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-IT

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 > o = 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, (outlined in Section 6.4.1.20):
a.If UC diagnosis precedes screening by > o = 8 years for pan-colitis or > o = 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
If chromoendoscopy has to be performed or > o = 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 subscore of > or = 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: corticosteroids, immunomodulators (azathioprine or 6 mercaptopurine), or biologics (anti-TNF, anti-integrin, or anti-IL-12/23) [Refer to Appendix 7]
Please see the protocol for the complete list
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 800
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80

Exclusion Criteria

Subjects may not be enrolled if they:
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 (ie, surgical procedure requiring general anesthesia) 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 > or = 3 biologics of > or = 3 different mechanisms of action (i.e., anti TNF,anti-integrin, and anti-IL12/23
10. Currently taking or has taken within 14 days prior to Day 1 any concomitant medication, herbal supplement or dietary substance known to be a strong inhibitor or inducer of P-glycoprotein (P-gp), breast cancer resistance protein (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 Day 1. 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 with 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 < or = 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 hepatitis 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 of the Study. Subject must be willing to avoid contact with any household member who has been vaccinated with a live attenuated vaccine within 2 weeks after vaccination.
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. Please see the protocol for the complete list

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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