Ulcerative Colitis, UnspecifiedPhase 2/3NCT06488625
Efficacy and Safety of Oral Controlled-Ileocolonic-Release Nicotinamide (CICR-NAM) in Patients With Mild to Moderately Active Ulcerative Colitis
A Phase 2/3 study testing Low-Dose CICR-NAM, High-Dose CICR-NAM and 0 g/d CICR-NAM (blinded) in people with Ulcerative Colitis, Unspecified, run by University Hospital Schleswig-Holstein at 25 sites in Germany.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Ulcerative Colitis, Unspecified
- What is being tested?
- Low-Dose CICR-NAM, High-Dose CICR-NAM and 0 g/d CICR-NAM (blinded)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 459 participants
- Where
- 25 sitesGermany
- Study dates
- 12 Sep 2024to Dec 2027
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- General:
- Male and female patients with UC and 18 to 80 years of age (at the time of signing the informed consent).
- Ability to understand and comply with the protocol.
- Signed written informed consent.
- Disease-specific:
- 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.
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- Histology supportive for the diagnosis of UC.
- Mild to moderate disease activity (at screening): modified Mayo score (mMS) 4-7 RB ≥ 1, endoscopic score ES ≥1 and SF ≥ 1.
- RHI > 4 (at screening endoscopy).
- Disease extent >15 cm from the anal verge (at screening endoscopy).
- 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).
- Full colonoscopy with no signs of malignancy either during screening or within one year before screening.
- Medication:
- 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.
Who cannot join
- General health and UC:
- Diagnosis of CD, microscopic colitis, ischaemic colitis, radiation colitis or indeterminate colitis.
- Infectious colitis, diverticulitis or segmental colitis associated with diverticulosis (SCAD) within the last 6 months before screening.
- Current or past diagnosis of complex fistulae, intra-abdominal or peritoneal abscesses, strictures with obstructive symptoms.
- Severe UC disease activity (modified Mayo score >7).
- Severe extraintestinal manifestations of UC requiring special treatment.
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- Steroid-dependent or steroid-refractory UC.
- Foreseeable need for hospitalisation.
- Previous colonic surgery, except for appendectomy.
- Stools positive for enteric pathogens; Clostridium difficile toxin (CDT)-positive infection; indications for other relevant infections including cytomegalovirus colitis, each at screening.
- 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.
- Moderate to severe anaemia (haemoglobin <9 g/dL) at screening.
- Moderate to severe renal impairment (glomerular filtration rate <60) at screening.
- Relevant bleeding or thrombotic disorders.
- Alcohol or drug abuse within the last 2 years.
- Medications:
- 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).
- Use of oral corticosteroids and/or oral budesonide ≤ 4 weeks prior to screening endoscopy.
- Previous use of immunosuppressants, Janus kinase inhibitors, sphingoside-1-phosphate receptor modulators or biologics.
- Use of antibiotics for the treatment of UC or probiotic medication within 6 weeks prior to screening endoscopy.
- Any need of parenteral therapies for the therapy of UC (except iron infusions).
- Known hypersensitivity towards any component of the CICR-NAM or placebo tablets.
- Regulatory requirements
- 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).
- 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.
- Patients who are dependent on the investigator or the sponsor.
- Other:
- Pregnant or breastfeeding women.
- Women of childbearing potential (WoCBP) not using highly effective contraception till at least 1 month after last dosing of IMP.
- 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.
- Indications that the patient may be unable to comply with the trial procedures, e.g. language barriers precluding adequate understanding or cooperation.
- 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.
Trial locations and contacts
25 sites in 1 country. Contact the study team or a site near you to ask about taking part.
