Clinical trial NCT05258773
Conditions: Hearing Loss
Sponsor: Sensorion
Start date: 2022-08-10; Completion date: 2024-05-31
Enrollment: 28 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The aim of this study is to detect the presence of SENS-401 in the perilymph of participants undergoing cochlear implant surgery after 7 days of oral administration of SENS-401.

Detailed description:
The study is a Phase IIa, open-label, randomized and controlled study investigating repeated twice-daily administration of oral SENS-401 in adult participants with moderately severe to profound hearing loss who have already agreed to undergo cochlear implant surgery justified by their hearing impairment.

After written informed consent is obtained and screening procedures completed, 27 eligible participants will be randomized on Day 1 to either Arm A or Arm B in ratio 2:1 (18 participants in Arm A and 9 participants in Arm B).

Arm A participants will commence dosing with twice-daily oral 43.5 mg SENS-401 for 7 days prior to their scheduled cochlear implant surgery on Day 8 and up to 42 days from day of surgery inclusive.

Arm B participants will not receive any treatment other than their scheduled cochlear implant surgery.

Arms: arm 1: Arm A: Participants scheduled for cochlear implantation and treated with oral 43.5 mg SENS-401 (R-Azasetron Besylate) twice daily for up to 49 days. arm 2: Arm B: Participants scheduled for cochlear implantation and not treated with SENS-401 (R-Azasetron Besylate).
Interventions: intervention 1: SENS-401 (R-Azasetron Besylate)
Intervention descriptions: intervention 1: Patients will receive SENS-401 ((R)-azasetron besylate) for 7 days B.I.D. before cochlear implant surgery and during 6 weeks after the surgery.

Protocol documents:
Prot_000.pdf: 
Protocol SENS-401-203 
Version 3.0, 08 February 2023 
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Page 1 of 71 
 
 
CLINICAL STUDY PROTOCOL 
A Phase IIa, Multicenter, Randomized, Controlled, 
Open-label Study to Evaluate the Presence of 
SENS-401 in the Perilymph after 7 days of repeated 
oral administration in Adult Participants Scheduled 
for Cochlear Implantation 
 
 
Protocol Number: 
SENS-401-203 
Investigational Product: 
SENS-401 ((R)-azesetron besylate) as oral tablet 
IND Number: 
Not applicable 
EudraCT Number: 
2021-006615-28 
Sponsor: 
Sensorion Australia Pty Ltd 
Suite 2003, 109 Pitt Street 
Sydney, NSW 2000 
Australia 
 
Sponsor Signatory: 
 
Chief Medical Officer 
 
CRO: 
 
 
 
Medical Monitor: 
 
Sensorion Australia Pty Ltd 
 
Date and Version: 
Version 3.0, 08 February 2023 
Confidentiality Statement 
This document contains the confidential information of Sensorion Australia Pty Ltd. It is 
provided to you as an Investigator or consultant for review by you, your personnel, and 
the applicable Ethics Committee (EC), Institutional Review Board (IRB), or regulatory 
authority. Your acceptance of this document constitutes an agreement that you will not 
disclose the information contained herein to others without the prior written consent of 
Sensorion Australia Pty Ltd, unless it is necessary to obtain informed consent from 
potential study participants. No other use or reproduction is authorized by Sensorion 
Australia Pty Ltd, nor does Sensorion Australia Pty Ltd assume any responsibility for 
unauthorized use of this protocol. 


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History of the protocol version 
 
Version 
Date 
Reasons 
2.0 
25 April 2022 
- 
3.0 
08 February 2023 
x 
No upper limit of age for participants 
x 
Screening period is 42 days maximum instead 
of 28 days maximum 
x 
Subjects can be randomised up to 8 to 14 days 
prior to the cochlear implant surgery 


Protocol SENS-401-203 
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1 PROTOCOL SUMMARY 
1.1 
PROTOCOL SYNOPSIS 
 
 
 
Protocol Title 
A Phase IIa, Multicenter, Randomized, Controlled, 
Open-label Study to Evaluate the Presence of 
SENS-401 in the Perilymph after 7 days of repeated oral 
administration in Adult Participants Scheduled for 
Cochlear Implantation 
IND Number 
Not applicable 
EudraCT Number 
2021-006615-28 
Protocol Number 
SENS-401-203 
Sponsor 
Sensorion Australia Pty Ltd 
Phase of Development 
Phase IIa 
Number of Study Sites 
Up to 5 study sites in Australia and France 
Investigational Medicinal 
Product and dose 
Oral SENS-401 supplied as 14.5 mg (10 mg free base) 
(R)-azasetron besylate tablets: 3 tablets of 14.5 mg 
SENS-401 twice daily (morning and evening), oral 
route 
Comparator 
No treatment 
Treatment Groups 
Arm 
A: 
Participants 
scheduled 
for 
cochlear 
implantation and randomized to be treated with oral 
43.5 mg SENS-401 twice daily (b.i.d.) for 49 days (7 
days prior to cochlear implant surgery, and 42 days from 
day of surgery inclusive). 
Arm B: Participants scheduled for cochlear implants 
and randomized to not be treated with SENS-401. 
Participant Population 
Adults aged from 18 years and older with preoperative 
threshold levels in the impaired ear demonstrating 
unaided audiometric threshold of 80dB or better (i.e., 
 dB) at 500Hz, who meet the locally approved 
indication for, and have already consented to receiving, 
cochlear implant Cochlear™ Nucleus® C1622 prior to 
study entry. 
Duration of Study 
Participants will be on study for a maximum of 168 
days: 
x up to 42 days for the screening period; 
x up to 56 days for the treatment period; 


