Clinical Trial Results:
A Phase III multicenter, double-blind, placebo-controlled, study evaluating the safety, and efficacy of STR001 treatment (intratympanic injection + tablets) in adults with Sudden Sensorineural Hearing Loss
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Summary
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EudraCT number |
2017-000242-22 |
Trial protocol |
DE CZ PL |
Global end of trial date |
06 Feb 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Sep 2020
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First version publication date |
10 Sep 2020
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Other versions |
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Summary report(s) |
STR001-202_Statistical Analysis of Efficacy of Primary and Key Secondary Endpoints |
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 |
STR001-202
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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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 |
Alexander Bausch, PhD
CEO, Strekin AG, +41 797888252, alexander.bausch@strekin.com
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Scientific contact |
Viktor Boerlin, MD
Chief Medical Officer, Strekin AG, +41 791267335, viktor.boerlin@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 |
27 Jul 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
06 Feb 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Feb 2020
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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 |
The primary objectives of this study are:
- To evaluate the safety and tolerability of intratympanic administration of STR001-IT thermogel followed by oral treatment with STR001-ER in patients with Sudden Sensorineural Hearing Loss
- To assess the efficacy of intratympanic administration of STR001-IT thermogel followed by oral treatment with STR001-ER in measuring hearing improvement at week 12 by PTA measurement at the 3 most contiguous affected frequencies seen at baseline
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Protection of trial subjects |
Study reviewed by independent ethics committees in all countries according to regulations. Subjects were treated within the usual settings in participating sites or were referred to them by practising ENT physicians.
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Background therapy |
All patients received the local standard of care for sudden sensorineural hearing loss, including a corticosteroid preparation. | ||
Evidence for comparator |
The comparison for STR001 intratympanic injection and STR001 tablets were placebo formulations. No generally approved drug for the treatment of sudden sensorineural hearing loss is available. | ||
Actual start date of recruitment |
01 Jun 2017
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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 |
Poland: 18
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Country: Number of subjects enrolled |
Czech Republic: 18
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Country: Number of subjects enrolled |
Germany: 29
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Country: Number of subjects enrolled |
Russian Federation: 84
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Country: Number of subjects enrolled |
Switzerland: 16
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Worldwide total number of subjects |
165
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EEA total number of subjects |
65
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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) |
126
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From 65 to 84 years |
39
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85 years and over |
0
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Recruitment
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Recruitment details |
Recruitment period: 01-06-2017 to 06-12-2019 in 5 countries: Czech Republic, Germany, Poland, Russian Federation and Switzerland. First patient randomized on 24-10-2017. | ||||||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Patients were recruited when they had noticed severe sudden hearing loss and contacted one of the participating sites or were referred to them by a ear-nose-throat doctor in practice. The patients had an audiogram and when the diagnosis of severe or profound sudden sensorineural hearing loss was confirmed, they were candidates for the study | ||||||||||||||||||||||||||||||||||||||||
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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 |
Investigator, Monitor, Data analyst, Carer, Assessor, Subject | ||||||||||||||||||||||||||||||||||||||||
Blinding implementation details |
Since active and placebo suspension in the ampoules did not have exactly the same appearance, the syringe was prepared by an independent study site person and handed with a cover to the injecting investigator. The active and placebo tablets were of identical appearance and were distributed to the patients in bottles.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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STR-5: Active Treatment | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients randomized to Arm 1 received an intratympanic injection of STR001 at Day 1 and underwent a 3-month oral treatment with STR001 tablets | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
STR001 thermogel and STR001-ER (tablets)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion, Tablet
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Routes of administration |
Auricular use, Oral use
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Dosage and administration details |
On Day 1 all patients in Arm1 received an intratympanic injection of STR001 thermogel. For the following three months the patients were provided with STR001 tablets containing 5 mg of pioglitazone once daily.
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Arm title
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STR-0: STR001 intratympanic injection + placebo tablets | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients in Arm 2 received an intratympanic injection of STR001 at Day1, For the following three months they received one placebo tablet per day. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
All patients received at Day 1 an intratympanal injection of STR001. For the following three months they received one tablet of placebo per day.
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Arm title
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Placebo | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients in Arm 3 received an intratympanic injection of placebo at Day 1 and for the following three months a placebo tablet per day. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo injection solution and placebo tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection, Tablet
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Routes of administration |
Intratympanic use , Oral use
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Dosage and administration details |
On Day 1 all patients in Arm3 received an intratympanic injection of placebo thermogel. For the following three months the patients were provided with placebo tablets once daily.
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Baseline characteristics reporting groups
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Reporting group title |
STR-5: Active Treatment
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Reporting group description |
Patients randomized to Arm 1 received an intratympanic injection of STR001 at Day 1 and underwent a 3-month oral treatment with STR001 tablets | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
STR-0: STR001 intratympanic injection + placebo tablets
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Reporting group description |
Patients in Arm 2 received an intratympanic injection of STR001 at Day1, For the following three months they received one placebo tablet per day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Patients in Arm 3 received an intratympanic injection of placebo at Day 1 and for the following three months a placebo tablet per day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Intention-to-treat
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Includes all randomized patients
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Subject analysis set title |
Safety Set
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Includes patients who have received at least one dose of study drug.
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Subject analysis set title |
Per Protocol Set
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Patients who completed the trial according to the protocol without major protocol violations influencing the efficacy results.
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End points reporting groups
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Reporting group title |
STR-5: Active Treatment
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Reporting group description |
Patients randomized to Arm 1 received an intratympanic injection of STR001 at Day 1 and underwent a 3-month oral treatment with STR001 tablets | ||
Reporting group title |
STR-0: STR001 intratympanic injection + placebo tablets
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Reporting group description |
Patients in Arm 2 received an intratympanic injection of STR001 at Day1, For the following three months they received one placebo tablet per day. | ||
Reporting group title |
Placebo
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Reporting group description |
Patients in Arm 3 received an intratympanic injection of placebo at Day 1 and for the following three months a placebo tablet per day. | ||
Subject analysis set title |
Intention-to-treat
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Includes all randomized patients
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Subject analysis set title |
Safety Set
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Includes patients who have received at least one dose of study drug.
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Subject analysis set title |
Per Protocol Set
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Patients who completed the trial according to the protocol without major protocol violations influencing the efficacy results.
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End point title |
Absolute hearing improvement using average pure tone audiogram thresholds [1] | ||||||||||||||||||||
End point description |
Improvement of absolute hearing measured as the average of the three most affected contiguous frequencies using pure tone audiometry.
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End point type |
Primary
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End point timeframe |
Baseline to Week 12
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The statistical analysis was planned in two steps: firstly the comparison of STR-5 and placebo for the endpoints, secondly the comparison of STR-0 and placebo. Details are in the attachment |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Improvement of speech recognition at 60 dB | |||||||||||||||
End point description |
Improvement in the percentage of 20 words in local language at 60dB understood
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End point type |
Secondary
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End point timeframe |
From Baseline to Week 12
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End point title |
Improvement in speech recognition at 80 dB | |||||||||||||||
End point description |
Improvement in the percentage of words out of 20 in local language understood at 80 dB
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End point type |
Secondary
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End point timeframe |
Baseline to Week 12
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| No statistical analyses for this end point | ||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Patients were followed for 24 Weeks after randomization. After Week 12, the patients did not receive any study medication.
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Adverse event reporting additional description |
Advere events were collected from patient reporting, physical findings and laboratory results.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20
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Reporting groups
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Reporting group title |
STR-5
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Reporting group description |
See description in the results section: STR001 intratympanic injection at Day1 followed by three months oral tablet treatment with 5 mg of STR001. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
STR-0
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Reporting group description |
Patients in this treatment group received at Day 1 an intratympanic injection of STR001, followed by three months once daily intake of a placebo tablet. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Patients received at Day 1 an intratympanic injection of placebo followed by a three months oral administration of placebo tablets once daily. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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Date |
Amendment |
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18 Feb 2018 |
Amendment 1 - substantial
- Change and clearer description of secondary study objectives
- Increase in severity of hearing loss from average pure tone audiometric threshold from 60 dB to 75 dB. Change in inclusion criterion 4.
- Removal of exclusion criterion 2: no upper limit of hearing threshold defined.
- Change in exclusion criterion 5: definition of air-bone gap in the most affected frequencies at baseline.
- Amendment of protective measures for contraception
- Change in storage condition requirement for study drug tablets
- Addition of hyperbaric oxygen therapy among the prohibited treatments during study
- Restriction of time frame to one month prior baseline for capturing medications in the eCRF
- Change for guidance in microscopic urinalysis (only if positive findings with dipstick)
- Reduction of blood safety parameters to be analysed
- Change in BCTA frequency assessment
- Plan for blinded interim analysis (not conducted eventually)
- Minor change in schedule of assessments |
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05 Jul 2019 |
Amendment 2 - considered administrative amendment
Change affected the timepoint of a blinded interim analysis for the primary endpoint. It was moved to the time when all patients had reached the Week 12 visit and terminated study treaments. This analysis was performed by an independent statistician and the study team were kept blinded with regard to individual data. |
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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. | |||
| The template did not allow to enter the statistical analyses data. Therefore they will be supplied by a summary attachment of the statistical analyses for the primary and the key secondary endpoint. | |||
