Evaluation of Efficacy and Safety of Oral Controlled-Ileocolonic-Release Nicotinamide in Mild to Moderately Active Ulcerative Colitis Patients

Trial ID: 2024-510807-13-00
Protocol: ORNATUS 1
Sponsor: Universitaetsklinikum Schleswig-Holstein AöR

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Diseases & Conditions

Colitis ulcerative

Objectives

The primary objective of this study is to evaluate the **efficacy** of oral controlled-ileocolonic-release nicotinamide (CICR-NAM) in achieving symptomatic remission and endoscopic response and/or histologic improvement after 12 weeks, as well as clinical remission after 52 weeks, in patients with mildly to moderately active **ulcerative colitis**. This is clinically relevant as it aims to determine the potential of CICR-NAM as a therapeutic option for inducing and maintaining remission in this patient population, thereby potentially improving patient outcomes and quality of life.

Secondary objectives include assessing the efficacy of CICR-NAM on clinical remission, symptomatic remission, endoscopic response and remission, endoscopic response and/or histologic/biomarker improvement, and endoscopic healing at various timepoints up to 52 weeks of treatment. These objectives are crucial for understanding the broader therapeutic impact of CICR-NAM on disease activity and progression in ulcerative colitis.

Participants

The clinical trial involves participants diagnosed with **ulcerative colitis**, specifically targeting individuals with mildly to moderately active disease. The study population includes both male and female subjects aged between 18 to 80 years. Participants are required to have a documented diagnosis of ulcerative colitis with a minimum disease duration of three months prior to screening and at least one clinically defined relapse within the last 12 months. The trial does not involve a vulnerable population. The sponsor has not provided the total number of participants. Key lifestyle considerations include the management of oral 5-ASA therapy, which must be stable prior to and during the study, with specific guidelines on dosage adjustments. The trial population was selected based on specific inclusion criteria, ensuring participants have a modified Mayo score indicating mild to moderate disease activity and a Robarts Histology Index greater than 4, among other clinical parameters.

Plans and Procedures

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the efficacy and safety of oral controlled-ileocolonic-release **nicotinamide** (CICR-NAM) in patients with mild to moderately active **ulcerative colitis**. The trial aims to assess symptomatic remission and endoscopic response and/or histologic improvement after 12 weeks, and clinical remission after 52 weeks. The study will involve male and female patients aged 18 to 80 years with a documented diagnosis of ulcerative colitis, a minimum disease duration of 3 months, and at least one relapse within the last 12 months. The trial will exclude any patients who do not meet these criteria.

The trial will span an estimated duration from August 2024 to December 2027. Participants will be involved for a maximum of 52 weeks, with the possibility of early termination if they do not adhere to the study protocol or if they experience adverse effects that necessitate withdrawal. The study will include several key visits: an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor progress and assess primary and secondary endpoints, and a final end-of-study visit to evaluate overall outcomes.

During the screening visit, eligibility will be confirmed through assessments such as the modified Mayo score and Robarts Histology Index. Follow-up visits will occur at regular intervals to monitor symptomatic and endoscopic responses, with primary endpoints assessed at Week 12 and Week 52. Secondary endpoints will include symptomatic and endoscopic remission and response at these time points. The end-of-study visit will provide a comprehensive evaluation of the participant's condition and the treatment's efficacy. Participants will be randomly assigned to receive either the active treatment, CICR-NAM, or a placebo, with both groups receiving identical film-coated tablets to maintain blinding. The trial will ensure that all participants receive consistent care and monitoring throughout the study period.

Treatment

The clinical trial involves the administration of **CICR-NAM**, an experimental medication formulated as a **film-coated tablet**. The active substance in CICR-NAM is **nicotinamide**, a chemical compound. The medication is designed for oral administration, with a maximum daily dose of 3 grams and a total maximum dose of 1092 grams over a treatment period of up to 52 weeks. The primary objective of the trial is to evaluate the efficacy of CICR-NAM in achieving symptomatic remission and endoscopic response, as well as histologic improvement in patients with mild to moderately active **ulcerative colitis**. The trial will assess these outcomes after 12 weeks and clinical remission after 52 weeks.

In addition to the experimental treatment, a **placebo** is used as a comparator in this double-blind, placebo-controlled trial. The placebo is referred to as CICR-NAM Placebo and does not contain any active substance. The placebo is administered in a manner consistent with the experimental treatment to maintain the study's blinding and integrity. The trial design ensures that neither the participants nor the investigators are aware of the treatment assignments, thereby minimizing bias and ensuring the reliability of the results.

Efficacy

The efficacy of the investigational product, CICR-NAM, will be assessed in a randomized, double-blind, placebo-controlled clinical trial involving patients with mild to moderately active **ulcerative colitis**. The primary endpoints for evaluating efficacy include symptomatic remission and endoscopic response and/or histologic improvement at Week 12, as well as clinical remission at Week 52. For patients with a constant Mayo endoscopic score (ES) of 1 from baseline, clinical remission at Week 52 requires an objective second marker of improvement, specifically histologic improvement to a Robarts Histology Index (RHI) of ≤ 4.

Secondary endpoints include symptomatic remission and endoscopic remission at Week 52, symptomatic response at Week 12, endoscopic response and/or histologic improvement at Week 12, clinical remission at Week 52 in responders at Week 12, symptomatic remission at Week 12, endoscopic healing at Week 52, and histologic improvement at Week 12. These efficacy parameters will be measured using validated scales and indices, such as the modified Mayo score and the Robarts Histology Index, at specified timepoints throughout the trial duration.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Male and female patients with UC and 18 to 80 years of age (at the time of signing the informed consent).
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.
Mild to moderate disease activity (at screening): modified Mayo score 4–7 with Mayo rectal bleeding (RB) subscore ≥ 1, Mayo endoscopic score (ES) subscore ≥ 1 and Mayo stool frequency (SF) subscore ≥ 1.
Robarts Histology Index > 4 (at screening endoscopy).
Disease extent >15 cm from the anal verge (at screening endoscopy).
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.

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Exclusion Criteria

Diagnosis of Crohn`s disease, 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.
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.
Pregnant or breastfeeding women.