Treat-to-Target of Endoscopic Remission in Patients With IBD in Symptomatic Remission

Ulcerative Colitis Clinical Trial

— QUOTIENT  

Official title:

Treat-to-Target of Endoscopic Remission in Patients With IBD in Symptomatic Remission

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05230173
• Other study ID #: RCT01519
• Status: Recruiting
• Phase: N/A
• Start date: October 5, 2022
• Est. completion date: June 1, 2028

Study information

• Verified date: April 2024
• Source: University of California, San Diego
• Contact: Siddharth Singh, MD
• Phone: 858-246-2352
• Email: sis040[@]health.ucsd.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the effectiveness and safety of a strategy of switching to an alternative targeted immunomodulator (TIM) therapy to treat to a target of endoscopic remission, versus continuing index TIM in patients with inflammatory bowel disease (IBD) (Crohn's disease or ulcerative colitis [UC]) in symptomatic remission with moderate to severe endoscopic inflammation despite optimization of index TIM in a real-world setting.

Description:

This is a pragmatic, open-label, multicenter randomized control trial (RCT) conducted in asymptomatic patients with IBD who have persistent moderate to severe endoscopic inflammation despite optimization of index TIM. This study plans to recruit approximately 250 participants in the United States, who will either switching to treatment with alternative TIM to treat to a target of endoscopic remission or continue index optimized TIM. After randomization, patients will be followed prospectively within routine clinical practice over 2 years (104 weeks). This trial will be conducted within select active sites in the United States and Canada

The primary outcome will be time from randomization to treatment failure, as a composite of:

1. Moderate severe symptomatic relapse based on PRO2 (2-item patient reported outcome), with objective confirmation of inflammation within 2 months of event (fecal calprotectin [FC] >150 mcg/g, or C reactive protein [CRP] >5mg/L, or endoscopy showing moderate-severe inflammation, or magnetic resonance enterography (MRE)/computed tomography enterography (CTE)/intestinal ultrasound (IUS) showing active inflammation) with need for escalation of therapy;

2. Need for rescue therapy with corticosteroids for a documented symptomatic IBD flare;

3. IBD related hospitalization;

4. IBD-related surgery;

5. IBD-related structural complications (CD: symptomatic stricture, fistula or abscess; UC:

symptomatic stricture);

6. Treatment-emergent adverse event requiring drug discontinuation.

Secondary outcomes will include time from randomization to each of the components in the primary outcome, quality of life (overall quality of life, fatigue, IBD-related disability), burden of treatment (financial burden, burden of monitoring, treatment side effects), treatment satisfaction, and safety.

In compliance with the pragmatic methodology of this study embedded in routine clinical care, there is no study visit mandated per study protocol. Participant visit schedules will follow local SOC with any additional visits at the treating physician's discretion. Data on all effectiveness, treatment burden and safety outcomes will be captured using a REDCap (Research Electronic Data Capture) database hosted at CCF. Data for the study will be extracted from medical record information and entered into the EDC system at baseline and then approximately every 6 months (at a minimum) thereafter, up to a 2-year follow-up period. Patient-reported outcome (PRO) measures (self-assessment questionnaires) will be utilized in this study to determine primary (efficacy) and secondary (quality of life and treatment burden and satisfaction) outcomes. Participants will complete the PRO2 at baseline and approximately every 12 weeks during a 2-year follow-up period; additional questionnaires (IBD-Control, PROMIS-7, Short Inflammatory Bowel Disease Questionnaire [SIBDQ], IBD Disability Index [IBD-DI], Treatment Burden Questionnaire, and Treatment Satisfaction Questionnaire for Medication) will be completed at baseline (following randomization) and up to 3 more additional times during a 2-year follow-up period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: June 1, 2028
• Est. primary completion date: March 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

INCLUSION CRITERIA:

1. Male or nonpregnant, nonlactating females, = 18 years of age.

2. An established diagnosis of CD or UC for at least 6 months based on standard clinical criteria, confirmed by the treating provider.

