CT to Assess the Efficacy and Safety of Adding GMA to Infliximab in Paediatric Patients With Steroid-refractory Ulcerative Colitis

Study Overview
=================
Brief Summary
-----------------
The primary endpoint will be evaluated through the following variables: PUCAI score, IFX levels, and steroid treatment. Clinical response to IFX will be evaluated through the PUCAI score. The response will be considered clinically significant if PUCAI points continue maintained below 30 during the study period. The IFX response will also be determined by IFX serum levels. A therapeutic IFX level, i.e. for achieving an adequate clinical response, is established above 6 μg/mL. Finally, the necessity, or not, of a steroid treatment during the study period will also be indicative of successful efficacy with GMA.

Detailed Description
-----------------
The trial has the following objectives: Primary objective (PO): The primary endpoint will be evaluated through the following variables: PUCAI score, IFX levels, and steroid treatment. Clinical response to IFX will be evaluated through the PUCAI score. The response will be considered clinically significant if PUCAI points continue maintained below 30 during the study period. The IFX response will also be determined by IFX serum levels. A therapeutic IFX level, i.e. for achieving an adequate clinical response, is established above 6 μg/mL. Finally, the necessity, or not, of a steroid treatment during the study period will also be indicative of successful efficacy with GMA. Secondary objectives (SO): Quantification of IFX trough and ATI levels, and description of the IFX dose at baseline, 12 and 40 weeks of follow-up. Measurement of PUCAI score at baseline, 12 and 40 weeks of follow-up. Patients maintaining clinical response off steroids, 12 and 40 weeks of follow-up. Patients experiencing flares-ups during the study period. Quantification of fecal calprotectin level at baseline, 12 and 40 weeks of follow-up. Fecal calprotectin is associated with clinical remission with levels higher than 150 μg/g. Measurement of C-reactive protein, erythrocyte sedimentation rate, hemoglobin, albumin, platelet levels at baseline, 12 and 40weeks of follow-up. Quantification of leucocyte counts in peripheral blood at baseline, 12 and 40 weeks of followup. Monitoring of AEs during the study period

Official Title
-----------------
Clinical Trial to Assess the Efficacy and Safety of Adding GMA to Infliximab in Paediatric Patients With Steroid-refractory Ulcerative Colitis

Conditions
-----------------
Ulcerative Colitis

Intervention / Treatment
-----------------
* Device: Adacolumn


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients under 18 years of age and weighing ≥25 kg at the time of study initiation. Patients with diagnosis of UC. Patients who started IFX treatment due to the lack of response to corticosteroids following an UC flare-up (steroid-refractory UC). Patients who have received IFX between 12 and 16 weeks prior to the study initiation. Patients who have showed a clinical response to IFX at the time of study initiation (defined as a reduction of at least 15 points in PUCAI score and being maintained below 30 points). Patients with therapeutic IFX blood levels (above 6 μg/mL) at the time of study initiation. Patient´s legal guardian must be willing and able to give written informed consent, and the patient must be willing to give written informed assent (if applicable as determined by the Ethics Committee) and comply with the Study visit Schedule. Exclusion Criteria: Patients who have received another anti-TNF prior to entry in the study. Patients with a peripheral circulation count of less than 2,000 granulocytes per μL. Pregnant and lactating of childbearing potential patients. Participation in another study or use of any experimental therapy within 30 days before day 1 of Study initiation.

Ages Eligible for Study
-----------------
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adacolumn<br>Adacolumn is a non-pharmacological treatment which reduces the inflammation by removing specifically targeted white blood cells from the blood circulation. The Adacolumn is designed to be used in combination with the Adamonitor and its Adastand, and the Adacircuit. The column has a capacity of 335 mL and is filled with cellulose acetate beads of 2 mm in diameter as the column adsorptive leukocytapheresis carriers. The carriers are bathed in 130 mL of sterile saline until use when the column is primed with additional sterile saline and then with heparinized saline prior to use. Patients will receive 10 sessions with Adacolumn. It would be reduced between 5 - 10, according to the patient´s response and following PI valuation. Patients will receive Adacolumn with IFX for that period of time. Patients will have received previously IFX for 12-16 weeks. visits will be conducted every week, for the application of Adacolumn. | Device: Adacolumn<br>* The study will consist of 10 sessions of Adacolumn® treatment (once per week) and a follow-up period (from week 12 to week 40 since study inclusion).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary objective:evaluate if Adacolumn® can sustain clinical response to IFX for 12 weeks of follow-up (V.11) or 40 weeks of follow-up (V18). Clinical response to IFX will be evaluated through PUCAI SCORE | Description of PUCAI score as continuous variable at V.11 and at V.18 will be performed. Response to IFX will be clinically significant if PUCAI score continues maintained below 30 during the study (follow-up visits), so the nº and % of patients with a PUCAI score below 30 points in all visits between baseline to V.11 and baseline to V.18 will be described. Furthermore, comparison scores in both visits (baseline vs. V.11 and baseline vs. V.18) will be performed, by means of absolute and relative changes | Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) | 
| Primary objective: evaluate if Adacolumn® can sustain clinical response to IFX for 12 weeks of follow-up (V.11) or 40 weeks of follow-up (V18). Clinical response to IFX will be evaluated through IFX-LEVELS | Description of IFX levels as continuous variable at V.11 and at V.18 will be performed. Response to IFX will be clinically significant if IFX levels > 6 μg/mL during the study, so the nº and % of patients with a IFX level > 6 μg/mL in all visits between baseline to V.11 and baseline to V.18 will be described. Furthermore, comparison between IFX levels in both visits will be performed, by means of absolute and relative changes | Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) | 
| Primary objective:evaluate if Adacolumn® can sustain clinical response to IFX for 12 weeks of follow-up (V.11) or 40 weeks of follow-up (V18). Clinical response to IFX will be evaluated through STEROIDS USE | Description of the number and percentage of patients with a change in steroids treatment from baseline to V.11 and from baseline to V.18. Furthermore, comparison between visits will be performed. | Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the IFX and ATI level variations in the treatment regimen during the study period. Quantification of IFX trough and ATI levels, and description of the IFX dose at baseline, 12 and 40 weeks of follow-up | Description of IFX blood and ATI levels as continuous variables at baseline visit, Visit 11 (12 weeks) and Visit 18 (40 weeks) will be performed. Their variation between visits (baseline vs. Visit 11 and baseline vs. Visit 18) will be analysed by means of absolute and relative change. Moreover, description of IFX dose by kilogram will be described in these visits | Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) | 
| To measure the PUCAI score variation during the study period. Measurement of PUCAI score at baseline, 12 and 40 weeks of follow-up. | Description of PUCAI score as continuous variable at baseline visit, Visit 11 (12 weeks) and Visit 18 (40 weeks) will be performed. Its variation between visits (baseline vs. Visit 11 and baseline vs. Visit 18) will be analysed by means of absolute and relative change | Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) | 
| To determine the percentage of patients maintaining steroid-free response during the study period at 12 and 40 weeks. | Description of the number and percentage of patients changing the behaviour of steroids treatment (use or not use) from baseline visit to Visit 11 (12 weeks) and from baseline visit to Visit 18 (40 weeks) will be computed. Furthermore, comparison between visits (baseline vs. Visit 11 and baseline vs. Visit 18) will be performed | Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) | 
| To describe the number of flare-ups during the study period. Patients experiencing flares-ups during the study period. | Description of the number of patients experienced flare-ups and the accumulate number of flare-ups from baseline visit to Visit 11 and from baseline visit to Visit 18 will be computed. | Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) | 
| To measure faecal calprotectin level during the study period. Quantification of faecal calprotectin level at baseline, 12 and 40 weeks of follow-up. Faecal calprotectin is associated with clinical remission with levels higher than 150 μg/g. | Description of faecal calprotectin level as continuous variable at baseline visit, Visit 11 (12 weeks) and Visit 18 (40 weeks) will be performed. Their variation between visits (baseline vs. Visit 11 and baseline vs. Visit 18) will be analysed by means of absolute and relative change. As levels of faecal calprotectin > 150 μg/g are associated with clinical remission, the number and percentage of patients with faecal calprotectin > 150 μg/g will be described. Furthermore, comparison between visits (baseline vs. Visit 11 and baseline vs. Visit 18) will be performed. | Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) | 
| To monitor the evolution of biochemical markers of inflammatory activity in UC and other laboratory parameters. Measurement of C-reactive protein, ESR, haemoglobin, albumin, platelet levels, PT, granulocytes at baseline, 12(V11) and 40 weeks(V18) | Description of CRP, ESR, haemoglobin, albumin platelet levels, PT and granulocytes as continuous variables at baseline visit, Visit 11 (12 weeks) and Visit 18 (40 weeks) will be performed. Their variation between visits (baseline vs. Visit 11 and baseline vs. Visit 18) will be analysed by means of absolute and relative change. | Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) | 
| To determine the evolution of leucocyte counts in peripheral blood during the study period. Quantification of leucocyte counts in peripheral blood at baseline, 12 and 40 weeks of follow-up. | Description of leucocyte counts as continuous variable at Baseline visit, Visit 11 (12 weeks) and Visit 18 (40 weeks) will be performed. Its variation between visits (baseline vs. Visit 11 and baseline vs. Visit 18) will be analysed by means of absolute and relative change | Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) | 
| To evaluate the safety of Adacolumn® during the study period, all the recorded AEs will be described by: | The number of patients who suffer them The number of patients who suffer AEs related to Adacolumn® Their incidence and duration Their relationship with Adacolumn® Seriousness, severity, ongoing and outcome This analysis will be done on those patients belonging to the safety sample | Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ulcerative Colitis