The Role of Secondary Bile Acids in Intestinal Inflammation

Inclusion Criteria:

1. Written informed consent;

2. Male or female subjects, ≥18 years of age who have undergone an ileal pouch-analanastomosis (IPAA) for UC.

3. History of pouchitis Documented evidence of active pouchitis, based on endoscopy, symptoms andhistopathology, as follows:

4. Endoscopic score >=2 on the endoscopic component of a modified Mayo endoscopic score (where friability is scored as >2) Note: the area within 1 cm of the pouch staple,or pouch suture line, is not considered evaluable

5. Symptomatic disease (stool frequency): Subjects must demonstrate increased stool frequency compared to what is considered "normal" after their IPAA operation ("baseline"). Stool frequency must be anabsolute value of > 6 stools per day, and > 3 stools per day above the post-IPAA "baseline". Note: The measurement of stool frequency will be a 7-day average roundedto the nearest integer. The most recent 7 days of data will be used to calculate theaverage.

6. Histology: evidence of disease.

7. Modified PDAI (mPDAI) score >= 5. The mPDAI consists of the symptom (range: 0-6) andendoscopy (range: 0-6) subscores.

8. Must have chronic antibiotic refractory or antibiotic dependent pouchitis.

Exclusion Criteria:

1. Lack of effective contraception Women of childbearing potential may not participateunless they are surgically sterile or are using adequate contraception. The following contraceptive methods are acceptable: hormonal (eg oral, injection,transdermal patch, implant, cervical ring), barrier (eg condom or diaphragm withspermicidal agent), intrauterine system or intrauterine device. If hormonalcontraceptives are used by female subjects, they must be established for 6 weeksbefore the first administration of test product. Male sterilization is considered anacceptable form of contraception if the appropriate post-vasectomy documentation (absence of sperm) is provided in the subject's medical notes. Sexual abstinence isconsidered acceptable if this is in line with the preferred and usual lifestyle ofthe subject; periodic abstinence (eg calendar, ovulation, symptothermal,post-ovulation methods) and withdrawal are not acceptable methods of contraception. Male subjects with female partners of child-bearing potential and female subjectswho are neither surgically sterilized nor post-menopausal (defined as no menses forone year or a follicle-stimulating hormone value > 40 IU/L) will be required to useeffective contraception throughout the study and for 30 days after.

2. Women who are pregnant or breastfeeding;

3. History of allergy or adverse event to UDCA; Stable use of concomitant medications for pouchitis is generally permitted, doses ofconcomitant medication, where taken, should be optimised in accordance withlocal/national practice guidelines, and dose levels and types of baselinemedications for pouchitis will be documented and any changes during the study willbe recorded. Changes in use of medications for pouchitis and high doses of oralsteroids are not permitted. It is particularly important to maintain stablemedication through to measurement of the primary end-point at Week 10. Criteriawhich would lead to exclusion of subjects from the study are described below:

4. Changes in dose to strong analgesia, such as opioid containing compounds within 4weeks of the Screening Visit.

5. History of regular nonsteroidal anti-inflammatory drugs (NSAID) use.

6. Oral 5-aminosalicylate (5-ASA) compounds; exclude subjects who have discontinued orchanged doses of oral 5-ASA within 4 weeks of the Screening Visit.

7. Oral budesonide > 6.0 mg/day is not permitted; exclude subjects who have receivedbudesonide for < 6 weeks, or who have changed doses of budesonide within 4 weeks ofthe Screening Visit.

8. Oral steroids other than budesonide: exclude subjects who exceed a daily dose of 15mg prednisolone or equivalent, who have received oral steroids for < 6 weeks, or whohave changed dose within 4 weeks of the Screening Visit.

9. Use of rectal compounds is not permitted; these agents must be discontinued at theScreening Visit.

10. Immunosuppressant therapy (azathioprine, 6- mercaptopurine, methotrexate,cyclosporin); exclude subjects who have received treatment for < 12 weeks, or whohave changed doses within 8 weeks of the Screening Visit.

11. Biological agents (Anti-tumour necrosis factor (anti - TNF) therapy, vedolizumab and / or ustekinumab); exclude subjects who have received biological agents for <6months prior to the screening visit, or who changed doses of the biological agentwithin 6 months prior to the screening visit.

12. Previous use of UDCA is permitted: treatment course must have completed at least 12weeks prior to the Screening Visit.

13. All other agents targeted to pouchitis, including experimental agents, must havebeen discontinued at least 8 weeks prior to the Screening Visit, or for a periodequivalent to 5 half-lives (t1⁄2) of the agent (whichever is longer) It isacceptable to recruit subjects who remain on optimised, stable doses of oral 5-ASA,oral steroids (below the doses stipulated above) and immunosuppressants. It is acceptable to recruit subjects who terminated treatment with oral 5-ASA ororal steroids 4 weeks before the Screening Visit, or immunosuppressants 8 weeksbefore the Screening Visit. Note: Analgesic use should remain stable throughout the trial where possible.Paracetamol is the analgesic of choice. Note: VSL#3 probiotic treatment (and other probiotic treatments) will be permittedas long as maintained stable for 4 weeks prior to the Screening Visit, andmaintained at a stable dose throughout the trial Also excluded are subjects with:

14. Anastomotic stricture

15. Unable to undertake endoscopic evaluation

16. Faecal incontinence due to anal sphincter dysfunction

17. Infections to cytomegalovirus or Clostridium Difficile

18. Faecal transplantation within 12 weeks of screening

19. Intestinal malabsorption

20. Pancreatic maldigestion

21. Suspected irritable pouch syndrome

22. Cuffitis (inflammation of the anal mucosa). Subjects with active antibioticrefractory pouchitis as the predominant condition, but who also have cuffitis, maybe enrolled

23. Crohn's disease of the pouch; defined as either: a) complex perianal or pouchfistula and/or b) extensive pre-pouch ileitis with deep ulceration

24. Subjects with a history of neoplastic disease except for basal cell carcinoma ornonmetastatic squamous cell carcinoma of the skin

25. Subjects who are receiving or have received nasogastric/nasoenteric bottle feeding,an elemental diet, or total parenteral nutrition within the 2 weeks prior to Day 1

26. Subjects with a history of clinically significant and/or persistent haematologic,renal, hepatic, metabolic, psychiatric, central nervous system, pulmonary orcardiovascular disease; which in the investigator's opinion, would exclude entryinto the study

27. Subjects with any laboratory tests considered clinically significant at screening

28. Subjects who may be unavailable for the duration of the trial, likely to benoncompliant with the protocol, or who are felt to be unsuitable by the Investigatorfor any other reason including, for example, inability to retain an enemaformulation

29. Pelvic sepsis should be excluded