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Efficacy and Safety of TD-1473 in Crohn's Disease (DIONE)

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ClinicalTrials.gov Identifier: NCT03635112
Recruitment Status : Recruiting
First Posted : August 17, 2018
Last Update Posted : June 4, 2020
Sponsor:
Information provided by (Responsible Party):
Theravance Biopharma

Tracking Information
First Submitted Date  ICMJE July 31, 2018
First Posted Date  ICMJE August 17, 2018
Last Update Posted Date June 4, 2020
Actual Study Start Date  ICMJE November 19, 2018
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 14, 2018)
Improvement in Crohn's Disease Activity Index (CDAI) score from Baseline to Week 12 (PRIMARY) [ Time Frame: 12 weeks ]
To assess the effect of TD-1473 compared to placebo in improving Crohn's Disease Activity Index (CDAI) score at week 12 in subjects with moderately to severely active CD. The CDAI score is generated using regression coefficients for eight different predictors of disease activity: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Patients will report information regarding symptoms using a diary.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 22, 2018)
  • Clinical response measured by CDAI [ Time Frame: 12 weeks ]
    To assess the effects of TD-1473 given for 12 weeks compared to placebo. CDAI clinical response is determined by a CDAI score decreasing from baseline to Week 12 by a defined value or CDAI below a defined value by Week 12. Crohn's Disease Activity Index also known as CDAI is a research tool used to quantify the symptoms of patients with Crohn's disease.
  • CDAI clinical remission [ Time Frame: 12 weeks ]
    To assess the effects of TD-1473 given for 12 weeks compared to placebo. CDAI clinical remission is determined by a CDAI score being less than a defined value at Week 12. Crohn's Disease Activity Index also known as CDAI is a research tool used to quantify the symptoms of patients with Crohn's disease.
  • SES-CD (Simple Endoscopic Score for Crohn's Disease) change from baseline to Week 12 [ Time Frame: 12 weeks ]
    To assess the effects of TD-1473 given for 12 weeks compared to placebo. Simple Endoscopic Score for Crohn's Disease also known as SES-CD provides a quantitative assessment of Crohn's Disease across all 5 bowel segments and allow for comparison across populations and within an individual over time. The SES-CD incorporates 4 descriptors: the ulcer size, the proportion of surface covered by ulcer, the proportion of surface covered by other lesions, and the presence of stenosis. Each descriptor is graded from 0-3 and is scored in 5 segments (ileum, right colon, transverse colon, left colon, and rectum). The total score is calculated as the sum of all the items in each segment and can range from 0 to 60.
  • Endoscopic response [ Time Frame: 12 weeks ]
    To assess the effects of TD-1473 given for 12 weeks compared to placebo. Endoscopic Response is determined by a reduction of SES-CD (Simple Endoscopic Score for Crohn's Disease is also known as SES-CD) score or Endoscopic Remission at Week 12. Simple Endoscopic Score for Crohn's Disease also known as SES-CD provides a quantitative assessment of Crohn's Disease across all 5 bowel segments and allow for comparison across populations and within an individual over time. The SES-CD incorporates 4 descriptors: the ulcer size, the proportion of surface covered by ulcer, the proportion of surface covered by other lesions, and the presence of stenosis. Each descriptor is graded from 0-3 and is scored in 5 segments (ileum, right colon, transverse colon, left colon, and rectum). The total score is calculated as the sum of all the items in each segment and can range from 0 to 60.
  • Stool Frequency and Abdominal Pain (SFAP) clinical remission [ Time Frame: 12 weeks ]
    To assess the effects of TD-1473 given for 12 weeks compared to placebo. Stool Frequency and Abdominal Pain (SFAP) clinical remission is determined using a patient reported Abdominal Pain score [which uses a scale of 0 - 3 with 0 representing 'no pain' and 3 representing 'severe pain'] and patient reported Stool Frequency.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 14, 2018)
  • Clinical response measured by CDAI [ Time Frame: 12 weeks ]
    To assess the effects of TD-1473 given for 12 weeks compared to placebo. CDAI clinical response is determined by a CDAI score decreasing from baseline to Week 12 by a defined value or CDAI below a defined value by Week 12. Crohn's Disease Activity Index also known as CDAI is a research tool used to quantify the symptoms of patients with Crohn's disease.
  • CDAI clinical remission [ Time Frame: 12 weeks ]
    To assess the effects of TD-1473 given for 12 weeks compared to placebo. CDAI clinical remission is determined by a CDAI score being less than a defined value at Week 12. Crohn's Disease Activity Index also known as CDAI is a research tool used to quantify the symptoms of patients with Crohn's disease.
  • SES-CD (Simple Endoscopic Score for Crohn's Disease) change from baseline to Week 12 [ Time Frame: 12 weeks ]
    To assess the effects of TD-1473 given for 12 weeks compared to placebo. Simple Endoscopic Score for Crohn's Disease also known as SES-CD provides a quantitative assessment of Crohn's Disease across all 5 bowel segments and allow for comparison across populations and within an individual over time. The SES-CD incorporates 4 descriptors: the ulcer size, the proportion of surface covered by ulcer, the proportion of surface covered by other lesions, and the presence of stenosis. Each descriptor is graded from 0-3 and is scored in 5 segments (ileum, right colon, transverse colon, left colon, and rectum). The total score is calculated as the sum of all the items in each segment and can range from 0 to 60.
  • Endoscopic response [ Time Frame: 12 weeks ]
    To assess the effects of TD-1473 given for 12 weeks compared to placebo. Endoscopic Response is determined by a reduction of SES-CD (Simple Endoscopic Score for Crohn's Disease is also known as SES-CD) score or Endoscopic Remission at Week 12.
  • Stool Frequency and Abdominal Pain (SFAP) clinical remission [ Time Frame: 12 weeks ]
    To assess the effects of TD-1473 given for 12 weeks compared to placebo. Stool Frequency and Abdominal Pain (SFAP) clinical remission is determined using a patient reported Abdominal Pain score [which uses a scale of 0 - 3 with 0 representing 'no pain' and 3 representing 'severe pain'] and patient reported Stool Frequency.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of TD-1473 in Crohn's Disease
Official Title  ICMJE A Phase 2 Multi-Center, Randomized, Double-Blind, Placebo˗Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Induction Therapy With 2 Doses of TD-1473 in Subjects With Moderately-to-Severely Active Crohn's Disease
Brief Summary A Phase 2 study to evaluate the efficacy, safety and tolerability of TD-1473 in subjects with moderately-to-severely active Crohn's Disease with up to 48 weeks of treatment.
Detailed Description A Phase 2 multi-center, randomized, double blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of 12 weeks of induction therapy with TD˗1473 in subjects with moderately-to-severely active CD. This study includes 3 phases: Screening, Induction, and Active Treatment Extension (ATE). The Induction phase of the study is a randomized, double blind, placebo controlled, parallel group study evaluating 2 oral dose levels of TD-1473 compared to placebo for 12 weeks in subjects with moderately to-severely active CD. Subjects who complete Induction will continue to receive TD-1473 in the ATE, for up to 48 additional weeks.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Crohn's Disease
Intervention  ICMJE
  • Drug: Placebo
    Placebo will be taken daily by mouth (orally) for up to 12 weeks in the morning before eating.
  • Drug: TD-1473
    TD-1473, at Dose A or Dose B depending upon arm, will be taken daily by mouth (orally) for up to 12 weeks in the morning before eating. An additional 48 weeks either at Dose A or Dose B, depending on arm, may be administered if subjects finish the 12 week induction period.
Study Arms  ICMJE
  • Active Comparator: Active Treatment TD-1473 with Dose A

    1 oral Dose A daily of TD-1473 for 12 weeks in subjects with moderately to-severely active CD.

    Subjects who complete Induction will continue to receive TD-1473 at Dose A in the Active Treatment Arm for up to 48 additional weeks.

    Intervention: Drug: TD-1473
  • Active Comparator: Active Treatment TD-1473 with Dose B

    1 oral Dose B daily of TD-1473 for 12 weeks in subjects with moderately to-severely active CD.

    Subjects who complete Induction will continue to receive TD-1473 at Dose B in the Active Treatment Arm for up to 48 additional weeks.

    Intervention: Drug: TD-1473
  • Placebo Comparator: Placebo

    1 oral dose daily of placebo for 12 weeks in subjects with moderately to-severely active CD.

    Subjects who complete Induction will receive TD-1473 at Dose A in the Active Treatment Arm for up to 48 additional weeks.

    Interventions:
    • Drug: Placebo
    • Drug: TD-1473
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: August 14, 2018)
160
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Is at least 18 years of age at screening
  • Males and females with clinical evidence of Crohn's disease for at least 3 months duration at screening
  • Moderately-to-severely active Crohn's Disease at baseline, as defined by a Crohn's Disease Activity Index (CDAI) score of 220-450 inclusive
  • SES-CD score of ≥ 3 with ulceration (corresponding to a score of 1) in at least 1 of the 5 ileocolonic segments on the Ulcerated Surface subscore of the SES-CD]
  • Is corticosteroid-dependent or has demonstrated inadequate response, or intolerance to conventional therapy (aminosalicylates, corticosteroids and immunomodulators such as azathioprine, 6-mercaptopurine, or methotrexate) or biologics (e.g., anti-TNF therapy, anti-IL-12/23 (anti-interleukin), anti-integrin).
  • Additional inclusion criteria apply

Exclusion Criteria:

  • Is currently receiving biologic (anti-TNF, anti-integrin, or anti-IL12/23) therapy
  • Has a current bacterial, parasitic, fungal, or viral infection
  • Has clinically significant abnormalities in laboratory evaluations
  • Prior exposure or potential exposure to a JAK inhibitor that was stopped due to intolerance or lack of efficacy
  • Subject has participated in another clinical trial of an investigational drug (or medical device) within 30 days prior to Screening or 5x the half-life of the investigational drug, whichever is longer, or is currently participating in another trial of an investigational drug (or medical device)
  • Subject has failed ≥ 3 biologic agents of 3 different mechanisms of action (i.e., anti-TNF, anti-integrin, and anti-IL12/23)
  • Additional exclusion criteria apply
Sex/Gender  ICMJE
Sexes Eligible for Study: All
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 Austria,   Bulgaria,   Croatia,   France,   Georgia,   Germany,   Greece,   Hungary,   Israel,   Poland,   Portugal,   Romania,   Russian Federation,   Serbia,   South Africa,   Spain,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03635112
Other Study ID Numbers  ICMJE 0173
2018-001272-37 ( EudraCT Number )
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
Plan Description: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.
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 June 2020

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