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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04281108
Recruitment Status : Recruiting
First Posted : February 24, 2020
Last Update Posted : July 17, 2020
Sponsor:
Information provided by (Responsible Party):
Adare Pharmaceuticals, Inc.

Brief Summary:

This is a 2-part randomized, double-blind, placebo-controlled study of APT-1011 in adults and adolescents (≥15 years) 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.

Part B will evaluate histological relapse-free status in patients re-randomized to continue APT-1011 or placebo (active treatment withdrawal) until Week 52.


Condition or disease Intervention/treatment Phase
Eosinophilic Esophagitis Drug: APT-1011 Drug: Placebo oral tablet Phase 3

Detailed Description:

This is a 2-part randomized, double-blind, placebo-controlled study of APT-1011 in adults and adolescents (≥15 years) 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, placebo histological non-responders will receive APT-1011 3mg HS. Placebo histological responders will continue placebo. Histological relapse-free status will be determined at the time of EGD in Part B (at or prior to Week 52, depending on unscheduled EGDs) and is defined as ≤15 peak eos/hpf.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Fluticasone Propionate Oral Dispersible Tablet Formulation in Eosinophilic Esophagitis: A Two-Part, Randomized, Double-blind, Placebo-Controlled Study of APT-1011 in Adult and Adolescent Subjects With Eosinophilic Esophagitis
Actual Study Start Date : January 30, 2020
Estimated Primary Completion Date : October 31, 2021
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Experimental: APT-1011
APT-1011 3 mg HS
Drug: APT-1011
APT-1011 is an orally disintegrating tablet that includes fluticasone propionate as its active ingredient.
Other Name: fluticasone propionate

Placebo Comparator: Placebo
HS
Drug: Placebo oral tablet
Placebo orally disintegrating tablet.
Other Name: PBO




Primary Outcome Measures :
  1. Week 12 histologic responder rates [ Time Frame: Week 12 ]
    To compare the Week 12 histologic responder rates (≤ 6 peak eosinophils [eos]/high power field [HPF]) change from baseline 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 and 22mm ocular

  2. Mean change in number of dysphagia episodes [ Time Frame: Week 12 ]
    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

  3. Week 52 histologic relapse-free rates [ Time Frame: Week 12 to Week 52 ]
    To compare the Week 52 histologic relapse-free rates (≤ 15 peak eos/HPF) for APT-1011 3 mg responders in Part A randomized to continue APT-1011 3 mg HS (maintenance) with that for placebo (withdrawal of APT-1011 3 mg HS)

  4. Mean change in number of dysphagia episodes from Week 12 to Week 52 [ Time Frame: Week 12 to Week 52 ]
    To compare mean change in number of dysphagia episodes from Week 12 to Week 52 for APT-1011 responders randomized to continue APT-1011 3 mg HS with those randomized to placebo (withdrawal of APT-1011 3 mg HS)


Secondary Outcome Measures :
  1. Change in EREFs from Week 0 to Week 12 [ Time Frame: 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. EREFs version 4-19 grades features of edema, rings, exudates, furrows, stricture, and crepe paper esophagus on a scale from 0 to up to 3, with 0 indicating absence of symptoms.

  2. Percentage of subjects with <1 peak eos)/HPF at Week 12 [ Time Frame: Week 12 ]
    To compare the percentage of subjects with <1 peak eosinophils/high power field (eosinophils (eos)/HPF) at Week 12 for APT-1011 3 mg HS with that for placebo.

  3. Mean change in PROSE Symptom Burden Score [ Time Frame: Week 12 ]
    To compare the mean change from baseline to Week 12 in the episode-level symptom burden utilizing the Patient Reported Outcomes Symptoms of EoE (PROSE) for APT-1011 3 mg HS with that for placebo.

  4. Mean change in PROSE Episode-level Severity Score [ Time Frame: Week 12 ]
    To compare the mean change from baseline to Week 12 in the episode-level severity utilizing the Patient Reported Outcomes Symptoms of EoE (PROSE) for APT-1011 3 mg HS with that for placebo.

  5. Histological Change from Baseline to Week 12 [ Time Frame: Week 12 ]
    To compare mean histologic change from baseline to Week 12 for APT-1011 3 mg HS with that for placebo.

  6. Percentage of Subjects with <15 peak eos/HPF [ Time Frame: Week 12 ]
    To compare the percentage of subjects with <15 peak eosinophils/high power field (eos/HPF) for APT-1011 3 mg HS with that for placebo.

  7. Mean Number of Dysphagia-free Days [ Time Frame: Week 12 ]
    To compare the mean number of dysphagia-free days from baseline to Week 12 for APT-1011 3 mg HS with that for placebo

  8. Mean Change in Endoscopic Appearance [ Time Frame: Week 12 to Week 52 ]
    To compare endoscopic appearance evaluated by the mean change from Week 12 to the esophagogastroduodenoscopy (EGD) conducted in Part B (at or prior to Week 52) in 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).

  9. Mean Histological Change in EDG [ Time Frame: Week 12 to Week 52 ]
    To compare the mean histologic change from Week 12 to EDG conducted in Part B (at or prior to Week 52) for APT-1011 responders randomized to continue APT-1011 3 mg HS with responders randomized to placebo (withdrawal of APT-1011 3 mg HS)

  10. Mean Change in PROSE Symptom Burden Score [ Time Frame: Week 12 to Week 52 ]
    To compare mean change in the episode-level symptom burden using the Patient Reported Outcomes Symptoms of EoE (PROSE) instrument from Week 12 to EGD conducted in Part B (at or prior to Week 52) for APT-1011 responders randomized to continue APT-1011 3 mg HS with responders randomized to placebo (withdrawal of APT-1011 3 mg HS). PROSE is a patient diary instrument which includes measures of EoE symptoms scaled from 0-10, with 10 being most severe.

  11. Mean change in PROSE Episode-level Severity Score [ Time Frame: Week 2 to Week 52 ]
    To compare mean change in the episode-level severity using the Patient Reported Outcomes Symptoms of EoE (PROSE) from Week 12 to EGD conducted in Part B (at or prior to Week 52) for APT-1011 responders. randomized to continue APT-1011 3 mg HS with responders randomized to placebo (withdrawal of APT-1011 3 mg HS). PROSE is a patient diary instrument which includes measures of EoE symptoms scaled from 0-10, with 10 being most severe.

  12. Mean Number of Dysphagia-free Days [ Time Frame: Week 12 to Week 52 ]
    To compare the mean number of dysphagia-free days from Week 12 to EGD conducted in Part B (at or prior to Week 52) for APT-1011 responders randomized to continue APT-1011 3 mg HS with responders randomized to placebo (withdrawal of APT-1011 3 mg HS)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   15 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult male or female ≥15 years of age at the time of informed consent or assent
  2. Each subject and/or their parents or legal guardian (for adolescents), must read, understand and provide consent or assent together with their parent(s) or guardian signature (for adolescents) on the ICF for this study and be willing and able to adhere to study-related treatment regimens, procedures and visit schedule
  3. 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 5-6 biopsies should be taken including both proximal and distal specimens (~3 each). Mid-esophageal biopsies are optional

    1. Esophagogastroduodenoscopies and biopsies are to be obtained during the Screening period
    2. Biopsies will be read by a central pathologist
    3. Esophagogastroduodenoscopies and biopsies performed outside the study will not be accepted to meet eligibility criteria
    4. 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
  4. Have a subject-reported history of ≥6 episodes of dysphagia in the 14 days prior to baseline
  5. Completion of the daily diary on at least 11 out of the 14 days during the 2-week Baseline Symptom Assessment

Exclusion Criteria:

  1. Have known contraindication, hypersensitivity, or intolerance to corticosteroids
  2. 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
  3. Have history of an esophageal stricture requiring dilatation within the 12 weeks prior to Screening
  4. Bone age more than 12 months behind chronological age for adolescent subjects
  5. 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)
  6. History or presence of oral or esophageal mucosal infection whilst using inhaled or nasal corticosteroids
  7. Have any mouth or dental condition that prevents normal eating (excluding braces)
  8. 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;19, hiatus hernia longer than 3 cm, Barrett's esophagus, and achalasia)
  9. Use of systemic (oral or parenteral) corticosteroids within 60 days before Screening, use of swallowed corticosteroids within 30 days before Screening
  10. Initiation of either inhaled or nasal corticosteroids or high-potency dermal topical corticosteroids within 30 days before Screening
  11. Use of calcineurin inhibitors or purine analogues (azathioprine, 6-mercaptopurine) in the 12 weeks before Screening
  12. Use of potent cytochrome P450 (CYP) 3A4 inhibitors (eg, ritonavir and ketoconazole) in the 12 weeks before Screening
  13. Initiation of an elimination diet or elemental diet within 30 days before Screening (diet must remain stable after signing ICF)
  14. 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 administered intramuscularly (ie, an abnormal result on the ACTH stimulation test)
  15. 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)
  16. 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
  17. 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
  18. Infection with hepatitis B, hepatitis C, or human immunodeficiency virus
  19. Have gastrointestinal bleeding or documented active peptic ulcer within 4 weeks prior to Screening or entering a new study period
  20. 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
  21. Have immunosuppression, immunodeficiency, malignancy (except treated non-melanoma skin cancer), or known severe bleeding disorder
  22. Have a history or presence of Crohn's disease, celiac disease, or other inflammatory disease of the gastrointestinal tract, including eosinophilic gastroenteritis
  23. Have current drug abuse in the opinion of the Investigator.
  24. Have current alcohol abuse in the opinion of the Investigator.
  25. Female subjects who are pregnant, breastfeeding, or planning to become pregnant during the study
  26. Sexually active females of childbearing potential who do not agree to follow highly effective contraceptive methods through the End of Study visit (see Section 8.6.4 and Appendix 1)
  27. 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
  28. Have participated in a prior study with investigational product APT-1011

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04281108


Contacts
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Contact: Karol Knoop, RN, BS, CCRA (609) 450-1312 karol.knoop@adarepharma.com
Contact: Gina Eagle Taran, MD (609) 450-1312 gina.eagletaran@adarepharma.com

Locations
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United States, Alabama
Adare Pharmaceuticals Recruiting
Montgomery, Alabama, United States, 36013
United States, Arizona
Adare Pharmaceuticals Recruiting
Phoenix, Arizona, United States, 85003
United States, Arkansas
Adare Pharmaceuticals Recruiting
Little Rock, Arkansas, United States, 72201
United States, California
Adare Pharmaceuticals Recruiting
Sacramento, California, United States, 94203
United States, Colorado
Adare Pharmaceuticals Recruiting
Denver, Colorado, United States, 80012
United States, Connecticut
Adare Pharmaceuticals Recruiting
Hartford, Connecticut, United States, 06101
United States, Florida
Adare Pharmaceuticals Recruiting
Tallahassee, Florida, United States, 32301
United States, Georgia
Adare Pharmaceuticals Recruiting
Atlanta, Georgia, United States, 30301
United States, Illinois
Adare Pharmaceuticals Recruiting
Springfield, Illinois, United States, 62701
United States, Indiana
Adare Pharmaceuticals Withdrawn
Indianapolis, Indiana, United States, 46201
United States, Iowa
Adare Pharmaceuticals Recruiting
Des Moines, Iowa, United States, 50301
United States, Louisiana
Adare Pharmaceuticals Recruiting
Baton Rouge, Louisiana, United States, 70801
United States, Maryland
Adare Pharmaceuticals Recruiting
Annapolis, Maryland, United States, 21401
United States, Massachusetts
Adare Pharmaceuticals Recruiting
Boston, Massachusetts, United States, 02108
United States, Michigan
Adare Pharmaceuticals Recruiting
Lansing, Michigan, United States, 48901
United States, Minnesota
Adare Pharmaceuticals Recruiting
Saint Paul, Minnesota, United States, 55101
United States, Missouri
Adare Pharmaceuticals Recruiting
Jefferson City, Missouri, United States, 65101
United States, Montana
Adare Pharmaceuticals Recruiting
Helena, Montana, United States, 59601
United States, Nebraska
Adare Pharmaceuticals Recruiting
Lincoln, Nebraska, United States, 68501
United States, New York
Adare Pharmaceuticals Recruiting
Albany, New York, United States, 12201
United States, North Carolina
Adare Pharmaceuticals Recruiting
Raleigh, North Carolina, United States, 27601
United States, Ohio
Adare Pharmaceuticals Recruiting
Columbus, Ohio, United States, 43081
United States, Oklahoma
Adare Pharmaceuticals Recruiting
Oklahoma City, Oklahoma, United States, 73101
United States, Oregon
Adare Pharmaceuticals Recruiting
Salem, Oregon, United States, 97301
United States, Pennsylvania
Adare Pharmaceuticals Recruiting
Harrisburg, Pennsylvania, United States, 17101
United States, South Dakota
Adare Pharmaceuticals Recruiting
Pierre, South Dakota, United States, 57501
United States, Tennessee
Adare Pharmaceuticals Recruiting
Nashville, Tennessee, United States, 37201
United States, Texas
Adare Pharmaceuticals Recruiting
Austin, Texas, United States, 73301
United States, Utah
Adare Pharmaceuticals Not yet recruiting
Salt Lake City, Utah, United States, 84101
United States, Virginia
Adare Pharmaceuticals Recruiting
Richmond, Virginia, United States, 23173
United States, Washington
Adare Pharmaceuticals Not yet recruiting
Olympia, Washington, United States, 98501
Sponsors and Collaborators
Adare Pharmaceuticals, Inc.
Investigators
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Principal Investigator: Evan Dellon, MD, MPH UNC Center for Eosphageal Diseases and Swallowing
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Responsible Party: Adare Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04281108    
Other Study ID Numbers: SP-1011-003
First Posted: February 24, 2020    Key Record Dates
Last Update Posted: July 17, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Adare Pharmaceuticals, Inc.:
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
Additional relevant MeSH terms:
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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
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents