24-Week Induction Study of APT-1011 in Adult Subjects With Eosinophilic Esophagitis (EoE) (FLUTE 3) (FLUTE-3)

Fluticasone Propionate Oral Disintegrating Tablet Formulation in Eosinophilic Esophagitis: A Randomized, Double-blind, Placebo-Controlled 24-Week Induction Study of APT-1011, Followed by a Single-arm Open-label Extension, in Adult Subjects With Eosinophilic Esophagitis

This is a 24-week randomized, double-blind, placebo-controlled induction study of APT-1011 in adults (≥18 years old) with eosinophilic esophagitis (EoE) followed by a single-arm, open-label extension. This study will evaluate the efficacy and safety of APT-1011 3 mg administered HS (hora somni, at bedtime) for the induction of response to treatment (symptomatic and histologic) over 24 weeks. The open-label extension will continue to evaluate long-term safety in subjects who consent to continue on open-label treatment with APT-1011.

Study Overview

• Status: Completed
• Conditions: Eosinophilic Esophagitis
• Intervention / Treatment: Drug: APT-1011; Drug: Placebo oral tablet; Procedure: Esophagogastroduodenoscopy

Detailed Description

The efficacy and safety of APT-1011 3 mg administered at bedtime will be evaluated for the induction of response (histologic and symptomatic) after 24 weeks of treatment. After completing 24 weeks of double-blind study treatment, subjects may consent to participate in the open-label extension, otherwise they will complete study drug treatment and enter a 2-week off treatment safety follow-up.

The duration of the double-blind portion of the study, screening through follow-up visit for subjects completing study drug at Week 24, will be up to 32 weeks long, i.e., 6-week screening period (the includes a 4-week run-in phase) followed by 24 weeks induction phase and 2 weeks off-treatment follow-up. For subjects consenting to participate in the open-label extension, the duration of the study will be determined by the Sponsor.

• Study Type: Interventional
• Enrollment (Actual): 218
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Windsor, Ontario, Canada, N8X 2G1
      • Joel Liem Medicine Professional Corporation
• United States
  • Alabama
    • Dothan, Alabama, United States, 36301
      • Digestive Health Specialists
    • Mobile, Alabama, United States, 36606
      • East View Medical Research LLC
  • Arizona
    • Scottsdale, Arizona, United States, 85255
      • Premier Allergy Asthma And Immunology
    • Tucson, Arizona, United States, 85715
      • Del Sol Research Management, LLC.
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Preferred Research Partners, Inc.
    • North Little Rock, Arkansas, United States, 72117
      • Arkansas Gastroenterology
  • California
    • Camarillo, California, United States, 93012
      • Om Research LLC
    • Mission Hills, California, United States, 91345
      • Providence Facey Medical Foundation
    • Murrieta, California, United States, 92563
      • United Medical Doctors
    • San Diego, California, United States, 92114
      • Precision Research Institute, LLC
    • San Diego, California, United States, 92108
      • TriWest Research Associates, LLC
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Peak Gastroenterology Associates
    • Wheat Ridge, Colorado, United States, 80033
      • Western States Clinical Research, Inc.
  • Connecticut
    • Hamden, Connecticut, United States, 06518
      • Medical Research Center of Connecticut, LLC
  • Florida
    • Inverness, Florida, United States, 34452
      • Nature Coast Clinical Research
    • Kissimmee, Florida, United States, 34741
      • I.H.S Health, LLC
    • Orlando, Florida, United States, 32803
      • Endoscopic Research Inc
    • Orlando, Florida, United States, 32807
      • Revival Clinical Research
  • Georgia
    • Macon, Georgia, United States, 31201
      • Gastroenterology Associates of Central Georgia, LLC
  • Illinois
    • Glenview, Illinois, United States, 60026
      • GI Alliance - Glenview
    • Gurnee, Illinois, United States, 60031
      • Gi Alliance - Gurnee
  • Indiana
    • Evansville, Indiana, United States, 47715
      • Deaconess Clinic Allergy
    • New Albany, Indiana, United States, 47150
      • Gastroenterology Health Partners, PLLC
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Velocity Clinical Research, Inc.
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • MGG Group Co., Inc., Chevy Chase Clinical Research
    • Columbia, Maryland, United States, 21045
      • Gastro Center of Maryland, LLC
    • Rockville, Maryland, United States, 20854
      • Velocity Clinical Research, Inc.
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Boston Specialists
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Clinical Research Institute of Michigan, LLC
    • Novi, Michigan, United States, 48377
      • Henry Ford Health System
    • Troy, Michigan, United States, 48098
      • Clinical Research Institute of Michigan, LLC
    • Wyoming, Michigan, United States, 49519
      • Gastroenterology Associates of Western Michigan
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • MNGI Digestive Health, P.A.
  • Missouri
    • Chesterfield, Missouri, United States, 63005
      • Clinical Research Professionals
  • Montana
    • Bozeman, Montana, United States, 59715
      • Bozeman Health
  • Nevada
    • Reno, Nevada, United States, 89511
      • Advanced Research Institute
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • New Mexico Clinical Research & Osteoporosis Center, Inc.
  • New York
    • New York, New York, United States, 10075
      • New York Gastroenterology Associates
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7064
      • UNC Clinical and Translational Research Center (CTRC)
    • Charlotte, North Carolina, United States, 28207
      • Charlotte Gastroenterology & Hepatology, PLLC
    • Greenville, North Carolina, United States, 27834
      • Carolina Research
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Bernstein Clinical Research
    • Columbus, Ohio, United States, 43213
      • Centricity Research Columbus
    • Westlake, Ohio, United States, 44145
      • Northshore Gastroenterology Research, LLC
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Vital Prospects Clinical Research Institute., PC
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Perelman Center for Advanced Medicine
    • Uniontown, Pennsylvania, United States, 15401
      • Frontier Clinical Research, LLC
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Medical Center, LLP
  • Texas
    • Harlingen, Texas, United States, 78550
      • Texas Digestive Specialists
    • Lubbock, Texas, United States, 79410
      • GI Alliance
    • Mansfield, Texas, United States, 76063
      • GI Alliance
    • San Antonio, Texas, United States, 78229
      • Southern Star Research Institute, LLC.
    • Webster, Texas, United States, 77598
      • GI Alliance
  • Utah
    • Ogden, Utah, United States, 84405
      • Advanced Research Institute
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital
    • Sandy, Utah, United States, 84092
      • Advanced Research Institute
  • Virginia
    • Lynchburg, Virginia, United States, 24502
      • Blue Ridge Medical Research
  • Washington
    • Bellevue, Washington, United States, 98004
      • Washington Gastroenterology, PLLC dba GI Alliance
    • Tacoma, Washington, United States, 98405
      • GI Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult male or female ≥18 years of age at the time of informed consent
2. Each subject must read, understand, and provide consent 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 in total from both proximal and distal esophageal mucosal areas (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 (0.3 mm^2) and 22 mm ocular.

   1. Esophagogastroduodenoscopies and biopsies are to be obtained during the Screening period
   2. Biopsies will be read by a central pathologist
   3. Esophagogastroduodenoscopies and biopsies performed outside the study will not be accepted to meet eligibility criteria
   4. 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 to a maximum of 30 episodes of dysphagia in a 14-consecutive-day period within 18 days prior to baseline
5. Completion of the evening eDiary on at least 11 out of the 14-consecutive-day observation period during the 4-week run-in period (Baseline Symptom Assessment).The minimum requirement of 11 days need not be consecutive.

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 (8-10 mm) endoscope
3. Have history of an esophageal stricture requiring dilatation within the 12 weeks prior to Screening
4. 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
5. History of recurrent or current oral or esophageal mucosal infection due to inhaled or nasal corticosteroids
6. Have any mouth or dental condition that prevents normal eating (excluding braces)
7. 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)
8. Use of systemic (oral or parenteral) corticosteroids within 30 days before Screening, use of swallowed corticosteroids within 30 days before Screening
9. Initiation of either inhaled or nasal corticosteroids or high-potency dermal topical corticosteroids within 30 days before Screening
10. Use of calcineurin inhibitors or purine analogues (azathioprine, 6-mercaptopurine) in the 12 weeks before Screening
11. Use of potent cytochrome P450 (CYP) 3A4 inhibitors (e.g., ritonavir and ketoconazole) in the 4 weeks before Screening
12. Initiation of an elimination diet or elemental diet within 30 days before Screening (diet must remain stable after signing ICF)
13. Abnormal 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
14. Use of biologic immunomodulators, including dupilumab for EoE, with dose last administered within 6 months before Screening (allergy desensitization injection or oral therapies allowed as long as the course of therapy is not altered during the study period)
15. 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 during Screening. If already receiving these drugs, the dosage must remain constant throughout the study
16. Subjects who have initiated PPIs within 8 weeks before qualifying endoscopy. If already receiving PPIs, the dosage regimen must remain constant throughout the study
17. Have gastrointestinal bleeding or documented active peptic ulcer within 4 weeks prior to Screening or entering a new study period
18. 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 or who live in, or travel to, high endemic areas should be assessed locally for tuberculosis before consideration for the study
19. Immunosuppression or immunodeficiency disorder
20. Current malignancy or malignancy within 3 years of Screening, with the exception of skin cancers other than melanoma. Subjects in remission for at least 3 years post-treatment may be enrolled.
21. Have a history or presence of Crohn's disease, celiac disease, or other inflammatory disease of the gastrointestinal tract, including non-EoE eosinophilic gastrointestinal disorders (EGIDs)
22. Have current drug abuse in the opinion of the Investigator
23. Have current alcohol abuse in the opinion of the Investigator
24. Female subjects who are pregnant, breastfeeding, or planning to become pregnant during the study
25. Sexually active females of childbearing potential who do not agree to follow highly effective contraceptive methods through the End of Study visit
26. Have received an investigational product as part of a clinical trial within 30 days (or 5 half-lives, whichever is longest) of Screening. Subjects who are currently participating in observational studies or enrolled in patient registries are allowed in this study
27. Have participated in a prior study with investigational product APT-1011

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: APT-1011; APT-1011 3 mg HS	Drug: APT-1011; APT-1011 is an orally disintegrating tablet that includes fluticasone propionate as its active ingredient. Other Names: fluticasone propionate; Procedure: Esophagogastroduodenoscopy; 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
Placebo Comparator: Placebo; Placebo HS	Drug: Placebo oral tablet; Placebo orally disintegrating tablet. Other Names: PBO; Procedure: Esophagogastroduodenoscopy; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Histological Remission (Co-Primary Outcome Measure)	To evaluate the percentage of subjects with histological remission (defined ≤ 6 peak eosinophils [eos]/high power field [HPF] on esophageal mucosal biopsies at Week 24). 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	Week 24
Complete Symptomatic Response (Co-Primary Outcome Measure)	To evaluate the percentage of subjects with complete symptomatic response at Week 24 (defined as zero dysphagia episodes in the 14 consecutive days prior to Week 24)	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinicopathologic Responder Rate	To compare the percentage of clinicopathologic responders, defined as having complete symptomatic AND histological response at Week 24 (defined as zero dysphagia episodes in the 14 consecutive days prior to Week 24 AND ≤ 6 peak eos/HPF on esophageal mucosal biopsies)	Week 24
Percentage of Subjects with ≥70% Reduction in Dysphagia Frequency	To evaluate the percentage of subjects with ≥70% reduction in dysphagia frequency at Week 24 as compared to baseline (as measured over the 14 consecutive days prior to each visit)	Week 24
Mean Change in Dysphagia Frequency	To compare the mean change from baseline to Week 24 in dysphagia frequency (as measured over the 14 consecutive days prior to each visit)	Week 24
Mean Change in PROSE Difficulty Swallowing	To compare the mean change from baseline to Week 24 in difficulty swallowing using the Patient Reported Outcomes Symptoms of Eosinophilic Esophagitis (PROSE)	Week 24
Mean Change in PROSE Pain with Swallowing	To compare the mean change from baseline to Week 24 in pain with swallowing using the PROSE	Week 24
Mean Number of Dysphagia-Free Days	To compare the mean number of dysphagia-free days from baseline to Week 24	Week 24
Percentage of Responders (Strictures and ≥Grade 2 rings)	To compare the percentage of responders, defined as no longer having strictures and/or ≥Grade 2 rings which were present at baseline, at Week 24	Week 24
Percentage of Responders (Strictures)	To compare the percentage of responders, defined as no longer having strictures which were present at baseline, at Week 24	Week 24
Percentage of Responders (≥Grade 2 rings)	To compare the percentage of responders, defined as no longer having ≥Grade 2 rings which were present at baseline, at Week 24	Week 24
Mean Change in EREFs	To compare endoscopic appearance evaluated by the mean change from baseline to Week 24 in Eosinophilic Esophagitis Endoscopic Reference Score (EREFs)	Week 24
Time to First Complete Symptom Response	Time to first complete symptom response (defined as zero dysphagia episodes in a 14-consecutive-day period)	Week 24

Collaborators and Investigators

• Sponsor: Ellodi Pharmaceuticals, LP
• Investigators: Principal Investigator: Evan Dellon, MD, MPH, UNC Center for Esophageal Diseases and Swallowing

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2022
• Primary Completion (Actual): August 12, 2024
• Study Completion (Actual): August 12, 2024

Study Registration Dates

• First Submitted: November 22, 2022
• First Submitted That Met QC Criteria: November 22, 2022
• First Posted (Actual): December 2, 2022

Study Record Updates

• Last Update Posted (Actual): August 13, 2025
• Last Update Submitted That Met QC Criteria: August 11, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Esophagitis; Hematologic Diseases; Eosinophilic Esophagitis; Eosinophilia; Esophageal Diseases; Peripheral Nervous System Agents; Anti-Asthmatic Agents; APT-1011; Leukocyte Disorders; Fluticasone; Anti-Inflammatory Agents; Bronchodilator Agents; Autonomic Agents; Respiratory System Agents; Anti-Allergic Agents; FLUTE 3; FLUTE III; Flute
• Additional Relevant MeSH Terms: Immune System Diseases; Digestive System Diseases; Gastrointestinal Diseases; Hypersensitivity, Immediate; Hypersensitivity; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Esophageal Diseases; Gastroenteritis; Esophagitis; Eosinophilic Esophagitis
• Other Study ID Numbers: SP-1011-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No