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

NCT03191864 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: SP-1011-0022016-004749-10
• Study Type: interventional
• Target: 106
• Locations: 6 countries
• Sites: 75

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.

Conditions

Eosinophilic Esophagitis

Keywords

Esophagitis; Eosinophilic Esophagitis; Fluticasone; Dysphagia; Safety; Efficacy; Pharmacokinetics; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Glucocorticoids; Orally Disintegrating Tablet

Outcome Measures

Primary Outcomes (1)

• Percentage of Subjects With ≤6 Peak Eosinophils/High-power Field (HPF)

  Histology (eosinophils per high power field \[HPF\]): percentage of subjects with ≤6 PEAK eosinophils/HPF after assessing at least 5-6 biopsies from the proximal and distal esophagus (\~3 each) where the HPF area is 235 square microns (40 magnification lens with a 22 mm ocular).

  Week 12

Secondary Outcomes (15)

• Percentage of Subjects Who Met the Primary Endpoint at Week 12 and Maintained the Primary Endpoint at Weeks 26 and 52

  Week 26, and Week 52

• Change From Baseline Eosinophilic Esophagitis Endoscopic Reference Score (EREFs) at Week 12, 26, and 52

  Week 12, Week 26, and Week 52

• Percentage of Subjects With a Peak Eosinophils/HPF Number <1 and <15

  Week 12, Week 26, and Week 52

• Change From Baseline Global EoE Symptom Score

  Week 4, 8, 12, 14, 18, 22, 26, 28, 36, 44, and 52

• Change in the Number of Dysphagia Episodes

  Week 12, Week 26 and Week 52

Other Outcomes (5)

• Number of Subjects Discontinuing Due to HPA Axis Suppression

  baseline to Week 52

• Number of Subjects With Oral and Esophageal Candidiasis

  baseline to Week 52

• Number of Subjects With Treatment-Emergent Adverse Events Leading to Study Discontinuation in Part 1

  baseline to Week 12

Study Arms (5)

APT-1011 1.5 mg HS

EXPERIMENTAL

Placebo after breakfast, APT-1011 1.5 mg HS

Drug: APT-1011; Drug: Placebo

APT-1011 1.5 mg BID

EXPERIMENTAL

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

Drug: APT-1011

APT-1011 3 mg HS

EXPERIMENTAL

Placebo after breakfast, APT-1011 3 mg HS

Drug: APT-1011; Drug: Placebo

APT-1011 3 mg BID

EXPERIMENTAL

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

Drug: APT-1011

Placebo BID

PLACEBO COMPARATOR

Placebo 30 minutes after breakfast and HS

Drug: Placebo

Interventions

APT-1011 DRUG

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

Also known as: Fluticasone propionate ODT

APT-1011 1.5 mg BID; APT-1011 1.5 mg HS; APT-1011 3 mg BID; APT-1011 3 mg HS

Placebo DRUG

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

Also known as: Matching placebo dose

APT-1011 1.5 mg HS; APT-1011 3 mg HS; Placebo BID

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Adare Pharmaceuticals, Inc.: lead

Study Sites (75)

Del Sol Research Management, LLC

Chandler, Arizona, 85224, United States

Location

Del Sol Research Management, LLC

Tucson, Arizona, 85710, United States

Location

Arkansas Gastroenterology, P.A.

Sherwood, Arkansas, 72120, United States

Location

Hope Clinical Research

Canoga Park, California, 91303, United States

Location

TriWest Research Associates, LLC

El Cajon, California, 92020-4124, United States

Location

SC Clinical Research, Inc.

Garden Grove, California, 92844, United States

Location

Beverly Hills Center for Digestive Health

Los Angeles, California, 90048, United States

Location

Focilmed

Oxnard, California, 93030, United States

Location

Precision Research Institute, LLC

San Diego, California, 92114, United States

Location

Medical Associates Research Group, Inc.

San Diego, California, 92123, United States

Location

Care Access Research LLC

San Pablo, California, 94806, United States

Location

Stanford University School of Medicine

Stanford, California, 94305-2200, United States

Location

St. Jude Healthcare

Yorba Linda, California, 92886, United States

Location

Western Connecticut Health Network

Danbury, Connecticut, 06810, United States

Location

Medical Research Center of Connecticut, LLC

Hamden, Connecticut, 06518, United States

Location

Eastern Research, Inc.

Hialeah, Florida, 33013, United States

Location

Nature Coast Clinical Research, LLC

Inverness, Florida, 34452, United States

Location

Sunrise Medical Research

Lauderdale Lakes, Florida, 33319, United States

Location

DBC Research, Corp

Pembroke Pines, Florida, 33029, United States

Location

Northwestern Medical Faculty Foundation

Chicago, Illinois, 60611, United States

Location

Southwest Gastroenterology

Oak Lawn, Illinois, 60453-3767, United States

Location

Rockford Gastroenterology Associates, Ltd.

Rockford, Illinois, 61107, United States

Location

MediSphere Medical Research Center, an AMR affiliate

Evansville, Indiana, 47714, United States

Location

Cotton-O'Neil Clinical Research Center, Digestive Health

Topeka, Kansas, 66606, United States

Location

Gastroenterology Associates

Hazard, Kentucky, 41701, United States

Location

Clinical Trials of America, Inc.

West Monroe, Louisiana, 71291, United States

Location

Henry Ford Medical Center

Novi, Michigan, 48377-3600, United States

Location

Metro Health

Wyoming, Michigan, 49519, United States

Location

St. Louis Center for Clinical Research

St Louis, Missouri, 63128, United States

Location

Long Island Gastrointestinal Research Group, LLP

Great Neck, New York, 11023, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Research Institute of the Carolinas, PLC

Mooresville, North Carolina, 28117, United States

Location

Carolina's GI Research, LLC

Raleigh, North Carolina, 27607, United States

Location

Wake Research Associates, LLC

Raleigh, North Carolina, 27612, United States

Location

PMG Research of Salisbury, LLC

Salisbury, North Carolina, 28144, United States

Location

Bernstein Clinical Research Center, LLC

Cincinnati, Ohio, 45231, United States

Location

Aventiv Research Inc.

Columbus, Ohio, 43231, United States

Location

Unity Clinical Research

Oklahoma City, Oklahoma, 73118, United States

Location

Allergy and Asthma Center of South Oregon

Medford, Oregon, 97504, United States

Location

University of Pennsylvania

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

Advanced Gastroenterology

Union City, Tennessee, 38261, United States

Location

Avant Research Associates, LLC - Austin

Austin, Texas, 78704, United States

Location

Avant Research Associates, LLC

Beaumont, Texas, 77702, United States

Location

DHAT Research Institute

Richardson, Texas, 75082, United States

Location

Advanced Research Institute

Ogden, Utah, 84405, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Care Access Research LLC

Salt Lake City, Utah, 84124, United States

Location

Verity Research Inc

Fairfax, Virginia, 22031, United States

Location

AZ Sint-Lucas

Bruges, 8310, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

AZ Groeninge - Kennedylaan

Kortrijk, 8500, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

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

Vancouver, British Columbia, V6Z 2K5, Canada

Location

Viable Clinical Research

Bridgewater, Nova Scotia, B4V 3N2, Canada

Location

Viable Clinical Research

Lindsay, Ontario, K9V 5G6, Canada

Location

London Health Science Centre

London, Ontario, N6A 5A5, Canada

Location

Taunton Surgical Centre

Oshawa, Ontario, L1H 7K4, Canada

Location

Klinikum rechts der Isar der TU Muenchen

Munich, Bavaria, 81675, Germany

Location

Staedisches Klinikum Brandenburg

Brandenburg, Brandenburg, 14770, Germany

Location

Praxis am Germania

Münster, North Rhine-Westphalia, 48159, Germany

Location

Universitaetsklinikum Leipzig AoeR

Leipzig, Saxony, 4103, Germany

Location

Universitaetsklinikum Schleswig-Holstein

Kiel, Schleswig-Holstein, 24105, Germany

Location

Hospital General de Tomelloso

Tomelloso, Ciudad Real, 13700, Spain

Location

Hospital General Universitario de Alicante

Alicante, 3010, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Hospital Universitario de La Princesa

Madrid, 28006, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Clinico Universitario Lozano Blesa

Zaragoza, 50009, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, 1011, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 35181572 DERIVED

MeSH Terms

Conditions

Eosinophilic Esophagitis; Esophagitis; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Interventions

APT-1011

Condition Hierarchy (Ancestors)

Gastroenteritis; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Pharyngeal Diseases; Otorhinolaryngologic Diseases

Results Point of Contact

• Title: Senior Director Clinical Operations and Medical Affairs
• Organization: Ellodi Pharmaceuticals (Formerly Adare Pharmaceuticals)

karol.knoop@ellodipharma.com

(609) 450-1312

Study Officials

• Peter C Richardson

  Adare Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2017
• First Posted: June 19, 2017
• Study Start: June 22, 2017
• Primary Completion: January 3, 2019
• Study Completion: October 23, 2019
• Last Updated: April 26, 2023
• Results First Posted: April 26, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (9); CH (1); BE (4); US (51); CA (5); DE (5)