Ulcerative Colitis, Active Moderate, Ulcerative Colitis, Active Severe
Conditions
Keywords
Ulcerative Colitis, Active Moderate and Severe
Brief summary
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.
Interventions
DRUGTD-1473
DRUGPlacebo
Sponsors
Theravance Biopharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ctissue in plasma | Day 28 | Tissue Concentration of TD-1473 |
| Tlast in plasma | Day 1 and Day 14 | Time to Last Quantifiable Concentration of TD-1473 |
| Ctrough in plasma | Day 14 (Pre-dose) | Trough Concentration of TD-1473 |
| AUC0-4 in plasma | Day 1 and Day 14 | Area Under the Concentration-time Curve from Time Zero to 4 hours Post-Dose of TD-1473 |
| Treatment-emergent Adverse Events (TEAE) | Baseline to end of follow-up (a maximum of 42 days) | Number of participants who experience one or more treatment-emergent Adverse Events (TEAE) |
| Moderate or Severe Treatment-emergent Adverse Events (TEAE) | Baseline to end of follow-up (a maximum of 42 days) | Number of participants who experience one or more moderate or severe treatment-emergent Adverse Events (TEAE) |
| Serious Treatment-emergent Adverse Events (TEAE) | Baseline to end of follow-up (a maximum of 42 days) | Number of participants who experience one or more serious treatment-emergent Adverse Events (TEAE) |
| Clinical Laboratory Measurements | Baseline to end of follow-up (a maximum of 42 days) | Number of participants who experienced a Clinically Significant Clinical Laboratory Measurements |
| Electrocardiogram | Baseline to Day 14 | Number of participants who experienced a Clinically Significant Electrocardiogram (ECG) Result |
| Vital Signs | Baseline to end of follow-up (a maximum of 42 days) | Number of participants who experienced a Clinically Significant Vital Sign Measurement |
| Cmax in plasma | Day 1 and Day 14 | Maximum Observed Plasma Concentration of TD-1473 |
| Tmax in plasma | Day 1 and Day 14 | Time to Reach Maximum Observed Plasma Concentration (Cmax) of TD-1473 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fecal Calprotectin | Baseline and Day 28 | Mean Change in Fecal Calprotectin |
| Partial Mayo score | Baseline, Day 14 and Day 28 | Mean Change in Partial Mayo Score |
| C-reactive protein (CRP) | Baseline, Day 14 and Day 28 | Mean Change in Serum C-reactive Protein (CRP) |
Countries
Georgia, Moldova, Romania, United States
Outcome results
None listed