Cisplatin-induced hearing loss
Conditions
Interventions
Product Code: SENS-401
Pharmaceutical Form: Tablet
INN or Proposed INN: ARAZASETRON
Current Sponsor code: SENS-401
Other descriptive name: R-AZASETRON BESILATE
Concentration unit: mg milligram(s)
Conc
Sponsors
SENSORION PHARMA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years at the time of signing the ICF. 2. Capable of giving signed informed consent as described in Appendix 2Appendix 2, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. 3. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and = 1 of the following conditions applies: - Not a woman of childbearing potential (WOCBP) - A WOCBP who agrees to follow the contraceptive guidance at least until the randomization if she is allocated to the Arm A and for the Arms B and C, for = 30 days after the last dose of investigational medicinal product (IMP), ie, SENS-401. A male subject must agree to use contraception and refrain from donating sperm as detailed in Appendix 6 of this protocol at least until the randomization if he is allocated to the Arm A and for the Arms B and C for = 30 days after the last dose of SENS-401. 4. Neoplastic subjects that regardless of participation in this study are planned to be treated with a chemotherapy that includes a cumulative cisplatin dose of at least 200 mg/m2. 5. Subjects with PTA threshold = 30 dB at 500 Hz, 40 dB for 1-2-4 kHz, and 60 dB for 8 kHz and above. 6. In the opinion of the Investigator, minimum life expectancy of = 6 months. 7. Vaccinated against coronavirus disease 2019 (COVID-19) or previously contracted the disease and recovered. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 42 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: 1. Any condition or past medical history that, in the opinion of the Investigator, may compromise the safety or compliance of the subject or would preclude the subject from successful completion of the study. 2. Subject is the Investigator or anyone from his/her team directly involved in the conduct of the protocol. 3. A subject not willing to participate to the 2 stages of the study in case of Arm C allocation. 4. Mentally unable to understand the nature, objectives, and possible consequences of the study or refusing its constraints. 5. A congenital or hereditary disease known to decrease hearing function (eg, Otoferlin [OTOF] related deafness). 6. Any medical history affecting the middle ear function such as chronic otitis, cholesteatoma, or tympanic membrane perforation. 7. Any inner ear disease that is likely to decrease hearing function according to the Investigator’s judgment (eg, herpes zoster oticus; Meniere’s disease; purulent labyrinthitis; vestibular schwannoma). 8. Having history of sudden sensory neural hearing loss. 9. Having a fluctuating hearing loss (eg, due to Meniere’s disease, vestibular aqueduct syndrome, or autoimmune inner ear disease). 10. History of head trauma with hearing loss. 11. History of meningitis. 12. For a subject expected to receive radiotherapy during the course of the study, anticipated risk to expose the auditory system (ie, inner ear within the expected irradiation zone). 13. History of significant arrhythmia or conditions known to increase proarrhythmic risk (eg, congestive heart failure, long QT syndrome, hypokalemia). 14. Significant clinically relevant electrocardiogram (ECG) abnormality that, in the opinion of the Investigator, precludes study eligibility. 15. Significant abnormal laboratory result, physical examination, vital signs, or ear-nose-throat (ENT) evaluation (otoscopy and immittance audiometry), in the opinion of the Investigator. 16. Neurological disorder including stroke, demyelinating disease, or brain stem or cerebellar dysfunction. 17. Moderate to severe renal impairment defined by a creatinine clearance = 60 mL/minute (calculated with the Cockcroft-Gault formula for subjects < 65 years old and with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation or with the Modification of Diet in Renal Disease (MDRD) equation for subjects = 65 years old; see Appendix 3). 18. Receiving statins at Screening. 19. Receipt of concomitant treatment known or suspected to induce an ototoxicity within 6 months prior to Screening (ie, minoglycosides, loop diuretics, quinine) and any other treatments listed in Appendix 5. 20. Treatment with any investigational agent within 4 weeks prior to Screening or 5 half-lives of the investigational drug (whichever is longer). 21. Known or suspected ongoing active infection of human immunodeficiency virus (HIV), or COVID-19. 22. Known hypersensitivity, allergy or intolerance to the study medication or any history of severe abnormal drug reaction.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of SENS-401 (43.5 mg given orally twice daily [BID] for 13 weeks) versus control to prevent or treat ototoxicity in adult subjects with a neoplastic disease and under cisplatin-based chemotherapy treatment.;Secondary Objective: * Exploratory To explore the correlation between biomarkers already pre-identified (eg, prestin) or that will be identified in the future with clinical features of interest (like prediction of ototoxicity). * To evaluate the performance of an application (headphone and tablet) to evaluate hearing level in a range of frequencies. * Safety To assess the safety of SENS-401 (43.5 mg given orally BID for 13 weeks) in adult subjects with a neoplastic disease and under cisplatin-based chemotherapy treatment.;Primary end point(s): Proportion of more than Grade 1 ototoxic ears defined as hearing loss from baseline = 15 dB above 1 kHz on 2 contiguous frequencies (Common Terminology Criteria for Adverse Events [CTCAE], Version 5.0) as assessed by pure tone audiometry (PTA) over a period of 9 months from the start of the cisplatin-based chemotherapy treatment.;Timepoint(s) of evaluation of this end point: From day -2 to -28 (screening period) Every week for 9 Month (Through out study) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Proportion of more than Grade 2 ototoxic ears defined as hearing loss from baseline = 25 dB above 1 kHz on 2 contiguous frequencies (CTCAE V5.0) as assessed by PTA over a period of 9 months from the start of the cisplatin-based chemotherapy treatment. - Proportion of more than Grade 3 ototoxic ears defined as hearing loss from baseline = 25 dB above 1 kHz on 3 contiguous frequencies (CTCAE V5.0) as assessed by pure-tone audiometry [PTA]) over a period of 9 months from the start of the cisplatin-based chemotherapy treatment. - Exploratory endpoint: Serum/plasma concentrations of selected biomarkers at baseline (ie., Visit 2 prior to cisplatin administration) and at Visits 2 (just after rehydration post cisplatin treatment), 3, 4 and 11. - Sensitivity and specificity of hearing thresholds measured by auto-testing in each frequency tested in comparison with PTA values. - Safety Incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs).;Timepoint(s) of evaluation of this end point: From day -2 to -28 (screening period) Every week for 9 Month (Through out study) | — |
Countries
France, Israel
Contacts
Public ContactValérie SALENTEY
Sensorion Pharma
Outcome results
None listed