A clinical trial to investigate the Efficacy and Safety of TD-1473 for the Treatment of Moderately-to-Severely Active Ulcerative Colitis

Phase 1

Conditions: Moderately-to-Severely Active Ulcerative Colitis
MedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: EUCTR2018-002136-24-PT

Lead Sponsor: Theravance Biopharma Ireland Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 239

Inclusion Criteria

1. Are male or female 18 years of age or older at Screening
2. Has = 3 months history of UC prior to screening (with involvement beyond the rectum to at least 15 cm from the anal verge)
a. Diagnosed by sigmoidoscopy or colonoscopy AND
b. If possible, corroborated by histology report or documentation of
histological results in a physician note. However, if there was no biopsy done previously or if no prior endoscopy or histology report is available for review, the subject must have a colonoscopy instead of a sigmoidoscopy at screening.
3. Must be willing to have a sigmoidoscopy or colonoscopy at screening.
Colonoscopy will be performed instead of a sigmoidoscopy at screening in the following scenarios: a. If UC diagnosis precedes screening by = 8 years for pan-colitis or =12 years for left-sided colitis and the subject does not have documentation of a surveillance colonoscopy within 12 months prior to screening to rule out dysplasia (report must be reviewed by the investigator and included in the source documents). During colonoscopy, if chromoendoscopy or surveillance biopsies are indicated as per locally adopted guidelines, these should be performed.
b. If UC diagnosis precedes screening by < 12 years and the subject does not have documentation of a colonoscopy within 2 years prior to screening (report must be reviewed by investigator and included in the source documents).
c. If there is no documented histology report from prior endoscopy
showing chronic colitis or other signs of UC. In this case, consideration should be made to do biopsies during the screening endoscopy with histology sent locally to confirm diagnosis of UC, if there is doubt of diagnosis.
d. If chromoendoscopy has to be performed or = 10 biopsies are to be collected for dysplasia surveillance, either should be done after
completion of a full colonoscopy to avoid chromoendoscopy dye or
biopsy-related bleeding artifact from interfering with endoscopic images for central reading.
4. Has moderately-to-severely active UC, defined as having:
a. a centrally read Mayo endoscopic sub score of = 2 points based on the results of the Screening Stage 2 endoscopy and
b. an adapted Mayo score between 4 and 9 points, inclusive, on Day 1.
5. Is corticosteroid-dependent or had intolerance or inadequate
response to any of the following: aminosalicylates, corticosteroids,
immunomodulators (azathioprine or 6-mercaptopurine), or biologics (anti-TNF, or anti-integrin, or anti-IL-12/23) [Refer to Appendix 7 of the protocol]
NOTE: for subjects in Portugal, subject must have had intolerance or inadequate response to biologics
6. If currently receiving an oral corticosteroid, subject is eligible if:
a. the subject has been on corticosteroids for a minimum of 4 weeks prior to Day 1 AND
b. the dose is equivalent to or less than prednisone 25 mg/day or
beclomethasone diproprionate (ie, Clipper) at 5 mg/day or budesonide 9
mg/day AND
c. the dose is stable for at least 2 weeks prior to Screening Stage 2 visit
7. If subject is currently receiving oral aminosalicylate (eg, mesalamine products, balsalazide, or sulfasalazine): subject is eligible provided the subject has been on it at a stable dose for = 4 weeks prior to Day 1.
8. During the Study and for 7 days after receiving the last dose of the Study drug, females of childbearing potential or men capable of
fathering children must agree to use highly effective birth control
measures (failure rate <1% when used consist

Exclusion Criteria

1. Has symptoms or signs suggestive of fulminant colitis, toxic megacolon, intestinal perforation
2. Has primary sclerosing cholangitis
3. Is likely to require surgery for UC or any other type of major surgery during the Study
4. Has had a clinically significant prior intestinal resection for UC or for other GI diseases
5. Has carried/carries a diagnosis of Crohn's disease, microscopic colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, or indeterminate colitis, or the subject has a current or past diagnosis of a fistula or abdominal abscess
6. Has unresected colonic mucosal dysplasia or history of resected high-grade colonic dysplasia within 3 years prior to screening
7. Taken or taking any prohibited medications as listed in the protocol
8. If subject has recently discontinued aminosalicylates or corticosteroids, these must have been stopped at minimum of 2 weeks
before screening endoscopic procedure
9. Has had inadequate response =3 biologics of =3 different mechanisms of action
10. Currently taking or has taken within 14 days prior to Day1 any concomitant medication, herbal supplement or dietary substance known to be a strong inhibitor or inducer of P-gp, BCRP, or CYP450 3A4 or is a substrate of P-gp or BCRP and has a narrow therapeutic index
11. Taking non-UC concomitant prescription medications that may confound the safety assessment of the study drug and that have started or have had a dose adjustment within 28 days prior to Day1 (with the exception of corticosteroids, antibiotics for infections, sedating agents for sigmoidoscopy or colonoscopy, hormonal contraceptives, hormone replacement therapy, iron, vitamin D, insulin therapy, and replacement thyroid hormone). Anti diarrheal medications and probiotics are allowed only if dose has been stable for minimum of 14 days prior to Day 1
12.Taking OTC medications or dietary supplements that may confound the safety assessment of the study drug and that have started or have had a dose adjustment within 14 days prior to Day 1 with the exception of up to 3 times per week use of NSAID or acetaminophen used on an as needed basis, aspirin =325 mg per day for cardiovascular prophylaxis, and OTC doses of vitamin D
13. Subject is positive for:
a. HBV surface antigen
b. HBV core antibody (unless subject has positive HB surface antibody and undetectable serum HB DNA)
c. HCV antibody unless there is evidence of undetectable viral load measured twice 6 months apart after successful completion of treatment regimen and viral load during Screening is undetectable
d. Hepatitis E IgM antibody
e. HIV antibody
14. Subject has had a live viral vaccine within 4 weeks prior to screening and/or is unwilling or unable to avoid live viral vaccines during the Study and for 8 weeks following completion
15. Has or may have untreated active or latent TB
16. Has any of the following:
a. An active, clinically significant, bacterial, parasitic, fungal, mycobacterial (including atypical infection), or viral infection, except for
local skin or nail bed infection, within 2 weeks prior to Day 1
b. Any infection requiring IV antibiotics within 30 days prior to screening
c. Any infection requiring oral antimicrobial treatment within 2 weeks prior to Day 1
d. A history of >2 episodes of herpes zoster or =1 episodes of disseminated/complicated herpes zoster or disseminated herpes simplex
e. Has had a chest radiograph or equivalent chest imaging within 90 day

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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