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

Inclusion Criteria:

1. Native speaker of English
2. Able and willing to give consent for the study
3. Age 18-75 years (inclusive) at the time of signing the informed consent
4. Report binaural, chronic, constant, subjective tinnitus for at least 6 months
5. Hearing thresholds within normal limits (≤ 20 dB HL at 0.25 to 8 kHz, plus 3 and 6 kHz)
6. Speech-in-noise deficit (at least 3 dB SNR loss in comparison to normative value of the AE-Matrix test) in both ears
7. No concurrent tinnitus treatment
8. Be considered as reliable and capable of adhering to the protocol, according to the judgment of the investigator
9. 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:

1. Montreal Cognitive Assessment (MoCA) score < 26
2. 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)
3. 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)
4. History of otologic surgery (apart from tympanostomy tube insertion if more than one year prior to inclusion visit)
5. Untreated hypothyroidism
6. Use of prohibited concomitant therapies as described in § 6.10
7. Current use or history of platinum-based chemotherapy
8. Concurrent malignancies that require treatment
9. Abnormal otoscopy as defined by less than 90% of the tympanic membrane visible (e.g., occluding cerumen, ear drum perforation)
10. Current middle ear pathology (e.g., otitis media, tympanic membrane perforation)
11. Abnormal tympanogram (other than type A)
12. Conductive hearing loss (> 10 dB difference between air- and bone-conduction hearing thresholds)
13. Asymmetric hearing thresholds (more than 15 dB difference between left and right ear) at 0.25 to 8 kHz, plus 3 and 6 kHz
14. 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

15. Liver Enzyme Lab Outcomes within the previous 2 months (or assessed at Baseline if not available at Screening ), see § 12.1.1:

    1. Bilirubin > upper limit normal (ULN)
    2. Liver transaminases (Aspartate Aminotransferase [AST] and Alanine Aminotransferase [ALT]) > 2 times ULN
    3. Gamma-glutamyltransferase (GGT) > 2 times ULN

16. Clinically significant electrocardiogram (ECG) abnormalities:

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

17. History of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
18. 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)
19. 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
20. 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