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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04281108




Registration number
NCT04281108
Ethics application status
Date submitted
20/02/2020
Date registered
24/02/2020
Date last updated
12/06/2023

Titles & IDs
Public title
Efficacy and Safety APT-1011 in Adult Subjects With Eosinophilic Esophagitis (EoE) (FLUTE-2)
Scientific 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
Secondary ID [1] 0 0
SP-1011-003
Universal Trial Number (UTN)
Trial acronym
FLUTE-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Eosinophilic Esophagitis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Inflammatory and Immune System 0 0 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - APT-1011
Treatment: Drugs - Placebo oral tablet
Treatment: Surgery - Esophagogastroduodenoscopy

Experimental: APT-1011 - APT-1011 3 mg HS

Placebo comparator: Placebo - HS


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

Treatment: Drugs: Placebo oral tablet
Placebo orally disintegrating tablet.

Treatment: Surgery: Esophagogastroduodenoscopy
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.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Week 12 histologic responder rates
Timepoint [1] 0 0
Week 12
Primary outcome [2] 0 0
Mean change in number of dysphagia episodes
Timepoint [2] 0 0
Week 0 to Week 12
Primary outcome [3] 0 0
Histologic responder rates at the end of the Randomized Withdrawal Phase (RWS)
Timepoint [3] 0 0
Week 12 to Week 52
Primary outcome [4] 0 0
Percentage subjects with complete symptomatic response at the end of the RWS
Timepoint [4] 0 0
Week 0 to Week 52
Secondary outcome [1] 0 0
Change in EREFs from Week 0 to Week 12
Timepoint [1] 0 0
Week 0 to Week 12
Secondary outcome [2] 0 0
Percentage of subjects with <1 peak eos/HPF at Week 12
Timepoint [2] 0 0
Week 12
Secondary outcome [3] 0 0
Mean change in PROSE Symptom Burden Score
Timepoint [3] 0 0
Week 0 to Week 12
Secondary outcome [4] 0 0
Mean Change in PROSE Day-Level Difficulty Swallowing
Timepoint [4] 0 0
Week 0 to Week 12
Secondary outcome [5] 0 0
Mean Histologic Change from Baseline to Week 12
Timepoint [5] 0 0
Week 0 to Week 12
Secondary outcome [6] 0 0
Percentage of Subjects with <15 peak eos/HPF
Timepoint [6] 0 0
Week 12
Secondary outcome [7] 0 0
Mean Number of Dysphagia-free Days
Timepoint [7] 0 0
Week 0 to Week 12
Secondary outcome [8] 0 0
Mean Change in Dysphagia Episodes
Timepoint [8] 0 0
Week 0 to Week 52
Secondary outcome [9] 0 0
Mean Change in EREFs from Week 0 to Week 52
Timepoint [9] 0 0
Week 0 to Week 52
Secondary outcome [10] 0 0
Mean Histologic Change
Timepoint [10] 0 0
Week 0 to Week 52
Secondary outcome [11] 0 0
Mean Change in PROSE Day-Level Symptom Burden
Timepoint [11] 0 0
Week 0 to Week 52
Secondary outcome [12] 0 0
Mean Change in PROSE Day-Level Difficulty Swallowing
Timepoint [12] 0 0
Week 0 to Week 52
Secondary outcome [13] 0 0
Mean Change in Dysphagia-Free Days
Timepoint [13] 0 0
Week 0 to Week 52
Secondary outcome [14] 0 0
Mean Change in Number of Dysphagia Episodes
Timepoint [14] 0 0
Week 0 to Week 52

Eligibility
Key inclusion criteria
1. Male or female =18 years of age at the time of informed consent or assent
2. 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
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 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.

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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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. 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
5. History or presence of oral or esophageal mucosal infection whilst using inhaled or nasal corticosteroids
6. Have any mouth or dental condition that prevents normal eating (excluding braces)
7. 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)
8. Use of systemic (oral or parenteral) corticosteroids within 60 days before Screening, use of swallowed corticosteroids within 30 days before Screening
9. Initiation of either inhaled or nasal corticosteroids or high-potency dermal topical corticosteroids within 30 days before Screening
10. Use of calcineurin inhibitors or purine analogues (azathioprine, 6-mercaptopurine) in the 12 weeks before Screening
11. Use of potent cytochrome P450 (CYP) 3A4 inhibitors (eg, ritonavir and ketoconazole) in the 12 weeks before Screening
12. Initiation of an elimination diet or elemental diet within 30 days before Screening (diet must remain stable after signing ICF)
13. 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)
14. 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)
15. 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
16. 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
17. Infection with hepatitis B, hepatitis C, or human immunodeficiency virus
18. Have gastrointestinal bleeding or documented active peptic ulcer within 4 weeks prior to Screening or entering a new study period
19. 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
20. Immunosuppression or immunodeficiency disorder
21. Have a history or presence of Crohn's disease, celiac disease, or other inflammatory disease of the gastrointestinal tract, including eosinophilic gastroenteritis
22. Have current drug abuse in the opinion of the Investigator.
23. Have current alcohol abuse in the opinion of the Investigator.
24. Female subjects who are pregnant, breastfeeding, or planning to become pregnant during the study
25. Sexually active females of childbearing potential who do not agree to follow highly effective contraceptive methods through the End of Study visit
26. 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
27. Have participated in a prior study with investigational product APT-1011

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/01/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/10/2022
Sample size
Target
Accrual to date
Final
143
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
St. Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [2] 0 0
Swallow Clinic, St George Hospital - Kogarah
Recruitment hospital [3] 0 0
John Hunter Hospital - New Lambton
Recruitment hospital [4] 0 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [5] 0 0
St. Vincent's Hospital - Fitzroy
Recruitment hospital [6] 0 0
Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
2305 - New Lambton
Recruitment postcode(s) [4] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [5] 0 0
3065 - Fitzroy
Recruitment postcode(s) [6] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Georgia
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Minnesota
Country [13] 0 0
United States of America
State/province [13] 0 0
Missouri
Country [14] 0 0
United States of America
State/province [14] 0 0
Montana
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Oklahoma
Country [19] 0 0
United States of America
State/province [19] 0 0
Pennsylvania
Country [20] 0 0
United States of America
State/province [20] 0 0
South Dakota
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Utah
Country [23] 0 0
United States of America
State/province [23] 0 0
Virginia
Country [24] 0 0
Spain
State/province [24] 0 0
Ciudad Real
Country [25] 0 0
Spain
State/province [25] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Ellodi Pharmaceuticals, LP
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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) 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.
Trial website
https://clinicaltrials.gov/study/NCT04281108
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Evan Dellon, MD, MPH
Address 0 0
UNC Center for Eosphageal Diseases and Swallowing
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04281108