Moderately-to-Severely Active Crohn’s Disease (CD) MedDRA version: 20.0 Level: LLT Classification code 10013099 Term: Disease Crohns System Organ Class: 100000004856
Conditions
Sponsors
Theravance Biopharma Ireland Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria for Induction: 1. Subject is willing and able to provide written, signed informed consent at Screening Part 1 prior to start of any study-related procedures 2. Subject is a male or female at least 18 years of age at the time of Screening 3. Subject has a diagnosis of CD with involvement of at least the ileum or any portion of the colon at a minimum, diagnosed by radiology, endoscopy, and/or histology at least 3 months prior to Screening by ileocolonoscopy and confirmed on histology. The report of a previous diagnostic exam (endoscopy, radiology, and/or pathology) must be reviewed by the investigator and included in the source documents. 4. Subjects must have up-to-date colorectal cancer screening as per locally adopted guidelines (e.g., if subject has had = 8 years of disease involving >30% of the colon, surveillance biopsies or chromoendoscopy should be performed if either is indicated as per locally adopted guidelines but has not been performed within the 12 months prior to Screening. If indicated, the surveillance biopsies (if = 10) and chromoendoscopy need to be performed during Screening Stage 2 ileocolonoscopy after recording of a full ileocolonoscopy has been completed to avoid dye or biopsy related bleeding artifact on the recorded images.) 5. Subject has CDAI score = 220 and = 450 (required in order to proceed to endoscopy during Screening Stage 2 visit) ge 2 visit) 6.Subject has a 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, as assessed by central reading, during Screening a.Up to approximately 10% of the study population will have SES-CD score of between 3 and 5, inclusive, with the presence of ulceration in any 1 of the 5 ileocolonic segments, all other subjects (approximately 90% of the study population) will require an SES-CD score of = 6 (= 4 if isolated ileal disease) 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 7.Subject is corticosteroid-dependent or had intolerance or inadequate response to any of the following: aminosalicylates, corticosteroids, immunomodulators (azathioprine, 6 mercaptopurine, or methotrexate), or biologics (anti-TNF anti-IL-12/IL-23 therapy, or anti-integrin) 8. If subject is currently receiving an oral corticosteroid, subject is eligible if: a. the subject has been on corticosteroid for a minimum of 4 weeks prior to Day 1 AND b. the dose is equivalent to or less than prednisone 25 mg/day or budesonide 9 mg/day or beclomethasone at 5 mg/day AND c. the dose is stable for at least 2 weeks prior to Screening Stage 2 AND d. the subject is willing to continue on the same dose as warranted until Week 8 9. If subject is currently receiving oral aminosalicylate (including, but not limited to sulfasalazine or mesalamine), the subject is eligible provided the subject has been on a stable dose for = 4 weeks prior to Day 1 and is willing to stay on the same dose as warranted until Week 12 Inclusion Criteria for ATE: 1. Subject has completed Induction Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 140 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: Exclusion Criteria Pertinent to GI: 1. Subject with a confirmed or suspected diagnosis or history of primary sclerosing cholangitis (PSC) 2. Subject has had extensive colonic resection (i.e., more than half of colon), subtotal or total colectomy, intestinal resection within 6 months of Screening, > 2 small bowel resections or carries a diagnosis of short bowel syndrome or currently has an ostomy 3. Subject has a history of unresected colonic mucosal dysplasia. Subjects will not be excluded from the study because of a pathology finding of indefinite dysplasia with reactive atypia or because of adenomas that have been completely resected Exclusion Criteria Pertinent to Medications: 1. Medications of exclusion (Refer to Section 6.4.29 and Appendix 11 for prohibited medications) below must be discontinued within the timeframe specified (if applicable) • azathioprine, 6-mercaptopurine, or methotrexate taken within the 14 days prior to Day 1 • anti-TNFs (e.g., adalimumab, infliximab, golimumab, etanercept, certolizumab, or biosimilars) taken within the 60 days or 5 half-lives, whichever is shorter, prior to Day 1 • intravenous corticosteroids within the 14 days prior to Day 1 • rectal mesalamine or corticosteroid (i.e., enemas or suppositories) taken within the 14 days prior to Day 1 • prior exposure to vedolizumab, ustekinumab, mycophenolic acid, tacrolimus, sirolimus, or cyclosporine taken within 60 days prior to Day 1 • Any prior exposure to natalizumab, rituximab, efalizumab, fingolimod, cyclophosphamide, or thalidomide • NSAIDs taken on a regular (more than 3 times per week, on average) basis (regular use of aspirin = 325 mg per day for cardiovascular protection is allowed). • anakinra or any other immune-modifying biologic agent taken within 90 days prior to Day 1 •A JAK inhibitor (e.g., tofacitinib) within 60 days prior to Day 1 2.Prior exposure or potential exposure to a JAK inhibitor that was stopped due to intolerance or lack of efficacy. This does not include subjects with prior exposure to another JAK inhibitor that was stopped for any other reason (e.g., loss/lack of insurance coverage or end of study) 3. 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) 4. Subject has failed = 3 biologic agents of 3 different mechanisms of action (i.e., anti-TNF, anti-integrin, and anti-IL12/23) Exclusion Criteria Pertinent to Infections: 1. Subject is positive for: a. hepatitis B virus (HBV) surface antigen b. hepatitis B virus core antibody (unless subject has positive hepatitis B surface antibody and undetectable serum hepatitis B DNA) c. hepatitis C virus (HCV) antibody unless: a) there is evidence of undetectable viral load measured twice six months apart after completion of treatment regimen and b) viral load during Screening is undetectable d. hepatitis E Immunoglobumin M (IgM) antibody e. human immunodeficiency virus (HIV) antibody 2. The subject has or may have untreated active or latent TB as evidenced by any of the following: a. Two indeterminate or one positive QuantiFERON®-TB Gold result within 90 days prior to screening or during the Screening Period, without having completed an adequate treatment for latent or active TB before Screening OR b. Chest X-ray or equ
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of the study are as follows: • 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 • To assess the safety and tolerability of TD-1473;Secondary Objective: The secondary objectives of the study are to assess the effects of TD-1473 given for 12 weeks compared to placebo as follows: • To induce clinical remission • To induce clinical response • To induce endoscopic response • To improve the Simplified Endoscopy Score for Crohn’s Disease (SES-CD);Primary end point(s): The primary endpoint is: • CDAI score change from baseline at Week 12;Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are: • CDAI clinical response (defined as reduction from baseline of = 100 points or CDAI < 150) at Week 12 • CDAI clinical remission (defined as CDAI < 150) at Week 12 • SES-CD change from baseline at Week 12 • Endoscopic response (SES-CD reduction of = 50% from baseline or endoscopic remission) at Week 12 • SFAP clinical remission defined as abdominal pain score = 1 (on a scale of 0-3), stool frequency = 2.8, and both not worse than baseline at Week 12 Study Safety Endpoints: • Changes from baseline in vital signs, ECGs, and clinical laboratory results • Incidence and severity of AEs;Timepoint(s) of evaluation of this end point: Week 12 | — |
Countries
Australia, Austria, Bulgaria, Croatia, France, Georgia, Germany, Greece, Hungary, Israel, Korea, Republic of, New Zealand, Poland, Portugal, Romania, Russian Federation, Serbia, South Africa, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Operations - CC
Theravance Biopharma US Inc.
Outcome results
None listed