Eosinophilicesophagitis (EoE) in Esophageal atresia (EA). MedDRA version: 20.1 Level: PT Classification code 10064212 Term: Eosinophilic oesophagitis System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Product Name: Budesonide
Product Code: [na]
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: Budesonide
CAS Number: 51333-22-3
Current Sponsor code: NA
Concentration unit: mg milli
Sponsors
IRCCS, OSPEDALE PEDIATRICO BAMBINO GESÙ DI ROMA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Informed consent form of subjects fully capable of providing consent or parent/s, legal representative of minors according to the national law; assent in pre-pubertal (6-11 years) and (12-17 years). - Male/female subjects aged 31 month- =18 years -Patients operated for EA (direct anastomosis) with eosinophilic esophagitis, diagnosed histologically after endoscopy no more than 3 months before joining the trial and defined according to the most recent guidelines on EoE and according to Paediatric Gastrointestinal Endoscopy guidelines: 15 or more eosinophils per high- power field (0.3 mm2), as peak concentration in esophageal biopsy samples (at least 3 sites, with at least 1-2 biopsies from the proximal, medium and distal esophagus). -Potentially fertile patients (post-menarcal girls) must have a negative pregnancy test at screening before inclusion in the study Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: -Patients operated for esophageal atresia with jejunal or colonic interposition -Presence of concomitant esophago-gastrointestinal disorders - Weight less than 10 kg -Eosinophilia in other gastrointestinal tracts -Participation in other clinical trials - Allergic asthma and rhinitis during the month before the biopsy required for the study - Allergic reactions - Anticoagulant and immunomodulatory concomitant use - Topical/systemic steroids during the month before the biopsy required for the study - Hypersensitivity to the active substance, to any of the excipients - Inability or difficulty swallowing the drug - Chronic viral infections or immunodeficiency - Ongoing oropharyngeal candidiasis - Neurological development delay known cardiac, hepatic and renal disorders: condition of severe renal insufficiency at screening in terms of estimated GFR 3 × ULN and total Bilirubin> 1.7x ULN; heart failure (NYHA or Ross stage equal to or greater than 2) - Any laboratory abnormality which, in the opinion of the investigator, would make the patient unsuitable for the study. - If applicable, potentially fertile patients unable or unwilling to undergo pregnancy tests and to practice contraceptive measures from the time of informed consent up to 30 days after the last administration of the IMP
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective is the study of efficacy during therapy with oral viscous budesonide, through evaluation of histological features ofesophageal mucosa before and after 3 months of therapy, in a group of patients between 1 month and 18 years old affected by EA with concomitant EoE. Intramucosal eosinophils < 15 eosinophils/HPF at the end of the therapeutic cycle will determine the efficacyof budesonide.;Secondary Objective: Secondary objectives are clinical efficacy and safety evaluation after 3 months of therapy and after 3 months of follow-up, through assessment of clinical signs of esophagealstricture, number of relapses and quality of life of patients (dysphagia score) and adverse reactions to budesonide. The study will also assess the Pharmacokinetics (PK) of budesonide.;Primary end point(s): Percentage of enrolled patients with histological response after 12 weeks of therapy. The histological responseis defined as the histological count of eosinophils/HPF. Patients will be classified as responders (0-14 eos/HPF), and non-responder (= 15 eos / HPF);Timepoint(s) of evaluation of this end point: 12 weeks of therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Percentageof patients in remission at 3 months and at 6 months according to PEESS 2.0 score. -Percentage of patients with histological response at 3 months according to the histological score of esophagitis. -Difference of EREFS score after 3 months of therapy (comparison of the score at screening and at end of study)in terms of average and standard deviation -Difference of clinical response according to PEESS 2.0 score at 3 months after the end of therapy and at 6 monthsof follow up versus baseline (comparison of score at screening and at end of study) in terms of average and standard deviation (SD). -Minimum plasmatic concentration(C through), maximum plasma concentration(C max), Time to maximum (Tmax) AndHalf Maximum (T1/2) Plasma Concentration, Area Under The Plasma Concentration-Time Curve (AUC) From Time Zero to Time of The Last Measurable Concentration (AUC0-last), according to a population PK model of viscous budesonide and cortisol, after 3 months of therapy, assessing if plasmatic concentrations are > (LOQ). - Difference of serum levels of morning cortisol and basal glucose versus baseline, at 3 months (end of therapy)and at 6 months of follow up, in terms of average and SD -Serious and non-serious adverse events (possibly oropharyngeal candidiasis) according to MedDRA as measure ofsafety and tolerability at 3 months and at 3 months of follow up.;Timepoint(s) of evaluation of this end point: Please see section secondary time points (time point is given under listed secondary end point). | — |
Countries
Italy
Contacts
Public ContactCentro Trials
Ospedale Pediatrico Bambino Gesù
Outcome results
None listed