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x up to 70 days for the follow-up period. 
Objectives 
Primary: 
To detect the presence of SENS-401 in the perilymph of 
participants undergoing cochlear implant surgery after 7 
days of oral administration of SENS-401. 
Secondary: 
x To measure the SENS-401 concentrations in the 
perilymph and plasma of participants undergoing 
cochlear implant surgery after 7 days of oral 
administration of SENS-401. 
x To compare the SENS-401 concentrations in 
perilymph and plasma of participants undergoing 
cochlear implant surgery after 7 days of oral 
administration of SENS-401. 
x To 
assess 
the 
efficacy 
of 
repeated 
oral 
administration with SENS-401 to protect against 
residual low frequency hearing loss in participants 
undergoing cochlear implant surgery at the Day 49 
visit and at EOS/ET. 
x To assess the safety and tolerability of SENS-401 
for the whole duration of the study. 
Exploratory: 
x To 
assess 
the 
efficacy 
of 
repeated 
oral 
administration with SENS-401 to protect against 
residual low frequency hearing loss in participants 
undergoing 
cochlear 
implant 
surgery; 
here 
performed on a subset of participants with no 
electrophysiological evidence of basilar membrane 
fixation as described in Section 6.4.2. 
x To collect and store a biobank of plasma and serum 
to be able if necessary and possible to explore the 
correlation between biomarkers already pre- 
identified (e.g., prestin) or that will be identified in 
the future with clinical features of interest. 
Endpoints 
Primary: 
x Percentage of participants from Arm A with levels 
of SENS-401 in the perilymph above the Limit of 
Quantification on day of cochlear implant surgery 
after seven days of SENS-401. 
Secondary: 
Pharmacokinetics: 


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x SENS-401 perilymph concentration on day of 
cochlear implant surgery after seven days of SENS- 
401. 
x SENS-401 plasma concentration on day of cochlear 
implant surgery after seven days of SENS-401. 
Efficacy: 
x Change of hearing threshold from baseline in the 
implanted 
ear 
at 
500 
Hz 
after 
repeated 
administration of SENS-401, as assessed by pure 
tone audiometry (PTA) at the Day 49 visit and at 
EOS/ET. 
x Change of hearing threshold from baseline in the 
implanted ear at 250 Hz and 750 Hz after repeated 
administration of SENS-401, as assessed by pure 
tone audiometry (PTA) at the Day 49 visit and at 
EOS/ET. 
Safety: 
x Incidence of treatment emergent AEs and SAEs in 
each participant until the end of their study 
participation. 
x Exploratory: In a subset of participants assessed by 
a neurophysiologist to have no electrophysiological 
evidence of basilar membrane fixation: 
- 
Change of hearing threshold from baseline in the 
implanted ear at 500 Hz after repeated 
administration of SENS-401, as assessed by pure 
tone audiometry (PTA). 
- 
Change of hearing threshold from baseline in the 
implanted ear at 250 Hz and 750 Hz after 
repeated administration of SENS-401, as 
assessed by pure tone audiometry (PTA). 
x Serum/plasma 
concentrations 
of 
selected 
biomarkers at baseline (i.e., Day 1, and pre-dose for 
Arm A), at the Day 49 visit, and at EOS/ET. 
Study Description 
The study is a Phase IIa, open-label, randomized and 
controlled study investigating repeated twice-daily 
administration of oral SENS-401 in adult participants 
with preoperative threshold levels in the impaired ear 
demonstrating unaided audiometric threshold of 80 dB 
or better (i.e.,  dB) at 500 Hz), who meet the locally 
approved indication for, and have already consented to 
receiving, cochlear implant Cochlear™ Nucleus® 
C1622. 
After written informed consent is obtained and 
screening  procedures  completed,  27  eligible 


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participants will be randomized on Day 1 to either Arm 
A or Arm B in ratio 2:1 (18 participants in Arm A and 9 
participants in Arm B). Arm A participants will 
commence dosing with twice-daily oral 43.5 mg SENS- 
401 for 7 to 13 days prior to their cochlear implant 
surgery scheduled from Day 8 to Day 14. Dosing will 
continue on the day of surgery. Arm B participants will 
not receive any treatment other than their scheduled 
cochlear implant surgery. All participants will undergo 
audiometric testing at screening and Day 1 (baseline). 
From Day 1, Arm A participants will record each 
administration of SENS-401 into a study diary. Blood 
and perilymph samples for determining SENS-401 
concentration will be collected from Arm A participants 
only on the day of cochlear implant surgery (blood 
sampling before the morning dose of SENS-401 and 
perilymph sampling during the course of the surgery). 
Electrocochleography will be performed for all 
participants (Arm A and Arm B) during cochlear 
implant surgery. All participants (Arm A and Arm B) 
will attend the Day 49 visit, when efficacy and safety 
assessments will be performed. Arm A participants will 
continue to take SENS-401 until this visit. All 
participants (Arm A and Arm B) will then return to the 
study site for the EOS on Day 105 for final safety and 
efficacy assessments. Blood samples for exploratory 
biomarker research will also be collected from all 
participants (Arm A and Arm B) on Day 1, Day 49 visit, 
and EOS. 
All the subjects receiving SENS-401 will have before 
EOS at least 4 weeks of follow-up after their last dose 
of SENS-401. 
Sample Size 
27 randomized participants. 
The sample size of this study is based on empirical 
considerations for the pharmacokinetic evaluation 
(primary objective of this study). 
For PK and safety: Although the sample size is not 
calculated based on statistical hypotheses, eighteen 
participants are generally considered sufficient to 
characterize the PK of a small molecule. In addition, the 
systemic PK profile of two dose levels of SENS-401 
was previously evaluated in a Phase I healthy volunteer 
study and further documented in a phase 2a study 
(SENS-401-201). The main purpose here of the PK 
sampling is to determine if SENS-401 can be detected 
in the perilymph and to compare the levels of SENS-401 
in two different body compartments. 


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For efficacy: 27 participants are expected to provide 
enough data to evaluate a trend of efficacy. 
A sufficient number of participants will be screened in 
order to randomize 27 participants. 
Inclusion Criteria 
Potential participants must fulfil all of the following 
inclusion criteria to be eligible for the study: 
1. Adults aged from 18 years and older. 
2.  Meets the locally approved indication for cochlear 
implantation with the Cochlear™ Nucleus® C1622 
and has preoperative threshold levels in the impaired 
ear demonstrating unaided audiometric threshold of 
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individual must have freely consented to the 
cochlear implant surgery before being offered to 
participate in the SENS-401-203 study. 
3. Signed and dated written informed consent. 
4. Females who have or may have male sexual partners 
must meet one of the following criteria at Screening: 
x Postmenopausal (defined as 12 consecutive 
months with no menses without an alternative 
medical cause), surgically sterile, or abstinent; 
or 
x A woman of childbearing potential (WOCBP) 
(any female who has experienced menarche and 
who 
is 
not 
permanently 
sterile 
or 
postmenopausal) practicing a method of highly 
effective birth control that is listed in Appendix 
11.1 and is willing to continue to use highly 
effective contraception (as per Appendix 11.1) 
for the duration of study participation and for at 
least 30 days after the final dose of study drug. 
All WOCBP must have a negative serum 
pregnancy test at screening before the first dose of 
study drug is taken. Participants randomized to 
Arm B on Day 1 will not be required to further 
adhere to the contraception requirements of the 
study. 
Note: No contraception measures are needed for 
male participants, including those with pregnant or 
non-pregnant WOCBP partner. 
5. Vaccinated against coronavirus disease 2019 
(COVID-19) 
per 
local 
vaccination 
schema 
requirement or previously contracted the disease and 
recovered within the last six months. 


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Exclusion Criteria 
Individuals will be excluded from the study if any of the 
following criteria apply: 
1. Moderate to severe renal impairment defined by a 
FUHDWLQLQH FOHDUDQFH   POPLQ FDOFXODWHG ZLWK
the Cockcroft-Gault formula for individuals <65 
years old and with the Chronic Kidney Disease 
Epidemiology Collaboration (CKD-EPI) creatinine 
equation or the Modification of Diet in Renal 
Disease Study (MDRD) equation for individuals 
 years old). 
2. Any condition that, in the opinion of the 
Investigator, may compromise the safety or 
compliance of the participant or would preclude the 
participant from successful completion of the study. 
3. Unable or unwilling to comply with the protocol 
requirements. 
4. Any 
therapy 
known 
as 
ototoxic 
(e.g. 
aminoglycosides, cisplatin, quinine etc.) at the 
current time or in the past 6 months prior to study 
inclusion. Loop diuretics at normal therapeutic 
doses are permitted. 
5. Known hypersensitivity, allergy or intolerance to 
the study medication or any history of severe 
abnormal drug reaction. 
6. Pregnant or breast-feeding. 
7. Treatment with any investigational agent within 4 
weeks prior to screening or 5 half-lives of the 
investigational drug (whichever is longer). 
8. Either a history of significant arrhythmia, or a 
history of conditions known to increase the 
proarrhythmic risk (e.g., congestive heart failure, 
long QT Syndrome, hypokalemia) . 
9. Radiological evidence of bony obliteration of the 
round window membrane on pre-operative high- 
resolution CT imaging of the temporal bone. 
10. Loss of cochlear fluid signals on pre-operative MRI 
imaging, suggestive of fibrosis or ossification of the 
cochlea. 
11. Any probihited concomitant therapy listed in the 
§5.8.1 Other prohibited concomitant therapies. 
Statistical Analysis 
Pharmacokinetic (PK) Analysis: 
The number and percentage of participants from Arm A 
with levels of SENS-401 in the perilymph above the 
Limit of Quantification on day of cochlear implant will 
be summarised. Paired tests will be performed for 


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comparison of drug concentration between perilymph 
and plasma. 
Efficacy Analysis: 
All efficacy data will be tabulated by treatment group 
and overall. The primary efficacy analysis will be 
performed using the Full Analysis Set (FAS). 
ANCOVA: analysis of covariance model will be used to 
assess changes in the values from baseline at Day 49 
visit and at EOS/ET. 
Safety Analysis: 
All safety data will be presented in tables and listings. 
Adverse events (AEs) will be coded using Medical 
Dictionary for Regulatory Activities (MedDRA). The 
number and percentage of participants with AEs and the 
number of AEs will be presented in tables by system 
organ class (SOC) and preferred term (PT), as well as 
by relationship to the study drug and by severity grade. 
At the same time, each participant will be counted only 
once within system organ class and preferred term with 
relationship to the study drug and the highest severity 
grade. Serious AEs (SAEs) will be additionally 
presented in separate tables. 
Laboratory data 
Statistical characteristics of laboratory test findings will 
be presented in tables. All laboratory data will also be 
presented in listings. 
Vital signs, physical examination, body measurements 
and 12-Lead ECG will be listed for all participants and 
(except 
for 
physical 
examination) 
descriptively 
summarised per treatment group and overall. 
Exploratory analysis: 
Participants who have impairment of the basilar 
membrane as detected by the ECochG latency shift 
and/or mid peak amplitude will be listed, grouped by 
arm. 
The number and percentage of participants with 
impairment of the basilar membrane will be summarised 
by arm. 
ANCOVA analysis and descriptive statistics to assess 
changes in hearing threshold from baseline, at Day 49 
visit and at EOS/ET, will be repeated excluding 
participants with impairment of the basilar membrane. 


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Biomarker exploratory analyses (if performed) will be 
described in the statistical analysis plan (SAP) finalized 
before database lock. 


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1.2
SCHEMA


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1.3 
SCHEDULE OF ASSESSMENTS 
Table 1: Schedule of Assessments 
Study Period 
Screening 
Treatment Perioda 
Follow-up 
Period 
 
 
 
 
Implantb 
 
 
EOS/ETc 
Study day  
Day 1a 
 
Day 8b 
 
Day 49c 
Day 105 
Visit window 
D-42 to D-1  
 
Day 8 to 14  
± 7 days 
± 21 days 
Visit numberd 
1 
2 
Pre-implant 
Outpatient 
3 
Post-implant 
Outpatient 
4 
5 
Informed Consente 
X 
 
 
 
 
 
 
Demographics, medical history, prior medicine/treatment 
X 
 
 
 
 
 
 
Height (cm), weight (kg) 
X 
 
 
 
 
 
 
Physical examinationf 
X 
 
 
 
 
X 
X 
12-lead resting ECGg 
X 
 
 
 
 
X 
X 
Vital signs (SBP, DBP, HR, RR, Temp)h 
X 
 
 
 
 
X 
X 
Clinical Laboratory testing (haematology, chemistry)i 
X 
 
 
 
 
X 
X 
Pregnancy test for WOCBPj 
X 
 
 
 
 
X 
X 
Concomitant medication/treatmentsk 
X 
Xk 
 
X 
 
X 
X 
Inclusion and exclusion criterial 
X 
X 
 
 
 
 
 
Testing for COVID-19m 
 
X 
 
 
 
 
 
Biomarker blood samplingn 
 
Xn 
 
 
 
X 
X 
Randomization, dispensing of SENS-401 & diaryo 
 
X 
 
 
 
 
 
SENS-401 43.5 mg twice dailya (Arm A) 
 
X 
X 
X 
X 
X 
 


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Study Period 
Screening 
Treatment Perioda 
Follow-up 
Period 
 
 
 
 
Implantb 
 
 
EOS/ETc 
Study day  
Day 1a 
 
Day 8b 
 
Day 49c 
Day 105 
Visit window 
D-42 to D-1  
 
Day 8 to 14  
± 7 days 
± 21 days 
Visit numberd 
1 
2 
Pre-implant 
Outpatient 
3 
Post-implant 
Outpatient 
4 
5 
Check study diary and perform drug reconciliationp 
 
 
 
X 
 
X 
 
SENS-401 plasma collectionq (Arm A) 
 
 
 
X 
 
 
 
SENS-401 perilymph collectionr (Arm A) 
 
 
 
X 
 
 
 
Hearing Test – PTA (0.125 to 4 kHz)s 
X 
Xs 
 
 
 
X 
X 
Otoscopic Examinations 
X 
Xs 
 
 
 
X 
X 
Immitance Audiometrys 
X 
Xs 
 
 
 
X 
X 
Cochlear Implant Surgeryt 
 
 
 
X 
 
 
 
Electrocochleographyu 
 
 
 
X 
 
 
 
AEs/ SAEsv 
 
Xv 
X 
X 
X 
X 
X 
ABBREVIATIONS: AE = adverse event; b.i.d. = twice daily; COVID-19 = coronavirus 2019; D = study day; DBP = diastolic blood pressure; ECG = electrocardiogram; EOS 
= end of study visit; ET = early termination visit; HR = heart rate; PTA = pure tone audiometry; RR = respiratory rate; SAE = serious adverse event; SBP = systolic blood 
pressure; Temp = temperature (ºCelcius); WOCBP = woman of child-bearing potential. 
a. See Section 6.1.2. All participants must attend Day 1 visit ensuring that if randomized to Arm A, they will adhere to the fasting restrictions (see Section 5.1.1). Only 
participants randomized to Arm A will be treated with study drug (see footnote [o]). On the morning of Day 1, Arm A participants will be dispensed one kit (12 bottles of 
30 tablets each) and will take the first dose under supervision at the study site as per Section 5.1.1. Study staff will explain dosing and storage instructions and importance 
of treatment compliance (at least 70% compliance in the 3 days prior to cochlear implant surgery and for the morning dose on day of surgery [i.e. no more than 2 missed 
doses], and at least 70% compliant overall for the dosing period prior to surgery [i.e. no more than 4 missed doses if surgery occurred at Day 8, 5 if at Day 9 or 10, and 6 
if at Day 11],…). Treatment period: Commencing Day 1, 43.5 mg oral SENS-401 will be administered as described in Section 5.1.1 twice-daily from 7 to 13 days (see 
also footnote [b]), on the day of cochlear implant surgery (morning dose after blood collection for PK), and twice-daily until attending the Day 49 visit. 
b. All participants will undergo cochlear implant surgery between Day 8 and 14 as indicated in footnote [t]. Participants must have consented to cochlear implant surgery 
prior to being approached for this study.. 


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c. All participants will attend the study site for the Day 49 visit (Arm A participants will continue to take study drug until attending this visit) and for the EOS. Arm A 
participants will return all study drug containers (even if empty) and any unused study drug at the Day 49 visit. Both visits should ideally but not necessarily coincide with 
standard-of-care cochlear implant assessment visits. If a participant withdraws or is withdrawn from the study, they will be asked to attend an early termination (ET) visit 
with the same procedures as EOS, including audiometric testing and biomarker sampling if willing. Visit windows: Day 49 visit ± 7 days; EOS: Day 105 ± 21 days. 
d. All participants will attend the study site for 5 visits as indicated and will be advised to contact the study site during outpatient periods if they have queries or concerns. 
Such contact will be documented. Unscheduled visits for study-related safety are at the discretion of the Investigator and will be documented in source document and in 
the eCRF. 
e. 
Voluntary, signed, informed consent on forms approved by the Ethics Committee is required prior to the first screening assessment. 
f. 
Physical examination will be conducted by the Investigator (physician) as per Section 7.1. Unscheduled symptom-directed physical examination during the study are at the 
discretion of the Investigator if required for safety. 
g. Single 12-lead ECG will be performed after participant supine for at least 10 minutes (see Section 7.3). Unscheduled ECGs during the study are at the discretion of the 
Investigator if required for safety. 
h. Vital signs will be measured after the participant is supine for at least 5 minutes (see Section 7.2.1). Unscheduled vital signs during the study are at the discretion of the 
Investigator if required for safety. 
i. 
Fasting blood samples will be collected from all participants (Arm A and Arm B) for haematology and chemistry (see Section 7.4.1; fasted for at least 8 hours). Unscheduled 
samples collected for clinical laboratory testing during the study are at the discretion of the Investigator if required for safety. 
j. 
Blood samples will be collected from all WOCBP for serum pregnancy testing (human chorionic gonadotropin [hCG]) at screening, and urine samples collected from 
Arm A WOCBP only for pregnancy testing (hCG) at the Day 49 visit and EOS/ET. 
k. All concomitant medications and treatments will be documented and entered into the eCRF. On Day 1: to be checked before randomization with any concomitant 
medication/treatment required on Day 1 after randomization also recorded. 
l. 
Eligibility for all participants must be confirmed prior to randomization and first dose on Day 1. 
m. Participants will be tested for SARS-Cov-2 (COVID-19) on Day 1 prior to randomization as per Section 7.4.3. If positive, the participant will be deemed a screen failure 
and must not be randomized. Any other COVID-19 screening or testing will be as per Institutional and local regulatory guidelines and requirements. 
n. Blood samples will be collected from all participants (Arm A and Arm B) for biomarker research as per Section 6.6. On Day 1: to be collected after randomization for 
both Arm A (pre-first dose) and Arm B participants. 
o. In the morning of Day 1 after confirming eligibility, participants will be randomized pre-dose to either Arm A or Arm B. Arm A will be dispensed SENS-401 kit and study 
diary (see footnote [p]) on Day 1 and treated with SENS-401 as per footnote (a). Arm B (control group) will not be treated with SENS-401 at any time. The study is open- 
label and there is no placebo treatment. 
p. Study staff will give Arm A participants a paper study diary on Day 1 and will explain how to record times and dates of study drug administration including number of 
tablets taken (daily first and last meal times will also be recorded). Participants will be reminded to bring the study diary and unused study drug with all empty or full 
bottles to subsequent site visits, at which study staff will review the study diary for treatment compliance and perform drug reconciliation. Study staff will transcribe drug 
administration details from the study diary into the eCRF. The study diary and study drug will be returned to the participant on Day 8 and reminded to return both (including 
empty bottles) at the visit on Day 49. The diary will be considered source document and study staff will retain the diary at the Day 49 visit. 


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q. One blood sample will be taken from Arm A participants only prior to the morning dose on the day of cochlear implant surgery to determine SENS-401 plasma 
concentration. See Section 6.2.1. Blood samples are not required from Arm B participants on Day 8. 
r. 
During the cochlear implant surgery, one (1) perilymph sample of at least 1 μL will be collected from Arm A participants only to determine SENS-401 concentration as 
per Section 6.2.2. Perilymph samples are not required from Arm B participants. 
s. 
See Section 6.3 for audiometric testing and Section 6.4.1 for otoscopic examination. At Screening, on Day 1, on Day 49, and EOS/ET, audiometric assessments will be 
conducted for all participants (Arm A and Arm B). On Day 1: to be conducted after randomization for both Arm A participants (pre-first dose) and Arm B participants. 
On Day 49 and EOS/ET: to be conducted with the Cochlear™ Nucleus® C1622 turned off. 
t. 
Cochlear implant surgery will be performed as standard of care using model Cochlear™ Nucleus® C1622. See Section 6.5. 
u. Electrocochleography will be performed during cochlear implant surgery for all participants (Arm A and Arm B) as per Section 6.4.2. 
v. Adverse events will be recorded throughout the study from the time of informed consent for all participants (Arm A and Arm B). See Section 7.5. On Day 1: to be checked 
before randomization and any AEs experienced on Day 1 post-randomization also recorded. 


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TABLE OF CONTENTS 
1 
PROTOCOL SUMMARY ...................................................................................... 3 
1.1 
PROTOCOL SYNOPSIS ................................................................................... 3 
1.2 
SCHEMA ............................................................................................................ 11 
1.3 
SCHEDULE OF ASSESSMENTS ............................................................................ 12 
TABLE OF CONTENTS ............................................................................................... 16 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ............................... 20 
2 
INTRODUCTION AND RATIONALE ............................................................... 25 
2.1 
DISEASE BACKGROUND .................................................................................... 25 
2.2 
SENS-401: ORAL (R)-AZASETRON BESYLATE .................................................. 25 
2.2.1 Clinical Studies ............................................................................................ 26 
2.2.2 Nonclinical Studies ...................................................................................... 27 
2.2.3 Safety and Risk/Benefit Assessment ............................................................. 29 
2.3 
RATIONALE ....................................................................................................... 29 
2.3.1 Rationale for the Study ................................................................................. 29 
2.3.2 Rationale for the dose and the duration of the treatment exposure ............. 30 
3 
STUDY OBJECTIVES AND ENDPOINTS ........................................................ 31 
4 
INVESTIGATIONAL PLAN ................................................................................ 33 
4.1 
DESCRIPTION OF OVERALL STUDY DESIGN AND PLAN ...................................... 33 
4.2 
DISCUSSION OF STUDY DESIGN INCLUDING CHOICE OF CONTROL GROUPS ...... 34 
4.3 
SELECTION OF STUDY POPULATION .................................................................. 34 
4.3.1 Inclusion Criteria ......................................................................................... 34 
4.3.2 Exclusion Criteria ........................................................................................ 35 
4.3.3 Screen Failures ............................................................................................ 35 
4.3.4 Withdrawal of Participants .......................................................................... 36 
4.3.4.1 
Replacement of Withdrawn/Discontinued Participants ....................... 37 
4.3.5 Lost to Follow-Up ........................................................................................ 37 
4.3.6 Study Discontinuation .................................................................................. 37 
4.3.7 Treatment Discontinuation – Safety Stopping Rules.................................... 37 
4.3.8 Emergency Unblinding of Study Subjects .................................................... 38 
5 
TRIAL INTERVENTIONS/TREATMENTS ...................................................... 39 
5.1 
INVESTIGATIONAL MEDICINAL PRODUCT (IMP) ............................................... 39 
5.1.1 SENS-401 ..................................................................................................... 39 
5.2 
SELECTION OF DOSE IN THE STUDY .................................................................. 40 
5.3 
SELECTION AND TIMING OF DOSE FOR EACH PARTICIPANT ............................... 40 
5.4 
DOSE INTERRUPTIONS AND REDUCTIONS .......................................................... 40 
5.5 
SUPPLY, PACKAGING AND LABELLING OF STUDY TREATMENTS ....................... 40 
5.6 
STORAGE OF STUDY TREATMENTS .................................................................... 41 
5.7 
ACCOUNTABILITY, RECONCILIATION AND RETURN OF THE STUDY TREATMENTS 
41 
5.8 
PROHIBITED CONCOMITANT THERAPY .............................................................. 42 
5.8.1 Other prohibited concomitant therapies ...................................................... 42 
5.9 
TREATMENT COMPLIANCE ................................................................................ 43 
5.10 
MEASURES TO MINIMIZE BIAS .......................................................................... 43 


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5.10.1 Randomization Procedures .......................................................................... 43 
5.10.2 Blinding ........................................................................................................ 44 
6 
STUDY ASSESSMENTS AND PROCEDURES ................................................ 45 
6.1 
STUDY CONDUCT SCHEDULE ............................................................................ 45 
6.1.1 Screening Day -42 to Day -1 ....................................................................... 45 
6.1.2 Day 1 Randomization and First dose ........................................................... 45 
6.1.3 Pre-implant Outpatient Period .................................................................... 46 
6.1.4 Day 8 to 14 Cochlear Implant Surgery ....................................................... 46 
6.1.5 Post-implant Outpatient Period ................................................................... 47 
6.1.6 Day 49 Visit.................................................................................................. 47 
6.1.7 End of Study Visit (EOS) .............................................................................. 47 
6.1.8 Permitted Visit Windows .............................................................................. 48 
6.2 
PHARMACOKINETICS ......................................................................................... 48 
6.2.1 Blood Sampling for SENS-401 Concentration ............................................. 48 
6.2.2 Perilymph Sampling for SENS-401 Measurement – Primary Endpoint ...... 48 
6.3 
AUDIOMETRIC TESTING .................................................................................... 48 
6.3.1 Pure Tone Audiometry (PTA) ...................................................................... 48 
6.3.2 Immitance Audiometry ................................................................................. 49 
6.4 
EAR EXAMINATION ........................................................................................... 49 
6.4.1 Otoscopic Examination ................................................................................ 49 
6.4.2 Electrocochleography .................................................................................. 49 
6.5 
COCHLEAR IMPLANT SURGERY ......................................................................... 50 
6.6 
BIOMARKERS .................................................................................................... 50 
7 
SAFETY ASSESSMENTS .................................................................................... 52 
7.1 
PHYSICAL EXAMINATION .................................................................................. 52 
7.2 
VITAL SIGNS AND BODY MEASUREMENTS ........................................................ 52 
7.2.1 Vital Signs .................................................................................................... 52 
7.2.2 Body Measurements ..................................................................................... 52 
7.3 
12-LEAD ECGS ......................................................................................................................... 52 
7.4 
CLINICAL LABORATORY TESTS ......................................................................... 53 
7.4.1 Safety Blood Tests – Chemistry and Haematology ...................................... 53 
7.4.2 Pregnancy Testing ........................................................................................ 54 
7.4.3 Testing for SARS-CoV-2 (COVID-19) ......................................................... 54 
7.5 
ADVERSE EVENTS (AES)................................................................................... 54 
7.5.1 Definitions .................................................................................................... 55 
7.5.2 Causal Relationship to Investigational Medicinal Product and Other Study 
Treatments/Procedures............................................................................................. 56 
7.5.3 Severity Grading of Adverse Events ............................................................. 57 
7.5.4 Documentation of Adverse Events ............................................................... 57 
7.5.5 Adverse Events of Special Interest ............................................................... 58 
7.5.6 Treatment of Overdose ................................................................................. 58 
7.6 
SERIOUS ADVERSE EVENTS (SAES) .................................................................. 59 
7.6.1 Definitions of Serious Adverse Events (SAEs) ............................................. 59 
7.6.2 Pregnancy .................................................................................................... 60 
7.6.3 Reporting for Serious Adverse Events (24 hours) ........................................ 60 
7.7 
SAFETY REVIEW COMMITTEE OR DSMB .......................................................... 60 
8 
STATISTICAL ANALYSES ................................................................................. 61 


