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

Eosinophilic Esophagitis Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05634746
• Other study ID #: SP-1011-005
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 29, 2022
• Est. completion date: March 2025

Study information

• Verified date: May 2024
• Source: Ellodi Pharmaceuticals, LP
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 218
• Est. completion date: March 2025
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Eosinophilic Esophagitis
• Esophagitis

Intervention

Drug:
• APT-1011
APT-1011 is an orally disintegrating tablet that includes fluticasone propionate as its active ingredient. Other Names: fluticasone propionate
• 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

Locations

Country	Name	City	State
Canada	Joel Liem Medicine Professional Corporation	Windsor	Ontario
United States	New Mexico Clinical Research & Osteoporosis Center, Inc.	Albuquerque	New Mexico
United States	Washington Gastroenterology, PLLC dba GI Alliance	Bellevue	Washington
United States	Boston Specialists	Boston	Massachusetts
United States	Bozeman Health	Bozeman	Montana
United States	Om Research LLC	Camarillo	California
United States	UNC Clinical and Translational Research Center (CTRC)	Chapel Hill	North Carolina
United States	Charlotte Gastroenterology & Hepatology, PLLC	Charlotte	North Carolina
United States	Clinical Research Institute of Michigan, LLC	Chesterfield	Michigan
United States	Clinical Research Professionals	Chesterfield	Missouri
United States	MGG Group Co., Inc., Chevy Chase Clinical Research	Chevy Chase	Maryland
United States	Bernstein Clinical Research	Cincinnati	Ohio
United States	Peak Gastroenterology Associates	Colorado Springs	Colorado
United States	Gastro Center of Maryland, LLC	Columbia	Maryland
United States	Centricity Research Columbus	Columbus	Ohio
United States	Digestive Health Specialists	Dothan	Alabama
United States	Deaconess Clinic Allergy	Evansville	Indiana
United States	GI Alliance - Glenview	Glenview	Illinois
United States	Carolina Research	Greenville	North Carolina
United States	GI Alliance - Gurnee	Gurnee	Illinois
United States	Medical Research Center of Connecticut, LLC	Hamden	Connecticut
United States	Texas Digestive Specialists	Harlingen	Texas
United States	Nature Coast Clinical Research	Inverness	Florida
United States	I.H.S Health, LLC	Kissimmee	Florida
United States	Preferred Research Partners, Inc.	Little Rock	Arkansas
United States	GI Alliance	Lubbock	Texas
United States	Blue Ridge Medical Research	Lynchburg	Virginia
United States	Gastroenterology Associates of Central Georgia, LLC	Macon	Georgia
United States	GI Alliance	Mansfield	Texas
United States	Providence Facey Medical Foundation	Mission Hills	California
United States	East View Medical Research LLC	Mobile	Alabama
United States	United Medical Doctors	Murrieta	California
United States	Gastroenterology Health Partners, PLLC	New Albany	Indiana
United States	New York Gastroenterology Associates	New York	New York
United States	Arkansas Gastroenterology	North Little Rock	Arkansas
United States	Henry Ford Health System	Novi	Michigan
United States	Advanced Research Institute	Ogden	Utah
United States	Endoscopic Research Inc	Orlando	Florida
United States	Revival Clinical Research	Orlando	Florida
United States	Velocity Clinical Research, Inc.	Overland Park	Kansas
United States	Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	MNGI Digestive Health, P.A.	Plymouth	Minnesota
United States	Rapid City Medical Center, LLP	Rapid City	South Dakota
United States	Advanced Research Institute	Reno	Nevada
United States	Velocity Clinical Research, Inc.	Rockville	Maryland
United States	University of Utah Hospital	Salt Lake City	Utah
United States	Southern Star Research Institute, LLC.	San Antonio	Texas
United States	Precision Research Institute, LLC	San Diego	California
United States	TriWest Research Associates, LLC	San Diego	California
United States	Advanced Research Institute	Sandy	Utah
United States	Premier Allergy Asthma and Immunology	Scottsdale	Arizona
United States	GI Alliance	Tacoma	Washington
United States	Clinical Research Institute of Michigan, LLC	Troy	Michigan
United States	Del Sol Research Management, LLC.	Tucson	Arizona
United States	Vital Prospects Clinical Research Institute., PC	Tulsa	Oklahoma
United States	Frontier Clinical Research, LLC	Uniontown	Pennsylvania
United States	GI Alliance	Webster	Texas
United States	Northshore Gastroenterology Research, LLC	Westlake	Ohio
United States	Western States Clinical Research, Inc.	Wheat Ridge	Colorado
United States	Gastroenterology Associates of Western Michigan	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Ellodi Pharmaceuticals, LP

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Mean Number of Dysphagia-Free Days	To compare the mean number of dysphagia-free days from baseline to Week 24	Week 24
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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