Clinical Trial Results:
A phase I/II multiple ascending dose open-label safety and efficacy study of the Notch Inhibitor LY3056480 in patients with mild to moderate sensorineural hearing loss.
Summary
|
|
EudraCT number |
2016-004544-10 |
Trial protocol |
GB GR DE |
Global end of trial date |
07 Oct 2020
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
31 Mar 2022
|
First version publication date |
31 Mar 2022
|
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 |
AUT-001
|
||
Additional study identifiers
|
|||
ISRCTN number |
ISRCTN59733689 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Audion Therapeutics BV
|
||
Sponsor organisation address |
Hogeweg 54, Amsterdam, Netherlands, 1098CE
|
||
Public contact |
Clinical Trial Information, Audion Therapeutics, 0031 o6 46767255, rjrutten@audiontherapeutics.com
|
||
Scientific contact |
Clinical Trial Information, Audion Therapeutics, 0031 06 46767255, rjrutten@audiontherapeutics.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 |
16 Jul 2021
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
07 Oct 2020
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
07 Oct 2020
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
The main objectives of this trial (Part B) are:
1. Main objective is to establish the efficacy of local treatment with LY3056480 in terms of hearing at 12 weeks;
2. To establish the efficacy of local treatment with LY3056480 in terms of hearing at 6 weeks;
3. To assess the safety and tolerance of local treatment with LY3056480
|
||
Protection of trial subjects |
Informed consent, insurance
|
||
Background therapy |
NA | ||
Evidence for comparator |
NA | ||
Actual start date of recruitment |
08 Nov 2017
|
||
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 |
United Kingdom: 39
|
||
Country: Number of subjects enrolled |
Germany: 12
|
||
Country: Number of subjects enrolled |
Greece: 8
|
||
Worldwide total number of subjects |
59
|
||
EEA total number of subjects |
20
|
||
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) |
44
|
||
From 65 to 84 years |
15
|
||
85 years and over |
0
|
|
|||||||||||
Recruitment
|
|||||||||||
Recruitment details |
From January 24 to October 17, 2018, 15 Phase I trial patients were enrolled at the UK site. From January 30 to August 5, 2019, 44 Phase IIa patients were enrolled in the UK (N=24), Germany (N=12) and Greece (N=8). | ||||||||||
Pre-assignment
|
|||||||||||
Screening details |
In phase I 27 patients were screened, N = 12 were not enrolled (Eligibility criteria = 8, Sponsor decision = 2, Withdrew consent = 3). In phase IIa 55 patients were screened, N = 11 were not enrolled (Eligibility criteria = 8, Withdrew consent = 3). | ||||||||||
Period 1
|
|||||||||||
Period 1 title |
Study duration (overall period)
|
||||||||||
Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
|
||||||||||
Blinding used |
Not blinded | ||||||||||
Blinding implementation details |
NA
|
||||||||||
Arms
|
|||||||||||
Arm title
|
LY3056480 | ||||||||||
Arm description |
In phase I three injections of LY3056480 were administered trans-tympanically into one ear. The patients were treated in ascending dose cohorts of 25µg, 125µg, 200µg and 250µg applied in a volume of 500 µl (sterile diluent). In phase IIa patients received three injections of 250µg of LY3056480 applied in 500 µL. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
LY3056480
|
||||||||||
Investigational medicinal product code |
LY3056480
|
||||||||||
Other name |
|||||||||||
Pharmaceutical forms |
Solution for injection
|
||||||||||
Routes of administration |
Transdermal use
|
||||||||||
Dosage and administration details |
Three injections of LY3056480 were administered trans-tympanically into one ear.
The patients were treated with 25µg, 125µg, 200µg and 250µg applied in a volume of 500 µl (sterile diluent).
|
||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Study duration (overall period)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
all subjects enrolled | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
LY3056480
|
||
Reporting group description |
In phase I three injections of LY3056480 were administered trans-tympanically into one ear. The patients were treated in ascending dose cohorts of 25µg, 125µg, 200µg and 250µg applied in a volume of 500 µl (sterile diluent). In phase IIa patients received three injections of 250µg of LY3056480 applied in 500 µL. | ||
Subject analysis set title |
Part B
|
||
Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
analysis partB
|
||
Subject analysis set title |
week12
|
||
Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
week 12
|
|
|||||||||||||
End point title |
PTA | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
3 months
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mixed-effect model | ||||||||||||
Statistical analysis description |
For Phase IIa we set a recruitment target of 40 patients, based on 87% power to detect a 10 dB(HL) change (standard deviation 20 dB(HL)) corresponding to an effect size of 0.5024. We performed exploratory analyses for all efficacy points of Phase IIa and subgroup analyses per trial site. A three-level linear mixed-effect model was used to account for repeated measures and the multilevel structure of the pure-tone audiometry and speech-in-noise data.
|
||||||||||||
Comparison groups |
LY3056480 v Part B
|
||||||||||||
Number of subjects included in analysis |
86
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
> 0.05 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
- | ||||||||||||
upper limit |
- | ||||||||||||
Variability estimate |
Standard deviation
|
|
|||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From informed consent until month 12
|
||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||
Dictionary version |
21.1
|
||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||
Reporting group title |
LY3056480
|
||||||||||||||||||||||||||||||
Reporting group description |
all patients who have received at least 1 dose of LY3056480 | ||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
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 |
||
01 Jun 2017 |
see protocol |
||
17 Jul 2017 |
see protocol |
||
20 Mar 2018 |
see protocol |
||
04 Dec 2018 |
see protocol |
||
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 |