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

Launched by UNIVERSITY HOSPITAL SCHLESWIG-HOLSTEIN · Jul 3, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called oral controlled-ileocolonic-release nicotinamide (CICR-NAM) for patients with mild to moderately active ulcerative colitis (UC). The goal is to see if CICR-NAM can help reduce inflammation in the intestines and improve gut health. Participants will receive either the treatment in two different doses (2 grams or 3 grams per day) or a placebo (a harmless pill that contains no active medication) to compare the effects. This trial is currently recruiting patients aged 18 to 80 who have been diagnosed with UC for at least three months and have experienced at least one relapse in the past year.

To participate, individuals must meet certain criteria, including having mild to moderate UC symptoms and specific test results indicating inflammation. Participants can expect to take their assigned treatment for a set period and will be monitored regularly by the study team to assess their health and any changes in symptoms. It's important to note that some patients, such as those with severe UC or certain other medical conditions, will not be eligible to join the trial. If you're interested in participating or want to learn more, it's a good idea to discuss this with your healthcare provider.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• General:
• • 1. Male and female patients with UC and 18 to 80 years of age (at the time of signing the 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 to screening and ≥ 1 relapse, clinically defined using established criteria within the last 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 the screening period (levels above the reference range, measured by local laboratories).
• • 10. Full colonoscopy with no signs of malignancy either during screening or within one year before screening.
• Medication:
• • 11. In the case of no oral 5-aminosalicylate (5-ASA) therapy within the last 2 weeks before entry into screening with informed consent, any prior oral 5-ASA therapy is permitted and the patient is not allowed to receive 5-ASA during the study. In the case of oral 5-ASA therapy within 2 weeks before entry into screening with informed consent, the 5-ASA therapy should have been ongoing for \> 3 months and should be stable ≥ 4 weeks before screening endoscopy with ≤ 3 g/d (up to 3 days with \> 3 g/d acceptable). This 5-ASA baseline medication must be kept stable in the induction period 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 or indeterminate colitis.
• • 2. Infectious colitis, diverticulitis or segmental colitis associated with diverticulosis (SCAD) within the last 6 months before screening.
• • 3. Current or past diagnosis of complex fistulae, intra-abdominal or peritoneal abscesses, 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)-positive infection; indications for other relevant infections including cytomegalovirus colitis, each at screening.
• • 10. Current or history of colon carcinoma, high grade colonic dysplasia or other malignancies except for completely resected basal cell carcinoma and squamous cell carcinoma 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 or suppositories) ≤ 2 weeks prior to screening endoscopy (up to 3 single doses allowed).
• • 16. Use of oral corticosteroids and/or oral budesonide ≤ 4 weeks prior to screening endoscopy.
• • 17. Previous use of immunosuppressants, Janus kinase inhibitors, sphingoside-1-phosphate receptor modulators or biologics.
• • 18. Use of antibiotics for the treatment of UC or probiotic medication within 6 weeks prior 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 trial or intake of an investigational medicinal product (IMP) within the last 8 weeks or 5 half-lives (whichever is longer) prior to screening (or longer if necessary in the investigator's discretion).
• • 22. Patients under legal supervision or guardianship, including patients, who are committed to an institution by virtue of an order issued either by the judicial or the 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 contraception till at least 1 month after last dosing of IMP.
• • 26. Male participants with female partners of childbearing potential who are not willing to use a highly effective contraception till at least 1 month after last dosing of IMP.
• • 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 participation and lead the investigator to assess the patient as unsuitable for trial participation for any other reason.