TD-1473 for Active Ulcerative Colitis (UC)

Study Overview
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Brief Summary
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This study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TD-1473 in subjects with moderately-to-severely active UC over 28 days. This exploratory study will also serve as a signal seeking endeavor to demonstrate biologic effect associated with TD-1473 through biomarker analysis and clinical, endoscopic, and histologic assessments.

Official Title
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A Phase 1b Multi-Center, Randomized, Double-Blind, Multi-Dose, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Plasma Exposure of TD-1473 in Subjects With Moderately-to-Severely Active Ulcerative Colitis

Conditions
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Ulcerative Colitis, Active Moderate, Ulcerative Colitis, Active Severe

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a history of ulcerative colitis diagnosis at least 3 months prior to screening Is intolerant, refractory, or only partially responsive to aminosalicylates, corticosteroids, immunomodulators, or biologics. If subject is currently receiving an oral aminosalicylate, he or she is eligible and can stay on that dose of aminosalicylate provided the dose has been stable for at least 2 weeks prior to screening. If the subject is currently receiving an oral corticosteroid, he or she is eligible if the dose is equivalent to or less than prednisone 20 mg/day or budesonide 9 mg/day and stable for at least 2 weeks prior to screening sigmoidoscopy if the subject has been on corticosteroids for more than 2 weeks. Has a rectal bleeding score ≥ 1 and a bowel frequency score ≥ 1 on the patient-reported outcome 2 (PRO2) on screening sigmoidoscopy day and on Day 1 in addition to a modified Mayo endoscopic subscore of ≥ 2 during screening Women of childbearing potential must have a negative pregnancy test and either abstain from sexual intercourse or use a highly effective method of birth control Willing and able to give informed consent Additional inclusion criteria apply Exclusion Criteria: Has fulminant colitis, toxic megacolon, primary sclerosing cholangitis, Crohn's disease, history of colitis-associated colonic dysplasia, active peptic ulcer disease Medications of exclusion: a) azathioprine, 6-mercaptopurine, or methotrexate within the 28 days prior to Day 1, b) adalimumab, infliximab, golimumab, etanercept, or certolizumab within the 60 days prior to Day 1, c) intravenous corticosteroids within the 14 days prior to Day 1, d) topical mesalamine or steroid (i.e., enemas or suppositories) within the 14 days prior to Day 1, e) any prior exposure to mycophenolic acid, tacrolimus, sirolimus, cyclosporine, natalizumab, rituximab, efalizumab, ustekinumab, fingolimod, or thalidomide, f) NSAIDs on a daily basis, g) tofacitinib within the 60 days prior to Day 1; h) vedolizumab within 120 days prior to Day 1 Has a current bacterial, parasitic, fungal, or viral infection Is positive for hepatitis A, B or C, HIV or tuberculosis Has clinically significant abnormalities in laboratory evaluations Participated in another clinical trial of an investigational drug (or medical device) within 30 days prior to screening (or within 60 days prior to screening if investigational drug was a biologic or another Janus kinase (JAK) inhibitor, or is currently participating in another trial of an investigational drug (or medical device) Use of prescription medications started or with a dose adjustment within 4 weeks prior to study enrollment, or over-the-counter medications or supplements started or with a dose adjustment within 2 weeks prior study enrollment. Anti-diarrheal medications are allowed only if dose has been stable at least 2 weeks prior to study enrollment Additional exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Experimental: TD-1473 low dose<br>10 subjects will be randomized to receive low-dose TD-1473 orally daily for 28 days | Drug: TD-1473<br> <br> |
| Experimental: TD-1473 mid dose<br>10 subjects will be randomized to receive mid-dose TD-1473 orally daily for 28 days | Drug: TD-1473<br> <br> |
| Experimental: TD-1473 high dose<br>10 subjects will be randomized to receive high-dose TD-1473 orally daily for 28 days | Drug: TD-1473<br> <br> |
| Placebo Comparator: Placebo<br>10 subjects will be randomized to receive placebo orally daily for 28 days | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-emergent Adverse Events (TEAE) | Number of participants who experience one or more treatment-emergent Adverse Events (TEAE) | Baseline to end of follow-up (a maximum of 42 days) | 
| Moderate or Severe Treatment-emergent Adverse Events (TEAE) | Number of participants who experience one or more moderate or severe treatment-emergent Adverse Events (TEAE) | Baseline to end of follow-up (a maximum of 42 days) | 
| Serious Treatment-emergent Adverse Events (TEAE) | Number of participants who experience one or more serious treatment-emergent Adverse Events (TEAE) | Baseline to end of follow-up (a maximum of 42 days) | 
| Clinical Laboratory Measurements | Number of participants who experienced a Clinically Significant Clinical Laboratory Measurements | Baseline to end of follow-up (a maximum of 42 days) | 
| Electrocardiogram | Number of participants who experienced a Clinically Significant Electrocardiogram (ECG) Result | Baseline to Day 14 | 
| Vital Signs | Number of participants who experienced a Clinically Significant Vital Sign Measurement | Baseline to end of follow-up (a maximum of 42 days) | 
| Cmax in plasma | Maximum Observed Plasma Concentration of TD-1473 | Day 1 and Day 14 | 
| Tmax in plasma | Time to Reach Maximum Observed Plasma Concentration (Cmax) of TD-1473 | Day 1 and Day 14 | 
| Tlast in plasma | Time to Last Quantifiable Concentration of TD-1473 | Day 1 and Day 14 | 
| Ctrough in plasma | Trough Concentration of TD-1473 | Day 14 (Pre-dose) | 
| AUC0-4 in plasma | Area Under the Concentration-time Curve from Time Zero to 4 hours Post-Dose of TD-1473 | Day 1 and Day 14 | 
| Ctissue in plasma | Tissue Concentration of TD-1473 | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-reactive protein (CRP) | Mean Change in Serum C-reactive Protein (CRP) | Baseline, Day 14 and Day 28 | 
| Fecal Calprotectin | Mean Change in Fecal Calprotectin | Baseline and Day 28 | 
| Partial Mayo score | Mean Change in Partial Mayo Score | Baseline, Day 14 and Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ulcerative Colitis, Active Moderate and Severe