3. Current treatment with an approved TIM for treatment of IBD, including biologic agents (e.g., TNFa antagonists, ustekinumab, vedolizumab) and small molecule inhibitors (e.g., Janus kinase inhibitors, ozanimod), including future TIMs that become commercially available during the conduct of the trial.

4. Dose of TIM should be stable for 3 or more months prior to qualifying endoscopy/radiology. No treatment escalation of TIM or addition of IMM, corticosteroid, or mesalamines after the qualifying endoscopy/radiology procedure up to randomization is permitted. Dose de-escalation after qualifying procedure is permissible at the discretion of the treating provider.

5. In corticosteroid-free symptomatic remission based on validated PROs (PRO2 score) and deemed to be experiencing no other IBD-related symptoms in the opinion of the treating provider. Includes patients who may be in medically induced remission (on index TIM); or surgically induced remission with post-op initiation of index TIM for prophylaxis and colonoscopy/imaging performed at least 3 months after initiation/optimization of TIM showing moderate-severe bowel inflammation. Validated PROs are defined as:

1. CD: PRO2 (2-item patient reported outcome) mean daily score of abdominal pain score =1 and stool frequency score = 3; or

2. UC: PRO2, with absence of rectal bleeding (rectal bleeding score = 0) and with stool frequency score =1.

6. Evidence of moderate to severe bowel inflammation on local reading of colonoscopy, flexible sigmoidoscopy, balloon-assisted enteroscopy, capsule endoscopy or MR, CT enterography, or intestinal ultrasound, performed within 6 months prior to screening, defined at the investigator's discretion or as follows:

1. CD: Colonoscopy showing moderately to severely active inflammation based on 1 of the following variables/scores:

• Simple Endoscopic Score for Crohn's Disease (SES-CD) score =7 or score =4 for those with isolated ileal disease, or

• Presence of mucosal ulcers >5 mm in size if SES-CD has not been recorded, or

• Simplified Endoscopic Mucosal Assessment for Crohn's Disease (SEMA-CD) score =2, or

• Rutgeerts score i2b or higher for patients in surgically induced remission with post-operative endoscopic recurrence [Note, either SES-CD or Rutgeerts score can be used for participants with post-operative recurrence]; or

2. CD: MRE or CTE showing moderately to severely active inflammation based on 1 of the following variables:

• Increased bowel wall thickness, or

• Mural hyperenhancement, or

• Peri-enteric fat stranding, or

• Radiographic features of ulceration, or

• Intramural T2 signal on fat suppressed images; or

3. CD: Capsule endoscopy showing moderately to severely active small bowel disease based on Lewis score >790 (in case the disease is not accessible via endoscopy), or per local endoscopist if Lewis score is not reported; or

4. CD: Gastrointestinal ultrasound showing at least 1 of the following variables:

• Increased bowel wall thickness >5 mm, or

• Color doppler score >5/cm2, or

• Bowel stenosis, or

• Bowel stratification, or

• Fatty wrapping; or

5. UC: modified MES score of 2 to 3, or documentation of any endoscopic feature that would define an MES of 2 to 3 (e.g., friability, ulceration, spontaneous bleeding, complete loss of vascular pattern), if an MES has not been recorded.

7. Eligible to receive at least 1 alternative TIM (excluding their index TIM) for the treatment of their disease per approved drug label, based on clinical and reimbursement guidelines.

8. Able to participate fully in all aspects of this clinical trial.

9. Informed consent must be obtained and documented.

EXCLUSION CRITERIA:

1. Presence of ostomy or ileoanal pouches.

2. Serious underlying disease other than UC or CD that in the opinion of the investigator may interfere with the participant's ability to participate fully in the study.

3. History of alcohol or drug abuse or any other medical or health condition that in the opinion of the investigator may interfere with the participant's ability to comply with the study procedures.

4. Prior enrolment in the current study.

5. Mild endoscopic disease activity, where treating providers would not consider switching TIM.

Related Conditions & MeSH terms

• Crohn Disease
• Ulcerative Colitis

Intervention

Other:
• Pragmatic
Patients randomized to a strategy of switching TIM will be switched to one of the preferred agents recommended by clinical guidelines and covered by the patients' insurance formulary as part of routine care, and at the discretion of the site investigator and treating provider. No study-related medications will be provided. Patients (and their providers) in either treatment arm will be allowed to stop or start new TIMs and other IBD-directed therapies in case of symptomatic relapse or intolerance to therapies, at the discretion of the treating provider-patient team.

Locations

Country	Name	City	State
United States	University of Colorado	Aurora	Colorado
United States	Saratoga Schenectady Gastroenterology Associates	Burnt Hills	New York
United States	University of Virginia	Charlottesville	Virginia
United States	University of Chicago Medicine	Chicago	Illinois
United States	University of Texas Southwestern	Dallas	Texas
United States	GastroOne	Germantown	Tennessee
United States	Baylor College of Medicine	Houston	Texas
United States	Hoag Hospital	Irvine	California
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	UC San Diego Health	La Jolla	California
United States	Dartmouth Hitchcock	Lebanon	New Hampshire
United States	Cedars-Sinai	Los Angeles	California
United States	Yale University	New Haven	Connecticut
United States	Cornell University	New York	New York
United States	NYU Langone Health	New York	New York
United States	Hightower Clinical	Oklahoma City	Oklahoma
United States	Sutter Health	Palo Alto	California
United States	Oregon Clinic	Portland	Oregon
United States	Gastroenterology Associates	Providence	Rhode Island
United States	University of Rochester	Rochester	New York
United States	University of Utah Health	Salt Lake City	Utah
United States	MedStar Georgetown University Hospital	Washington	District of Columbia

Sponsors (5)

Lead Sponsor	Collaborator
University of California, San Diego	Baylor College of Medicine, Crohn's and Colitis Foundation, Patient-Centered Outcomes Research Institute, Western University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Treatment Failure	Time to treatment failure, as a composite of: (1) moderate severe symptomatic relapse based on PRO2, with objective confirmation of inflammation within 2 months of event (FC >250 mcg/g, or CRP >5mg/L, or endoscopy showing moderate-severe inflammation, or MRE/CTE/IUS showing active inflammation) with need for escalation of therapy; (2) need for rescue therapy with corticosteroids for a documented symptomatic IBD flare; (3) IBD related hospitalization; (4) IBD-related surgery; (5) IBD-related structural complications (CD: symptomatic stricture, fistula or abscess; UC: symptomatic stricture); (6) treatment-emergent adverse event requiring drug discontinuation	From randomization up to 104 weeks
Secondary	Treatment failure as defined in the composite primary outcome	Treatment failure as defined in the composite primary outcome	Binary, 104 weeks
Secondary	Time to each individual component of the composite primary outcome	Time to each individual component of the composite primary outcome	From randomization up to 104 weeks
Secondary	Overall Quality of Life	A) Scores of the SIBDQ. B) Scores of the IBD-Control. C) Scores of the PROMIS 7 scale. D) Scores of the on IBD-DI.	Continuous, until 104 weeks or Early Discontinuation
Secondary	Treatment Burden/Satisfaction	A) Scores of Treatment Burden Questionnaire, including medication, time and administrative, lifestyle change, social life and financial burden.; B) Scores of Treatment Satisfaction Questionnaire for Medication, measuring treatment satisfaction across domains of effectiveness, side effects, convenience and global satisfaction.; C) Scores of the CoPaQ, including out-of-pocket costs, for management of IBD, including treatment, monitoring, outpatient visits, and any unplanned healthcare utilization.	Continuous, until 104 weeks or Early Discontinuation
Secondary	Overall Safety	A) Treatment-related serious adverse events (SAEs) or unexpected SAEs. B) Serious infections, defined as infections requiring hospitalization and/or intravenous antibiotics.	Continuous, until 104 weeks or Early Discontinuation