Clinical Trial Results:
A Phase II multicenter, placebo-controlled, proof-of-concept study evaluating the safety, and efficacy of intratympanic STR001 thermogel to preserve residual hearing in adults undergoing cochlear implant surgery
Summary
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EudraCT number |
2015-002672-25 |
Trial protocol |
DE ES IT |
Global end of trial date |
15 Nov 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Sep 2019
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First version publication date |
25 Sep 2019
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
STR001-201
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Strekin AG
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Sponsor organisation address |
Hochbergerstrasse 60C, Basel, Switzerland, 4057
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Public contact |
CEO, Strekin AG, 0041 797888252, Alexander.bausch@strekin.com
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Scientific contact |
CEO, Strekin AG, 0041 797888252, Alexander.bausch@strekin.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
22 Dec 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
15 Nov 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Nov 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the safety and tolerability of STR001 thermogel in patients receiving cochlear implants
To assess the efficacy of STR001 thermogel in preserving hearing 6 weeks after cochlear implant surgery as determined by average Pure Tone Audiometry (aPTA) values
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Protection of trial subjects |
Study reviewed by idependent ethics committees in all countries according to regulations. Subjects were treated within the usual setting and procedure of receiving a cochela implant surgery. In order to keep the potential adverse events of a local intratympanic injection lowest possible, the patient was put in a lying position and the study drug thermogel was put on body temperature before administration.
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Background therapy |
All patients eligible for the study were candidates to receive a cochlea implant surgery. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 Jan 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 26
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Country: Number of subjects enrolled |
France: 16
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Country: Number of subjects enrolled |
Germany: 66
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Country: Number of subjects enrolled |
Italy: 2
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Worldwide total number of subjects |
110
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EEA total number of subjects |
110
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
81
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From 65 to 84 years |
29
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85 years and over |
0
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Recruitment
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Recruitment details |
Recruitment period: 25-Jan-2015 to 06-Oct-2017 in 4 countries: Germany, France, Italy and Spain | |||||||||
Pre-assignment
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Screening details |
Patients were eligible for the study, if they had a moderate to severe hearing loss and were candidates to receive a cochlea implant surgery. No other specific screening details were required in the study. | |||||||||
Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer, Assessor | |||||||||
Blinding implementation details |
Since active and placebo suspension did not have the same appearance the syringe was prepared by an unblinded study site personnel and handed over with a cover (foil) to the investigator for study drug application.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Active Treatment | |||||||||
Arm description |
Receiving STR001 thermogel drug substance as an intratympanic injection | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
STR001 Thermogel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Dispersion for injection/infusion
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Routes of administration |
Auricular use
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Dosage and administration details |
STR001 1.2% Thermogel for application of 1ml as an intratympanal injection
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Arm title
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Placebo | |||||||||
Arm description |
Receiving STR001 Placebo Thermogel for intratympanic injection | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
STR001 Placebo Thermogel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Auricular use
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Dosage and administration details |
STR001 Placebo Thermogel for 1mL intratymanal injection of study drug
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Baseline characteristics reporting groups
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Reporting group title |
Active Treatment
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Reporting group description |
Receiving STR001 thermogel drug substance as an intratympanic injection | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Receiving STR001 Placebo Thermogel for intratympanic injection | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
ITT Analysis
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Includes all randomised patients. ITT patients will be analysed in the treatment group they were randomized to, regardless of the treatment they may have received.
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End points reporting groups
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Reporting group title |
Active Treatment
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Reporting group description |
Receiving STR001 thermogel drug substance as an intratympanic injection | ||
Reporting group title |
Placebo
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Reporting group description |
Receiving STR001 Placebo Thermogel for intratympanic injection | ||
Subject analysis set title |
ITT Analysis
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Includes all randomised patients. ITT patients will be analysed in the treatment group they were randomized to, regardless of the treatment they may have received.
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End point title |
Pure Tone Audiometry Threshold of the implanted ear as the average (aPTA) of the following frequencies: 125, 250, 500 and 750 Hz at Week 6 | ||||||||||||||||
End point description |
To assess the efficacy of STR001 thermogel in preserving hearing 6 weeks after
cochlear implant surgery as determined by average Pure Tone Audiometry (aPTA)
values
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End point type |
Primary
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End point timeframe |
Baseline - week 6
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Attachments |
Untitled (Filename: Efficacy chart for result posting.JPG) |
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Statistical analysis title |
aPTA (average pure tone audiometry threshold) | ||||||||||||||||
Statistical analysis description |
Descriptive statistics and change from baseline to Week 6, were performed on PTA values for original imputation method (no significant treatment effect favouring STR001 was detected, no conservative analysis performed)
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Comparison groups |
Placebo v Active Treatment
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Number of subjects included in analysis |
107
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | ||||||||||||||||
P-value |
< 5 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||
Point estimate |
10.5
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Confidence interval |
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95% | ||||||||||||||||
sides |
1-sided
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lower limit |
10.5 | ||||||||||||||||
upper limit |
- | ||||||||||||||||
Variability estimate |
Standard deviation
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Dispersion value |
20
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Notes [1] - The average postoperative hearing loss was in the same range for both treatment arms. For the STR001 arm the average hearing loss was 25±16 dB while for the placebo arm the average hearing loss was 27±16 dB. The nominal difference between the two groups was not statistically significant. The primary study objective was not met. |
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Adverse events information
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Timeframe for reporting adverse events |
Baseline - week 6
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19
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Reporting groups
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Reporting group title |
Active Treatment STR001
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Reporting group description |
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Reporting group title |
Placebo Treatment Group
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Reporting group description |
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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27 Oct 2015 |
Amendment 1 - non substantial
To clarify inconsistencies in Day numbering throughout the protocol. |
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19 Nov 2015 |
Amendment 2 - non substantial (France only)
To clarify vaccination eligibility -vaccination against Streptococcus pneumoniae must be allowed.
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24 Nov 2015 |
Amendment 3 - non substantial (Germany only)
to clarify sample size justification |
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04 Dec 2015 |
Amendment 4 - non substantial (Germany only)
to remove text in the protocol not applicable for study population. |
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26 Jan 2016 |
Amendment 5 - non substantial
To harmonize the inclusion criterion number 2 with the primary objective. |
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26 Jan 2016 |
Amendment 6 - non-substantial (France only)
To clarify vaccination eligibility following the request of the French Health Authorities. |
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09 Feb 2016 |
Amendment 7 - non-substantial (France only)
To address a request from the French Health Authorities in order to comply with eligibility criteria of patients for Cochlear Implant surgery in France. |
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25 Feb 2016 |
Amendment 8 - non-substantial
the average differences of BCTA and PTA are removed from the protocol as an inclusion criterion as well as in the definition of the efficacy analysis population. |
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10 Jun 2016 |
Amendment 9 - non-substantial
include more electrodes/increase age for inclusion criterion/add clarification of use of steroids/adapt number of countries and sites |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |