Efficacy, Safety, and Pharmacokinetics of APT-1011 in Subjects With Eosinophilic Esophagitis (EoE)

NCT ID: NCT03191864

Last Updated: 2023-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-22
• Study Completion Date: 2019-10-23

Brief Summary

Eosinophilic esophagitis (EoE) is an inflammatory disease of the esophagus, characterized by eosinophilic infiltration and gastrointestinal symptoms. Swallowed, topically acting corticosteroids, such as fluticasone, appear to be effective in resolving acute clinical and pathological features of EoE.

APT-1011 is an orally disintegrating tablet (ODT) formulation of fluticasone propionate. This study is designed to compare the efficacy and safety of APT-1011 with placebo in adults with EoE for an initial 12-week treatment period, followed by an additional 40-week maintenance treatment phase. Histologic response, pharmacokinetics, and dysphagia will be assessed.

Detailed Description

FLUTE is a phase 2b randomized, double-blind, placebo-controlled dose-ranging clinical trial of APT-1011 versus placebo in 100 adult subjects (≥18 years of age) diagnosed with EoE. Efficacy (including histologic, endoscopic, and symptomatic response), safety, and PK of APT-1011 will be examined. Participants will be given an electronic diary to record symptoms and medication intake daily.

FLUTE will be conducted in several parts (Screening [4 weeks], followed by a 4-week Baseline Symptom Assessment, and 2 treatment parts [Part 1: 14-week Induction and Part 2: 38-week Maintenance]), with a follow-up visit to occur 2 weeks after the final dose of study drug.

In Part 1 of the study, approximately 100 subjects will be randomized 1:1:1:1:1 to receive placebo or one of 4 active doses of APT-1011. All subjects will receive one tablet 30 minutes after breakfast and one tablet at bedtime (HS). The dosing groups include: 1.5 mg HS APT-1011, 1.5 mg twice daily (BID) (total daily dose of 3 mg) APT-1011, 3 mg HS APT-1011, and 3 mg BID (total daily dose of 6 mg) APT-1011, and placebo BID.

In Part 2, all subjects classified as histologic responders at Week 12 will continue to be treated according to the dosing group to which they were randomized, and non-responders will receive single-blind 3 mg BID. All subjects who are histologic non-responders at Week 26 will stop treatment at Week 28 and enter the 2-week follow-up and exit the study. Histologic responders at Week 26 will continue on the same dose until end-of-study at Week 52.

Subjects will complete a follow-up visit 2 weeks after the final dose of study drug. All subjects must have a final EGD within 3 weeks prior to completing the Follow-up Visit unless the subject withdraws consent or has a contraindication to EGD.

Conditions

Eosinophilic Esophagitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

APT-1011 1.5 mg HS

Placebo after breakfast, APT-1011 1.5 mg HS

Group Type: EXPERIMENTAL

APT-1011

Intervention Type: DRUG

APT-1011 is an orally disintegrating tablet formulation of fluticasone propionate

Placebo

Intervention Type: DRUG

Placebo tablets are identical in composition to APT-1011 except they exclude the active ingredient.

APT-1011 1.5 mg BID

APT-1011 1.5 mg after breakfast, APT-1011 1.5 mg HS

Group Type: EXPERIMENTAL

APT-1011

Intervention Type: DRUG

APT-1011 is an orally disintegrating tablet formulation of fluticasone propionate

APT-1011 3 mg HS

Placebo after breakfast, APT-1011 3 mg HS

Group Type: EXPERIMENTAL

APT-1011

Intervention Type: DRUG

APT-1011 is an orally disintegrating tablet formulation of fluticasone propionate

Placebo

Intervention Type: DRUG

Placebo tablets are identical in composition to APT-1011 except they exclude the active ingredient.

APT-1011 3 mg BID

APT-1011 3 mg after breakfast, APT-1011 3 mg HS

Group Type: EXPERIMENTAL

APT-1011

Intervention Type: DRUG

APT-1011 is an orally disintegrating tablet formulation of fluticasone propionate

Placebo BID

Placebo 30 minutes after breakfast and HS

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo tablets are identical in composition to APT-1011 except they exclude the active ingredient.

Interventions

APT-1011

APT-1011 is an orally disintegrating tablet formulation of fluticasone propionate

Intervention Type: DRUG

Placebo

Placebo tablets are identical in composition to APT-1011 except they exclude the active ingredient.

Intervention Type: DRUG

Other Intervention Names

Fluticasone propionate ODT; Matching placebo dose

Eligibility Criteria

Inclusion Criteria

• Male or female between ≥18 and ≤75 years of age at the time of informed consent
• Signed informed consent
• Evidence of EoE defined by ≥15 peak eosinophils per HPF as measured from proximal and distal biopsies
• Subject-reported history of ≥3 episodes of dysphagia in the 7 days prior to Screening
• 7-day Global EoE Symptom Score >3 at baseline and at screening
• Willing and able to adhere to study-related treatment regimens, procedures, and visit schedule

Exclusion Criteria

• Have known contraindication, hypersensitivity, or intolerance to corticosteroids;
• 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;
• Presence of oral or esophageal mucosal infection of any type;
• Have any mouth or dental condition that prevents normal eating;
• Have any condition affecting the esophageal mucosa or altering esophageal motility other than EoE;
• Use of systemic corticosteroids within 60 days prior to Screening, use of inhaled/swallowed corticosteroids within 30 days prior to Screening, or extended use of high-potency dermal topical corticosteroids within 30 days prior to Screening;
• Initiation of an elimination diet or elemental diet within 30 days before Screening (diet must remain stable after signing ICF);
• Morning serum cortisol level ≤5 μg/dL (138 nmol/L);
• Use of biologic immunomodulators in the 24 weeks prior to Screening;
• Use of calcineurin inhibitors or purine analogues, or potent cytochrome P450 (CYP) 3A4 inhibitors in the 12 weeks prior to Screening;
• Have a contraindication to or factors that substantially increase the risk of EGD or esophageal biopsy or have narrowing of the esophagus that precludes EGD with a standard 9 mm endoscope;
• Have a history of an esophageal stricture requiring dilatation within the previous 12 weeks prior to Screening;
• Have initiated, discontinued or changed dosage regimen of PPIs, H2 antagonists, antacids or antihistamines for any condition such as GERD or allergic rhinitis within 4 weeks prior to qualifying endoscopy. These drugs must remain constant throughout the study.
• A serum cortisol level <18 μg/dL (497 nmol/L) at 60 minutes with adrenocorticotropic hormone (ACTH) stimulation test using 250 μg cosyntropin (i.e., a positive result on the ACTH stimulation test).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Adare Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter C Richardson

Role: STUDY_DIRECTOR

Adare Pharmaceuticals, Inc.

Locations

Del Sol Research Management, LLC

Chandler, Arizona, United States

Del Sol Research Management, LLC

Tucson, Arizona, United States

Arkansas Gastroenterology, P.A.

Sherwood, Arkansas, United States

Hope Clinical Research

Canoga Park, California, United States

TriWest Research Associates, LLC

El Cajon, California, United States

SC Clinical Research, Inc.

Garden Grove, California, United States

Beverly Hills Center for Digestive Health

Los Angeles, California, United States

Focilmed

Oxnard, California, United States

Precision Research Institute, LLC

San Diego, California, United States

Medical Associates Research Group, Inc.

San Diego, California, United States

Care Access Research LLC

San Pablo, California, United States

Stanford University School of Medicine

Stanford, California, United States

St. Jude Healthcare

Yorba Linda, California, United States

Western Connecticut Health Network

Danbury, Connecticut, United States

Medical Research Center of Connecticut, LLC

Hamden, Connecticut, United States

Eastern Research, Inc.

Hialeah, Florida, United States

Nature Coast Clinical Research, LLC

Inverness, Florida, United States

Sunrise Medical Research

Lauderdale Lakes, Florida, United States

DBC Research, Corp

Pembroke Pines, Florida, United States

Northwestern Medical Faculty Foundation

Chicago, Illinois, United States

Southwest Gastroenterology

Oak Lawn, Illinois, United States

Rockford Gastroenterology Associates, Ltd.

Rockford, Illinois, United States

MediSphere Medical Research Center, an AMR affiliate

Evansville, Indiana, United States

Cotton-O'Neil Clinical Research Center, Digestive Health

Topeka, Kansas, United States

Gastroenterology Associates

Hazard, Kentucky, United States

Clinical Trials of America, Inc.

West Monroe, Louisiana, United States

Henry Ford Medical Center

Novi, Michigan, United States

Metro Health

Wyoming, Michigan, United States

St. Louis Center for Clinical Research

St Louis, Missouri, United States

Long Island Gastrointestinal Research Group, LLP

Great Neck, New York, United States

Weill Cornell Medical College

New York, New York, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Research Institute of the Carolinas, PLC

Mooresville, North Carolina, United States

Carolina's GI Research, LLC

Raleigh, North Carolina, United States

Wake Research Associates, LLC

Raleigh, North Carolina, United States

PMG Research of Salisbury, LLC

Salisbury, North Carolina, United States

Bernstein Clinical Research Center, LLC

Cincinnati, Ohio, United States

Aventiv Research Inc.

Columbus, Ohio, United States

Unity Clinical Research

Oklahoma City, Oklahoma, United States

Allergy and Asthma Center of South Oregon

Medford, Oregon, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Digestive Disease Associates, Ltd.

Wyomissing, Pennsylvania, United States

Rapid City Medical Center, LLP

Rapid City, South Dakota, United States

Advanced Gastroenterology

Union City, Tennessee, United States

Avant Research Associates, LLC - Austin

Austin, Texas, United States

Avant Research Associates, LLC

Beaumont, Texas, United States

DHAT Research Institute

Richardson, Texas, United States

Advanced Research Institute

Ogden, Utah, United States

University of Utah

Salt Lake City, Utah, United States

Care Access Research LLC

Salt Lake City, Utah, United States

Verity Research Inc

Fairfax, Virginia, United States

AZ Sint-Lucas

Bruges, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

AZ Groeninge - Kennedylaan

Kortrijk, , Belgium

UZ Leuven

Leuven, , Belgium

(G.I.R.I.) GI Research Institute

Vancouver, British Columbia, Canada

Viable Clinical Research

Bridgewater, Nova Scotia, Canada

Viable Clinical Research

Lindsay, Ontario, Canada

London Health Science Centre

London, Ontario, Canada

Taunton Surgical Centre

Oshawa, Ontario, Canada

Klinikum rechts der Isar der TU Muenchen

Munich, Bavaria, Germany

Staedisches Klinikum Brandenburg

Brandenburg, Brandenburg, Germany

Praxis am Germania

Münster, North Rhine-Westphalia, Germany

Universitaetsklinikum Leipzig AoeR

Leipzig, Saxony, Germany

Universitaetsklinikum Schleswig-Holstein

Kiel, Schleswig-Holstein, Germany

Hospital General de Tomelloso

Tomelloso, Ciudad Real, Spain

Hospital General Universitario de Alicante

Alicante, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Universitario de La Princesa

Madrid, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Hospital Clinico Universitario Lozano Blesa

Zaragoza, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Countries

United States; Belgium; Canada; Germany; Spain; Switzerland

References

Dellon ES, Lucendo AJ, Schlag C, Schoepfer AM, Falk GW, Eagle G, Nezamis J, Comer GM, Knoop K, Hirano I. Fluticasone Propionate Orally Disintegrating Tablet (APT-1011) for Eosinophilic Esophagitis: Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2022 Nov;20(11):2485-2494.e15. doi: 10.1016/j.cgh.2022.02.013. Epub 2022 Feb 16.

Reference Type: DERIVED

PMID: 35181572 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-004749-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SP-1011-002

Identifier Type: -

Identifier Source: org_study_id