Phase IIa Randomized, Double-blind, and Placebo-controlled Multicenter Split Body Trial of Repeated Doses of ACOU085 for the Prevention of Hearing Loss in Testicular Cancer Patients Receiving Cisplatin
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 10
- 主要终点
- PTA air
研究概览
简要总结
Randomized, double-blind, placebo-controlled, multicenter phase IIa clinical trial in adult male TCa patients with the risk to suffer from sensorineural hearing loss (SNHL) due to cisplatin therapy within a chemotherapeutic regimen of testicular cancer. Patients will have an indication for a cisplatin-containing chemotherapy according to current guidelines and trial site tumor board recommendations. The trial is designed to show efficacy, safety, and tolerability of ACOU085 administered into the middle ear using 3 transtympanic injections per ear prior to 3 planned and corresponding 3-week chemotherapeutic cycles. The intra-individual control will be done by placebo injection into the respective contralateral middle ear.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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 three 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 clinically significant)
- •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 start (V1)
- •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
排除标准
- •Suspected or diagnosed genetic predisposition to hearing loss (incl. DFNA2 rel. to KCNQ4)
- •History of middle ear pathology or surgery, otitis externa, chronic otitis media, or recent acute otitis media (within ≤3 months)
- •History of otologic surgery (excluding myringotomy tubes or simple tympanoplasty)
- •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
- •Hearing loss of >45 dB averaged at 6 and 8 kHz in either ear
- •Sudden hearing loss or conductive hearing loss >10 dB at two frequencies in either ear
- •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
- •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
- •Previous radiation exposure >35 Gray to complete or parts of the cochlea
- •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
- •Planned consumption of medications, herbal preparations, and specific food ingredients to treat hearing problems and/or tinnitus during the trial period
- •Hypersensitivity against any primary or secondary ingredient of IMP/Placebo medication
- •Male patients with female partners who are pregnant or planning to become pregnant during 6 months after trial start (V1)
- •Use of any other investigational medicinal product (IMP) within five times the half-life of that IMP/relevant metabolites or one month (whichever is longer) prior to screening and planned use during the trial or up to 30 days after trial completion
- •Patient has any dependent relationship or employment status with respect to the trial site, the sponsor, the investigator, or any supervisor
研究组 & 干预措施
Active ear
An ACOU085 retard formulation is transtympanically injected into the round window niche of the middle ear.
干预措施: ACOU085 (bimokalner) (Drug)
Placebo ear
A matching placebo retard formulation is transtympanically injected into the round window niche of the contralateral middle ear.
干预措施: Placebo (Drug)
结局指标
主要结局
PTA air
时间窗: Visit 4 at 9 weeks
Proportion of patients showing a difference of ≥10 dB between the 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)
次要结局
- Distortion Product Otoacoustic Emissions (DPOAE)(150 days)
- Freiburger Test(150 days)
- PTA bone(150 days)
- Oldenburger Test (speech understanding)(150 days)