A Study Testing Safety and Efficacy of Transtympanic Paliroden for the Treatment of Cochlear Synaptopathy in Participants With Chronic, Constant Tinnitus

Inclusion criteria

• Native speaker of English
• Able and willing to give consent for the study
• Age 18-75 years (inclusive) at the time of signing the informed consent
• Report binaural, chronic, constant, subjective tinnitus for at least 6 months
• Hearing thresholds within normal limits (≤ 20 dB HL at 0.25 to 8 kHz, plus 3 and 6 kHz)
• Speech-in-noise deficit (at least 3 dB SNR loss in comparison to normative value of the AE-Matrix test) in both ears
• No concurrent tinnitus treatment
• Be considered as reliable and capable of adhering to the protocol, according to the judgment of the investigator
• Signed informed consent as described in § 11.3 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol

Exclusion criteria

• Montreal Cognitive Assessment (MoCA) score < 26
• History of somatic/objective tinnitus as defined by AAO-HNS guidelines (e.g., pulsatile/whooshing sounds pulsating in synchrony with heartbeat, or caused by temporo-mandibular joint dysfunction)
• Known otologic pathology (e.g., otosclerosis, history of autoimmune hearing loss, radiation-induced hearing loss, fluctuating hearing, endolymphatic hydrops, Ménière's disease, vestibular schwannoma, history of sudden sensorineural hearing loss, Neurofibromatosis Type 2)
• History of otologic surgery (apart from tympanostomy tube insertion if more than one year prior to inclusion visit)
• Untreated hypothyroidism
• Use of prohibited concomitant therapies as described in § 6.10
• Current use or history of platinum-based chemotherapy
• Concurrent malignancies that require treatment
• Abnormal otoscopy as defined by less than 90% of the tympanic membrane visible (e.g., occluding cerumen, ear drum perforation)
• Current middle ear pathology (e.g., otitis media, tympanic membrane perforation)
• Abnormal tympanogram (other than type A)
• Conductive hearing loss (> 10 dB difference between air- and bone-conduction hearing thresholds)
• Asymmetric hearing thresholds (more than 15 dB difference between left and right ear) at 0.25 to 8 kHz, plus 3 and 6 kHz
• Lactation, known pregnancy, positive pregnancy test at either Screening (urine) or Baseline (serum) for Women of Childbearing Potential (WOCBP), or plan to become pregnant during the study
• Liver Enzyme Lab Outcomes within the previous 2 months (or assessed at Baseline if not available at Screening ), see § 12.1.1:

• Bilirubin > upper limit normal (ULN)
• Liver transaminases (Aspartate Aminotransferase [AST] and Alanine Aminotransferase [ALT]) > 2 times ULN
• Gamma-glutamyltransferase (GGT) > 2 times ULN
• Clinically significant electrocardiogram (ECG) abnormalities:

a. Marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 450 ms)

• History of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
• Concurrent participation in another clinical study or participation in another clinical study within 30 days or five half-lives of the experimental drug (whichever is longer) prior to screening visit (V0)
• Diagnosed anxiety disorders, psychosis, depression, schizophrenia, attempted suicide, or other significant psychiatric conditions that could impact their ability to cooperate and comply with the study protocol
• Major surgery (at the discretion of the Principal Investigator or medically qualified designee) within eight weeks before screening or scheduled/planned surgery within the time frame of the study