Clinical trial NCT05634746: 24-Week Induction Study of APT-1011 in Adult Subjects with Eosinophilic Esophagitis (EoE) (FLUTE 3)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Eosinophilic Esophagitis
Keywords: APT-1011
Esophagitis
Eosinophilic Esophagitis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Eosinophilia
Leukocyte Disorders
Hematologic Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Fluticasone
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Anti-Allergic Agents
FLUTE 3
FLUTE III
Flute
Lead sponsor: Ellodi Pharmaceuticals, LP
Sponsor class: INDUSTRY
First posted: 2022-12-02
Enrollment: 218
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Histological Remission (Co-Primary Outcome Measure)
timeFrame: Week 24
measure: Complete Symptomatic Response (Co-Primary Outcome Measure)
timeFrame: Week 24
Secondary outcomes:
measure: Clinicopathologic Responder Rate
timeFrame: Week 24
measure: Percentage of Subjects with ≥70% Reduction in Dysphagia Frequency
timeFrame: Week 24
measure: Mean Change in Dysphagia Frequency
timeFrame: Week 24
measure: Mean Change in PROSE Difficulty Swallowing
timeFrame: Week 24
measure: Mean Change in PROSE Pain with Swallowing
timeFrame: Week 24
measure: Mean Number of Dysphagia-Free Days
timeFrame: Week 24
measure: Percentage of Responders (Strictures and ≥Grade 2 rings)
timeFrame: Week 24
measure: Percentage of Responders (Strictures)
timeFrame: Week 24
measure: Percentage of Responders (≥Grade 2 rings)
timeFrame: Week 24
measure: Mean Change in EREFs
timeFrame: Week 24
measure: Time to First Complete Symptom Response
timeFrame: Week 24
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Digestive Health Specialists
state: Alabama
city: Mobile
country: United States
facility: East View Medical Research LLC
state: Alabama
city: Scottsdale
country: United States
facility: Premier Allergy Asthma and Immunology
state: Arizona
city: Tucson
country: United States
facility: Del Sol Research Management, LLC.
state: Arizona
city: Little Rock
country: United States
facility: Preferred Research Partners, Inc.
state: Arkansas
city: North Little Rock
country: United States
facility: Arkansas Gastroenterology
state: Arkansas
city: Camarillo
country: United States
facility: Om Research LLC
state: California
city: Mission Hills
country: United States
facility: Providence Facey Medical Foundation
state: California
city: Murrieta
country: United States
facility: United Medical Doctors
state: California
city: San Diego
country: United States
facility: TriWest Research Associates, LLC
state: California
city: San Diego
country: United States
facility: Precision Research Institute, LLC
state: California
city: Colorado Springs
country: United States
facility: Peak Gastroenterology Associates
state: Colorado
city: Wheat Ridge
country: United States
facility: Western States Clinical Research, Inc.
state: Colorado
city: Hamden
country: United States
facility: Medical Research Center of Connecticut, LLC
state: Connecticut
city: Inverness
country: United States
facility: Nature Coast Clinical Research
state: Florida
city: Kissimmee
country: United States
facility: I.H.S Health, LLC
state: Florida
city: Orlando
country: United States
facility: Endoscopic Research Inc
state: Florida
city: Orlando
country: United States
facility: Revival Clinical Research
state: Florida
city: Macon
country: United States
facility: Gastroenterology Associates of Central Georgia, LLC
state: Georgia
city: Glenview
country: United States
facility: GI Alliance - Glenview
state: Illinois
city: Gurnee
country: United States
facility: GI Alliance - Gurnee
state: Illinois
city: Evansville
country: United States
facility: Deaconess Clinic Allergy
state: Indiana
city: New Albany
country: United States
facility: Gastroenterology Health Partners, PLLC
state: Indiana
city: Overland Park
country: United States
facility: Velocity Clinical Research, Inc.
state: Kansas
city: Chevy Chase
country: United States
facility: MGG Group Co., Inc., Chevy Chase Clinical Research
state: Maryland
city: Columbia
country: United States
facility: Gastro Center of Maryland, LLC
state: Maryland
city: Rockville
country: United States
facility: Velocity Clinical Research, Inc.
state: Maryland
city: Boston
country: United States
facility: Boston Specialists
state: Massachusetts
city: Chesterfield
country: United States
facility: Clinical Research Institute of Michigan, LLC
state: Michigan
city: Novi
country: United States
facility: Henry Ford Health System
state: Michigan
city: Troy
country: United States
facility: Clinical Research Institute of Michigan, LLC
state: Michigan
city: Wyoming
country: United States
facility: Gastroenterology Associates of Western Michigan
state: Michigan
city: Plymouth
country: United States
facility: MNGI Digestive Health, P.A.
state: Minnesota
city: Chesterfield
country: United States
facility: Clinical Research Professionals
state: Missouri
city: Bozeman
country: United States
facility: Bozeman Health
state: Montana
city: Reno
country: United States
facility: Advanced Research Institute
state: Nevada
city: Albuquerque
country: United States
facility: New Mexico Clinical Research & Osteoporosis Center, Inc.
state: New Mexico
city: New York
country: United States
facility: New York Gastroenterology Associates
state: New York
city: Chapel Hill
country: United States
facility: UNC Clinical and Translational Research Center (CTRC)
state: North Carolina
city: Charlotte
country: United States
facility: Charlotte Gastroenterology & Hepatology, PLLC
state: North Carolina
city: Greenville
country: United States
facility: Carolina Research
state: North Carolina
city: Cincinnati
country: United States
facility: Bernstein Clinical Research
state: Ohio
city: Columbus
country: United States
facility: Centricity Research Columbus
state: Ohio
city: Westlake
country: United States
facility: Northshore Gastroenterology Research, LLC
state: Ohio
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute., PC
state: Oklahoma
city: Philadelphia
country: United States
facility: Perelman Center for Advanced Medicine
state: Pennsylvania
city: Uniontown
country: United States
facility: Frontier Clinical Research, LLC
state: Pennsylvania
city: Rapid City
country: United States
facility: Rapid City Medical Center, LLP
state: South Dakota
city: Harlingen
country: United States
facility: Texas Digestive Specialists
state: Texas
city: Lubbock
country: United States
facility: GI Alliance
state: Texas
city: Mansfield
country: United States
facility: GI Alliance
state: Texas
city: San Antonio
country: United States
facility: Southern Star Research Institute, LLC.
state: Texas
city: Webster
country: United States
facility: GI Alliance
state: Texas
city: Ogden
country: United States
facility: Advanced Research Institute
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Sandy
country: United States
facility: Advanced Research Institute
state: Utah
city: Lynchburg
country: United States
facility: Blue Ridge Medical Research
state: Virginia
city: Bellevue
country: United States
facility: Washington Gastroenterology, PLLC dba GI Alliance
state: Washington
city: Tacoma
country: United States
facility: GI Alliance
state: Washington
city: Windsor
country: Canada
facility: Joel Liem Medicine Professional Corporation
state: Ontario
Study officials:
affiliation: UNC Center for Esophageal Diseases and Swallowing
name: Evan Dellon, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: