SENS-401 to Prevent the Ototoxicity induced by Cisplatin in Adult Subjects with a Neoplastic Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sensorion

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Otorhinolaryngologic Diseases [C09]

Trial duration

30 Dec 2022 → 12 Jun 2025

Decision date (initial)

2024-08-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-511713-38-00

EudraCT number

2021-002705-10

ClinicalTrials.gov

NCT05628233

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the efficacy of SENS-401 given at the dose of 43.5 mg b.i.d. (bis in die) for up to 23 weeks to prevent the ototoxicity induced by cisplatin in subjects with a neoplastic disease, 4 weeks after the completion of the last cisplatin treatment.

Secondary objectives 1

1. To further evaluate the efficacy of SENS-401 given at the dose of 43.5 mg b.i.d. for up to 23 weeks to prevent the ototoxicity induced by cisplatin in subjects with a neoplastic disease, 4 and 12 weeks after the completion of the last cisplatin treatment.

Conditions and MedDRA coding

Cisplatine induced hearing loss

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age ≥ 18 years at the time of signing the ICF.
2. Capable of giving signed informed consent as described in Appendix 2 of this protocol, 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 (see Appendix 6), not breastfeeding, and ≥ 1 of the following conditions apply: • Not a woman of childbearing potential (WOCBP) as defined in Appendix 6. • A WOCBP who agrees to follow the contraceptive guidance in Appendix 6 for at least 30 days after the last dose of SENS-401 if cisplatin is not received or 6 months after the last dose of cisplatin.
4. A male subject must agree to use contraception and refrain from donating sperm as detailed in Appendix 6 of this protocol for at least 30 days after the last dose of SENS-401 if cisplatin is not received or 6 months after the last dose of cisplatin.
5. Neoplastic subject that, regardless of participation in this study, is planned to be treated with a chemotherapy that includes a dose of cisplatin of at least 70 mg/m2 per cycle and a cumulative dose of cisplatin of at least 210 mg/m2.
6. 6b. Subjects with a PTA threshold of ≤ 30 dB at 500 Hz AND ≤ 40 dB at 1-2 kHz AND ≤ 60 dB at 4-6 kHz AND ≤ 80 dB at 8 kHz, in either both ears or one ear for a maximum of 30% of the subjects in each study arm.
7. In the opinion of the Investigator, a life expectancy of ≥ 6 months.
8. Inclusion Criterion 8 about COVID-19 has been removed from study protocol v4.0.

Exclusion criteria 25

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. Mentally unable to understand the nature, objectives, and possible consequences of the study or refusing its constraints.
4. A congenital or hereditary disease known to decrease hearing function (e.g. Otoferlin [OTOF]-related deafness).
5. Any medical history affecting the middle ear function such as chronic otitis, cholesteatoma, or tympanic membrane perforation.
6. Any inner ear disease that is likely to decrease hearing function according to the Investigator’s judgment (e.g. herpes zoster oticus; Meniere’s disease; purulent labyrinthitis; vestibular schwannoma).
7. Having a history of sudden sensory neural hearing loss.
8. Having a fluctuating hearing loss (e.g. due to Meniere’s disease, vestibular aqueduct syndrome, or autoimmune inner ear disease).
9. History of head trauma with hearing loss.
10. History of meningitis.
11. For a subject expected to receive radiotherapy during the course of the study, an anticipated risk of exposure of the auditory system (i.e. inner ear within the expected irradiation zone).
12. History of significant arrhythmia or conditions known to increase proarrhythmic risk (e.g. congestive heart failure, long QT syndrome, hypokalemia).
13. Significant clinically relevant electrocardiogram (ECG) abnormality that, in the opinion of the Investigator, precludes study eligibility.
14. Significant abnormal laboratory result, physical examination, vital signs, or ear-nose-throat (ENT) evaluation (otoscopy and immittance audiometry), in the opinion of the Investigator.
15. Neurological disorder including stroke, demyelinating disease, or brain stem or cerebellar dysfunction.
16. Moderate to severe renal impairment defined by a creatinine clearance ≤ 60 mL/min (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
17. Exclusion Criterion 17 about statins has been removed from study protocol v4.0.
18. Having received concomitant treatment known or suspected to induce an ototoxicity within 6 months prior to Screening (i.e. aminoglycosides, loop diuretics, quinine) and any other treatments listed in Appendix 5. Previous treatment with a platinum treatment should be considered as an exclusion criterion.
19. Treatment with any investigational agent within 4 weeks prior to screening or 5 half-lives of the investigational drug (whichever is longer).
20. 20b. Known or suspected ongoing active infection of human immunodeficiency virus (HIV)
21. 21. Known hypersensitivity, allergy or intolerance to the study medication or any history of severe abnormal drug reaction.
22. Known hypersensitivity, allergy or intolerance to cisplatin or any history of severe abnormal drug reaction.
23. Receiving phenytoin at screening (as it is contraindicated with cisplatin).
24. Myelosuppressed at screening (as it is contraindicated with cisplatin).
25. Any condition or health state at screening contraindicating the use of rehydration solution before each cisplatin cycle if requested (as dehydration state is contraindicated with cisplatin).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline of the average of the hearing threshold of 3 contiguous hearing frequencies assessed with a 0.5-12.5 kHz audiogram 4 weeks after the completion of the last cisplatin treatment in each eligible ear of each subject.

Secondary endpoints 1

1. Please cf Protocol (there is too many caracters to be put here)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sensorion

Sponsor organisation

Sensorion

Address

375 Rue Du Professeur Blayac

City

Montpellier

Postcode

34080

Country

France

Scientific contact point

Organisation

Sensorion

Contact name

Lionel HOVSEPIAN

Public contact point

Organisation

Sensorion

Contact name

Lionel HOVSEPIAN

Third parties 4

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications