Efficacy and Safety APT-1011 in Adult Subjects With Eosinophilic Esophagitis (EoE) (FLUTE-2)

NCT04281108 | Completed Phase 3 FDA Drug

• 1 other identifier: SP-1011-003
• Study Type: interventional
• Target: 143
• Locations: 3 countries
• Sites: 56

Brief Summary

This is a 2-part randomized, double-blind, placebo-controlled study followed by an open-label extension (OLE) of APT-1011 in adults with EoE. Part A will evaluate the efficacy and safety of APT-1011 3 mg administered hora somni (HS; at bedtime) for the induction of response to treatment (histologic and symptomatic) over 12 weeks. Part B will evaluate histological relapse-free status in patients re-randomized to continue APT-1011 or placebo (active treatment withdrawal) until Week 52. Part C, the OLE, will continue until regulatory approval of APT-1011 or Sponsor termination of the study.

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

Outcome Measures

Primary Outcomes (4)

• Week 12 histologic responder rates

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

• Histologic responder rates at the end of the Randomized Withdrawal Phase (RWS)

  To compare the histologic responder rates (≤ 6 peak eos/HPF) for APT-1011 responders randomized to continuing APT-1011 3 mg HS (maintenance) with responders randomized to placebo (withdrawal of APT-1011 3 mg HS) at the end of the RWS

  Week 12 to Week 52

• Percentage subjects with complete symptomatic response at the end of the RWS

  Percentage of subjects with complete symptomatic response (i.e., no dysphagia episodes for the 14 consecutive days prior to the end of the randomized withdrawal phase) at the end of the randomized withdrawal phase, in the RWS APT-1011 3 mg HS arm versus placebo arm

  Week 0 to Week 52

Secondary Outcomes (14)

• 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

• Mean 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; Procedure: Esophagogastroduodenoscopy

Placebo

PLACEBO COMPARATOR

HS

Drug: Placebo oral tablet; Procedure: Esophagogastroduodenoscopy

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

Esophagogastroduodenoscopy PROCEDURE

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.

APT-1011; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥18 years of age at the time of informed consent or assent
• 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
• 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 including 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, if 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
• Have history of an esophageal stricture requiring dilatation within the 12 weeks prior to Screening
• 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
• History or presence of oral or esophageal mucosal infection whilst using 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 cytochrome P450 (CYP) 3A4 inhibitors (eg, 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 adrenocorticotropic hormone (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 (allergy desensitization injection or oral therapy is allowed as long as the course of therapy is not altered during the study period)
• Subjects who have initiated, discontinued, or changed dosage regimen of histamine H2 receptor antagonists, antacids or antihistamines for any condition such as gastro-esophageal reflux disease within 4 weeks before qualifying endoscopy during Screening. If already receiving these drugs, the dosage must remain constant throughout the study

Sponsors & Collaborators

• Ellodi Pharmaceuticals, LP: lead

Study Sites (56)

Pinnacle Research Group, LLC

Anniston, Alabama, 36207, United States

Location

Gut P.C., dba; Digestive Health Specialists of the Southeast

Dothan, Alabama, 36305, United States

Location

East View Medical Research, LLC

Mobile, Alabama, 36606, United States

Location

Del Sol Research Management, LLC

Tucson, Arizona, 85712, United States

Location

Preferred Research Partners Inc.

Little Rock, Arkansas, 72211, United States

Location

Arkansas Gastroenterology

North Little Rock, Arkansas, 72117, United States

Location

Camarillo Endoscopy Center

Camarillo, California, 93012, United States

Location

Hope Clinical Research

Canoga Park, California, 91303, United States

Location

Facey Medical Foundation

Mission Hills, California, 91345, United States

Location

United Medical Doctors

Murrieta, California, 92563, United States

Location

Medical Associates Research Group

San Diego, California, 92123, United States

Location

Asthma and Allergy Associates, PC

Colorado Springs, Colorado, 80907, United States

Location

Peak Gastroenterology Associates

Colorado Springs, Colorado, 80907, United States

Location

Western States Clinical Research Inc.

