|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Ulcerative colitis (US) is a chronic relapsing inflammatory bowel disease of the large intestine characterized by bloody diarrhoea, abdominal cramps and fatigue. UC is characterized by inflammation and ulceration of mainly the mucosal and occasionally submucosal intestinal layers.
|Medical condition in easily understood language
|Ulcerative colitis is a long-term condition where the large intestine (colon) and rectum become inflamed. Small ulcers can develop on the colon's lining, and can bleed and produce pus.
|Diseases [C] - Digestive System Diseases [C06]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|Evaluate safety, tolerability and efficacy of PN-943 treatment in subjects with moderate to severe active ulcerative colitis compared to placebo.
|Secondary objectives of the trial
|Evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and biomarker responses to PN-943 in subjects with moderate to severe active ulcerative colitis.
|Trial contains a sub-study
|Principal inclusion criteria
|1. Male and female subjects age 18 (or the minimum country specific ageof consent if >18) to 75 years.
2. Subject understands the study procedures and agrees to participate inthe study by giving written informed consent.
3. Diagnosis of UC supported by appropriate documentation of biopsy results consistent with UC
4. Moderate to severe active UC
5. Demonstrated inadequate response, loss of response, or intolerance ofat least 1 of oral aminosalicylates (5-ASAs), corticosteroids, immunomodulators, or a biologic.
See protocol for further inclusion criteria
|Principal exclusion criteria
|1. Subject with a current diagnosis of Crohn's disease (CD), indeterminate colitis (IC), microscopic colitis, ischemic colitis, radiation colitis
2. History of colonic dysplasia (other than completely removed low-grade dysplastic lesion.
3. History of active bacterial, viral, fungal or mycobacterial infection requiring hospitalization or IV antibiotic/anti-infective treatment within 4 weeks of screening or oral antibiotics/antiinfectives within 2 weeks of screening.
4. Positive stool test for C. difficile
5. Chronic recurrent or serious infection.
6. Known primary or secondary immunodeficiency.
7. Pregnant or lactating female or considering becoming pregnant during the study or within 30 days after the last dose of study medication.
8. History of any major neurological disorders.
See protocol for further exclusion criteria
|E.5 End points
|Primary end point(s)
Proportion of subjects achieving clinical remission at Week 12 compared to placebo.
|Timepoint(s) of evaluation of this end point
|Secondary end point(s)
|• Comparison of PN-943 high dose and low dose individually to placebo:
a) Proportion of subjects with endoscopic improvement at Week 12
b) Proportion of subjects achieving endoscopic remission at Week 12
c) Proportion of subjects with histological improvement at Week 12
d) Proportion of subjects achieving histological remission at Week 12
• Proportion of subjects achieving clinical remission at Week 52.
Clinical remission is determined using the Adapted Mayo score (sum of 3 subscores from the Mayo score):
- Stool frequency subscore (SFS)
- Rectal bleeding subscore (RBS)
- Endoscopic subscore (ESS)
|Timepoint(s) of evaluation of this end point
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Korea, Republic of
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days