Safety, tolerability, and efficacy of ACOU085 for prevention of hearing loss in testicular cancer patients receiving cisplatin

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Acousia Therapeutics GmbH

Participant type

Patients

Age range

18-64 years

Gender

Male

Therapeutic area

Diseases [C] - Otorhinolaryngologic Diseases [C09]

Trial duration

10 Nov 2023 → 20 Mar 2026

Decision date (initial)

2023-09-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Acousia Therapeutics GmbH

External identifiers

EU CT number

2023-503696-15-00

WHO UTN

U1111-1287-5166

ClinicalTrials.gov

NCT06521190

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Primary Objective is to investigate the potential of ACOU085 for prevention of hearing loss after ototoxic damage induced by cis-Pt in testicular cancer (TCa) patients using an intraindividual comparison of functional hearing parameters.

Secondary objectives 1

1. Secondary Objectives are to assess the efficacy, safety, and tolerability profile of ACOU085 following three administrations (local transtympanic injections in the ears) in cis-Pt treated TCa patients.

Conditions and MedDRA coding

sensorineural hearing loss (SNHL)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. • Confirmed diagnosis of testicular cancer with indication for a cis-Pt-containing chemotherapeutic regimen according to current treatment guidelines and site-specific tumor board recommendations • Male adult patients at an age between 18 and 45 years • Planned cis-Pt treatment with a cumulative dose of ≥ 300 mg/m2 which has to be administered in 3 chemotherapeutic cycles • Normal or not clinically relevant otoscopic findings in both ears • Normal hearing at both ears according to current WHO criteria for air-conduction 4PTA (0.5/1/2/4 kHz; 0 to 19 dB HL; average of audiometric thresholds at 0.5/1/2/4 kHz) at baseline • Normal hearing at both ears according to ASHA criteria with a hearing threshold at any frequency (0.25 to 12 kHz) not exceeding 20 dB and a 4PTA (0.5/1/2/4 kHz) showing ≤15 dB HL at baseline • Normal distortion product oto-acoustic emissions (DPOAE) present in both ears at baseline • Patient shows normal results at trial start (V1) concerning heart rate (50 to 90 bpm), blood pressure (according to commonly accepted ranges), ECG (no pathological findings), and laboratory parameters (ie, liver and renal function values not exceeding the upper limits of normal) • Male patients and their female partner(s) must agree to use 2 forms of contraception (one of which must be a barrier method) during 6 months after trial initiation • Patient is cooperative, able to understand all aspects of the trial, and able to speak German comparable to native speakers as per the investigator's discretion • Patient has signed an approved informed consent form indicating that he understands the purpose of and procedures required for the trial, will follow the trial-specific measures, and is willing to participate in the trial

Exclusion criteria 1

1. 1) Suspected or diagnosed genetic predisposition to hearing loss (incl. DFNA2 rel. to KCNQ4) 2) History of middle ear pathology or surgery, otitis externa, chronic otitis media, or recent acute otitis media (within ≤ 3 months) 3) History of otologic surgery (excluding myringotomy tubes or simple tympanoplasty) 4) Meniere‘s disease or secondary endolymphatic hydrops, auto immune hearing loss, inner ear pathology, fluctuating hearing loss, perilymph fistula, cochlear baro-trauma, radiation-induced hearing loss, retro-cochlear lesion, severe tympanosclerosis, atrophic tympanic membrane 5) Hearing loss of >45 dB averaged at 6 and 8 kHz in either ear 6) Sudden hearing loss or conductive hearing loss >10 dB at two frequencies in either ear 7) Asymmetry in hearing thresholds between left and right ear ≥20 dB at any single frequency or ≥10 dB at any 3 consecutive frequencies ≤ 8 kHz 8) Intake of any ototoxic drugs other than the intended cis-Pt-containing chemotherapeutic drug regimen prior to start of the trial and during the trial period 9) Previous radiation exposure >35 Gray to complete or parts of the cochlea 10) Severe concomitant diseases such as heart failure (NYHA II-IV), COPD, bronchial asthma, ongoing malignancies other than testicular cancer, auto-immune or chronic-inflammatory diseases, endocrinological diseases, advanced hepatic or renal failure, and primary complaint of tinnitus 11) Planned consumption of medications, herbal preparations, and specific food ingredients to treat hearing problems and/or tinnitus during the trial period 12) Hypersensitivity against any primary or secondary ingredient of IMP/Placebo medication 13) Male patients with female partners who are pregnant or planning to become pregnant during 6 months after trial initiation 14) Use of any other investigational medicinal product (IMP) within one month prior to screening and planned use during the trial or up to 30 days after trial completion 15) Patient has any dependent relationship or employment status with respect to the trial site, the sponsor, the investigator, or any supervisor

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients showing a difference of ≥10 dB between both ears in at least two frequencies for air conduction in PTA focused on high (4, 6, 8 kHz) and extended high frequencies (10, 12, 14, 16 kHz) between baseline (V1; prior to first initiation of cis-Pt containing chemotherapy) and end of chemotherapeutic cycle 3 (V4; Day 64).

Secondary endpoints 9

1. Efficacy Protection for single audiometric variables (ie, intra-individual differences between both ears) including pure tone and speech audiometry in quiet and noise as well as otoacoustic emissions (DPOAEs) in terms of verum- vs. placebo-treated ear between V1 (baseline) and V2/V3/V4/V5, as defined in the following:
2. Proportion of patients showing a difference of ≥10 dB between both ears for speech reception thresholds (SRT) in quiet for the Freiburger numbers and/or the Oldenburger sentence tests
3. Proportion of patients showing a difference of ≥10 dB between both ears for speech discrimination in quiet at 50 and/or 65 dB SPL for the Freiburger monosyllable speech test
4. Proportion of patients showing a difference of ≥10 dB between both ears for speech discrimination in noise of ≥1.5 dB SNR for the Oldenburger sentence test (fixed noise at 65 dB SPL)
5. Proportion of patients showing a difference of ≥10 dB between both ears across all (0.25 to 12 kHz) and high frequencies (4 to 12 kHz) calculated as the geometric mean of air conduction hearing thresholds
6. Proportion of patients showing a difference of ≥5 dB between both ears for otoacoustic emissions
7. Safety and Tolerability: Changes from baseline (differences in time and between both ears) in terms of facial nerve function (H. Brackmann/Stennert Index), cochlear function (tinnitus level/intensity and tympanometry/stapedius reflex), and vestibular function (nystagmus test and dizziness handicap inventory)
8. Changes from baseline for vital signs, physical examinations, ECGs, and laboratory parameters
9. Incidence, severity, and relationship of adverse events including injection site or local reactions at both ears during the trial course

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Acousia Therapeutics GmbH

Sponsor organisation

Acousia Therapeutics GmbH

Address

Sindelfinger Strasse 3, Weststadt Weststadt

City

Tuebingen

Postcode

72070

Country

Germany

Scientific contact point

Organisation

Acousia Therapeutics GmbH

Contact name

Tim Bölke

Public contact point

Organisation

Acousia Therapeutics GmbH

Contact name

Tim Bölke

Third parties 2

Locations

1 EU/EEA country · 16 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 37 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