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

A Phase II/III, Randomised, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Oral Controlled-Ileocolonic-Release Nicotinamide (CICR-NAM) for Induction and Maintenance Therapy in Patients With Mild to Moderately Active Ulcerative Colitis

Double-blind, randomised, placebo-controlled phase II / III trial evaluating efficacy and safety of two different doses (2 g/d or 3 g/d) of oral controlled-ileocolonic-release nicotinamide (CICR-NAM) compared to placebo in patients with ulcerative colitis (UC).

The intended therapeutic use of CICR-NAM is to improve intestinal inflammation in adults with UC by topically increasing nicotinamide supply in the ileocolonic region and thus favourably influencing the composition of intestinal microbiota

Study Overview

• Status: Recruiting
• Conditions: Ulcerative Colitis, Unspecified
• Intervention / Treatment: Drug: Low-Dose CICR-NAM; Drug: High-Dose CICR-NAM; Drug: 0 g/d CICR-NAM (blinded); Drug: Open-Label

Detailed Description

ORNATUS 1 is a double-blind randomised trial evaluating the efficacy and safety of CICR-NAM in patients with mild to moderately active UC. The trial includes a 12-week induction period and a 40-week maintenance period. Patients will be randomised 1:1:1 placebo vs. 2 g/d CICR-NAM vs. 3 g/d CICR-NAM prior to induction treatment and will remain in the allocated dose level in the maintenance period, which results in a 52-week treatment in a treat-through design. An optional open label arm with 3 g/d CICR-NAM will be implemented for patients that have completed the induction period and show worsening of disease activity at the end of the induction period.

• Study Type: Interventional
• Enrollment (Estimated): 459
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Stefan Schreiber, Prof. Dr. Dr. hc.; Phone Number: +4943150022200; Email: s.schreiber@mucosa.de
• Study Contact Backup: Name: Friso Muijsers; Phone Number: +4943150030751; Email: info@zks.uni-kiel.de

Study Locations

• Germany
  • Aachen, Germany, 52074
    • Not yet recruiting
    • Universitaetsklinikum Aachen AöR
    • Contact: Karim Hamesch, Dr.; Phone Number: +492418085660; Email: khamesch@ukaachen.de
  • Augsburg, Germany, 86156
    • Recruiting
    • Universitaetsklinikum Augsburg
    • Contact: Elisabeth Schnoy, Prof. Dr. med.; Phone Number: +498214002635; Email: studie-3.med@uk-augsburg.de
  • Bamberg, Germany, 96049
    • Recruiting
    • Sozialstiftung Bamberg
    • Contact: Jost Langhorst, Prof. Dr. med.; Phone Number: +4995150311251; Email: jost.langhorst@sozialstiftung-bamberg.de
  • Berlin, Germany, 12559
    • Recruiting
    • DRK Kliniken Berlin
    • Contact: Benjamin Moser, Dr.; Phone Number: +4915201573335; Email: b.moser@drk-kliniken-berlin.de
  • Berlin, Germany, 12203
    • Recruiting
    • Charite Universitaetsmedizin Berlin KöR
    • Contact: Britta Siegmund, Prof. Dr.; Phone Number: +4930450514322; Email: britta.siegmund@charite.de
  • Berlin, Germany, 10117
    • Recruiting
    • Charite Universitaetsmedizin Berlin KöR
    • Contact: Elisabeth Blüthner, Dr.; Phone Number: +4930450665209; Email: elisabeth.bluethner@charite.de
  • Bremen, Germany, 28205
    • Recruiting
    • Gesundheit Nord gGmbH Klinikverbund Bremen
    • Contact: Johann Ockenga, Prof. Dr.; Phone Number: +4942149772502; Email: johann.ockenga@klinikum-bremen-mitte.de
  • Cologne, Germany, 51103
    • Recruiting
    • Evangelisches Krankenhaus Kalk gGmbH
    • Contact: Konrad Streetz, Prof. Dr. med.; Phone Number: +4922182892100; Email: konrad.streetz@evkk.de
  • Dachau, Germany, 85221
    • Withdrawn
    • Medical Care Unit Dachau
  • Darmstadt, Germany, 64293
    • Recruiting
    • Gastroenterologie am Herrengarten
    • Contact: Jörg Carl Hoffmann, Prof. Dr.; Phone Number: +49615195057614; Email: hoffmann@praxis-gastroenterologie-darmstadt.de
  • Dornstadt, Germany, 89160
    • Recruiting
    • Gastroenterologische Schwerpunktpraxis Prof. Dr. Ludwig & Dr. med. Güthle
    • Contact: Leopold Ludwig, Prof. Dr.; Phone Number: +4973489671747; Email: l.ludwig@praxis-endoskopie.de
  • Dresden, Germany, 01307
    • Recruiting
    • Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR
    • Contact: Renate Schmelz, Dr.; Phone Number: +4935148519719; Email: schmelz.studien@ukdd.de
  • Frankfurt, Germany, 60590
    • Recruiting
    • Goethe University Frankfurt
    • Contact: Irina Blumenstein, Prof. Dr.; Phone Number: +4969630187769; Email: blumenstein@em.uni-frankfurt.de
  • Frankfurt am Main, Germany, 60431
    • Recruiting
    • Agaplesion Frankfurter Diakonie Kliniken gGmbH
    • Contact: Axel Dignaß, Prof. Dr.; Phone Number: +496995332201; Email: axel.dignass@agaplesion.de
  • Halle, Germany, 06120
    • Recruiting
    • Martin-Luther-Universitaet Halle-Wittenberg
    • Contact: Jens Walldorf, Prof. Dr. med.; Phone Number: +49345557665; Email: jens.walldorf@uk-halle.de
  • Hamburg, Germany, 20246
    • Not yet recruiting
    • University Medical Center Hamburg-Eppendorf
    • Contact: Thorben Fründt, Dr.; Phone Number: +4940741018056; Email: t.fruendt@uke.de
  • Hamm, Germany, 59073
    • Recruiting
    • Gastropraxis an der St. Barbara-Klinik
    • Contact: Frank Lenze, Prof. Dr.; Phone Number: +4923816811223; Email: lenze@gastro-praxis-hamm.de
  • Hanover, Germany, 30449
    • Recruiting
    • Practice for Gastroenterology
    • Contact: Jens Seiger, Dr.; Phone Number: +495113536740; Email: seiger@gastro-han.de
  • Heidelberg, Germany, 69115
    • Recruiting
    • Private Practice for Gastroenterology
    • Contact: Robert Ehehalt, Prof. Dr.; Phone Number: +49622125346; Email: re@hd-gastro.de
  • Ludwigshafen, Germany, 67067
    • Recruiting
    • St. Marien Und St. Annastiftskrankenhaus
    • Contact: Tanja Kühbacher, Prof. Dr.; Phone Number: +4962155012224; Email: tanja.kuehbacher@st-marienkrankenhaus.de
  • Lübeck, Germany, 23538
    • Recruiting
    • Universitaetsklinikum Schleswig-Holstein AöR
    • Contact: Jens Marquardt, Prof. Dr.; Phone Number: +4945150044100; Email: jens.marquardt@uksh.de
  • Magdeburg, Germany, 39104
    • Recruiting
    • Gastropraxis Magdeburg
    • Contact: Lars Zimmermann, Dr.; Phone Number: +4939150963429; Email: zimmermann@gastropraxis-md.de
  • Mannheim, Germany, 68167
    • Recruiting
    • Universitat Heidelberg
    • Contact: Anne Thomann, Dr.; Phone Number: +496213834010; Email: anne.thomann@medma.uni-heidelberg.de
  • Münster, Germany, 48149
    • Not yet recruiting
    • Universitaet Muenster
    • Contact: Jonel Trebicka, Prof. Dr.; Phone Number: +4925183578687; Email: jonel.trebicka@ukmuenster.de
  • Ulm, Germany, 89081
    • Recruiting
    • Universitaetsklinikum Ulm AöR
    • Contact: Jochen Klaus, Dr.; Phone Number: +4973150044727; Email: jochen.klaus@uniklinik-ulm.de
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Recruiting
      • Universitaetsklinikum Schleswig-Holstein AöR
      • Contact: Susanna Nikolaus, Prof. Dr.; Phone Number: +4943150022201; Email: s.nikolaus@mucosa.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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-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, should not be increased ≥ 4 weeks before screening endoscopy and should remain stable for ≥ 1 week before screening endoscopy at the maximum dose according to label or lower. 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. In cases in which 5-ASA is dosed higher than the approved dose, the dose will be adjusted to the maximum approved dose at the time of randomization.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-Dose (2 g/d CICR-NAM (blinded)); To maintain blinding for patients and investigators in the induction and maintenance treatment, all patients self-administer 6 tablets per day. In the low-dose arm, subjects receive 4 tablets of verum CICR-NAM and 2 tablets of placebo CICR-NAM per day, resulting in a total daily intake of 2 g/d CICR-NAM	Drug: Low-Dose CICR-NAM; 2 g/d CICR-NAM (blinded)
Experimental: High-Dose (3 g/d CICR-NAM (blinded)); To maintain blinding for patients and investigators in the induction and maintenance treatment, all patients self-administer 6 tablets per day. In the high-dose arm, subjects receive 6 tablets of verum CICR-NAM and 0 tablets of placebo CICR-NAM per day, resulting in a total daily intake of 3 g/d CICR-NAM	Drug: High-Dose CICR-NAM; 3 g/d CICR-NAM (blinded)
Placebo Comparator: Placebo (0 g/d CICR-NAM (blinded)); To maintain blinding for patients and investigators in the induction and maintenance treatment, all patients self-administer 6 tablets per day. For the placebo arm, subjects receive 0 tablets of verum CICR-NAM and 6 tablets of placebo CICR-NAM per day, resulting in a total daily intake of 0 g/d CICR-NAM	Drug: 0 g/d CICR-NAM (blinded); Placebo (blinded)
Experimental: Open-Label (3 g/d CICR-NAM (blinded)); Patients that have completed the induction period and show worsening of disease activity at the end of the induction period will be allowed to switch to the open-label arm to receive 6 tablets of verum CICR-NAM of 0 tablets of placebo CICR-NAM per day, resulting in a total daily intake of 3 g/d CICR-NAM	Drug: Open-Label; 3 g/d CICR-NAM (open label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptomatic remission	The proportion of subjects that show symptomatic remission. Symptomatic remission is achieved if: Mayo SF = 0 or 1 (and SF no greater than baseline) and Mayo RB = 0 as well as a reduction from Mayo ES = 2 or 3 at baseline by at least one point or a reduction from Mayo ES = 1 at baseline to Mayo ES = 0 or, in case of a constant Mayo ES = 1 from baseline, an objective second marker of improvement (histologic improvement to RHI ≤ 4)	Baseline - Week 12
Clinical remission	The proportion of subjects that show clincial remission. Clinical remission is achieved if: Mayo SF = 0 (or SF = 1 with a ≥ 1-point decrease from baseline), Mayo RB = 0, and Mayo ES ≤ 1 (excluding friability) (for constant Mayo ES = 1 from baseline, histologic improvement to RHI ≤ 4)	Baseline - Week 52

Collaborators and Investigators

• Sponsor: University Hospital Schleswig-Holstein
• Collaborators: Gesellschaft für Therapieforschung mbH; Ced Service GmbH; Funded by the German Federal Ministry of Research, Technology and Space (01KG2006)
• Investigators: Principal Investigator: Stefan Schreiber, Prof. Dr. Dr. hc., University Medical Center Schleswig-Holstein (UKSH) Campus Kiel, Arnold-Heller-Str. 3, 24105 Kiel

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: June 26, 2024
• First Submitted That Met QC Criteria: July 3, 2024
• First Posted (Actual): July 5, 2024

Study Record Updates

• Last Update Posted (Actual): June 11, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: ORNATUS 1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No