Efficacy and Safety APT-1011 in Adolescent Subjects With Eosinophilic Esophagitis (EoE) - A Sub-Study of the FLUTE-2 Trial

NCT05083312 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: SP-1011-003a
• Study Type: interventional
• Target: 6
• Locations: 2 countries
• Sites: 3

Brief Summary

This is a randomized, double-blind, placebo-controlled study of APT-1011, followed by an open-label extension (OLE) in adolescents (≥12 to \<18 years) with EoE.

Conditions

Eosinophilic Esophagitis

Keywords

APT-1011; Esophagitis; Eosinophilic Esophagitis; Esophageal Diseases; Gastrointestinal 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

Outcome Measures

Primary Outcomes (2)

• Week 12 histologic responder rates

  To compare the Week 12 histologic responder rates (≤ 6 peak eosinophils / high power field \[eos/HPF\]) for APT-1011 3 mg hora somni (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

  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

  Week 0 to Week 12

Secondary Outcomes (7)

• Mean change in EREFs from Week 0 to Week 12

  Week 0 to Week 12

• Percentage of subjects with <1 peak eos/HPF at Week 12

  Week 12

• Mean change in PROSE Symptom Burden Score

  Week 0 to Week 12

• Mean change in PROSE day-level difficulty swallowing

  Week 0 to Week 12

• Histologic Change from Baseline to Week 12

  Week 0 to Week 12

Study Arms (2)

APT-1011

EXPERIMENTAL

APT-1011 3 mg HS

Drug: APT-1011

Placebo

PLACEBO COMPARATOR

HS

Drug: Placebo oral tablet

Interventions

APT-1011 DRUG

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

Also known as: fluticasone propionate

APT-1011

Placebo oral tablet DRUG

Placebo orally disintegrating tablet

Also known as: PBO

Placebo

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female ≥12 and \<18 years of age
• Each subject and their parents or legal guardian, must read, understand and provide consent or assent on the ICF for this study and be willing and able to adhere to study-related treatment regimens, procedures and visit schedule
• 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 from both proximal and distal specimens (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.
• Esophagogastroduodenoscopies and biopsies are to be obtained during the Screening period
• Biopsies will be read by a central pathologist
• Esophagogastroduodenoscopies and biopsies performed outside the study will not be accepted to meet eligibility criteria
• 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
• Have a subject-reported history of ≥6 episodes of dysphagia in the 14 days prior to baseline
• Completion of the daily diary on at least 11 out of the 14 days during the 2-week Baseline Symptom Assessment

You may not qualify if:

• Have known contraindication, hypersensitivity, or intolerance to corticosteroids
• 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 9 mm endoscope at screening
• Have history of an esophageal stricture requiring dilatation within the 12 weeks prior to Screening
• Bone mineral density \>2 SD below height-adjusted for age
• 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 or may increase risk of corticosteroid toxicity (e.g., abnormal bone mineral density)
• History of recurrent (persistent) or current oral or esophageal mucosal infection due to inhaled or nasal corticosteroids
• Have any mouth or dental condition that prevents normal eating (excluding braces)
• 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)
• Use of systemic (oral or parenteral) corticosteroids within 60 days before Screening, use of swallowed corticosteroids within 30 days before Screening
• Initiation of either inhaled or nasal corticosteroids or high-potency dermal topical corticosteroids within 30 days before Screening
• Use of calcineurin inhibitors or purine analogues (azathioprine, 6-mercaptopurine) in the 12 weeks before Screening
• Use of potent CYP 3A4 inhibitors (e.g., ritonavir and ketoconazole) in the 12 weeks before Screening
• Initiation of an elimination diet or elemental diet within 30 days before Screening (diet must remain stable after signing ICF)
• Morning (07:00 to 09:00, or as close to that window as possible) serum cortisol level ≤5 μg/dL (138 nmol/L) that is not responsive to 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 (i.e., an abnormal result on the ACTH stimulation test)
• Use of biologic immunomodulators in the 24 weeks before Screening (environmental allergen desensitization injection or oral therapy (excluding food allergen desensitization) is allowed as long as the course of therapy is not altered during the study period)

Sponsors & Collaborators

• Ellodi Pharmaceuticals, LP: lead

Study Sites (3)

IU School of Medicine Department of Pediatrics

Indianapolis, Indiana, 46202, United States

Location

Boston Specialists

Boston, Massachusetts, 02111, United States

Location

Royal Children's Hospital

Melbourne, Victoria, 3052, Australia

Location

MeSH Terms

Conditions

Eosinophilic Esophagitis; Esophagitis; Esophageal Diseases; Gastrointestinal Diseases; Gastroenteritis; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Interventions

APT-1011; Fluticasone

Condition Hierarchy (Ancestors)

Digestive System Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Mirna Chehade, MD, MPH

  Mount Sinai Center for Eosinophilic Disorders

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2021
• First Posted: October 19, 2021
• Study Start: September 30, 2021
• Primary Completion: September 5, 2022
• Study Completion: September 5, 2022
• Last Updated: September 21, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); AU (1)