale of 0-3, where higher numbers reflect greater severity.


  6. Maintenance of clinical response at mWeek 44 [ Time Frame: mWeek 44 ]
  7. Endoscopic healing at mWeek 44 [ Time Frame: mWeek 44 ]

    Endoscopic Healing is defined as an Endoscopic subscore ≤ 1.

    Endoscopic subscore is measured using scale of 0-3, where higher numbers reflect greater severity.


  8. Symptomatic remission at mWeek 44 [ Time Frame: mWeek 44 ]

    Symptomatic remission is defined as stool frequency score ≤ 1 and a rectal bleeding subscore of 0.

    Stool frequency score and rectal bleeding score are each measured using scale of 0-3, where higher numbers reflect greater severity.


  9. Corticosteroid-free remission at mWeek 44 [ Time Frame: mWeek 44 ]
  10. Maintenance of clinical remission at mWeek 44 in those who were in remission at mWeek 0 [ Time Frame: mWeek 44 ]
  11. Mucosal healing at mWeek 44 [ Time Frame: mWeek 44 ]

    Mucosal healing is defined as Mayo endoscopic score ≤ 1 and achieving histologic healing.

    Mayo endoscopic subscore is measured using scale of 0-3, where higher numbers reflect greater severity.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Is at least 18 years of age at screening
  • Has a history of UC for at least 3 months prior to screening
  • Has moderately-to-severely active UC, as defined by a Mayo endoscopic subscore of ≥2 points and an adapted Mayo score between 4 - 9 points inclusive
  • Is corticosteroid-dependent or has demonstrated inadequate response, or intolerance to conventional therapy (aminosalicylates, corticosteroids, immunomodulators) or biologics
  • Willing to use highly-effective methods of contraception during the study and for 7 days after the last dose
  • Additional inclusion criteria apply

Exclusion Criteria:

  • Has symptoms suggestive of fulminant colitis, megacolon or intestinal perforation
  • Likely to require surgery for UC or other major surgeries
  • Has previously received / is currently receiving prohibited medications within specified timeframe
  • Is refractory to 3 biologics with ≥2 mechanisms of action
  • Has a current bacterial, parasitic, fungal, or viral infection
  • Has clinically significant abnormalities in laboratory evaluations
  • Has had any prior exposure to an approved Janus kinase (JAK) inhibitor or potential exposure to an investigational JAK inhibitor that was stopped due to intolerance or lack of efficacy
  • Additional exclusion criteria apply

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03758443


Contacts
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Contact: Theravance Biopharma Call Center 1-855-633-8479 medinfo@theravance.com

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Sponsors and Collaborators
Theravance Biopharma
Investigators
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Study Director: Medical Monitor Theravance Biopharma

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Responsible Party: Theravance Biopharma
ClinicalTrials.gov Identifier: NCT03758443     History of Changes
Other Study ID Numbers: 0157
First Posted: November 29, 2018    Key Record Dates
Last Update Posted: December 10, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Theravance Biopharma:
TD-1473
Janus kinase inhibitor
JAK inhibitor
Inflammatory Bowel Disease
IBD
Ulcerative colitis
UC
Gut selective
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases