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Eosinophilic EsophagitisPhase 3FLUTE-2NCT04281108

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

A Phase 3 study testing APT-1011 and Esophagogastroduodenoscopy in people with Eosinophilic Esophagitis, run by Ellodi Pharmaceuticals, LP at 56 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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)… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Eosinophilic Esophagitis
What is being tested?
APT-1011 and Esophagogastroduodenoscopy
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
143 participants
Where
56 sitesin 3 countries
Study dates
30 Jan 2020to 24 Oct 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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)
Show all 27Show fewer
  • 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
  • Subjects who have changed dosage regimen of PPIs within 8 weeks before qualifying endoscopy. If already receiving PPIs, the dosage must remain constant throughout the study
  • Infection with hepatitis B, hepatitis C, or human immunodeficiency virus
  • Have gastrointestinal bleeding or documented active peptic ulcer within 4 weeks prior to Screening or entering a new study period
  • 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
  • Immunosuppression or immunodeficiency disorder
  • Have a history or presence of Crohn's disease, celiac disease, or other inflammatory disease of the gastrointestinal tract, including eosinophilic gastroenteritis
  • Have current drug abuse in the opinion of the Investigator.
  • Have current alcohol abuse in the opinion of the Investigator.
  • Female subjects who are pregnant, breastfeeding, or planning to become pregnant during the study
  • Sexually active females of childbearing potential who do not agree to follow highly effective contraceptive methods through the End of Study visit
  • 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
  • Have participated in a prior study with investigational product APT-1011

Trial locations and contacts

56 sites in 3 countries.

56 sites in 3 countries

United States48 sites

  • Michigan Medicine, University of Michigan

    Ann Arbor, Michigan, 48109

  • Pinnacle Research Group, LLC

    Anniston, Alabama, 36207

  • Summit Clinical Research

    Athens, Georgia, 30607

  • Bozeman Health GI Clinic

    Bozeman, Montana, 59715

  • Camarillo Endoscopy Center

    Camarillo, California, 93012

  • Hope Clinical Research

    Canoga Park, California, 91303

  • University of North Carolina Health Systems (UNC Hospital)

    Chapel Hill, North Carolina, 27599

  • Clinical Research Institute of Michigan LLC

    Chesterfield, Michigan, 48047

  • Clinical Research Professionals

    Chesterfield, Missouri, 63005

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

    Chevy Chase, Maryland, 20815

  • Consultants for Clinical Research

    Cincinnati, Ohio, 45219

  • Bernstein Clinical Research Center, LLC

    Cincinnati, Ohio, 45231

  • Asthma and Allergy Associates, PC

    Colorado Springs, Colorado, 80907

  • Peak Gastroenterology Associates

    Colorado Springs, Colorado, 80907

  • Gastro Center of Maryland

    Columbia, Maryland, 21045

  • Western Connecticut Medical Group - Gastroenterology

    Danbury, Connecticut, 06810

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

    Dothan, Alabama, 36305

  • Verity Research, Inc.

    Fairfax, Virginia, 22031

  • Fleming Island Center for Clinical Research

    Fleming Island, Florida, 32003

  • DHAT Research Institute

    Garland, Texas, 75044

  • Long Island Gastrointestinal Research Group LLP

    Great Neck, New York, 11023

  • Carolina Research

    Greenville, North Carolina, 27834

  • Medical Research Center of Connecticut, LLC

    Hamden, Connecticut, 06518

  • Nature Coast Clinical Research

    Inverness, Florida, 34452

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • Encore Borland Groover Clinical Research

    Jacksonville, Florida, 32256

  • Preferred Research Partners Inc.

    Little Rock, Arkansas, 72211

  • Blue Ridge Medical Research

    Lynchburg, Virginia, 24502

  • Great Lakes Gastroenterology Research, LLC

    Mentor, Ohio, 44060

  • Facey Medical Foundation

    Mission Hills, California, 91345

  • East View Medical Research, LLC

    Mobile, Alabama, 36606

  • United Medical Doctors

    Murrieta, California, 92563

  • Arkansas Gastroenterology

    North Little Rock, Arkansas, 72117

  • Henry Ford Health System

    Novi, Michigan, 48377

  • Advanced Research Institute

    Ogden, Utah, 84405

  • Endoscopic Research, Inc.

    Orlando, Florida, 32803

  • DBC Research USA

    Pembroke Pines, Florida, 33029

  • Perelman Center for Advanced Medicine

    Philadelphia, Pennsylvania, 19104

  • Minnesota Gastroenterology, P.A.

    Plymouth, Minnesota, 55446

  • Rapid City Medical Center LLP

    Rapid City, South Dakota, 57701

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Medical Associates Research Group

    San Diego, California, 92123

  • Del Sol Research Management, LLC

    Tucson, Arizona, 85712

  • Vital Prospects Clinical Research Institute, P.C.

    Tulsa, Oklahoma, 74136

  • Northshore Gastroenterology Research, LLC

    Westlake, Ohio, 44145

  • Western States Clinical Research Inc.

    Wheat Ridge, Colorado, 80033

  • West Michigan Clinical Research Center

    Wyoming, Michigan, 49519

  • Digestive Disease Associates LTD

    Wyomissing, Pennsylvania, 19610

Other trials in United States

Australia6 sites

  • St. Vincent's Hospital Sydney

    Darlinghurst, New South Wales, 2010

  • Lyell McEwin Hospital

    Elizabeth Vale, South Australia, 5112

  • St. Vincent's Hospital

    Fitzroy, Victoria, 3065

  • Swallow Clinic, St George Hospital

    Kogarah, New South Wales, 2217

  • Alfred Hospital

    Melbourne, Victoria, 3004

  • John Hunter Hospital

    New Lambton, New South Wales, 2305

Other trials in Australia

Spain2 sites

  • Hospital Universitario Ramón y Cajal (Madrid)

    Madrid, 28034

  • Hosital General de Tomelloso

    Tomelloso, Ciudad Real, 13700

Other trials in Spain

About this study

Official title: Fluticasone Propionate Oral Dispersible Tablet Formulation in Eosinophilic Esophagitis: A Two-Part, Randomized, Double-blind, Placebo-Controlled Study of APT-1011 With an Open-label Extension, in Adult Subjects With Eosinophilic Esophagitis

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.

Read the detailed description

This is a 2-part randomized, double-blind, placebo-controlled study followed by an OLE of APT-1011 in adults with EoE.

Part A will evaluate the efficacy and safety of APT-1011 3 mg administered HS for the induction of response to treatment (histologic and symptomatic) over 12 weeks.

At Week 14, subjects will move into Part B. Subjects with histological response to APT-1011, defined as ≤6 peak eos/HPF, will be re-randomized to continue APT-1011 or receive placebo (active treatment withdrawal). APT-1011 histological non-responders will continue APT-1011, and placebo histological non-responders will receive APT-1011 3 mg HS. Placebo histological responders will continue placebo. The double-blind will be sustained throughout Part B. Histological responder status will be determined at the time of esophagogastroduodenoscopy (EGD) in Part B (at or prior to Week 52, depending on unscheduled EGDs performed when the Investigator deems the subject's symptoms necessitate EGD) and is defined as ≤6 peak eos/HPF.

At Week 52, subjects may enter Part C, an open-label single-arm extension phase, and continue study drug uninterrupted. Part C will terminate upon regulatory approval of APT-1011 or Sponsor termination of the study.

Being tested
APT-1011, Placebo oral tablet, Esophagogastroduodenoscopy
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
Medical subject headings
Eosinophilic Esophagitis, Esophagitis, Esophageal Diseases, Gastrointestinal Diseases, Digestive System Diseases, Gastroenteritis, Eosinophilia, Leukocyte Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • APT-1011Drug

    Also called fluticasone propionate

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

  • Placebo oral tabletDrug

    Also called PBO

    Placebo orally disintegrating tablet.

  • EsophagogastroduodenoscopyProcedure or surgery

    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 groups in NCT04281108
Study groupRoleWhat they receive
APT-1011ExperimentalAPT-1011 3 mg HS
Receives: Drug: APT-1011; Procedure: Esophagogastroduodenoscopy
PlaceboPlacebo comparatorHS
Receives: Drug: Placebo oral tablet; Procedure: Esophagogastroduodenoscopy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Week 12

  2. 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

    Measured: Week 0 to Week 12

  3. 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

    Measured: Week 12 to Week 52

  4. 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

    Measured: Week 0 to Week 52

Secondary outcomes (14)

  1. Change in EREFs from Week 0 to Week 12

    To compare endoscopic appearance evaluated by the mean change from baseline to Week 12 in Eosinophilic Esophagitis Endoscopic Reference Score (EREFs) for APT-1011 3 mg HS with that for placebo.

    Measured: Week 0 to Week 12

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

    To compare the percentage of subjects with <1 peak eos/HPF at Week 12 for APT-1011 3 mg HS with that for placebo.

    Measured: Week 12

  3. Mean change in PROSE Symptom Burden Score

    To compare the mean change from baseline to Week 12 in the day-level symptom burden utilizing the Patient Reported Outcomes Symptoms of EoE (PROSE) for APT-1011 3 mg HS with that for placebo.

    Measured: Week 0 to Week 12

  4. Mean Change in PROSE Day-Level Difficulty Swallowing

    To compare the mean change from baseline to Week 12 in day-level difficulty swallowing using the Patient Reported Outcomes Symptoms of EoE (PROSE) for APT-1011 3 mg HS with that for placebo. Each symptom is rated on a numeric rating scale (NRS) with values ranging from 0 (not at all) to 10 (as bad as I can imagine).

    Measured: Week 0 to Week 12

  5. Mean Histologic Change from Baseline to Week 12

    To compare mean histologic change from baseline to Week 12 for APT-1011 3 mg HS with that for placebo.

    Measured: Week 0 to Week 12

  6. Percentage of Subjects with <15 peak eos/HPF

    To compare the percentage of subjects with <15 peak eos/HPF for APT-1011 3 mg HS with that for placebo.

    Measured: Week 12

  7. Mean Number of Dysphagia-free Days

    To compare the mean number of dysphagia-free days from baseline to Week 12 for APT-1011 3 mg HS with that for placebo

    Measured: Week 0 to Week 12

  8. Mean Change in Dysphagia Episodes

    To compare mean change in number of dysphagia episodes from baseline to the end of RWS for APT-1011 responders randomized to continue APT-1011 3 mg HS with responders randomized to placebo (withdrawal of APT-1011 3 mg HS)

    Measured: Week 0 to Week 52

  9. Mean Change in EREFs from Week 0 to Week 52

    To compare endoscopic appearance evaluated by the mean change from baseline to the end of RWS, in Eosinophilic Esophagitis Endoscopic Reference Score (EREFs) for APT-1011 responders randomized to continue APT-1011 3 mg HS with responders randomized to placebo (withdrawal of APT-1011 3 mg HS). The EREF score has a range from 0-9, with 9 being worst result.

    Measured: Week 0 to Week 52

  10. Mean Histologic Change

    To compare the mean change from baseline to the end of the RWS in peak eosinophil counts for APT-1011 responders randomized to APT-1011 3 mg HS with those randomized to placebo in the RWS.

    Measured: Week 0 to Week 52

  11. Mean Change in PROSE Day-Level Symptom Burden

    To compare the mean change in day-level symptom burden using the Patient Reported Outcomes Symptoms of EoE (PROSE) from baseline to the end of RWS, for APT-1011 responders randomized to continue APT-1011 3 mg HS with responders randomized to placebo (withdrawal of APT-1011 3 mg HS). Day-level symptom burden has values ranging from 0 (no symptoms) to 10 (symptoms are as bad as I can imagine).

    Measured: Week 0 to Week 52

  12. Mean Change in PROSE Day-Level Difficulty Swallowing

    To compare the mean change in day-level difficulty swallowing using the Patient Reported Outcomes Symptoms of EoE (PROSE) from baseline to the end of randomized withdrawal phase, for APT-1011 responders randomized to continue APT-1011 3 mg HS with responders randomized to placebo (withdrawal of APT-1011 3 mg HS). Each symptom is rated on a numeric rating scale (NRS) with values ranging from 0 (not at all) to 10 (as bad as I can imagine).

    Measured: Week 0 to Week 52

  13. Mean Change in Dysphagia-Free Days

    To compare the mean number of dysphagia-free days from baseline to the end of RWS, for APT-1011 responders randomized to continue APT-1011 3 mg HS with responders randomized to placebo (withdrawal of APT-1011 3 mg HS)

    Measured: Week 0 to Week 52

  14. Mean Change in Number of Dysphagia Episodes

    To compare mean change in number of dysphagia episodes from baseline at or prior to Week 52 (based on timing of > 6 peak eos/HPF) for APT-1011 responders randomized to continue APT-1011 3 mg HS with those randomized to placebo (withdrawal of APT-1011 3 mg HS)

    Measured: Week 0 to Week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Feb 2020
  2. Study start30 Jan 2020
  3. Primary completion5 May 2022
  4. Study completion24 Oct 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
143 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04281108
Sponsor's protocol ID
SP-1011-003
Acronym
FLUTE-2
Status last verified
Jun 2023
First submitted
20 Feb 2020
Last updated
12 Jun 2023
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing APT-1011 and Esophagogastroduodenoscopy in people with Eosinophilic Esophagitis, run by Ellodi Pharmaceuticals, LP at 56 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 56 sites in United States, Australia, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Week 12 histologic responder rates (time frame: Week 12). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04281108.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2023.

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