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

NCT06488625 | Recruiting Phase 2 DMC

• 1 other identifier: ORNATUS 1
• Study Type: interventional
• Target: 459
• Locations: 1 country
• Sites: 1

Brief 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). 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

Conditions

Ulcerative Colitis, Unspecified

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (4)

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

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

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

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

Drug: Open-Label

Interventions

Low-Dose CICR-NAM DRUG

2 g/d CICR-NAM (blinded)

Low-Dose (2 g/d CICR-NAM (blinded))

High-Dose CICR-NAM DRUG

3 g/d CICR-NAM (blinded)

High-Dose (3 g/d CICR-NAM (blinded))

0 g/d CICR-NAM (blinded) DRUG

Placebo (blinded)

Placebo (0 g/d CICR-NAM (blinded))

Open-Label DRUG

3 g/d CICR-NAM (open label)

Open-Label (3 g/d CICR-NAM (blinded))

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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-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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University Hospital Schleswig-Holstein: lead
• Ced Service GmbH: collaborator
• Gesellschaft für Therapieforschung mbH: collaborator
• German Federal Ministry of Education and Research: collaborator

Study Sites (1)

Universitaetsklinikum Schleswig-Holstein AöR

Kiel, Schleswig-Holstein, 24105, Germany

RECRUITING

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Stefan Schreiber, Prof. Dr. Dr. hc.

  University Medical Center Schleswig-Holstein (UKSH) Campus Kiel, Arnold-Heller-Str. 3, 24105 Kiel

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stefan Schreiber, Prof. Dr. Dr. hc.

CONTACT

+4943150022200; s.schreiber@mucosa.de

Friso Muijsers

CONTACT

+4943150030751; info@zks.uni-kiel.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2024
• First Posted: July 5, 2024
• Study Start: September 12, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: November 6, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)