Efficacy and Safety of Oral Controlled-Ileocolonic-Release Nicotinamide (CICR-NAM) in Patients with Mild to Moderately Active Ulcerative Colitis

Inclusion Criteria:

General:

1. Male and female patients with UC and 18 to 80 years of age (at the time of signingthe informed consent).

2. Ability to understand and comply with the protocol.

3. Signed written informed consent. Disease-specific:

4. Documented diagnosis of UC, with a minimum disease duration of 3 months prior toscreening and ≥ 1 relapse, clinically defined using established criteria within thelast 12 months.

5. Histology supportive for the diagnosis of UC.

6. Mild to moderate disease activity (at screening): modified Mayo score (mMS) 4-7 RB ≥ 1, endoscopic score ES ≥1 and SF ≥ 1.

7. RHI > 4 (at screening endoscopy).

8. Disease extent >15 cm from the anal verge (at screening endoscopy).

9. Elevated level(s) of C-reactive protein (CRP) and/or faecal calprotectin during thescreening period (levels above the reference range, measured by local laboratories).

10. Full colonoscopy with no signs of malignancy either during screening or within oneyear before screening. Medication:

11. In the case of no oral 5-aminosalicylate (5-ASA) therapy within the last 2 weeksbefore entry into screening with informed consent, any prior oral 5-ASA therapy ispermitted and the patient is not allowed to receive 5-ASA during the study. In thecase of oral 5-ASA therapy within 2 weeks before entry into screening with informedconsent, the 5-ASA therapy should have been ongoing for > 3 months and should bestable ≥ 4 weeks before screening endoscopy with ≤ 3 g/d (up to 3 days with > 3 g/dacceptable). This 5-ASA baseline medication must be kept stable in the inductionperiod and may be reduced (but not increased again) in the maintenance period.

Exclusion Criteria:

General health and UC:

1. Diagnosis of CD, microscopic colitis, ischaemic colitis, radiation colitis orindeterminate colitis.

2. Infectious colitis, diverticulitis or segmental colitis associated withdiverticulosis (SCAD) within the last 6 months before screening.

3. Current or past diagnosis of complex fistulae, intra-abdominal or peritonealabscesses, strictures with obstructive symptoms.

4. Severe UC disease activity (modified Mayo score >7).

5. Severe extraintestinal manifestations of UC requiring special treatment.

6. Steroid-dependent or steroid-refractory UC.

7. Foreseeable need for hospitalisation.

8. Previous colonic surgery, except for appendectomy.

9. Stools positive for enteric pathogens; Clostridium difficile toxin (CDT)-positiveinfection; indications for other relevant infections including cytomegaloviruscolitis, each at screening.

10. Current or history of colon carcinoma, high grade colonic dysplasia or othermalignancies except for completely resected basal cell carcinoma and squamous cellcarcinoma of the skin.

11. Moderate to severe anaemia (haemoglobin <9 g/dL) at screening.

12. Moderate to severe renal impairment (glomerular filtration rate <60) at screening.

13. Relevant bleeding or thrombotic disorders.

14. Alcohol or drug abuse within the last 2 years. Medications:

15. Rectal topical 5-ASA and/or rectal budesonide therapy (enemas, foams orsuppositories) ≤ 2 weeks prior to screening endoscopy (up to 3 single dosesallowed).

16. Use of oral corticosteroids and/or oral budesonide ≤ 4 weeks prior to screeningendoscopy.

17. Previous use of immunosuppressants, Janus kinase inhibitors, sphingoside-1-phosphatereceptor modulators or biologics.

18. Use of antibiotics for the treatment of UC or probiotic medication within 6 weeksprior to screening endoscopy.

19. Any need of parenteral therapies for the therapy of UC (except iron infusions).

20. Known hypersensitivity towards any component of the CICR-NAM or placebo tablets. Regulatory requirements

21. Participation in a clinical trial within 4 weeks prior to screening for this trialor intake of an investigational medicinal product (IMP) within the last 8 weeks or 5half-lives (whichever is longer) prior to screening (or longer if necessary in theinvestigator's discretion).

22. Patients under legal supervision or guardianship, including patients, who arecommitted to an institution by virtue of an order issued either by the judicial orthe administrative authorities.

23. Patients who are dependent on the investigator or the sponsor. Other:

24. Pregnant or breastfeeding women.

25. Women of childbearing potential (WoCBP) not using highly effective contraceptiontill at least 1 month after last dosing of IMP.

26. Male participants with female partners of childbearing potential who are not willingto use a highly effective contraception till at least 1 month after last dosing ofIMP.

27. Indications that the patient may be unable to comply with the trial procedures, e.g.language barriers precluding adequate understanding or cooperation.

28. Any circumstances or medical conditions which could contradict a trial participationand lead the investigator to assess the patient as unsuitable for trialparticipation for any other reason.