NCT02256462

Pediatric Crohn's Disease AdalImumab Level-based Optimization Treatment (PAILOT) Trial

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 82 (actual)
• Sponsor: Schneider Children's Medical Center, Israel · Academic / Other
• Sex: All
• Age: 6 Years – 17 Years
• Healthy volunteers: Not accepted

Summary

Objectives: To examine the effect of drug level-based personalized treatment of adalimumab in children with Crohn's disease. Design: A prospective, randomized, open label study. Setting: Pediatric gastroenterology centers. Participants: Children 6 year to 17 years who are diagnosed with CD and are planned to receive adalimumab treatment. Main outcome measures: Pediatric Crohn's Activity Index (PCDAI) at 48 and 72 weeks. Secondary outcome measures: Corticosteroids free remission rates and on adalimumab at 48 and 72 weeks. The effect of routine adalimumab drug monitoring-based treatment on trough levels and anti-adalimumab antibodies during therapy.

Detailed description

The efficacy of adalimumab in inducing and maintaining remission in both adults and children with moderate-to-severe Crohn's Disease has been demonstrated in multiple clinical trials. Despite efforts to optimize treatment, approximately 40% of patients who initially respond to anti-TNF ultimately lose response. Measurement of adalimumab (ADA) drug levels and antibodies to adalimumab (ATAs) in patients has been shown to assist decision making in patients who have lost response during the course of treatment. This approach is based on the observations showing that higher ADA concentrations are associated with higher treatment efficacy and that loss of response is primarily attributed to either undetectable drug levels or to the presence of high titers of ATAs. Existing data is mostly based on retrospective cohort studies, nevertheless, the concept of routine therapeutic drug monitoring in-order to improve efficacy is still evolving. Recently, preliminary results of the Trough level Adapted infliXImab Treatment (TAXIT) study, performed in adult IBD patients, have failed to demonstrate superiority of level-based treatment over clinically-based treatment regarding rates of response over time. Nevertheless, it is premature to conclude that patients do not benefit from a tailored approach as the reported abstract did not stratify patients according to type of disease (CD vs. ulcerative colitis) and as some significant advantages such as reduced rate of antibodies and reduction of CRP were described in the level-based arm. Anti-TNF treatment in pediatric patients may differ from adults due to a higher risk for developing the rare hepatosplenic T cell lymphomas (HSCTL) in young males treated with combination therapy including thiopurines and anti-TNF agents. Concomitant therapy (using immunomodulators, mainly azathioprine) which has demonstrated superiority over mono-therapy has become a standard of care in moderate to severe CD in adults. In-view of the concerns of pediatric gastroenterologist from concomitant therapy-induced adverse events the option to improve efficacy of mono-therapy by guiding it according to drug monitoring is further appealing. Therefore, our aim is to assess the efficacy of routine therapeutic drug monitoring based treatment in pediatric CD patients in a prospective randomized control trial. We hope that this study will further contribute to the understanding of the potential benefits of therapeutic drug monitoring based management in pediatric patients treated with anti-TNF agents.Hypothesis: We hypothesize that by routine measuring of ADA trough levels and ATAs titers we will achieve higher and stable trough levels resulting in greater corticosteroid free remission rates and decreased LOR rates. We assume that this will be associated with lower frequencies of ATAs. We further assume that the intervention will reduce the need for alteration of treatment schemes by adding immunomodulators or by switching treatment within class or out of class. Objectives: This is ADA therapy optimization study in patients starting or receiving ADA due to active disease. 1. Primary Efficacy Objective: To evaluate the effect of routine ADA drug monitoring-based treatment, in comparison to clinically-based monitoring on disease activity. 2. Secondary Objective: To evaluate the effect of routine ADA drug monitoring-based treatment on trough levels and ATAs during therapy.

Conditions

• Crohn's Disease

Interventions

Type	Name	Description
DRUG	Adalimumab	Eligible patients are those who are planned to start Adalimumab (ADA). Patients will be randomized at the first screening visits to either group 1 (interventional) or group 2 (clinical). Eligible patients, will start induction treatment (weeks 0,2) with ADA (\> 40kg 160/80/40 mg every 2 weeks or \< 40 kg 100/50/25 mg for m2 body surface area every 2 weeks). Interventions will start from the 4th injection for responding patients only (based on levels taken prior to the third injection). Responding patients will continue to the maintenance phase in which they will receive ADA every 2 weeks, either 40 mg or 25 mg/m2. At screening, and every 2 months all patients will be examined and have height, weight, PCDAI performed as well as comprehensive laboratory examinations.

Timeline

• Start date: 2015-05-01
• Primary completion: 2019-01-31
• Completion: 2019-01-31
• First posted: 2014-10-03
• Last updated: 2021-09-28

Locations

1 site across 1 country: Israel