E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute sensorineural hearing loss (ASNHL), which may be triggered by acoustic trauma, middle or inner ear surgery, i.e. known or evident insults to the inner ear. ASNHL may also result from a variety of other insults such as bacterial or viral infections, inflammation, vascular compromise, autoimmune disorders or mechanical damage, which may not be directly observable. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040016 |
E.1.2 | Term | Sensorineural hearing loss |
E.1.2 | System Organ Class | 10013993 - Ear and labyrinth disorders |
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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 objective of the study is the evaluation of the therapeutic benefit of a single intratympanic AM 111 injection in comparison to placebo in the treatment of acute sensorineural hearing loss (ASNHL) |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are (a) the confirmation of the safety and local tolerance of intratympanic AM 111 injection and (b) identification of the optimal dose of AM-111 in the treatment of ASNHL |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients with unilateral acute sensorineural hearing loss (ASNHL) with onset 48 hours or less ago • Mean hearing loss compared with the unaffected contralateral ear* of at least 30 dB in the 3 most affected contiguous frequencies • Age ≥ 18 years and ≤ 60 years • Negative pregnancy test for women of childbearing potential • Able to attend the on-study visits • Written informed consent before participation in the study
* For patients with asymmetric hearing or bilateral ASNHL resulting from acoustic trauma (most affected ear is treated), hearing loss is determined against a pre-existing audiogram (not older than 3 years), or, if no pre-existing audiogram is available, age- and sex-adjusted normative values according to ISO 7029:2000 (“Statistical distribution of hearing thresholds as a function of age adjusting for the age-related hearing loss”). |
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E.4 | Principal exclusion criteria |
• Bilateral ASNHL, if not resulting from acoustic trauma • Suspected perilymph fistula or membrane rupture • Barotrauma • Average air bone gap higher than 20 dB in 3 contiguous frequencies • History of Meniere disease, autoimmune hearing loss, radiation-induced hearing loss, endolymphatic hydrops, suspected retro-cochlear lesion or fluctuating hearing loss • Previous ASNHL incident within the past 6 weeks • Evidence of acute or chronic otitis media or otitis externa on examination • Any drug-based therapy for inner ear hearing loss that is ongoing or was performed in the past 2 weeks • Any therapy known as ototoxic (e.g. aminoglycosides, cisplatin, loop diuretics, quinine etc.) in the past 6 months prior to study inclusion
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E.5 End points |
E.5.1 | Primary end point(s) |
• The absolute improvement of PTA given in dB between D0 and D7 based on the average of the three most affected contiguous frequencies
• Number of patients with clinical significant hearing loss in the treated ear at D7 |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
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.8.3 |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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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6.4.2. Discontinuation of entire study Randomisation and patient enrolment will be stopped if based on a review of safety and tolerability data by the safety officer further treatments are deemed not acceptable.
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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 | |
E.8.9.1 | In the Member State concerned months | 15 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 15 |