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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief 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 Summary:

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
Sponsor: Schneider Children's Medical Center, Israel

Current Primary Outcome: Loss of response (LOR) during treatment. [ Time Frame: Week 72 ]

Patients with loss of response are defined as those with a good initial clinical response to anti-TNFα, with a later clinical and biochemical relapse defined as PCDAI>10 (for patients in remission) or an increase of 15 points PCDAI from post induction baseline and CRP> 1mg/dl and/or calprotectin>50µgr/gr


Original Primary Outcome: A change in disease activity index [ Time Frame: 48 and 72 weeks ]

Disease activity defined by Pediatric Crohn's Disease Activity Index


Current Secondary Outcome:

  • Corticosteroids free complete clinical remission, on ADA, [ Time Frame: 48 and 72 weeks ]
    Patients with PCDAI<10, and quiescent disease by physician global assessment (PGA).
  • Trough levels [ Time Frame: 8, 16, 32, 48, 72 weeks ]
    Mean adalimumab trough levels
  • Antibodies to adalimumab [ Time Frame: 8, 16, 32, 48, 72 weeks ]
    Presence of antibodies to adalimumab (ATAs)
  • Anthropometric indices [ Time Frame: 0, 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, weeks ]
    Anthropometric indices (weight, height, BMI) and growth assessment during scheduled visits
  • Laboratory markers [ Time Frame: 0, 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, weeks ]
    Laboratory surrogate markers (CBC, ESR, CRP, albumin, fecal calprotectin) during scheduled visits
  • Adverse events [ Time Frame: 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, weeks ]
    Medication associated adverse events
  • The need for treatment modification during therapy [ Time Frame: Week 72 ]
    Addition of immunomodulator, switch within/out of class
  • Disease activity defined by PCDAI [ Time Frame: 48 and 72 weeks ]
    Pediatric Crohn's Disease Activity Index


Original Secondary Outcome:

  • Complete clinical remission [ Time Frame: 48 and 72 weeks ]
    Corticosteroids free complete clinical remission, on drug
  • Trough levels [ Time Frame: 8, 16, 32, 48, 72 weeks ]
    Mean adalimumab trough levels
  • Antibodies to adalimumab [ Time Frame: 8, 16, 32, 48, 72 weeks ]
    Presence of antibodies to adalimumab (ATAs)
  • Anthropometric indices [ Time Frame: 0, 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, weeks ]
    Anthropometric indices (weight, height, BMI) and growth assessment during scheduled visits
  • Laboratory markers [ Time Frame: 0, 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, weeks ]
    Laboratory surrogate markers (CBC, ESR, CRP, albumin, fecal calprotectin) during scheduled visits
  • Adverse events [ Time Frame: 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, weeks ]
    Medication associated adverse events


Information By: Schneider Children's Medical Center, Israel

Dates:
Date Received: September 26, 2014
Date Started: May 2015
Date Completion: January 2019
Last Updated: December 6, 2016
Last Verified: December 2016