Wheat Ridge, Colorado, 80033, United States

Location

Western Connecticut Medical Group - Gastroenterology

Danbury, Connecticut, 06810, United States

Location

Medical Research Center of Connecticut, LLC

Hamden, Connecticut, 06518, United States

Location

Fleming Island Center for Clinical Research

Fleming Island, Florida, 32003, United States

Location

Nature Coast Clinical Research

Inverness, Florida, 34452, United States

Location

Encore Borland Groover Clinical Research

Jacksonville, Florida, 32256, United States

Location

Endoscopic Research, Inc.

Orlando, Florida, 32803, United States

Location

DBC Research USA

Pembroke Pines, Florida, 33029, United States

Location

Summit Clinical Research

Athens, Georgia, 30607, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

MGG Group Co., Inc., Chevy Chase Clinical Research

Chevy Chase, Maryland, 20815, United States

Location

Gastro Center of Maryland

Columbia, Maryland, 21045, United States

Location

Michigan Medicine, University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Clinical Research Institute of Michigan LLC

Chesterfield, Michigan, 48047, United States

Location

Henry Ford Health System

Novi, Michigan, 48377, United States

Location

West Michigan Clinical Research Center

Wyoming, Michigan, 49519, United States

Location

Minnesota Gastroenterology, P.A.

Plymouth, Minnesota, 55446, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Clinical Research Professionals

Chesterfield, Missouri, 63005, United States

Location

Bozeman Health GI Clinic

Bozeman, Montana, 59715, United States

Location

Long Island Gastrointestinal Research Group LLP

Great Neck, New York, 11023, United States

Location

University of North Carolina Health Systems (UNC Hospital)

Chapel Hill, North Carolina, 27599, United States

Location

Carolina Research

Greenville, North Carolina, 27834, United States

Location

Consultants for Clinical Research

Cincinnati, Ohio, 45219, United States

Location

Bernstein Clinical Research Center, LLC

Cincinnati, Ohio, 45231, United States

Location

Great Lakes Gastroenterology Research, LLC

Mentor, Ohio, 44060, United States

Location

Northshore Gastroenterology Research, LLC

Westlake, Ohio, 44145, United States

Location

Vital Prospects Clinical Research Institute, P.C.

Tulsa, Oklahoma, 74136, United States

Location

Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Digestive Disease Associates LTD

Wyomissing, Pennsylvania, 19610, United States

Location

Rapid City Medical Center LLP

Rapid City, South Dakota, 57701, United States

Location

DHAT Research Institute

Garland, Texas, 75044, United States

Location

Advanced Research Institute

Ogden, Utah, 84405, United States

Location

Verity Research, Inc.

Fairfax, Virginia, 22031, United States

Location

Blue Ridge Medical Research

Lynchburg, Virginia, 24502, United States

Location

St. Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Swallow Clinic, St George Hospital

Kogarah, New South Wales, 2217, Australia

Location

John Hunter Hospital

New Lambton, New South Wales, 2305, Australia

Location

Lyell McEwin Hospital

Elizabeth Vale, South Australia, 5112, Australia

Location

St. Vincent's Hospital

Fitzroy, Victoria, 3065, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Hosital General de Tomelloso

Tomelloso, Ciudad Real, 13700, Spain

Location

Hospital Universitario Ramón y Cajal (Madrid)

Madrid, 28034, Spain

Location

MeSH Terms

Conditions

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

Interventions

APT-1011; Fluticasone; Endoscopy, Digestive System

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures

Study Officials

• Evan Dellon, MD, MPH

  UNC Center for Eosphageal Diseases and Swallowing

  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: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2020
• First Posted: February 24, 2020
• Study Start: January 30, 2020
• Primary Completion: May 5, 2022
• Study Completion: October 24, 2022
• Last Updated: June 12, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (48); AU (6); ES (2)