TD-1473 for Active Ulcerative Colitis (UC)

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

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.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis, Active Severe; Ulcerative Colitis, Active Moderate
• Intervention / Treatment: Drug: Placebo; Drug: TD-1473

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Georgia
  • Tbilisi, Georgia, 0141
    • Theravance Biopharma Investigational Site
• Moldova, Republic of
  • Chisinau, Moldova, Republic of, MD-2025
    • Theravance Biopharma Investigational Site
• Romania
  • Bucharest, Romania, 50152
    • Theravance Biopharma Investigational Site
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Theravance Biopharma Investigational Site
  • Louisiana
    • Monroe, Louisiana, United States, 71201
      • Theravance Biopharma Investigational Site
  • Tennessee
    • Hermitage, Tennessee, United States, 37076
      • Theravance Biopharma Investigational Site
  • Texas
    • Houston, Texas, United States, 77004
      • Theravance Biopharma Investigational Site
    • San Antonio, Texas, United States, 78215
      • Theravance Biopharma Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TD-1473 low dose; 10 subjects will be randomized to receive low-dose TD-1473 orally daily for 28 days	Drug: TD-1473
Experimental: TD-1473 mid dose; 10 subjects will be randomized to receive mid-dose TD-1473 orally daily for 28 days	Drug: TD-1473
Experimental: TD-1473 high dose; 10 subjects will be randomized to receive high-dose TD-1473 orally daily for 28 days	Drug: TD-1473
Placebo Comparator: Placebo; 10 subjects will be randomized to receive placebo orally daily for 28 days	Drug: Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Theravance Biopharma

Publications and helpful links

General Publications

• 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.

Helpful 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

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2016
• Primary Completion (Actual): March 29, 2018
• Study Completion (Actual): March 29, 2018

Study Registration Dates

• First Submitted: June 23, 2016
• First Submitted That Met QC Criteria: June 27, 2016
• First Posted (Estimate): June 30, 2016

Study Record Updates

• Last Update Posted (Actual): September 30, 2021
• Last Update Submitted That Met QC Criteria: September 28, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Ulcerative Colitis, Active Moderate and Severe
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: 0144; 2016-001633-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No