A Phase 2a, Prospective, Randomized, Double-Blind, Placebo-Controlled, Single and Repeat-Dose, Multicenter, Exploratory Efficacy Study of FX-322 Administered by Intratympanic Injection in Adults With Stable Sensorineural Hearing Loss
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 95
- 试验地点
- 1
- 主要终点
- Word Recognition in Quiet
研究概览
简要总结
This is a phase 2a single and repeat dose exploratory efficacy study of intratympanic FX-322 compared to placebo in healthy male and female adults with stable sensorineural hearing loss.
详细描述
Sensorineural hearing loss (SNHL) accounts for about 90% of all cases of hearing loss. This phase 2a study will assess the exploratory efficacy, as well as the local and systemic safety of single and repeat intratympanic doses of FX-322 compared to placebo in approximately 96 subjects with stable mild to moderately severe sensorineural hearing loss, with a medical history consistent with either excessive noise exposure or idiopathic sudden sensorineural hearing loss.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged 18-65 years inclusive.
- •Established diagnosis of stable sensorineural hearing loss by standard audiometric measures for ≥ 6 months prior to the Screening visit (no changes in air conduction greater than 10 dB at a single frequency or greater than 5 dB at two contiguous frequencies from the prior audiogram to the Screening audiogram in the study ear).
- •Documented medical history consistent with hearing loss being caused by noise exposure or sudden sensorineural hearing loss.
- •Pure Tone Audiometry (PTA) within 26-70 dB in the ear to be injected.
- •Female subjects must be of non-childbearing potential or will need to utilize two methods of highly effective contraception during the study participation (e.g. hormonal contraception or an intrauterine device and condoms) or remain abstinent. Male subjects should use condoms with spermicide during the course of the study or remain abstinent. Subjects should not donate sperm or ova during the study period.
排除标准
- •Previous participation in FX-322 clinical trial.
- •Currently on any medication consisting of valproic acid, valproate sodium, or divalproex sodium.
- •Perforation of tympanic membrane or other tympanic membrane disorders that would interfere with the delivery and safety assessment of an intratympanic medication or reasonably be suspected to affect tympanic membrane healing after injection in study ear. This includes a current tympanostomy tube.
- •Any conductive hearing loss of greater than 15 dB at a single frequency or greater than 10 dB at two or more contiguous octave frequencies in the study ear at the Screening visit or on the prior audiogram (if the Investigator feels there is not a true conductive hearing loss, the Medical Monitor should be consulted).
- •Active chronic middle ear disease or a history of major middle ear surgery, as an adult, in the ear to be injected.
- •Subject has had an intratympanic injection in either ear within 6 months of the screening visit.
- •History of clinically significant vestibular symptoms at the discretion of the investigator.
- •History of clinically significant systemic autoimmune disease.
- •History of head or neck radiation treatment or exposure.
- •History of platinum-based chemotherapy treatment.
- •Exposure to another investigational drug within 28 days prior to injection of study drug.
- •Evidence of any active or chronic disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator following a detailed medical history, physical examination, and vital signs (systolic and diastolic blood pressure, pulse rate, body temperature).
- •History of substance abuse within 2 years of the Screening Visit.
- •Positive test for drugs of abuse at screening.
- •Positive urine pregnancy test or breast-feeding.
- •Any known factor, condition or disease that, in the view of the Investigator, might interfere with treatment compliance, study conduct or interpretation of the results (e.g. previous high-dose aminoglycoside treatment).
研究组 & 干预措施
FX-322 Single Dose, Placebo Three Doses
Four intratympanic injections of a hydrogel formulation, FX-322 Single Dose, Placebo Three Doses.
干预措施: FX-322 (One Dose) (Drug)
FX-322 Single Dose, Placebo Three Doses
Four intratympanic injections of a hydrogel formulation, FX-322 Single Dose, Placebo Three Doses.
干预措施: Placebo (Drug)
FX-322 Two Doses, Placebo Two Doses
Four intratympanic injections of a hydrogel formulation, FX-322 Two Doses, Placebo Two Doses.
干预措施: FX-322 (Two Doses) (Drug)
FX-322 Two Doses, Placebo Two Doses
Four intratympanic injections of a hydrogel formulation, FX-322 Two Doses, Placebo Two Doses.
干预措施: Placebo (Drug)
FX-322 Four Doses
Four intratympanic injections of a hydrogel formulation, FX-322 Four Doses.
干预措施: FX-322 (Four Doses) (Drug)
Placebo Four Doses
Four intratympanic injections of a hydrogel formulation, Placebo Four Doses.
干预措施: Placebo (Drug)
结局指标
主要结局
Word Recognition in Quiet
时间窗: Baseline to Day 210
Percent of subjects exceeding the Carney-Schlauch 95% confidence interval for improvement from baseline in number of words recognized from Consonant-Nucleus-Consonant (CNC) word lists
Treatment-emergent Adverse Events (TEAEs)
时间窗: Baseline to Day 210
Number of patients with treatment-related adverse events assessed by CTCAE v5.0
Words-in-Noise
时间窗: Baseline to Day 210
Mean absolute percent change in number of recognized words from CNC word lists
Pure Tone Audiometry
时间窗: Baseline to Day 210
Mean overall pure tone average (PTA) hearing thresholds in decibels (dB) derived by averaging the air conduction thresholds at 0.5, 1, 2 and 4kHZ frequencies
Tympanometry Abnormalities
时间窗: Baseline and Days 15, 60, 90, 150, 210
Number of treated ears with changes in middle ear compliance (mL), peak pressure (daPa), and/or ear canal volume (mL) from baseline
Otoscopy Abnormalities
时间窗: Baseline and Days 8, 15, 21 60, 90,150, and 210
Number of treated ears with abnormalities of the external ear canal, tympanic membrane and middle ear at each specified time point
次要结局
未报告次要终点