A Study to Evaluate the Efficacy, Safety and Tolerability of a Single Injection of AC102 into the Middle Ear Compared to Oral Steroid Treatment in Patients with Sudden Hearing Loss.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AudioCure Pharma GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Otorhinolaryngologic Diseases [C09]

Trial duration

8 Aug 2022 → 16 Jan 2026

Decision date (initial)

2024-07-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

AudioCure Pharma GmbH

External identifiers

EU CT number

2024-513658-31-00

EudraCT number

2021-004323-33

ClinicalTrials.gov

NCT05776459

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

Efficacy of a single dose administration of AC102 compared to oral steroids in patients with moderately-severe to profound ISSNHL. The evaluation will be based on the improvement of the hearing threshold (average of the three most affected consecutive frequencies) tested by pure tone audiometry from baseline to Day 28.

Secondary objectives 7

1. Improvement of the hearing threshold over the time course of the whole study duration (up to Day 84) tested by pure tone audiometry in all patients in the subgroup of patients with a baseline hearing ≥80 dB
2. Improvement of speech recognition in quiet over the time course of the study focusing on the final test at Day 84
3. Incidence of complete, partial and no recovery
4. Percentage of patients eligible for salvage therapy
5. Improvement of Hearing Handicap Inventory Score/ Quality of Life
6. Safety and tolerability
7. Incidence of patients qualifying for a hearing aid or a cochlear implant

Conditions and MedDRA coding

Idiopathic Sudden Sensorineural Hearing Loss

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Signed Institutional Review Board (IRB) / Independent Ethics Committee (IEC) approved informed consent form (ICF)
2. Female or male patients aged between 18 and 85 years (inclusive) at the day of Screening
3. Unilateral ISSNHL
4. Onset of unilateral ISSNHL between 24 to 120 hours prior to randomization
5. Patients with an absolute air conduction hearing threshold of at least 65 dB (average of the three most affected consecutive frequencies between 0.25 and 8 kHz)
6. Patients with a relative hearing loss of at least 30 dB compared to the current audiogram of the non-affected ear (average of the three most affected consecutive frequencies between 0.25 and 8 kHz).
7. Willing and able to attend the trial visits
8. Able to read and understand trial documents and follow Investigator and trial personnel instructions during visits. Willing and able to comply with procedures of audiological assessments (in particular pure tone audiometry and speech audiometry).
9. Female patients must meet one of the following criteria: - If of childbearing potential – have a negative urine pregnancy test and agree to use a highly effective medically accepted contraceptive method for at least 30 days after the last study medication intake. - If of non-childbearing potential – should be surgically sterile (i.e. has undergone complete hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or in a postmenopausal state (at least one year without menses at Screening).Male patients with sexual partners who could become pregnant must meet the following criteria:- Patient is unable to procreate, defined as surgically sterile (i.e. has undergone a vasectomy at last 6 months before Screening) -Patient agrees to use one of the accepted contraceptive regimens for at least 30 days after the last study medication intake

Exclusion criteria 27

1. Insufficient handling of the language used in the speech audiometry tests
2. a) Bilateral hearing loss b) Sudden hearing loss in the only hearing ear (i.e. pre-existing hearing loss in the contralateral ear of 40 dB or more measured by PTA in the range of 0.5-4 kHz)
3. Acute hearing loss from noise trauma, barotrauma or head trauma in either ear at any time
4. Congenital hearing loss
5. Conductive hearing loss or combined hearing loss (determined by a 4PTA > 10 dB). Only if the limit for bone conduction is reached, tympanogram type can be used (other than A).
6. Suspected perilymph fistula or round window membrane rupture in either ear
7. Otitis media or otitis externa that is ongoing or ended within 30 days prior to randomization or is occurring several times per year
8. Patients with abnormality of the tympanic membrane or the outer ear canal that would preclude intratympanic administration
9. Evidence or history of vestibular schwannoma (acoustic neuroma) or other retrocochlear damage in the affected ear
10. History of ISSNHL in the past 1 year in the affected ear.
11. History of radiation-induced hearing loss, fluctuating hearing, endolymphatic hydrops or Menière’s disease in either ear
12. History of chronic inflammatory or chronic suppurative ear disease or cholesteatoma in the affected ear
13. History of otosclerosis in the affected ear
14. Family history of hearing impairment other than age-related
15. If one of the following diseases is known: - Active disease and/or confirmed infection with immunodeficiency virus (HIV),- Active hepatitis B or hepatitis C virus infection; - Systemic mycosis and parasitosis (amoebic or worm infections) ; - Acute and chronic bacterial infections; -History of or active tubercolosis; - Severe osteoporosis; - Narrow and wide-angle glaucoma, corneal ulceration and corneal injury; -Severe ulcerative colitis with impending perforation, with abscesses or purulent inflammations; - Exercise-induced angina, known class III or IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system; - Gastric or duodenal ulcer, existing or treated within <1 year prior to randomization; -Myasthenia gravis o Patients with diagnosed anxiety disorders, psychosis, depression, schizophrenia, suicidal ideation or other significant psychiatric conditions. Inclusion only after critical evaluation by the Investigator
16. Uncontrolled systolic (>180 mmHg) or diastolic (>100 mmHg) blood pressure at Screening
17. Difficult to control diabetes
18. Treatment with medication listed in 4.4 of the protocol
19. Patients who have answered “yes” to questions 4 or 5 of the C-SSRS
20. Hypersensitivity to prednisolone
21. Concurrent participation in another clinical study or participation in another clinical study within 30 days or 5 half-lives of the respective experimental drug (whichever is longer) prior to Screening Visit
22. Women who are breast feeding, pregnant or plan to become pregnant during the study or women of childbearing potential who are unwilling or unable to practice an effective method of contraception
23. Patients who are involved in the organization of the clinical investigation or are in any way dependent on the Investigator or Sponsor
24. Major surgery within eight weeks before Screening or scheduled/planned surgery within the time frame of the study
25. Medical reasons which, in the opinion of the Investigator, preclude inclusion in the study
26. Legal incapacity or limited legal capacity
27. Patients who have been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean change in absolute hearing thresholds (average of the three most affected consecutive frequencies from 0.25 to 8 kHz) measured by PTA from baseline to Day 28

Secondary endpoints 8

1. Absolute improvement of speech recognition from baseline to Day 84
2. Mean change in absolute hearing thresholds of PTA from baseline to Day 14, 56 and 84 at the three mostly affected consecutive frequencies and mean change of 4PTA (PTA at the frequencies 0.5, 1, 2, and 4 kHz)
3. Percentage of patients with complete, partial or no remission on Day 28, 56 and 84 (no recovery: ≤ 10 dB, complete: within 10 dB to the contralateral ear)
4. Percentage of patients qualifying for a hearing aid or a cochlear implant at Day 84
5. Absolute improvement of speech recognition in quiet from baseline to Day 14, 28 and 56
6. Percentage of patients eligible for salvage therapy
7. Improvement of scoring in HHIA from baseline to Day 28 and 84
8. Mean change in absolute hearing thresholds of PTA from baseline to Day 14, 28, 56 and 84 at the three mostly affected consecutive frequencies and mean change of 4PTA (PTA at the frequencies 0.5, 1, 2, and 4 kHz) in patients with a baseline hearing threshold of ≥80 dB

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AudioCure Pharma GmbH

Sponsor organisation

AudioCure Pharma GmbH

Address

Schlegelstrasse 9, Mitte Mitte

City

Berlin

Postcode

10115

Country

Germany

Scientific contact point

Organisation

AudioCure Pharma GmbH

Contact name

Clinical Research

Public contact point

Organisation

AudioCure Pharma GmbH

Contact name

Clinical Research

Third parties 3

Locations

5 EU/EEA countries · 40 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 81 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications