Eosinophilic Esophagitis MedDRA version: 20.1 Level: LLT Classification code 10064220 Term: Eosinophilic esophagitis System Organ Class: 100000004856
Conditions
Sponsors
Adare Pharmaceuticals US, LP
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult male or female =12 years of age at the time of informed consent or assent 2. Each subject and/or their parents or legal guardian (for adolescents), must read, understand and provide consent or assent together with their parent(s) or guardian signature (for adolescents) on the ICF for this study and be willing and able to adhere to study-related treatment regimens, procedures and visit schedule 3. Diagnosis or presumptive diagnosis of EoE that is confirmed during the Screening period by histology that demonstrates =15 peak eos/HPF. In order to ensure that a diagnosis can be made, at least 6 biopsies should be taken from both proximal and distal specimens (at least 3 each). Mid-esophageal biopsies are not required (optional). HPF will be defined as a standard area of 235 square microns in a microscope with 40x lens and 22mm ocular. a) Esophagogastroduodenoscopies and biopsies are to be obtained during the Screening period b) Biopsies will be read by a central pathologist c) Esophagogastroduodenoscopies and biopsies performed outside the study will not be accepted to meet eligibility criteria d) Optional biopsies may be taken and processed locally for local use, only where specified in the local ICF. If serious pathology is unexpectedly encountered biopsies of such lesions must be processed locally 4. Have a subject-reported history of =6 episodes of dysphagia in the 14 days prior to baseline 5. Completion of the daily diary on at least 11 out of the 14 days during the 2-week Baseline Symptom Assessment Are the trial subjects under 18? yes Number of subjects for this age range: 20 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Have known contraindication, hypersensitivity, or intolerance to corticosteroids 2. Have a contraindication to, or factors that substantially increase the risk of, EGD procedure or esophageal biopsy or have narrowing of the esophagus that precludes EGD with a standard 9 mm endoscope 3. Have history of an esophageal stricture requiring dilatation within the previous 12 weeks prior to Screening 4. Bone age more than 12 months behind chronological age for adolescent subjects 5. Have any physical, mental, or social condition or history of illness or laboratory abnormality that in the Investigator’s judgment might interfere with study procedures or the ability of the subject to adhere to and complete the study or increase the safety risk to the subject such as uncontrolled diabetes or hypertension or may increase risk of corticosteroid toxicity (e.g. abnormal bone mineral density) 6. History of recurrent or current oral or esophageal mucosal infection due to inhaled or nasal corticosteroids 7. Have any mouth or dental condition that prevents normal eating 8. Have any condition affecting the esophageal mucosa or altering esophageal motility other than EoE, including erosive esophagitis (grade B or higher as per the Los Angeles Classification of Gastroesophageal Reflux Disease; hiatus hernia longer than 3 cm, Barrett’s esophagus, and achalasia) 9. Use of systemic (oral or parenteral) corticosteroids within 60 days before Screening, use of swallowed corticosteroids within 30 days before Screening 10. Initiation of either inhaled or nasal corticosteroids or high-potency dermal topical corticosteroids within 30 days before Screening 11. Use of calcineurin inhibitors or purine analogues (azathioprine, 6-mercaptopurine) in the 12 weeks before Screening 12. Use of potent cytochrome P450 (CYP) 3A4 inhibitors (eg, ritonavir and ketoconazole) in the 12 weeks before Screening 13. Initiation of an elimination diet or elemental diet within 30 days before Screening (diet must remain stable after signing ICF) 14. Morning (07:00 to 09:00, or as close to that window as possible) serum cortisol level =5 µg/dL (138 nmol/L) that is not responsive to ACTH stimulation: defined as a serum cortisol level <16 µg/dL (440 nmol/L) at 60 minutes with ACTH stimulation test using 250 µg cosyntropin administered intramuscularly (ie, an abnormal result on the ACTH stimulation test) 15. Use of biologic immunomodulators in the 24 weeks before Screening (allergy desensitization injection or oral therapy is allowed as long as the course of therapy is not altered during the study period) 16. Subjects who have initiated, discontinued, or changed dosage regimen of histamine H2 receptor antagonists, antacids or antihistamines, leukotriene inhibitors or sodium cromolyn within 4 weeks before qualifying endoscopy. If already receiving these drugs, the dosage must remain constant throughout the study 17. Subjects who have changed dosage regimen of PPIs within 8 weeks before qualifying endoscopy. If already receiving PPIs, the dosage must remain constant throughout the study 18. Infection with hepatitis B, hepatitis C, or human immunodeficiency virus 19. Have gastrointestinal bleeding or documented active peptic ulcer within 4 weeks prior to Screening or entering a new study period 20. Have chronic infection such as prior or active tuberculosis, active chicken pox or measles or absence of prior measles, mumps and rubella vaccine. Subjects with tuberculosis exposure
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A co-primary objectives: ? To compare the Week 12 histologic responder rates (= 6 peak eosinophils [eos]/high power field [HPF]) for APT-1011 3 mg hora somni (HS) with that for placebo. HPF will be defined as a standard area of 235 square microns in a microscope with 40x lens and 22mm ocular ? To compare mean change in number of dysphagia episodes from baseline to Week 12 for APT-1011 3 mg HS with that for placebo Part B key objectives: ? To compare the Week 52 histologic relapse-free rates (= 15 peak eos/HPF) for APT-1011 responders randomized to continuing APT-1011 3 mg HS (maintenance) with responders randomized to placebo (withdrawal of APT-1011 3 mg HS) ? To compare mean change in number of dysphagia episodes from Week 12 at or prior Week 52 (based on timing of histologic relapse) for APT-1011 responders randomized to continue APT-1011 3 mg HS with responders randomized to placebo (withdrawal of APT-1011 3 mg HS);Secondary Objective: Part A secondary objectives ? To compare endoscopic appearance evaluated by the mean change from baseline to Week 12 in REFs for APT-1011 3 mg HS with that for placebo ? To compare the percentage of subjects with 15 peak eos/HPF) by Week 52 ? Mean change from Week 12 in Part A responders in number of dysphagia episodes at time of EGD at or before Week 52;Timepoint(s) of evaluation of this end point: Part A co-primary endpoints: ? at Week 12 ? from baseline to Week 12 Part B key endpoints: ? by Week 52 in Part A ? from Week 12 in Part A and at or before Week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A secondary endpoints: ? Mean change from baseline in mean EREFs at Week 12 ? Percentage of subjects who achieve <1 eos/HPF at Week 12 ? Mean change from baseline in mean day-level symptom burden (PROSE) at Week 12 ? Mean change from baseline in mean day-level severity (PROSE) at Week 12 ? Mean change from baseline in mean eosinophils per HPF at Week 12 ? Percentage of subjects who achieve <15 eos/HPF at Week 12 ? Mean change from baseline in mean number of dysphagia-free days at Week 12 Part B secondary endpoints: ? Mean change from Week 12 in Part A responders in mean EREF scores at time of EGD at or before Week 52 ? Mean change from Week 12 in Part A responders in mean eosinophils per high power field at time of EGD at or before Week 52 ? Mean change from Week 12 in Part A responders in day-level symptom burden using the PROSE at time of EGD at or before Week 52 ? Mean change from Week 12 in Part A responders in day-level severity using the PROSE at time of EGD at or before Week 52 ? Mean change from Week 12 in Part A responders in mean number of dysphagia-free days at time of EGD at or before Week 52;Timepoint(s) of evaluation of this end point: Part A secondary endpoints: ? from baseline at Week 12 ? at Week 12 ? from baseline at Week 12 ? from baseline at Week 12 ? from baseline at Week 12 ? at Week 12 ? from baseline at Week 12 Part B secondary endpoints: ? from Week 12 in Part A or before Week 52 ? from Week 12 in Part A or before Week 52 ? from Week 12 in Part A or before Week 52 ? from Week 12 in Part A or before Week 52 ? from Week 12 in Part A or before Week 52 | — |
Countries
Australia, Germany, Spain, United States
Contacts
Public ContactPeter C. Richardson
Adare Pharmaceuticals US, LP
Outcome results
None listed