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

Study Overview
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Brief Summary
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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
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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 Crohn's Disease. 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.

Official Title
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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

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Placebo
* Drug: TD-1473


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Treatment TD-1473 with Dose A<br>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. | Drug: TD-1473<br>* 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.<br>|
| Active Comparator: Active Treatment TD-1473 with Dose B<br>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. | Drug: TD-1473<br>* 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.<br>|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* Placebo will be taken daily by mouth (orally) for up to 12 weeks in the morning before eating.<br>Drug: TD-1473<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Crohn's Disease Activity Index (CDAI) Score | The CDAI score was 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. Participants reported information regarding symptoms using a diary. The subscores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Benchmarks for disease activity as measured by the CDAI were: <150, clinical remission; 150 to 219, mildly active disease; 220-450, moderately active disease; and >450, very severe disease. | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Demonstrated a Clinical Response as Measured by CDAI | The CDAI score was 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. Participants reported information regarding symptoms using a diary. The subscores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Benchmarks for disease activity as measured by the CDAI were: <150, clinical remission; 150 to 219, mildly active disease; 220-450, moderately active disease; and >450, very severe disease. Clinical response was defined as a reduction from baseline of ≥100 points or CDAI <150 | Week 12 | 
| Number of Participants Who Demonstrated CDAI Clinical Remission | The CDAI score was 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. Participants reported information regarding symptoms using a diary. The subscores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Benchmarks for disease activity as measured by the CDAI were: <150, clinical remission; 150 to 219, mildly active disease; 220-450, moderately active disease; and >450, very severe disease. CDAI clinical remission was defined as a CDAI score less than 150 at Week 12. | Week 12 | 
| Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12 | The SES-CD incorporated 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 was scored in 5 segments (ileum, right colon, transverse colon, left colon, and rectum). The total score ranged from 0 to 56, with higher scores indicating a worse outcome. | Baseline to Week 12 | 
| Number of Participants With Endoscopic Response at Week 12 | Endoscopic Response was defined as a reduction of SES-CD score or Endoscopic Remission (defined as SES-CD ≤ 2) at Week 12. | Week 12 | 
| Number of Participants With Stool Frequency and Abdominal Pain (SFAP) Clinical Remission | SFAP clinical remission was defined as an abdominal pain score ≤1 (on a scale of 0-3 with 0 representing 'no pain' and 3 representing 'severe pain'), stool frequency ≤2.8, and both not worse than baseline at Week 12. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TD-1473, Janus kinase inhibitor, JAK inhibitor, Inflammatory Bowel Disease, IBD, Crohn's Disease, Intestinal restriction