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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03758443
Recruitment Status : Recruiting
First Posted : November 29, 2018
Last Update Posted : March 23, 2020
Sponsor:
Information provided by (Responsible Party):
Theravance Biopharma

Tracking Information
First Submitted Date  ICMJE November 19, 2018
First Posted Date  ICMJE November 29, 2018
Last Update Posted Date March 23, 2020
Actual Study Start Date  ICMJE March 11, 2019
Estimated Primary Completion Date June 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 27, 2018)
  • 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.
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 27, 2018)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Maintenance of clinical response at mWeek 44 [ Time Frame: mWeek 44 ]
  • 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.
  • 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.
  • Corticosteroid-free remission at mWeek 44 [ Time Frame: mWeek 44 ]
  • Maintenance of clinical remission at mWeek 44 in those who were in remission at mWeek 0 [ Time Frame: mWeek 44 ]
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy & Safety of TD-1473 in Ulcerative Colitis
Official Title  ICMJE 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
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Integrated and Adaptive Design
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Ulcerative Colitis (UC)
Intervention  ICMJE
  • Drug: TD-1473 Dose A
    See Arm description
  • Drug: TD-1473 Dose B
    See Arm description
  • Drug: TD-1473 Dose C
    See Arm description
  • Drug: Placebo
    See Arm description
Study Arms  ICMJE
  • 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.
    Intervention: Drug: TD-1473 Dose A
  • 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.
    Intervention: Drug: TD-1473 Dose B
  • 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.
    Intervention: Drug: TD-1473 Dose C
  • 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).
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 27, 2018)
880
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2025
Estimated Primary Completion Date June 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Theravance Biopharma Call Center 1-855-633-8479 medinfo@theravance.com
Listed Location Countries  ICMJE Bulgaria,   Georgia,   Greece,   Hungary,   Israel,   Japan,   Poland,   Portugal,   Serbia,   Slovakia,   South Africa,   Spain,   Taiwan,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03758443
Other Study ID Numbers  ICMJE 0157
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Theravance Biopharma
Study Sponsor  ICMJE Theravance Biopharma
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Monitor Theravance Biopharma
PRS Account Theravance Biopharma
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP