This is a 2-part randomized, double-blind, placebo-controlled study followed by an open-label extension (OLE) of APT-1011 in adults with EoE. Part A will evaluate the efficacy and safety of APT-1011 3 mg administered hora somni (HS; at bedtime) for the induction of response to treatment (histologic and symptomatic) over 12 weeks. Part B will evaluate histological relapse-free status in patients re-randomized to continue APT-1011 or placebo (active treatment withdrawal) until Week 52. Part C, the OLE, will continue until regulatory approval of APT-1011 or Sponsor termination of the study.
This is a 2-part randomized, double-blind, placebo-controlled study followed by an OLE of APT-1011 in adults with EoE. Part A will evaluate the efficacy and safety of APT-1011 3 mg administered HS for the induction of response to treatment (histologic and symptomatic) over 12 weeks. At Week 14, subjects will move into Part B. Subjects with histological response to APT-1011, defined as ≤6 peak eos/HPF, will be re-randomized to continue APT-1011 or receive placebo (active treatment withdrawal). APT-1011 histological non-responders will continue APT-1011, and placebo histological non-responders will receive APT-1011 3 mg HS. Placebo histological responders will continue placebo. The double-blind will be sustained throughout Part B. Histological responder status will be determined at the time of esophagogastroduodenoscopy (EGD) in Part B (at or prior to Week 52, depending on unscheduled EGDs performed when the Investigator deems the subject's symptoms necessitate EGD) and is defined as ≤6 peak eos/HPF. At Week 52, subjects may enter Part C, an open-label single-arm extension phase, and continue study drug uninterrupted. Part C will terminate upon regulatory approval of APT-1011 or Sponsor termination of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
143
APT-1011 is an orally disintegrating tablet that includes fluticasone propionate as its active ingredient.
Placebo orally disintegrating tablet.
Esophagogastroduodenoscopy (EGD) is a test that involves an endoscope, a lighted camera on the end of a tube, that is passed down a subject's throat to visualize their esophagus.
Pinnacle Research Group, LLC
Anniston, Alabama, United States
Gut P.C., dba; Digestive Health Specialists of the Southeast
Dothan, Alabama, United States
East View Medical Research, LLC
Mobile, Alabama, United States
Del Sol Research Management, LLC
Tucson, Arizona, United States
Preferred Research Partners Inc.
Little Rock, Arkansas, United States
Week 12 histologic responder rates
To compare the Week 12 histologic responder rates (≤ 6 peak eosinophils \[eos\]/high power field \[HPF\]) for APT-1011 3 mg HS with that for placebo. HPF will be defined as a standard area of 235 square microns in a microscope with 40x lens (0.3 mm\^2) and 22 mm ocular
Time frame: Week 12
Mean change in number of dysphagia episodes
To compare the mean change in number of dysphagia episodes from baseline to Week 12 for APT-1011 3 mg HS with that for placebo
Time frame: Week 0 to Week 12
Histologic responder rates at the end of the Randomized Withdrawal Phase (RWS)
To compare the histologic responder rates (≤ 6 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) at the end of the RWS
Time frame: Week 12 to Week 52
Percentage subjects with complete symptomatic response at the end of the RWS
Percentage of subjects with complete symptomatic response (i.e., no dysphagia episodes for the 14 consecutive days prior to the end of the randomized withdrawal phase) at the end of the randomized withdrawal phase, in the RWS APT-1011 3 mg HS arm versus placebo arm
Time frame: Week 0 to Week 52
Change in EREFs from Week 0 to Week 12
To compare endoscopic appearance evaluated by the mean change from baseline to Week 12 in Eosinophilic Esophagitis Endoscopic Reference Score (EREFs) for APT-1011 3 mg HS with that for placebo.
Time frame: Week 0 to Week 12
Percentage of subjects with <1 peak eos/HPF at Week 12
To compare the percentage of subjects with \<1 peak eos/HPF at Week 12 for APT-1011 3 mg HS with that for placebo.
Time frame: Week 12
Mean change in PROSE Symptom Burden Score
To compare the mean change from baseline to Week 12 in the day-level symptom burden utilizing the Patient Reported Outcomes Symptoms of EoE (PROSE) for APT-1011 3 mg HS with that for placebo.
Time frame: Week 0 to Week 12
Mean Change in PROSE Day-Level Difficulty Swallowing
To compare the mean change from baseline to Week 12 in day-level difficulty swallowing using the Patient Reported Outcomes Symptoms of EoE (PROSE) for APT-1011 3 mg HS with that for placebo. Each symptom is rated on a numeric rating scale (NRS) with values ranging from 0 (not at all) to 10 (as bad as I can imagine).
Time frame: Week 0 to Week 12
Mean Histologic Change from Baseline to Week 12
To compare mean histologic change from baseline to Week 12 for APT-1011 3 mg HS with that for placebo.
Time frame: Week 0 to Week 12
Percentage of Subjects with <15 peak eos/HPF
To compare the percentage of subjects with \<15 peak eos/HPF for APT-1011 3 mg HS with that for placebo.
Time frame: Week 12
Mean Number of Dysphagia-free Days
To compare the mean number of dysphagia-free days from baseline to Week 12 for APT-1011 3 mg HS with that for placebo
Time frame: Week 0 to Week 12
Mean Change in Dysphagia Episodes
To compare mean change in number of dysphagia episodes from baseline to the end of RWS for APT-1011 responders randomized to continue APT-1011 3 mg HS with responders randomized to placebo (withdrawal of APT-1011 3 mg HS)
Time frame: Week 0 to Week 52
Mean Change in EREFs from Week 0 to Week 52
To compare endoscopic appearance evaluated by the mean change from baseline to the end of RWS, in Eosinophilic Esophagitis Endoscopic Reference Score (EREFs) for APT-1011 responders randomized to continue APT-1011 3 mg HS with responders randomized to placebo (withdrawal of APT-1011 3 mg HS). The EREF score has a range from 0-9, with 9 being worst result.
Time frame: Week 0 to Week 52
Mean Histologic Change
To compare the mean change from baseline to the end of the RWS in peak eosinophil counts for APT-1011 responders randomized to APT-1011 3 mg HS with those randomized to placebo in the RWS.
Time frame: Week 0 to Week 52
Mean Change in PROSE Day-Level Symptom Burden
To compare the mean change in day-level symptom burden using the Patient Reported Outcomes Symptoms of EoE (PROSE) from baseline to the end of RWS, for APT-1011 responders randomized to continue APT-1011 3 mg HS with responders randomized to placebo (withdrawal of APT-1011 3 mg HS). Day-level symptom burden has values ranging from 0 (no symptoms) to 10 (symptoms are as bad as I can imagine).
Time frame: Week 0 to Week 52
Mean Change in PROSE Day-Level Difficulty Swallowing
To compare the mean change in day-level difficulty swallowing using the Patient Reported Outcomes Symptoms of EoE (PROSE) from baseline to the end of randomized withdrawal phase, for APT-1011 responders randomized to continue APT-1011 3 mg HS with responders randomized to placebo (withdrawal of APT-1011 3 mg HS). Each symptom is rated on a numeric rating scale (NRS) with values ranging from 0 (not at all) to 10 (as bad as I can imagine).
Time frame: Week 0 to Week 52
Mean Change in Dysphagia-Free Days
To compare the mean number of dysphagia-free days from baseline to the end of RWS, for APT-1011 responders randomized to continue APT-1011 3 mg HS with responders randomized to placebo (withdrawal of APT-1011 3 mg HS)
Time frame: Week 0 to Week 52
Mean Change in Number of Dysphagia Episodes
To compare mean change in number of dysphagia episodes from baseline at or prior to Week 52 (based on timing of \> 6 peak eos/HPF) for APT-1011 responders randomized to continue APT-1011 3 mg HS with those randomized to placebo (withdrawal of APT-1011 3 mg HS)
Time frame: Week 0 to Week 52
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