Clinical trial NCT02818686: TD-1473 for Active Ulcerative Colitis (UC)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ulcerative Colitis, Active Moderate
Ulcerative Colitis, Active Severe
Keywords: Ulcerative Colitis, Active Moderate and Severe
Lead sponsor: Theravance Biopharma
Sponsor class: INDUSTRY
First posted: 2016-06-30
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Treatment-emergent Adverse Events (TEAE)
timeFrame: Baseline to end of follow-up (a maximum of 42 days)
measure: Moderate or Severe Treatment-emergent Adverse Events (TEAE)
timeFrame: Baseline to end of follow-up (a maximum of 42 days)
measure: Serious Treatment-emergent Adverse Events (TEAE)
timeFrame: Baseline to end of follow-up (a maximum of 42 days)
measure: Clinical Laboratory Measurements
timeFrame: Baseline to end of follow-up (a maximum of 42 days)
measure: Electrocardiogram
timeFrame: Baseline to Day 14
measure: Vital Signs
timeFrame: Baseline to end of follow-up (a maximum of 42 days)
measure: Cmax in plasma
timeFrame: Day 1 and Day 14
measure: Tmax in plasma
timeFrame: Day 1 and Day 14
measure: Tlast in plasma
timeFrame: Day 1 and Day 14
measure: Ctrough in plasma
timeFrame: Day 14 (Pre-dose)
measure: AUC0-4 in plasma
timeFrame: Day 1 and Day 14
measure: Ctissue in plasma
timeFrame: Day 28
Secondary outcomes:
measure: C-reactive protein (CRP)
timeFrame: Baseline, Day 14 and Day 28
measure: Fecal Calprotectin
timeFrame: Baseline and Day 28
measure: Partial Mayo score
timeFrame: Baseline, Day 14 and Day 28
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Theravance Biopharma Investigational Site
state: Arizona
city: Monroe
country: United States
facility: Theravance Biopharma Investigational Site
state: Louisiana
city: Hermitage
country: United States
facility: Theravance Biopharma Investigational Site
state: Tennessee
city: Houston
country: United States
facility: Theravance Biopharma Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Theravance Biopharma Investigational Site
state: Texas
city: Tbilisi
country: Georgia
facility: Theravance Biopharma Investigational Site
city: Chisinau
country: Moldova, Republic of
facility: Theravance Biopharma Investigational Site
city: Bucharest
country: Romania
facility: Theravance Biopharma Investigational Site
Study officials:
affiliation: Theravance Biopharma
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Sandborn WJ, Nguyen DD, Beattie DT, Brassil P, Krey W, Woo J, Situ E, Sana R, Sandvik E, Pulido-Rios MT, Bhandari R, Leighton JA, Ganeshappa R, Boyle DL, Abhyankar B, Kleinschek MA, Graham RA, Panes J. Development of Gut-Selective Pan-Janus Kinase Inhibitor TD-1473 for Ulcerative Colitis: A Translational Medicine Programme. J Crohns Colitis. 2020 Sep 16;14(9):1202-1213. doi: 10.1093/ecco-jcc/jjaa049.