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

• ClinicalTrials.gov Identifier: NCT05634746
• Recruitment Status: Active, not recruiting
• First Posted: December 2, 2022
• Last Update Posted: May 6, 2024
• Sponsor: Ellodi Pharmaceuticals, LP
• Information provided by (Responsible Party): Ellodi Pharmaceuticals, LP

Tracking Information

• First Submitted Date: November 22, 2022
• First Posted Date: December 2, 2022
• Last Update Posted Date: May 6, 2024
• Actual Study Start Date: December 29, 2022
• Estimated Primary Completion Date: September 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 22, 2022)

• Histological Remission (Co-Primary Outcome Measure) [ Time Frame: Week 24 ]
  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
• Complete Symptomatic Response (Co-Primary Outcome Measure) [ Time Frame: Week 24 ]
  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)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 22, 2022)

• Clinicopathologic Responder Rate [ Time Frame: Week 24 ]
  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)
• Percentage of Subjects with ≥70% Reduction in Dysphagia Frequency [ Time Frame: Week 24 ]
  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)
• Mean Change in Dysphagia Frequency [ Time Frame: Week 24 ]
  To compare the mean change from baseline to Week 24 in dysphagia frequency (as measured over the 14 consecutive days prior to each visit)
• Mean Change in PROSE Difficulty Swallowing [ Time Frame: Week 24 ]
  To compare the mean change from baseline to Week 24 in difficulty swallowing using the Patient Reported Outcomes Symptoms of Eosinophilic Esophagitis (PROSE)
• Mean Change in PROSE Pain with Swallowing [ Time Frame: Week 24 ]
  To compare the mean change from baseline to Week 24 in pain with swallowing using the PROSE
• Mean Number of Dysphagia-Free Days [ Time Frame: Week 24 ]
  To compare the mean number of dysphagia-free days from baseline to Week 24
• Percentage of Responders (Strictures and ≥Grade 2 rings) [ Time Frame: Week 24 ]
  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
• Percentage of Responders (Strictures) [ Time Frame: Week 24 ]
  To compare the percentage of responders, defined as no longer having strictures which were present at baseline, at Week 24
• Percentage of Responders (≥Grade 2 rings) [ Time Frame: Week 24 ]
  To compare the percentage of responders, defined as no longer having ≥Grade 2 rings which were present at baseline, at Week 24
• Mean Change in EREFs [ Time Frame: Week 24 ]
  To compare endoscopic appearance evaluated by the mean change from baseline to Week 24 in Eosinophilic Esophagitis Endoscopic Reference Score (EREFs)
• Time to First Complete Symptom Response [ Time Frame: Week 24 ]
  Time to first complete symptom response (defined as zero dysphagia episodes in a 14-consecutive-day period)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Eosinophilic Esophagitis

Intervention

• Drug: APT-1011

  APT-1011 is an orally disintegrating tablet that includes fluticasone propionate as its active ingredient.

  Other Names:

  fluticasone propionate

• 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

Study Arms

• Experimental: APT-1011
  APT-1011 3 mg HS
  Interventions:

  • Drug: APT-1011
  • Procedure: Esophagogastroduodenoscopy
• Placebo Comparator: Placebo
  Placebo HS
  Interventions:

  • Drug: Placebo oral tablet
  • Procedure: Esophagogastroduodenoscopy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 10, 2024): 218
• Original Estimated Enrollment (submitted: November 22, 2022): 200
• Estimated Study Completion Date: March 2025
• Estimated Primary Completion Date: September 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT05634746
• Other Study ID Numbers: SP-1011-005
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ellodi Pharmaceuticals, LP
• Original Responsible Party: Same as current
• Current Study Sponsor: Ellodi Pharmaceuticals, LP
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Evan Dellon, MD, MPH; UNC Center for Esophageal Diseases and Swallowing

• PRS Account: Ellodi Pharmaceuticals, LP
• Verification Date: May 2024