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

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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.

Tracking Information
First Submitted Date  ICMJE February 20, 2020
First Posted Date  ICMJE February 24, 2020
Last Update Posted Date July 17, 2020
Actual Study Start Date  ICMJE January 30, 2020
Estimated Primary Completion Date October 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 20, 2020)
  • 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
  • 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
  • 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)
  • 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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2020)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
  • 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).
  • 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)
  • 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.
  • 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.
  • 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)
Original Secondary Outcome Measures  ICMJE
 (submitted: February 20, 2020)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
  • 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).
  • 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)
  • 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 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).
  • 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 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).
  • 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)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety APT-1011 in Subjects With Eosinophilic Esophagitis (EoE) (FLUTE-2)
Official Title  ICMJE 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
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Eosinophilic Esophagitis
Intervention  ICMJE
  • Drug: APT-1011
    APT-1011 is an orally disintegrating tablet that includes fluticasone propionate as its active ingredient.
    Other Name: fluticasone propionate
  • Drug: Placebo oral tablet
    Placebo orally disintegrating tablet.
    Other Name: PBO
Study Arms  ICMJE
  • Experimental: APT-1011
    APT-1011 3 mg HS
    Intervention: Drug: APT-1011
  • Placebo Comparator: Placebo
    HS
    Intervention: Drug: Placebo oral tablet
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 20, 2020)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date October 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 15 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04281108
Other Study ID Numbers  ICMJE SP-1011-003
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Adare Pharmaceuticals, Inc.
Study Sponsor  ICMJE Adare Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Evan Dellon, MD, MPH UNC Center for Eosphageal Diseases and Swallowing
PRS Account Adare Pharmaceuticals, Inc.
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP