TD-1473 for Active Ulcerative Colitis (UC)

Theravance Biopharma

Status and phase: Completed; Phase 1

Conditions: Ulcerative Colitis, Active Severe; Ulcerative Colitis, Active Moderate

Treatments: Drug: Placebo; Drug: TD-1473

Study type: Interventional

Funder types: Industry

Identifiers

NCT02818686

2016-001633-27 (EudraCT Number)

0144

Details and patient eligibility

About

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.

Enrollment: 40 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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40 participants in 4 patient groups, including a placebo group

TD-1473 low dose

Experimental group

Description:

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

Treatment:

Drug: TD-1473

TD-1473 mid dose

Experimental group

Description:

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

Treatment:

Drug: TD-1473

TD-1473 high dose

Experimental group

Description:

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

Treatment:

Drug: TD-1473

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo