A Study to Evaluate Biomarkers in Moderate to Severe Ulcerative Colitis (UC) Patients Treated With Different Targeted Therapies (ImmUniverse)

• ClinicalTrials.gov Identifier: NCT05456893
• Recruitment Status: Recruiting
• First Posted: July 13, 2022
• Last Update Posted: July 13, 2022
• Sponsor: Central Hospital, Nancy, France
• Information provided by (Responsible Party): Laurent Peyrin-Biroulet, Central Hospital, Nancy, France

Tracking Information

• First Submitted Date: June 30, 2022
• First Posted Date: July 13, 2022
• Last Update Posted Date: July 13, 2022
• Estimated Study Start Date: July 28, 2022
• Estimated Primary Completion Date: December 9, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 11, 2022)

• The percentage of subjects who achieve clinical response at week 14. [ Time Frame: The percentage of subjects who achieve clinical response at week 14 ]
  Clinical response will be defined as overall Mayo score of 2 or smaller with Mayo endoscopy score (Mayo ES) of 0 or 1 (without friability), and bleeding subscore of 0. The Clinical Response will be categorized in four subcategories:

  • Super responder: meets criteria of clinical response
  • Responder: Mayo Score: reduction of 50%/ improvement of ≥ 3 from baseline, but does not meet criteria of remission; endoscopic Mayo: does not meet criteria of clinical response, but shows reduction of Mayo ES
  • Partial responder: Mayo Score: reduction of up to 30%, endoscopic Mayo: no formal improvement by Mayo ES but in overall assessment by the physician slight improvement.
  • Non-responder: reduction of less than 30% and in endoscopy no improvement in the overall assessment
• The percentage of subjects who achieve deep clinical remission at week 14. [ Time Frame: The percentage of subjects who achieve deep clinical remission at week 14 ]
  Deep clinical remission will be defined as partial Mayo Score 0-1 with stool frequency (SF) ≤1 and rectal bleeding (RB) = 0.
• The percentage of subjects who achieve deep clinical remission at week 26. [ Time Frame: The percentage of subjects who achieve deep clinical remission at week 26. ]
  Deep clinical remission will be defined as partial Mayo Score 0-1 with stool frequency (SF) ≤1 and rectal bleeding (RB) = 0.
• The percentage of subjects who achieve deep clinical remission at week 52. [ Time Frame: The percentage of subjects who achieve deep clinical remission at week 52. ]
  Deep clinical remission will be defined as partial Mayo Score 0-1 with stool frequency (SF) ≤1 and rectal bleeding (RB) = 0.
• The percentage of subjects who achieve mucosal healing at week 14. [ Time Frame: The percentage of subjects who achieve mucosal healing at week 14. ]
  Mucosal healing will be defined as Mayo endoscopic score = 0; Nancy histology index: ulceration: 0, neutrophils: 0, chronic infiltrate: 0 or 1.
• The percentage of subjects who achieve mucosal healing at week 52. [ Time Frame: The percentage of subjects who achieve mucosal healing at week 52. ]
  Mucosal healing will be defined as Mayo endoscopic score = 0; Nancy histology index: ulceration: 0, neutrophils: 0, chronic infiltrate: 0 or 1.
• The percentage of subjects who achieve symptomatic remission at week 14. [ Time Frame: The percentage of subjects who achieve symptomatic remission at week 14. ]
  Symptomatic remission will be defined as reported by patient on PRO 2 (SF= 0-1 and RB= 0).
• The percentage of subjects who achieve symptomatic remission at week 26. [ Time Frame: The percentage of subjects who achieve symptomatic remission at week 26. ]
  Symptomatic remission will be defined as reported by patient on PRO 2 (SF= 0-1 and RB= 0).
• The percentage of subjects who achieve symptomatic remission at week 52. [ Time Frame: The percentage of subjects who achieve symptomatic remission at week 52. ]
  Symptomatic remission will be defined as reported by patient on PRO 2 (SF= 0-1 and RB= 0).

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: July 11, 2022)

• The percentage of subjects without any disease progression (e.g. flares) at week 14. [ Time Frame: The percentage of subjects without any disease progression (e.g. flares) at week 14. ]
  The percentage of subjects without any disease progression (e.g. flares) at week 14.
• The percentage of subjects without any disease progression (e.g. flares) at week 26. [ Time Frame: The percentage of subjects without any disease progression (e.g. flares) at week 26. ]
  The percentage of subjects without any disease progression (e.g. flares) at week 26.
• The percentage of subjects without any disease progression (e.g. flares) at week 52. [ Time Frame: The percentage of subjects without any disease progression (e.g. flares) at week 52. ]
  The percentage of subjects without any disease progression (e.g. flares) at week 52.
• The percentage of subjects who show an improvement on patient reported outcomes at week 14. [ Time Frame: The percentage of subjects who show an improvement on patient reported outcomes at week 14. ]
  Patient reported outcomes include: PRO 2 (stool frequency (SF) and rectal bleeding (RB)), FACIT-F (level of fatigue), PROMIS Depression (level of depression), SF-36 (level of quality of life), Euro-QoL-5D (level of quality of life).
• The percentage of subjects who show an improvement on patient reported outcomes at week 26. [ Time Frame: The percentage of subjects who show an improvement on patient reported outcomes at week 26. ]
  Patient reported outcomes include: PRO 2 (stool frequency (SF) and rectal bleeding (RB)), FACIT-F (level of fatigue), PROMIS Depression (level of depression), SF-36 (level of quality of life), Euro-QoL-5D (level of quality of life).
• The percentage of subjects who show an improvement on patient reported outcomes at week 52. [ Time Frame: The percentage of subjects who show an improvement on patient reported outcomes at week 52. ]
  Patient reported outcomes include: PRO 2 (stool frequency (SF) and rectal bleeding (RB)), FACIT-F (level of fatigue), PROMIS Depression (level of depression), SF-36 (level of quality of life), Euro-QoL-5D (level of quality of life).
• The percentage of subjects without the following complications until week 52 : [ Time Frame: week 52 ]
  The percentage of subjects without the following complications until week 52:

  • hospitalizations due to UC
  • treatment intensification including introduction of toxic long-term therapies (i.e. systemic glucocorticoids)
  • new stenosis
  • new fistula
  • new development of primary sclerosing cholangitis (PSC)
  • infections
  • intestinal surgery
• The percentage of subjects without long-term complications until week 104. [ Time Frame: The percentage of subjects without long-term complications until week 104. ]
  The percentage of subjects without long-term complications until week 104.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate Biomarkers in Moderate to Severe Ulcerative Colitis (UC) Patients Treated With Different Targeted Therapies
• Official Title: A Multicentre Prospective Longitudinal Observational Study to Evaluate Biomarkers in Moderate to Severe Ulcerative Colitis (UC) Patients Treated With Different Targeted Therapies

Brief Summary

UC is a chronic, idiopathic form of intestinal inflammatory disease (IBD) that affects the colon, most commonly afflicting adults aged 30-40 years and resulting in disability and lower quality of life (1). It is characterized by relapsing and remitting mucosal inflammation, starting in the rectum and extending to proximal segments of the colon. Although biologic therapies have provided clinical benefits to patients, these goals are still poorly met, due to the limited knowledge of the underlying mechanisms of immunopathology and the lack of predictive biomarkers that would allow proper patient stratification.

The hypothesis of this study is that by identifying new biomarkers in blood, stool and tissue that (i) predict response (or non-response) to therapy prior to the start of treatment and (ii) predict response to therapy in the early phase of treatment will allow to find the right treatment for the right patient (personalized medicine).

• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Case-Only; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Blood sampling (RNA and DNA profiling, PBMC isolation, Immunophenotyping, serum and plasma markers) Endoscopic biopsy sampling : Healthy and lesion area (DMSO) Stool sampling (RNA later)

• Sampling Method: Probability Sample
• Study Population: Patients with moderate to severe active UC with an indication to start a biologic treatment.

Condition

• Ulcerative Colitis
• Inflammatory Bowel Diseases

Intervention

• Procedure: Procedure: endoscopic biopsy
  Per-endoscopic biopsies
• Procedure: Blood sampling
  Blood sampling
• Procedure: stool sampling
  stool sampling

Study Groups/Cohorts

UC patients

All patients with an established ulcerative colitis

Interventions:

• Procedure: Procedure: endoscopic biopsy
• Procedure: Blood sampling
• Procedure: stool sampling

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 11, 2022): 95
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 9, 2027
• Estimated Primary Completion Date: December 9, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male and female patients ≥ 18 years of age (at the time of signing the ICF)
• Established diagnosis of ulcerative colitis with a minimum disease duration of 3 months
• Moderate to severe active UC defined by Mayo Score ≥ 6
• Moderate to severe active UC defined by endoscopy score of ≥2
• Indication to start any biological or small molecule agent (anti-TNF, anti- IL12/23, anti-integrin and JAK-inhibitors)
• In case of treatment with corticosteroid: stable dose for at least 3 weeks prior to baseline, dosage ≤ 20 mg prednisone
• Indication for an endoscopy for the assessment of disease activity as for standards of care and current guidelines
• Able to comply with the study procedures
• Person affiliated to or beneficiary of a social security plan
• Person informed about study organization and able to sign informed consent form

Exclusion Criteria:

• Diagnosis of indeterminate colitis, microscopic colitis, ischaemic colitis, infectious colitis, radiation colitis
• Absolute contraindications to endoscopy procedures or complication during previous endoscopy
• Bleeding disorders
• Indication for surgery for UC
• Rectal topical therapy (enemas or suppositories) ≤ 2 weeks prior to baseline
• Treatment with > 20 mg prednisone within 3 weeks prior to baseline
• Anaemia (haemoglobin < 10 g/dl) at baseline
• Any circumstances which could contradict a study participation and lead the Investigator to assess the patient as unsuitable for study participation for any other reason

• Person referred in articles L.1121-5, L. 1121-7 and L.1121-8 of the Public Health Code:

  • Pregnant, parturient or breastfeeding woman
  • Minor person (non-emancipated)
  • Adult person under legal protection (any form of public guardianship)
  • Adult person incapable of giving consent and not under legal protection
• Person deprived of liberty for judicial or administrative decision, person under psychiatric care as referred in articles L. 3212-1 and L. 3213-1

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Laurent MD Peyrin-Biroulet, PhD; 0383153661; peyrinbiroulet@gmail.com

• Listed Location Countries: France

Administrative Information

• NCT Number: NCT05456893
• Other Study ID Numbers: 021-A01092-39
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Laurent Peyrin-Biroulet, Central Hospital, Nancy, France
• Original Responsible Party: Same as current
• Current Study Sponsor: Central Hospital, Nancy, France
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Stefan MD SCHREIBER, PhD; Christian Albrechts Universität

• PRS Account: Central Hospital, Nancy, France
• Verification Date: July 2022