A trial to evaluate the efficacy and safety of oral controlled-ileocolonic-release nicotinamide (CICR-NAM) in patients with mild to moderately active ulcerative colitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Schleswig-Holstein AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

12 Sep 2024 → ongoing

Decision date (initial)

2024-04-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Funded by the German Federal Ministry of Research, Technology and Space (01KG2006)

External identifiers

EU CT number

2024-510807-13-00

ClinicalTrials.gov

NCT06488625

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

The primary objective is to assess the efficacy of CICR-NAM on symptomatic remission and endoscopic response and/or histologic improvement after 12 weeks and on clinical remission after 52 weeks in patients with mildly to moderately active ulcerative colitis (UC).

Secondary objectives 1

1. The key secondary objectives are to assess the efficacy of CICR-NAM on clinical remission, symptomatic remission, endoscopic response and remission, endoscopic response and/or histologic/biomarker improvement and endoscopic healing in patients with mildly to moderately active UC at timepoints up to 52 weeks of treatment.

Conditions and MedDRA coding

ulcerative colitis

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male and female patients with UC and 18 to 80 years of age (at the time of signing the informed consent).
2. 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.
3. 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.
4. Robarts Histology Index > 4 (at screening endoscopy).
5. Disease extent >15 cm from the anal verge (at screening endoscopy).
6. 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 10

1. Diagnosis of Crohn`s disease, 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. 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).
8. Use of oral corticosteroids and/or oral budesonide ≤ 4 weeks prior to screening endoscopy.
9. Previous use of immunosuppressants, Janus kinase inhibitors, sphingoside-1-phosphate receptor modulators or biologics.
10. Pregnant or breastfeeding women.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Symptomatic remission and endoscopic response and/or histologic improvement at Week 12.
2. Clinical remission at Week 52 (for patients with a constant Mayo ES = 1 from baseline, this requires an objective second marker of improvement (histologic improvement to RHI ≤ 4)).

Secondary endpoints 8

1. Symptomatic remission at Week 52.
2. Endoscopic remission at Week 52.
3. Symptomatic response at Week 12.
4. Endoscopic response and/or histologic improvement at Week 12.
5. Clinical remission at Week 52 in responders at Week 12.
6. Symptomatic remission at Week 12.
7. Endoscopic healing at Week 52.
8. Histologic improvement at Week 12.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Schleswig-Holstein AöR

Sponsor organisation

Universitaetsklinikum Schleswig-Holstein AöR

Address

Arnold-Heller-Strasse 3, Brunswik Brunswik

City

Kiel

Postcode

24105

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Schleswig-Holstein AöR

Contact name

Office of Prof. Schreiber

Public contact point

Organisation

Universitaetsklinikum Schleswig-Holstein AöR

Contact name

Office of Prof. Schreiber

Locations

1 EU/EEA country · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications