NCT03635112 - Efficacy and Safety of TD-1473 in Crohn's Disease | Crick

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

167

Conditions

Crohn's Disease

Interventions

PlaceboDRUG

Placebo will be taken daily by mouth (orally) for up to 12 weeks in the morning before eating.

TD-1473DRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (178)

Outcomes

Primary Outcomes

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.

Time frame: Baseline to Week 12

Secondary Outcomes

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

Time frame: 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.