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-BG
• Lead Sponsor: Theravance Biopharma Ireland Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-01-18
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 880

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, 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 rat

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 during the Study
4. Has had a clinically significant, as deemed by the investigator, prior
intestinal resection for UC or for other GI diseases
5. Has carried or 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
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 failed =3 biologics of = 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 (eg, grapefruit) 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 the
investigator deems 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 (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 - Refer to Appendix 6 for
Prohibited medications). Anti diarrheal medications and probiotics are allowed only if dose has been stable for minimum of 14 days prior to Day 1.
12. Taking over-the-counter medications or dietary supplements that the
investigator deems 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 non-steroid anti-inflammatory drugs or acetaminophen used on an as needed basis, aspirin = 325 mg per day for cardiovascular prophylaxis,
and over the counter 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: a) there is evidence of undetectable viral load
measured twice six months apart after successful completion of treatment regimen and b) 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified