Observational Study Evaluating the Effectiveness of Drug Concentration to Predict the Recapture of Response in Crohn's Disease Patients With Loss of Response ( PRADA )

Study Overview
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Brief Summary
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This is a multi-center study that explores the relationship between recapture of response with escalation to weekly adalimumab and trough adalimumab concentration before escalation in patients experiencing lack of response (LOR).

Official Title
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A Cohort Study to Evaluate the Effectiveness of Drug Concentrations in Predicting Recapture of Response With Weekly ADAlimumab in Crohn's Disease Subjects With Secondary Loss of Response (PRADA)

Conditions
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Crohn's Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of Crohn's Disease. Treatment with adalimumab, for a minimum of 16 weeks, as per clinical practice, at a dose of 160 mg at week 0, 80 mg at week 2, and then 40 mg q2w with a documented response as defined by the investigator. Current evidence of active inflammatory disease/LOR defined as the presence of active inflammation (confirmed with a CRP ≥ 5 mg/L and/or a fecal calprotectin ≥ 250µg/g. Ability of subject to participate fully in all aspects of this clinical trial. Written informed consent must be obtained and documented. Exclusion Criteria: Primary non-responders to 16 weeks of adalimumab therapy. Received any investigational drug within the 16 weeks of adalimumab therapy. Serious underlying disease other than CD that, in the opinion of the investigator, may interfere with the subject's ability to participate fully in the study. History of alcohol or drug abuse that, in the opinion of the investigator, may interfere with the subject's ability to comply with the study procedures. Stools positive for Clostridium difficile. Pregnant or lactating women. Current enrolment in any other interventional research study. Presence of perianal or abdominal abscess.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants with Crohn's disease<br>Participants who have developed LOR to adalimumab after a minimum of 16 weeks of treatment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Explore the relationship between drug concentration at baseline and recapture of response | Logistic regression analysis will be used to model the relationship between drug concentration at baseline and recapture of response. | At Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Explore the relationship between trough adalimumab concentrations at baseline and change in patient reported outcome 2 (PRO2) | Covariance analysis is used. | From Week 0 to Week 12 | 
| Explore the relationship between trough adalimumab concentrations at baseline and change in C-reactive protein (CRP) | Covariance analysis is used. | From Week 0 to Week 12 | 
| Explore the relationship between trough adalimumab concentrations at baseline and change in fecal calprotectin | Covariance analysis is used. | From Week 0 to Week 12 | 
| Proportion of participants requiring steroids or additional therapy | Assessing participants that require steroids or additional therapy | Up to Week 12 | 
| Proportion of participants with 50% drop from screening in CRP or calprotectin | Assessing participants with 50% drop in CRP or calprotectin. | At Week 12 | 
| Explore the relationship between changes in HBI between screening and final trough adalimumab concentrations | Covariance analysis is used. | At Week 12 | 
| Proportion of participants with clinical remission PRO2 < 8 | PRO2 was developed based on FDA guidance for use of patient reported outcomes. | At Week 12 | 
| Proportion of participants with normalization of CRP or fecal calprotectin | Assessing participants with normalization of CRP (<5mg/dl) or fecal calprotectin (<150ug/ml) | At Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Patient Reported Outcome 2 (PRO 2), C-Reactive Protein (CRP), Adalimumab, Harvey Bradshaw Index (HBI), Therapeutic Drug Monitoring (TDM), Anti-Adalimumab Antibody (AAA)