TDM Guided Early Optimization of ADAL in Crohn's Disease

Study Overview
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Brief Summary
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To investigate the influence of early therapeutic drug monitoring and dose optimization on disease outcome in Crohn's patients treated with Adalimumab.

Detailed Description
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This is an investigator initiated randomized open label study. This study is designed to compare whether increasing the dose of adalimumab based on the level the drug in the blood to a target level early in the treatment course would lead to better outcomes for patients as compared to the standard doses.

Official Title
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Therapeutic Drug Monitoring Guided Early Optimization of Adalimumab in Crohn's Disease; A Randomized Open Label Study

Conditions
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Crohn Disease, Drug Monitoring, Inflammatory Bowel Diseases

Intervention / Treatment
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* Biological: Adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 or older. Crohn's disease diagnosed based on standard objective methodology (clinical, biochemical, endoscopic, histological and radiological correlation). Active disease based on Harvey Bradshaw Index (HBI >5) and elevated C-reactive protein (CRP) (>normal reference range for local laboratory) OR fecal calprotectin (FCP) (>250 µg/g) Due to commence treatment with ADAL. Exclusion Criteria: Severe co-existing cardiopulmonary, hepatic, renal, neurologic, or rheumatologic disease. History of active HIV, hepatitis B or C infection, Patients with ileostomy/colostomy, ileal-pouch anal anastomosis or severe perianal fistulising disease. Pregnancy Prior exposure to ADAL

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard clinical care<br>Adalimumab induction as per standard clinical care: Week 0: 160 mg SC Week 2: 80 mg SC Followed by 40 mg SC every 2 weeks' maintenance therapy | Biological: Adalimumab<br> <br> * Other names: Humira;|
| Active Comparator: Active optimization<br>Same as Standard clinical care Arm, except: If ADAL trough ≤15 μg/ml, dose escalation with 80 mg SC at week 6 followed by 40 mg SC every week If ADAL trough >15 μg/ml, no dose escalation and continued standard of care dosing | Biological: Adalimumab<br> <br> * Other names: Humira;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who achieved remission | Clinical remission will be scored by a Harvey-Bradshaw Index < 5 AND Biochemical remission will be scored by C-reactive protein < 5 mg/l OR Fecal calprotectin <250 μg/g (combination endpoint) | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who achieved clinical response | Clinical response will be evaluated by a decreased in Harvey-Bradshaw Index score AND a decreased level of C-reactive protein OR Fecal calprotectin | From Week 0 to Week 12 | 
| Therapeutic drug monitoring | Adalimumab drug concentration at week 8 and 12 AND proportion of subjects with antibody to Adalimumab at Week 8 and 12 on the rate i. Clinical response/remission (HBI<5) ii. Biochemical response/remission (CRP within normal reference range) iii. Endoscopic response (SES-CD reduction of ≥50% from baseline) / remission (SES-CD ≤3) | At Week 8, 12 | 
| Proportion of steroid free subjects | Steroid free defined as patients being steroid free at Week 12 | At Week 12 | 
| Subjects well-being | Subjects well-being will be scored using the validated questionnaire Short inflammatory bowel disease questionnaire (SIBDQ) | From Week 0 to Week 12 | 
| Rates of complications | Rates of complications, including hospitalization, surgery, adverse reaction, and corticosteroid use. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IBD, Crohn, adalimumab, ADAL