TD-1473 for Active Ulcerative Colitis (UC)

Ulcerative Colitis, Active Moderate Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02818686
• Other study ID #: 0144
• Secondary ID: 2016-001633-27
• Status: Completed
• Phase: Phase 1
• Start date: October 3, 2016
• Est. completion date: March 29, 2018

Study information

• Verified date: September 2021
• Source: Theravance Biopharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: March 29, 2018
• Est. primary completion date: March 29, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis, Active Moderate
• Ulcerative Colitis, Active Severe

Intervention

Drug:
• TD-1473

• Placebo

Locations

Country	Name	City	State
Georgia	Theravance Biopharma Investigational Site	Tbilisi
Moldova, Republic of	Theravance Biopharma Investigational Site	Chisinau
Romania	Theravance Biopharma Investigational Site	Bucharest
United States	Theravance Biopharma Investigational Site	Hermitage	Tennessee
United States	Theravance Biopharma Investigational Site	Houston	Texas
United States	Theravance Biopharma Investigational Site	Monroe	Louisiana
United States	Theravance Biopharma Investigational Site	San Antonio	Texas
United States	Theravance Biopharma Investigational Site	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Theravance Biopharma

Countries where clinical trial is conducted

United States,  Georgia,  Moldova, Republic of,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	Electrocardiogram	Number of participants who experienced a Clinically Significant Electrocardiogram (ECG) Result	Baseline to Day 14
Primary	Vital Signs	Number of participants who experienced a Clinically Significant Vital Sign Measurement	Baseline to end of follow-up (a maximum of 42 days)
Primary	Cmax in plasma	Maximum Observed Plasma Concentration of TD-1473	Day 1 and Day 14
Primary	Tmax in plasma	Time to Reach Maximum Observed Plasma Concentration (Cmax) of TD-1473	Day 1 and Day 14
Primary	Tlast in plasma	Time to Last Quantifiable Concentration of TD-1473	Day 1 and Day 14
Primary	Ctrough in plasma	Trough Concentration of TD-1473	Day 14 (Pre-dose)
Primary	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
Primary	Ctissue in plasma	Tissue Concentration of TD-1473	Day 28
Secondary	C-reactive protein (CRP)	Mean Change in Serum C-reactive Protein (CRP)	Baseline, Day 14 and Day 28
Secondary	Fecal Calprotectin	Mean Change in Fecal Calprotectin	Baseline and Day 28
Secondary	Partial Mayo score	Mean Change in Partial Mayo Score	Baseline, Day 14 and Day 28

External Links

•   "Development of Gut-Selective Pan-Janus Kinase Inhibitor TD-1473 for Ulcerative Colitis: A Translational Medicine Programme" in the Journal of Crohn's and Colitis