E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064220 |
E.1.2 | Term | Eosinophilic esophagitis |
E.1.2 | System Organ Class | 100000004856 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Part A co-primary objectives:
To compare the Week 12 histologic responder rates (≤ 6 peak eosinophils [eos]/high power field [HPF]) for APT-1011 3 mg hora somni (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
To compare mean change in number of dysphagia episodes from baseline to Week 12 for APT-1011 3 mg HS with that for placebo
Part B key objectives:
To compare the Week 52 histologic relapse-free rates (≤ 15 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)
To compare mean change in number of dysphagia episodes from Week 12 at or prior Week 52 (based on timing of histologic relapse) for APT-1011 responders randomized to continue APT-1011 3 mg HS with responders randomized to placebo (withdrawal of APT-1011 3 mg HS) |
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E.2.2 | Secondary objectives of the trial |
Part A secondary objectives
To compare endoscopic appearance evaluated by the mean change from baseline to Week 12 in REFs for APT-1011 3 mg HS with that for placebo
To compare the percentage of subjects with <1 peak eos/high power field at Week 12 for APT-1011 3 mg HS with that for placebo.
Part B secondary objectives
To compare endoscopic appearance evaluated by the mean change from Week 12 to the first 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)
To compare the mean histologic change 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)
See the entire list in the protocol section Objectives in Page 4 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult male or female ≥12 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 6 biopsies should be taken from 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 and 22mm ocular.
a) Esophagogastroduodenoscopies and biopsies are to be obtained during the Screening period
b) Biopsies will be read by a central pathologist
c) Esophagogastroduodenoscopies and biopsies performed outside the study will not be accepted to meet eligibility criteria
d) Optional biopsies may be taken and processed locally for local use, only where 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 |
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E.4 | Principal 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 previous 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 of recurrent or current oral or esophageal mucosal infection due to inhaled or nasal corticosteroids
7. Have any mouth or dental condition that prevents normal eating
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; 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, leukotriene inhibitors or sodium cromolyn within 4 weeks before qualifying endoscopy. 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 high endemic areas should be assessed locally for tuberculosis before consideration for the study
21. Immunosuppression or immunodeficiency disorder
22. Current malignancy or malignancy within 3 years of Screening. Subjects in remission for at least 3 years post-treatment may be enrolled.
23. Known severe bleeding disorder
24. Have a history or presence of Crohn’s disease, celiac disease, or other inflammatory disease of the gastrointestinal tract, including eosinophilic gastroenteriti
25. Have current drug abuse in the opinion of the Investigator.
26. Have current alcohol abuse in the opinion of the Investigator.
27. Female subjects who are pregnant, breastfeeding, or planning to become pregnant during the study
28. Sexually active females of childbearing potential who do not agree to follow highly effective contraceptive methods through the End of Study visit (see Section 9.6.4 and Appendix 1)
29. 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
30. Have participated in a prior study with investigational product APT-1011 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part A co-primary endpoints:
Percentage of subjects who are histological responders (achieve ≤6 peak eos/HPF) at Week 12
Mean change from baseline to Week 12 in number of dysphagia episodes
Part B key endpoints:
Percentage of APT-1011 responders in Part A who relapse histologically (>15 peak eos/HPF) by Week 52
Mean change from Week 12 in Part A responders in number of dysphagia episodes at time of EGD at or before Week 52 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Part A co-primary endpoints:
at Week 12
from baseline to Week 12
Part B key endpoints:
by Week 52 in Part A
from Week 12 in Part A and at or before Week 52 |
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E.5.2 | Secondary end point(s) |
Part A secondary endpoints:
Mean change from baseline in mean EREFs at Week 12
Percentage of subjects who achieve <1 eos/HPF at Week 12
Mean change from baseline in mean day-level symptom burden (PROSE) at Week 12
Mean change from baseline in mean day-level severity (PROSE) at Week 12
Mean change from baseline in mean eosinophils per HPF at Week 12
Percentage of subjects who achieve <15 eos/HPF at Week 12
Mean change from baseline in mean number of dysphagia-free days at Week 12
Part B secondary endpoints:
Mean change from Week 12 in Part A responders in mean EREF scores at time of EGD at or before Week 52
Mean change from Week 12 in Part A responders in mean eosinophils per high power field at time of EGD at or before Week 52
Mean change from Week 12 in Part A responders in day-level symptom burden using the PROSE at time of EGD at or before Week 52
Mean change from Week 12 in Part A responders in day-level severity using the PROSE at time of EGD at or before Week 52
Mean change from Week 12 in Part A responders in mean number of dysphagia-free days at time of EGD at or before Week 52 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Part A secondary endpoints:
from baseline at Week 12
at Week 12
from baseline at Week 12
from baseline at Week 12
from baseline at Week 12
at Week 12
from baseline at Week 12
Part B secondary endpoints:
from Week 12 in Part A or before Week 52
from Week 12 in Part A or before Week 52
from Week 12 in Part A or before Week 52
from Week 12 in Part A or before Week 52
from Week 12 in Part A or before Week 52 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Germany |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 17 |