study in subjects with Eosinophilic Esophagitis

Phase 1

Conditions: Eosinophilic Esophagitis
MedDRA version: 20.0Level: LLTClassification code 10064220Term: Eosinophilic esophagitisSystem Organ Class: 100000013492
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: EUCTR2016-004749-10-ES

Lead Sponsor: Adare Pharmaceutical

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 100

Inclusion Criteria

Subjects must satisfy all of the following criteria:
Before entering 4-week Baseline Symptom Assessment
1. Male or female between =18 and =75 years of age at the time of informed consent;
2. Signed the informed consent form (ICF) and willing and able to adhere to all study procedures;
3. Diagnosis or presumptive diagnosis of EoE;
• Diagnosis of EoE must be confirmed by symptoms, histology, and historical documentation of failed treatment on =8 weeks of high-dose proton pump inhibitors (PPI). For the purposes of FLUTE, high dose PPI is defined as 20 mg BID omeprazole or 20 to 40 BID mg of any marketed PPI; maintenance doses of PPIs are not acceptable. A lack of response to PPI therapy is defined as =15 PEAK eosinophils/HPF with at least 5 biopsies including both proximal and distal specimens after 8 weeks of high dose PPI treatment.
• Documentation of PPI failure prior to initial diagnosis or by documentation of PPI failure at the time of Screening is required. The subjects may be pre-screened but should not be consented, sign an ICF, or be offered participation in FLUTE if they have not met the diagnostic criteria for EoE that requires that they fail an 8-week trial of high dose PPIs EXCEPT those that have taken PPIs for 8 weeks will use the EGD within the study for this documentation. The Investigator and potential subject must make the decision to complete a PPI trial independent of any considerations of the study. There is insufficient time to do the 8 week trial within the current study. Should a subject be consented in error and screen fails due to this point, they may be re screened as described in the protocol.
4. Have a subject reported history of =3 episodes of dysphagia (difficulty with food going down) in the 7 days prior to Screening;
5. Have a 7-day Global EoE Symptom Score >3 at baseline (EoE score must remain >3 at each of Visits 1, 2 and 3 before randomization). This will be performed on paper during the Screening visit.
6. Willing and able to adhere to study related treatment regimens, procedures, and visit schedule.
Before randomization
7. To be determined prior to randomization: have evidence of EoE, as defined by =15 PEAK eosinophils/HPF. In order to ensure that a diagnosis can be made, at least 5-6 biopsies should be taken including both proximal and distal specimens (~3 each);
• No EGDs and biopsies performed outside FLUTE are acceptable for meeting eligibility criteria.
• Optional biopsies may be taken and processed locally for local use, if specified in the local ICF.
• Biopsies are to be obtained PRIOR to the 4-week Baseline Symptom Assessment. Eligibility from a histological perspective will be based solely on the central pathologist’s assessment.
8. To be determined prior to randomization: in the daily diary, report at least 3 episodes of dysphagia (difficulty with food going down) for each of the last 7 days during the last 14 days of the 4-week Baseline Symptom Assessment
9. To be determined prior to randomization: completion of the daily diary on at least 5 out of each 7 days during the last 14 days of the 4-week Baseline Symptom Assessment.
Are the trial subjects under 18? no
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 95
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

Subjects will not be entered in FLUTE for any of the following reasons:
Before entering 4-week Baseline Symptom Assessment
1. Have known contraindication, hypersensitivity, or intolerance to corticosteroids;
2. 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;
3. Presence of oral or esophageal mucosal infection of any type;
4. Have any mouth or dental condition that prevents normal eating;
5. 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;
6. Use of systemic (oral or parenteral) corticosteroids within 60 days prior to Screening, use of inhaled/swallowed corticosteroids within 30 days prior to Screening, or extended use of high-potency dermal topical corticosteroids within 30 days prior to Screening;
7. Initiation of an elimination diet or elemental diet within 30 days before Screening (diet must remain stable after signing ICF);
8. Morning (0700 to 0800 hours, or as close to that window as possible) serum cortisol level =5 µg/dL (138 nmol/L);
9. Use of biologic immunomodulators in the 24 weeks prior to Screening;
10. Use of calcineurin inhibitors or purine analogues (azathioprine, 6 mercaptopurine) in the 12 weeks prior to Screening;
11. Use of potent cytochrome P450 (CYP) 3A4 inhibitors (e.g., ritonavir and ketoconazole) in the 12 weeks prior to Screening;
12. Have a contraindication to or factors that substantially increase the risk of EGD or esophageal biopsy or have narrowing of the esophagus that precludes EGD with a standard 9 mm endoscope;
13. Have history of an esophageal stricture requiring dilatation within the previous 12 weeks prior to Screening;
14. Subjects who have initiated, discontinued or changed dosage regimen of PPIs, H2 antagonists, antacids or antihistamines for any condition such as GERD or allergic rhinitis within 4 weeks prior to qualifying endoscopy. These drugs must remain constant throughout the study.
15. Infection with hepatitis B, hepatitis C, or human immunodeficiency virus (to be tested during Screening);
• The following parameters will be utilized to determine hepatitis B and hepatitis C infection: positive for hepatitis B surface antigen [HBsAg], total hepatitis B core antibody [anti HBc], or hepatitis C virus antibody. Subjects who are positive for hepatitis B surface antibody, but negative for HBsAg and anti HBc, will be eligible.
16. Have gastrointestinal (GI) bleeding within 4 weeks prior to Screening or between the Screening Visit and the Randomization Visit;
17. Have current (>30 days) chronic infection, immunosuppression, or immunodeficiency;
18. Have history or presence of Crohn’s disease, celiac disease, or other inflammatory disease of the GI tract, including eosinophilic gastroenteritis;
19. Have current alcohol or drug abuse in the opinion of the Investigator;
20. Female subjects who are pregnant, breastfeeding, or planning to become pregnant during the study;
• Serum pregnancy test at Screening and urine pregnancy test during 4-week Baseline Symptom Assessment in women of childbearing potential must be negative.
21. Sexually active females of childbearing potent