Clinical Study of TA-650 in Pediatric Patients With Crohn's Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of TA-650 using Pediatric Crohn's Disease Activity Index (PCDAI) in pediatric patients with moderate to severe Crohn's disease after TA-650 administration at a dose of 5 mg/kg at week 0, 2, and 6, then every 8 week after week 14 up to week 46, and at a dose of 10 mg/kg if the effect is attenuated. The safety and pharmacokinetics are also evaluated.

Detailed Description
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This is an open-label, uncontrolled, multicenter Phase 3 study conducted in Japan.

Official Title
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Clinical Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of TA-650 in Pediatric Patients With Moderate to Severe Crohn's Disease

Conditions
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Pediatric Crohn's Disease

Intervention / Treatment
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* Drug: TA-650


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have been diagnosed as Crohn's disease at least 3 months prior to screening. Have active Crohn's disease despite adequate conventional therapy. Exclusion Criteria: Patients with severe intestinal strictures (strictures which may affect the number of defecations, etc., or dilation of the colon or strictures in the proximal small bowel observed on barium radiograph, or strictures precluding the insertion of endoscope), a diagnosis of short bowel syndrome, or previous stoma surgery. Patients who have a history of treatment with infliximab, or biological products (anti-TNFα agents and anti-IL-6 agents, etc.).

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TA-650<br>Responder criteria: Case where PCDAI score on the evaluation day was decreased by at least 15 points from that in the screening period and was ≤30. Criteria for dose-increasing: When either of the following 2 items was satisfied after Week 14, the relevant patient would be considered to satisfy the criteria for dose increasing to 10 mg/kg. PCDAI score on the evaluation day was increased by at least 15 points compared to the lowest PCDAI score observed at Week 2, 6 or 10 PCDAI score on the evaluation day exceeds 30 | Drug: TA-650<br>* TA-650 will be intravenously infused at 5 mg/kg as an induction regimen at Week 0, 2, 6. For subjects who meet the responder criteria, TA-650 will be administered at 8-week intervals thereafter until week 46. If the criteria for a dosage escalation are met, TA-650 will be administered at a dosage of 10 mg/kg.<br>* Other names: Infliximab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Patients Who Achieved PCDAI Response | Crohn's Disease Activity Index(PCDAI) response was defined as a case where PCDAI on the evaluation day was decreased by at least 15 points compared to PCDAI in the screening period and decreased to not more than 30. PCDAI was the sum (0 to 100) of the scores of 5 large categories. A larger PCDAI score represented higher disease activity. 5 large categories were as follows, i.e. history score (0 to 30), laboratory score (0 to 20), growth score (0 to 20), physical examination score (0 to 20) and extraintestinal manifestation score (0 to 10). | Week 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, and the last time point during the period from administration of the study drug to Week 54 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PCDAI Score | Crohn's Disease Activity Index (PCDAI) was the sum (0 to 100) of the scores of 5 large categories. A larger PCDAI score represented higher disease activity. 5 large categories were as follows, i.e. history score (0 to 30), laboratory score (0 to 20), growth score (0 to 20), physical examination score (0 to 20) and extraintestinal manifestation score (0 to 10). | Week 0, 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, and the last time point during the period from administration of the study drug to Week 54 | 
| Change From Baseline of PCDAI Score | Crohn's Disease Activity Index (PCDAI) was the sum (0 to 100) of the scores of 5 large categories. A larger PCDAI score represented higher disease activity. 5 large categories were as follows, i.e. history score (0 to 30), laboratory score (0 to 20), growth score (0 to 20), physical examination score (0 to 20) and extraintestinal manifestation score (0 to 10). | Week 0, 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, and the last time point during the period from administration of the study drug to Week 54 | 
| Percent of Patients Who Achieved PCDAI-Based Remission Rate. | Crohn's Disease Activity Index(PCDAI)-based remission was defined as a case where PCDAI on the evaluation day was decreased to not more than 10. Patients who satisfied the criterion for PCDAI response at least once in the evaluation at Week 2, 6 and 10 were defined as responders at Week 10. PCDAI was the sum (0 to 100) of the scores of 5 large categories. A larger PCDAI score represented higher disease activity. 5 large categories were as follows, i.e. history score (0 to 30), laboratory score (0 to 20), growth score (0 to 20), physical examination score (0 to 20) and extraintestinal manifestation score (0 to 10). | Week 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54 and the last time point during the period from administration of the study drug to Week 54 | 
| Serum TA-650 Concentration | Median, Min and Max of serum TA-650 concentration at each evaluation point after dose of 5 mg/kg TA-650. | After dose of Week 0 to 54 or at the timing of discontinuation. On the blood sampling day, before administration of the study drug. Week 0, 22 and 46, before administration and one hour after the administration. Week 14, 30 and 38, before administration. | 
| The Percent of the Patients Who Experienced an Adverse Event |  | Until the last time point during the period from administration of the study drug to Week 54 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infliximab, REMICADE, TA-650, pediatric Crohn's disease