E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Sudden Sensorineural Hearing Loss (SSHL) including
- idiopathic unilateral Sensorineural Hearing Loss
- acute uni- or bilateral acoustic trauma-induced Sensorineural Hearing Loss |
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E.1.1.1 | Medical condition in easily understood language |
Sudden Sensorineural Hearing Loss (SSHL) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Ear, nose and throat diseases [C09] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040016 |
E.1.2 | Term | Sensorineural hearing loss |
E.1.2 | System Organ Class | 100000004854 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | 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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E.2.2 | Secondary objectives of the trial |
The secondary objectives for this study are:
- To evaluate speech recognition improvement after 12 and 24 weeks
- To evaluate the percentage (%) of patients with complete hearing recovery after 12 and 24 weeks measured with PTA
- To evaluate hearing recovery (change in aPTA) after 4 weeks in all tested frequencies using PTA
-To evaluate hearing recovery after 4 weeks in all tested frequencies for the profound hearing los (>90 dB HL at baseline) subgroup
- To evaluate earing recovery after 12 weeks in all tested frequencies using PTA
-To evaluate hearing recovery after 12 weeks in all tested frequencies for the profound hearing loss (>90 dB HL at baseline) subgroup
- To evaluate tinnitus burden after 12 and 24 weeks
- To evaluate vertigo assessment after 12 and 24 weeks
- To evaluate the systemic exposure of STR001 after intratympanic administration of STR001-IT thermogel followed by oral STR001-ER treatment after 4 and 12 weeks. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must meet all of the following criteria in order to be eligible for this study:
1. Male or female patients aged ≥ 18
2. Patients with a SSHL within 96 hours of its perception
3. Sudden Sensorineural Hearing Loss including
a. idiopathic unilateral Sudden Sensorineural Hearing Loss or
b. acute uni- or bilateral acoustic trauma-induced Sudden Sensorineural Hearing Loss
4. Mean hearing threshold of ≥ 75 dB determined by PTA averaged at the three most affected contiguous frequencies.
5. Mean hearing loss of ≥ 50 dB averaged across the 3 PTA frequencies compared to the contralateral ear, or reference value (in case of asymmetric hearing loss prior to the current case or acute bilateral acoustic trauma-induced SSHL).
6. Patients with an otoscopically intact eardrum
7. Patients must be willing and capable to perform all study procedures
8. Patients must be able to provide informed consent
9. Females must have a negative pregnancy test or must be post- menopausal
10. Patients willing and able to use adequate hearing protection and to refrain from engaging in acitivities or work involving loud noise exposure where sufficient hearing protection is not possible or ensured
11. Able and willing to provide written informed consent and to comply with the study protocol according to ICH and local regulations. |
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E.4 | Principal exclusion criteria |
Patients who meet any of the following criteria by the day of randomization are not eligible for this study :
1. Patients with a history of Meniere’s Disease
2. Patients with endolymphatic, hydrops or history of fluctuating hearing loss
3. Patients with suspected perilymph fistula, membrane rupture, retrocochlear lesions or a barotrauma
4. Patients with an air-bone gap of ≥ 20 dB in one of the 3 contiguous frequencies at baseline (frequencies defined with inclusion criterion 4)
5. Previous SSHL incident at the same ear
6. Patients with acute or chronic otitis media or otitis externa.
7. Patients with congenital hearing loss
8. Patients with known hypersensitivity to pioglitazone, other thiazolidindiones or any formulation component
9. Use of thiazolidinedione (e.g. pioglitazone, rosiglitazone) in the last 6 months prior to baseline
10. Any use of CYP450 2C8 inducers (e.g. rifampicine)
11. Patients with therapy of fibrates (e.g. gemfibrozil, fenofibrate) in the last 6 months prior to baseline
12. Patients where oral administration of pioglitazone is contraindicated (i.e. cardiac failure or history of cardiac failure (NYHA stages I to IV), hepatic impairment, diabetic ketoacidosis, current bladder cancer or a history of bladder cancer, uninvestigated macroscopic haematuria
13. Women who are breastfeeding, pregnant or plan to get pregnant during the trial duration
14. Women of childbearing potential unwilling or unable to practice effective method of contraception
15. Participation in other clinical trials in the last month prior to baseline |
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E.5 End points |
E.5.1 | Primary end point(s) |
The Primary Efficacy assessment is at 12 weeks, of AHI (Average Hearing Improvement over the 3 contiguously affected baseline frequencies, using PTA, air conduction). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
There are two key secondary endpoints in this study:
- Measurement of speech recognition using a list with 20 words in local language at week 12 and 24.
- Determination of the percentage of patients with complete hearing recovery after 12 weeks as assessed by PTA and |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | 3 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 |
Czech Republic |
Germany |
Poland |
Russian Federation |
Switzerland |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 8 |
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 |