Clinical Trial Results:
A randomized, placebo-controlled, double-blind trial evaluating the efficacy, tolerability and safety of ESO-101 in adult patients with active eosinophilic esophagitis
Summary
|
|
EudraCT number |
2020-000082-16 |
Trial protocol |
DE NL PL |
Global end of trial date |
09 Oct 2023
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
14 Jul 2024
|
First version publication date |
14 Jul 2024
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
ACESO
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT04849390 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
EsoCap AG
|
||
Sponsor organisation address |
Malzgasse 9, Basel, Switzerland, 4052
|
||
Public contact |
CEO, EsoCap AG, +43 69914950300, isabelle.racamier@esocapbiotech.com
|
||
Scientific contact |
CEO, EsoCap AG, +43 69914950300, isabelle.racamier@esocapbiotech.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
09 Oct 2023
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
09 Oct 2023
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
09 Oct 2023
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
To evaluate the efficacy based on the histological response
|
||
Protection of trial subjects |
This trial was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki, independent ethics committee (IEC) informed consent regulations, and ICH GCP Guidelines. In addition, all national and local regulatory requirements were followed. Before any clinical trial-related activities were performed, the investigator (or authorized designee)
reviewed the informed consent form and explained the trial to potential trial patients. The investigator ensured that the patient was fully informed about the aims, procedures, potential risks, any discomforts, and expected benefits of the clinical trial.
Insurance coverage for all participating patients was guaranteed according to applicable legal requirements.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Oct 2020
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Netherlands: 3
|
||
Country: Number of subjects enrolled |
Poland: 3
|
||
Country: Number of subjects enrolled |
Spain: 31
|
||
Country: Number of subjects enrolled |
Germany: 3
|
||
Country: Number of subjects enrolled |
Switzerland: 3
|
||
Worldwide total number of subjects |
43
|
||
EEA total number of subjects |
40
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
42
|
||
From 65 to 84 years |
1
|
||
85 years and over |
0
|
|
|||||||||||||||||||
Recruitment
|
|||||||||||||||||||
Recruitment details |
59 patients were screened: 9 patients at 2 centers in Germany, 6 patients at 2 centers in The Netherlands, 3 patients at 1 center in Poland, 38 patients at 8 centers in Spain, and 3 patients at 1 center in Switzerland. 16 patients were screening failures (6 in Germany, 3 in The Netherlands, and 7 in Spain) and 43 patients were randomized. | ||||||||||||||||||
Pre-assignment
|
|||||||||||||||||||
Screening details |
Patients who met all inclusion and none of the exclusion criteria were eligible to participate in the trial. | ||||||||||||||||||
Period 1
|
|||||||||||||||||||
Period 1 title |
Treatment period (overall period)
|
||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||
Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||
Blinding implementation details |
ESO-101 and placebo capsules were identical in appearance.
|
||||||||||||||||||
Arms
|
|||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||
Arm title
|
ESO-101 | ||||||||||||||||||
Arm description |
Dispersible polymer film (thin film) loaded with 800 µg mometasone furoate rolled in a hard gelatin capsule administered orally once-daily for 28 days. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
ESO-101
|
||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Oromucosal film, Capsule, hard
|
||||||||||||||||||
Routes of administration |
Oropharyngeal use
|
||||||||||||||||||
Dosage and administration details |
Patients took one oral capsule once daily in the evening at bedtime, ie, after eating dinner and after oral hygiene, for 28±2 consecutive days. Patients were not allowed to eat until they awoke the next morning and were not to drink for at least 2 hours after investigational medicinal product (IMP) intake.
|
||||||||||||||||||
Arm title
|
Placebo | ||||||||||||||||||
Arm description |
Dispersible polymer film (thin film) without drug substance rolled in a hard gelatin capsule administered orally once-daily for 28 days. | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
Placebo
|
||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Oromucosal film, Capsule, hard
|
||||||||||||||||||
Routes of administration |
Oropharyngeal use
|
||||||||||||||||||
Dosage and administration details |
Patients took one oral capsule once daily in the evening at bedtime, ie, after eating dinner and after oral hygiene, for 28±2 consecutive days. Patients were not allowed to eat until they awoke the next morning and were not to drink for at least 2 hours after IMP intake.
|
||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
ESO-101
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Dispersible polymer film (thin film) loaded with 800 µg mometasone furoate rolled in a hard gelatin capsule administered orally once-daily for 28 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Dispersible polymer film (thin film) without drug substance rolled in a hard gelatin capsule administered orally once-daily for 28 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
ESO-101
|
||
Reporting group description |
Dispersible polymer film (thin film) loaded with 800 µg mometasone furoate rolled in a hard gelatin capsule administered orally once-daily for 28 days. | ||
Reporting group title |
Placebo
|
||
Reporting group description |
Dispersible polymer film (thin film) without drug substance rolled in a hard gelatin capsule administered orally once-daily for 28 days. |
|
||||||||||||||||
End point title |
Change in peak eosinophil count | |||||||||||||||
End point description |
For the assessment of the eosinophil count, 6 biopsy samples of the esophagus were taken (2 each from the proximal, mid, and distal segment of the esophagus) at Visit 2 (Baseline) and Visit 5 (end of treatment [EOT]). In general only one biopsy per segment was analyzed. If the data were not conclusive, the second biopsy was analyzed. In each analyzed biopsy sample, the peak eosinophil count was determined in 3 hpfs. For the analysis all analyzed hpfs were considered. The number of eosinophils was normalized using a standard hpf size of 0.3 mm².
|
|||||||||||||||
End point type |
Primary
|
|||||||||||||||
End point timeframe |
Change from Baseline to EOT (Visit 5, Day 28)
|
|||||||||||||||
|
||||||||||||||||
Statistical analysis title |
Difference in change from Baseline | |||||||||||||||
Statistical analysis description |
The difference in the mean changes from Baseline between ESO-101 and placebo was tested using a 2-sided 2-sample t-test.
|
|||||||||||||||
Comparison groups |
ESO-101 v Placebo
|
|||||||||||||||
Number of subjects included in analysis |
40
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
equivalence [1] | |||||||||||||||
P-value |
= 0.0318 [2] | |||||||||||||||
Method |
t-test, 2-sided | |||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||
Point estimate |
-55.75
|
|||||||||||||||
Confidence interval |
||||||||||||||||
level |
95% | |||||||||||||||
sides |
2-sided
|
|||||||||||||||
lower limit |
-106.3 | |||||||||||||||
upper limit |
-5.2 | |||||||||||||||
Notes [1] - The null hypothesis was defined as H0: µ1 = µ2 with µ1 being the mean absolute chanage from Baseline to EOT in overall peak eosinophil count in the ESO-101 group and µ2 the mean absolute chanage from Baseline to EOT in overall peak eosinophil count in the placebo group. [2] - 5% confidence level |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From providing written informed consent until trial completion.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
ESO-101
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Dispersible polymer film (thin film) loaded with 800 µg mometasone furoate rolled in a hard gelatin capsule administered orally once-daily for 28 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Dispersible polymer film (thin film) without drug substance rolled in a hard gelatin capsule administered orally once-daily for 28 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
19 Oct 2021 |
Adaptation of 1 exclusion criterion for clarification and update of trial start and end dates |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |