|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Medical condition in easily understood language
|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
|Identify predictive fecal, blood, and tissue biomarkers
Identify pharmacodynamic fecal, blood, and tissue biomarkers
Identify a fecal, blood, and tissue biomarker signature as a surrogate measure
Identify whether colonic tissue phosphorylated signal transducers and activators of transcription, correlates with change from baseline in UC-100 score.
Determine the time-concentration profile of JAKi in samples.
Evaluate correlation of exposure of JAKi between stool, serum, and tissue samples.
Explore the exposure-response relationship of JAKi
Develop an exposure-response model of JAKi
Identify potential demographic and disease factors affecting the most relevant JAKi exposure-response relationships
Evaluate long-term hospitalization rates, surgery rates, and corticosteroid use up to 2 years after initiation of JAKi therapy
Measure adverse drug reactions, and clinical, endoscopic, and histologic response and remission rates to JAKi in a “real-world” population.
|Secondary objectives of the trial
|Trial contains a sub-study
|Principal inclusion criteria
|1. 18 years of age or older.
2. Male or nonpregnant, nonlactating females.
3. Diagnosis of UC for at least 3 months prior to screening.
4. Moderately to severely active UC (total MCS ≥ 6), with objective evidence of inflammation defined by a Mayo endoscopic subscore (MES) ≥ 2 and disease extending > 15 cm from the anal verge.
5. Physician plans to administer JAKi for at least 8 weeks of induction therapy as part of SOC.
6. Documentation of a negative test result for latent tuberculosis within the last 12 months, or according to routine clinical practice.
7. Able to participate fully in all aspects of this clinical trial, including collection of tissue biopsies.
8. Written informed consent must be obtained and documented.
|Principal exclusion criteria
|1. Diagnosis of CD or indeterminate colitis.
2. An active, serious infection, including localized infections.
3. Concomitant administration of biological therapies for UC or potent immunosuppressants, such as azathioprine and cyclosporine. Subjects with previous exposure to these treatments should undergo an appropriate washout period according to local practice prior to starting JAKi, in keeping with routine clinical practice.
Hematology laboratory results
(e.g. absolute lymphocyte count, absolute neutrophil count
4. and hemoglobin levels) that contraindicate the product label.
5. Interval between live vaccinations and initiation of JAKi therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents.
6. Serious underlying disease other than UC that in the opinion of the investigator may interfere with the subject’s ability to participate fully in the study.
|E.5 End points
|Primary end point(s)
|Efficacy Endpoints (Objectives 1-3): Proportion of subjects in clinical, endoscopic, and histologic response and remission and identification of biomarkers that are most reflective of disease severity. Association between disease activity as measured by changes in UC-100 and biomarkers.
pSTAT (Objective 4): Association between JAKi exposure and biomarker levels in colon biopsy samples.
Safety Endpoint (Objectives 5 & 6): Treatment-related adverse events and disease-related hospitalizations.
|Timepoint(s) of evaluation of this end point
|Week 8 and Week 24
2 years (safety endpoint)
|Secondary end point(s)
|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)
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
|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