25 sites in 1 country
Germany25 sites, 24 recruiting
- Not yet recruiting
Universitaetsklinikum Aachen AöR
Aachen, North Rhine-Westphalia, 52074
Karim Hamesch, Dr., +492418085660, khamesch@ukaachen.de
- Recruiting
Universitaetsklinikum Augsburg
Augsburg, Bavaria, 86156
Elisabeth Schnoy, Prof. Dr., +498214002635, studie-3.med@uk-augsburg.de
- Recruiting
Sozialstiftung Bamberg
Bamberg, Bavaria, 96049
Jost Langhorst, Prof. Dr., +4995150311251, jost.langhorst@sozialstiftung-bamberg.de
- Recruiting
Charite Universitaetsmedizin Berlin KöR
Berlin, State of Berlin, 10117
Elisabeth Blüthner, Dr., +4930450665209, elisabeth.bluethner@charite.de
- Recruiting
Charite Universitaetsmedizin Berlin KöR
Berlin, State of Berlin, 12203
Britta Siegmund, Prof. Dr., +4930450514322, britta.siegmund@charite.de
- Not yet recruiting
Gesundheit Nord gGmbH Klinikverbund Bremen
Bremen, Free Hanseatic City of Bremen, 28205
Johann Ockenga, Prof. Dr., +4942149772502, johann.ockenga@klinikum-bremen-mitte.de
- Recruiting
Evangelisches Krankenhaus Kalk gGmbH
Cologne, North Rhine-Westphalia, 51103
Konrad Streetz, Prof. Dr., +4922182892100, konrad.streetz@evkk.de
- Withdrawn
Medical Care Unit Dachau
Dachau, Bavaria, 85221
- Recruiting
Gastroenterologie am Herrengarten
Darmstadt, Hesse, 64293
Jörg Carl Hoffmann, Prof. Dr., +49615195057614, hoffmann@praxis-gastroenterologie-darmstadt.de
- Recruiting
Gastroenterologische Schwerpunktpraxis Prof. Dr. Ludwig & Dr. med. Güthle
Dornstadt, Baden-Wurttemberg, 89160
Leopold Ludwig, Prof. Dr., +4973489671747, l.ludwig@praxis-endoskopie.de
- Recruiting
Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR
Dresden, Saxony, 01307
Renate Schmelz, Dr., +4935145819719, schmelz.studien@ukdd.de
- Recruiting
Agaplesion Frankfurter Diakonie Kliniken gGmbH
Frankfurt am Main, Hesse, 60431
Axel Dignaß, Prof. Dr., +496995332201, axel.dignass@agaplesion.de
- Recruiting
Goethe University Frankfurt
Frankfurt am Main, Hesse, 60590
Irina Blumenstein, Prof. Dr., +4969630187769, blumenstein@em.uni-frankfurt.de
- Recruiting
Martin-Luther-Universitaet Halle-Wittenberg
Halle, Saxony-Anhalt, 06120
Jens Walldorf, Prof. Dr., +49345557665, jens.walldorf@uk-halle.de
- Not yet recruiting
University Medical Center Hamburg-Eppendorf
Hamburg, Free and Hanseatic City of Hamburg, 20246
Thorben Fründt, Dr., +4940741018056, t.fruendt@uke.de
- Recruiting
Gastropraxis an der St. Barbara-Klinik
Hamm, North Rhine-Westphalia, 59073
Frank Lenze, Prof. Dr., +4923816811223, lenze@gastro-praxis-hamm.de
- Recruiting
Practice for Gastroenterology
Hanover, Lower Saxony, 30449
Jens Seiger, Dr., +495113536740, seiger@gastro-han.de
- Recruiting
Private Practice for Gastroenterology
Heidelberg, Baden-Wurttemberg, 69115
Robert Ehehalt, Prof. Dr., +49622125346, re@hd-gastro.de
- Recruiting
Universitaetsklinikum Schleswig-Holstein AöR
Kiel, Schleswig-Holstein, 24105
Susanna Nikolaus, Prof. Dr., +4943150022201, s.nikolaus@mucosa.de
- Recruiting
Universitaetsklinikum Schleswig-Holstein AöR
Lübeck, Schleswig-Holstein, 23538
Jens Marquardt, Prof. Dr., +4945150044100, jens.marquardt@uksh.de
- Recruiting
St. Marien Und St. Annastiftskrankenhaus
Ludwigshafen am Rhein, Rhineland-Palatinate, 67067
Tanja Kühbacher, Prof. Dr., +4962155012224, tanja.kuehbacher@st-marienkrankenhaus.de
- Recruiting
Gastropraxis Magdeburg
Magdeburg, Saxony-Anhalt, 39104
Lars Zimmermann, Dr., +4939150963429, zimmermann@gastropraxis-md.de
- Recruiting
Universitat Heidelberg
Mannheim, Baden-Wurttemberg, 68167
Anne Thomann, Dr., +496213834010, anne.thomann@medma.uni-heidelberg.de
- Not yet recruiting
Universitaet Muenster
Münster, North Rhine-Westphalia, 48149
Jonel Trebicka, Prof. Dr., +4925183578687, jonel.trebicka@ukmuenster.de
- Recruiting
Universitaetsklinikum Ulm AöR
Ulm, Baden-Wurttemberg, 89081
Jochen Klaus, Dr., +4973150044727, jochen.klaus@uniklinik-ulm.de
About this study
Official title: 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
Read the 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.
- Conditions
- Ulcerative Colitis, Unspecified
- Being tested
- Low-Dose CICR-NAM, High-Dose CICR-NAM, 0 g/d CICR-NAM (blinded), Open-Label
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-Dose CICR-NAMDrug
2 g/d CICR-NAM (blinded)
High-Dose CICR-NAMDrug
3 g/d CICR-NAM (blinded)
0 g/d CICR-NAM (blinded)Drug
Placebo (blinded)
Open-LabelDrug
3 g/d CICR-NAM (open label)
| Study group | Role | What they receive |
|---|---|---|
| Low-Dose (2 g/d CICR-NAM (blinded)) | Experimental | 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 Receives: Drug: Low-Dose CICR-NAM |
| High-Dose (3 g/d CICR-NAM (blinded)) | Experimental | 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 Receives: Drug: High-Dose CICR-NAM |
| Placebo (0 g/d CICR-NAM (blinded)) | Placebo comparator | 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 Receives: Drug: 0 g/d CICR-NAM (blinded) |
| Open-Label (3 g/d CICR-NAM (blinded)) | Experimental | 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 Receives: Drug: Open-Label |
What is being measured
The primary outcome is the main question the study is designed to answer.
Symptomatic remission
Symptomatic remission (dichotom: YES / NO): Symptomatic remission = YES if the following conditions are achieved at week 12: Mayo stool frequency (SF) = 0 or 1 (and SF no greater than baseline) and Mayo rectal bleeding (RB) = 0 as well as a reduction from Mayo Endoscopic Score (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)
Measured: Baseline - week 12
Clinical remission
Clincial remission (dichotom: YES / NO). Clinical remission = YES if the following conditions are achieved at week 52: Mayo stool frequency (SF) = 0 (or SF = 1 with a ≥ 1-point decrease from baseline), Mayo rectal bleeding (RB) = 0, and Mayo endoscopy score (ES) ≤ 1 (excluding friability) (for constant Mayo ES = 1 from baseline, histologic improvement to RHI ≤ 4)
Measured: Baseline - Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2024
- Study start12 Sep 2024
- Primary completionOct 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ulcerative Colitis, UnspecifiedStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 459 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Schleswig-Holstein
- Sponsor type
- University, hospital or other
- Collaborators
- Gesellschaft für Therapieforschung mbH, Funded by the German Federal Ministry of Research, Technology and Space (01KG2006), Ced Service GmbH
- Responsible party
- Sponsor
- Investigators
- Stefan Schreiber, Prof. Dr. Dr. hc., Principal investigator, University Medical Center Schleswig-Holstein (UKSH) Campus Kiel, Arnold-Heller-Str. 3, 24105 Kiel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06488625
- Sponsor's protocol ID
- ORNATUS 1
- Status last verified
- Oct 2026
- First submitted
- 26 Jun 2024
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided