TD-1473 for Active Ulcerative Colitis (UC)

NCT ID: NCT02818686

Last Updated: 2021-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-03
• Study Completion Date: 2018-03-29

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.

Conditions

Ulcerative Colitis, Active Moderate; Ulcerative Colitis, Active Severe

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

TD-1473 low dose

10 subjects will be randomized to receive low-dose TD-1473 orally daily for 28 days

Group Type: EXPERIMENTAL

TD-1473

Intervention Type: DRUG

TD-1473 mid dose

10 subjects will be randomized to receive mid-dose TD-1473 orally daily for 28 days

Group Type: EXPERIMENTAL

TD-1473

Intervention Type: DRUG

TD-1473 high dose

10 subjects will be randomized to receive high-dose TD-1473 orally daily for 28 days

Group Type: EXPERIMENTAL

TD-1473

Intervention Type: DRUG

Placebo

10 subjects will be randomized to receive placebo orally daily for 28 days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

TD-1473

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Theravance Biopharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Theravance Biopharma

Locations

Theravance Biopharma Investigational Site

Scottsdale, Arizona, United States

Theravance Biopharma Investigational Site

Monroe, Louisiana, United States

Theravance Biopharma Investigational Site

Hermitage, Tennessee, United States

Theravance Biopharma Investigational Site

Houston, Texas, United States

Theravance Biopharma Investigational Site

San Antonio, Texas, United States

Theravance Biopharma Investigational Site

Tbilisi, , Georgia

Theravance Biopharma Investigational Site

Chisinau, , Moldova

Theravance Biopharma Investigational Site

Bucharest, , Romania

Countries

United States; Georgia; Moldova; Romania

References

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.

Reference Type: DERIVED

PMID: 32161949 (View on PubMed)

Other Identifiers

2016-001633-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

0144

Identifier Type: -

Identifier Source: org_study_id