CLINICAL TRIAL / NCT05230173
Treat-to-Target of Endoscopic Remission in Patients With IBD in Symptomatic Remission
- Interventional
- Recruiting
- NCT05230173
Treat-to-Target of Endoscopic Remission in Patients With IBD in Symptomatic Remission
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.
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.
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
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., TNFα 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.