- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04245215
Loss of RESponse to Ustekinumab Treated by Dose Escalation (REScUE)
Study Overview
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Ingrid V Arijs
- Phone Number: +320499566221 +32499317005
- Email: ingrid.arijs@birdgroup.be
Study Locations
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Zaventem, Belgium, 1930
- Ingrid Arijs
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- ≥18 years
- Diagnosis of Crohn's disease by endoscopic and/or radiologic examination.
- Patient currently treated with ustekinumab, independent of previous biological exposure.
- Patients treated with maintenance dose of ustekinumab subcutaneous 90 mg every 8 weeks
Documented primary response at any time point after induction (week 16) and during maintenance defined as a clinical response (physician discretion) AND confirmed by either any of the following:
a. if biomarker elevated at start of ustekinumab (C-reactive protein>5 mg/l or fecal calprotectin >250µg/g): i. decrease of C-reactive protein by 50 % or more compared to baseline( prior to ustekinumab induction) ii. C-reactive protein <5 mg/l iii. decrease of fecal calprotectin by 50 % or more compared to baseline( prior to ustekinumab induction) iv. fecal calprotectin<250µg/g b. Documented mucosal healing (simple endoscopic score for Crohn's disease (SES-CD)<3)
- Documented loss of response after induction (> week 16) assessed by the physician as Moderate to severe active Crohn's disease, defined as Patient Reported Outcome-2 (Abdominal Pain > 1 AND Stool Frequency > 3) AND C-reactive protein and/or fecal calprotectin increased by 25 % or more compared to the lowest value under ustekinumab treatment (C-reactive protein>5 mg/L and/or fecal calprotectin>250µg/g).
- Presence of mucosal ulcers in at least one segment of the ileum or colon and a simple endoscopic score for Crohn's disease (SES-CD) ≥6 (for patients with isolated ileitis ≥4), as assessed by ileocolonoscopy
- Adequate contraception in female of reproductive age
- Have the capacity to understand and sign an informed consent form.
- Be able to adhere to the study visit schedule and other protocol requirements.
Exclusion Criteria:
Ongoing treatment with
- other concomitant biological (vedolizumab, anti-TNF)
- Steroids >20 mg prednisolone or equivalent at baseline (budesonide >6 mg)
- Patient already receiving ustekinumab every 4 weeks
- Women that are pregnant, nursing, or planning pregnancy
Have screening laboratory test results within the following parameters:
- Haemoglobin < 8.5 g/dL
- Platelets < 100,000 /mm3
- Serum creatinine ≥ 1.7 mg/dL
- aspartate aminotransferase and alanine aminotransferase > 3 times the upper limit of normal range
- Direct (conjugated) bilirubin ≥ 3.0 mg/dL.
- Have current signs or symptoms of infection confirmed by positive stool or blood testing (including gastrointestinal pathogens, tuberculosis, human immunodeficiency virus, hepatitis B, hepatitis C).
- Patients with a positive stool sample for gastrointestinal pathogen including Clostridium difficile.
- Evidence of current or previous clinically significant disease, medical condition other than Crohn's Disease, finding of the medical examination, or laboratory value at the screening visit outside the reference range that is of clinical relevance, that in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data.
- Patients with an ileostomy
- Patients that received an intravenous re-induction with ustekinumab within the 6 months prior to baseline.
- Patients with an impassable stenosis even after attempt of endoscopic balloon dilation.
- Patients with an abscess
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: 1. Subcutaneous ustekinumab every 8 weeks
re-induction (≈6mg/kg) intravenous ustekinumab followed by 90 mg Subcutaneous ustekinumab every 8 weeks (Q8W) for 48 weeks - receiving Q8W placebo to mimic Q4W injections
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re-induction and dose escalation form every 8 weeks to every 4 weeks only in arm 2
Other Names:
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Active Comparator: 2. Subcutaneous ustekinumab every 4 weeks
re-induction (≈6mg/kg) intravenous ustekinumab followed by 90 mg Subcutaneous ustekinumab every 4 weeks (Q4W) for 48 weeks
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re-induction and dose escalation form every 8 weeks to every 4 weeks only in arm 2
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of patients with steroid free clinical remission and fecal calprotectin<250µg/g at week 48
Time Frame: week 48
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Proportion of patients with steroid free clinical remission (patient reported outcome-2 remission: abdominal pain ≤ 1 AND stool frequency ≤ 3) and fecal calprotectin<250µg/g at week 48.
[stool frequency (ST): average number of liquid stools for 1 week abdominal pain (AP): average scoring for abdominal pain for 1 week (0=none; 1=mild, 2=moderate; 3= severe)]
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week 48
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of patients with complete endoscopic remission at week 48
Time Frame: week 48
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Proportion of patients with complete endoscopic remission (simple endoscopic score for Crohn's disease (SES-CD )<3) at week 48
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week 48
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Proportion of patients with endoscopic remission at week 48
Time Frame: week 48
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Proportion of patients with endoscopic remission (simple endoscopic score for Crohn's disease (SES-CD) <5) at week 48
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week 48
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Proportion of patients with endoscopic response at week 48
Time Frame: week 48
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Proportion of patients with endoscopic response (≥50% decrease in simple endoscopic score for Crohn's disease (SES-CD)) at week 48
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week 48
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Proportion of patients with clinical remission at week 48
Time Frame: week 48
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Proportion of patients with clinical remission (patient reported outcome-2 remission: abdominal pain ≤ 1 AND stool frequency ≤ 3) at week 48
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week 48
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Proportion of patients with biomarker remission at week 48
Time Frame: week 48
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Proportion of patients with biomarker remission (C-reactive protein <5 mg/L and fecal calprotectin <250 µg/g) at week 48
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week 48
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Proportion of patients with at all time points after baseline ustekinumab trough concentration > 1.4 μg/mL
Time Frame: between baseline and week 48
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Proportion of patients with at all time points after baseline ustekinumab trough concentration > 1.4 μg/mL
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between baseline and week 48
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Proportion of patients with serious adverse events at week 48
Time Frame: Week 48
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Proportion of patients with serious adverse events at week 48
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Week 48
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Peter Bossuyt, MD, BIRD (Belgian IBD Research and Development) vzw
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- BIRD2018001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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