Efficacy, Safety, and Pharmacokinetics of APT-1011 in Subjects With Eosinophilic Esophagitis (EoE)
Condition: Eosinophilic Esophagitis
MeSH terms: Esophagitis; Eosinophilic Esophagitis
Intervention: APT-1011; Placebo
Intervention description: APT-1011 is an orally disintegrating tablet formulation of fluticasone propionate; Placebo tablets are identical in composition to APT-1011 except they exclude the active ingredient.
Intervention MeSH terms: Fluticasone; Xhance
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Double Blind
Enrollment: 106.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Esophagitis; Eosinophilic Esophagitis; Fluticasone; Dysphagia; Safety; Efficacy; Pharmacokinetics; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Glucocorticoids; Orally Disintegrating Tablet

Summary:

      Eosinophilic esophagitis (EoE) is an inflammatory disease of the esophagus, characterized by
      eosinophilic infiltration and gastrointestinal symptoms. Swallowed, topically acting
      corticosteroids, such as fluticasone, appear to be effective in resolving acute clinical and
      pathological features of EoE.

      APT-1011 is an orally disintegrating tablet (ODT) formulation of fluticasone propionate. This
      study is designed to compare the efficacy and safety of APT-1011 with placebo in adults with
      EoE for an initial 12-week treatment period, followed by an additional 40-week maintenance
      treatment phase. Histologic response, pharmacokinetics, and dysphagia will be assessed.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female between ≥18 and ≤75 years of age at the time of informed consent

          -  Signed informed consent

          -  Evidence of EoE defined by ≥15 peak eosinophils per HPF as measured from proximal and
             distal biopsies

          -  Subject-reported history of ≥3 episodes of dysphagia in the 7 days prior to Screening

          -  7-day Global EoE Symptom Score >3 at baseline and at screening

          -  Willing and able to adhere to study-related treatment regimens, procedures, and visit
             schedule

        Exclusion Criteria:

          -  Have known contraindication, hypersensitivity, or intolerance to corticosteroids;

          -  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;

          -  Presence of oral or esophageal mucosal infection of any type;

          -  Have any mouth or dental condition that prevents normal eating;

          -  Have any condition affecting the esophageal mucosa or altering esophageal motility
             other than EoE;

          -  Use of systemic 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;

          -  Initiation of an elimination diet or elemental diet within 30 days before Screening
             (diet must remain stable after signing ICF);

          -  Morning serum cortisol level ≤5 μg/dL (138 nmol/L);

          -  Use of biologic immunomodulators in the 24 weeks prior to Screening;

          -  Use of calcineurin inhibitors or purine analogues, or potent cytochrome P450 (CYP) 3A4
             inhibitors in the 12 weeks prior to Screening;

          -  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;

          -  Have a history of an esophageal stricture requiring dilatation within the previous 12
             weeks prior to Screening;

          -  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.

          -  A serum cortisol level <18 μg/dL (497 nmol/L) at 60 minutes with adrenocorticotropic
             hormone (ACTH) stimulation test using 250 μg cosyntropin (i.e., a positive result on
             the ACTH stimulation test).