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8.1 
SAMPLE SIZE ..................................................................................................... 61 
8.2 
GENERAL STATISTICAL APPROACH ................................................................... 61 
8.3 
ANALYSIS SETS ................................................................................................. 62 
8.3.1 PK Set ........................................................................................................... 62 
8.3.2 Full Analysis Set (FAS) ................................................................................ 62 
8.4 
DEMOGRAPHICS AND BASELINE CHARACTERISTICS .......................................... 62 
8.4.1 Demographics .............................................................................................. 62 
8.4.2 Medical History ........................................................................................... 62 
8.4.3 Prior Medications ........................................................................................ 62 
8.5 
PROTOCOL DEVIATIONS .................................................................................... 62 
8.6 
PARTICIPANT DISPOSITION ................................................................................ 62 
8.7 
TREATMENT COMPLIANCE ................................................................................ 63 
8.8 
PHARMACOKINETIC ENDPOINTS ........................................................................ 63 
8.8.1 Primary Endpoint ......................................................................................... 63 
8.8.2 Secondary Endpoint ..................................................................................... 63 
8.9 
EFFICACY ENDPOINTS ....................................................................................... 63 
8.9.1 Hearing threshold ........................................................................................ 63 
8.9.2 Exploratory Endpoints ................................................................................. 63 
8.9.2.1 
Assessment of Basilar Membrane Fixation .......................................... 63 
8.9.2.2 
Hearing threshold assessment excluding participants with IBM ......... 63 
8.9.2.3 
Biomarker Analysis.............................................................................. 63 
8.10 
SAFETY ENDPOINTS .......................................................................................... 63 
8.10.1 Adverse Events ............................................................................................. 63 
8.10.2 Vital Signs .................................................................................................... 64 
8.10.3 Body Measurements ..................................................................................... 64 
8.10.4 Physical Examination ................................................................................... 64 
8.10.5 12-Lead ECG ............................................................................................... 64 
8.10.6 Clinical Laboratory Tests ............................................................................ 64 
8.10.7 Pregnancy .................................................................................................... 65 
8.10.8 Testing for SARS-CoV-2 (COVID-19) ......................................................... 65 
9 
STUDY ADMINISTRATION ............................................................................... 66 
9.1 
ETHICAL CONSIDERATIONS ............................................................................... 66 
9.1.1 Ethical Principles ......................................................................................... 66 
9.1.2 Informed Consent ......................................................................................... 66 
9.1.3 Ethics Committee/Human Research Ethics Committee (HREC) Approval 66 
9.2 
PROTOCOL ADHERENCE .................................................................................... 66 
9.3 
PROTOCOL AMENDMENTS ................................................................................. 67 
9.4 
DATA HANDLING AND RECORD KEEPING ......................................................... 67 
9.5 
QUALITY CONTROL AND QUALITY ASSURANCE ............................................... 68 
9.6 
PUBLICATION POLICY ....................................................................................... 69 
9.7 
FINANCIAL DISCLOSURE ................................................................................... 69 
10 REFERENCES ....................................................................................................... 70 
11 APPENDICES ........................................................................................................ 71 
11.1 
HIGHLY EFFECTIVE METHODS OF CONTRACEPTION .......................................... 71 


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List of Tables in Text 
Table 1: Schedule of Assessments ................................................................................... 12 
Table 2: Pharmacokinetics of twice-daily 43.5 mg SENS-401 in Healthy Human 
Volunteers ........................................................................................................................ 26 
Table 3: Non clinical Toxicology Study Parameters for SENS-401 ................................ 28 
Table 4: Permitted Visit Windows ................................................................................... 48 


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
 
ABR 
Auditory brain stem responses 
ADR 
Adverse Drug Reaction 
AE 
Adverse event 
ALT 
Alanine transaminase 
ANCOVA 
Analysis of covariance model 
APTT 
Activated partial thromboplastin time 
AST 
Aspartate transaminase 
ATC 
Anatomical therapeutic class 
AUC0-24 
Area under the plasma concentration-time curve from time 0 to 
time 24 hours 
b.i.d. 
Twice daily 
CI 
Confidence interval 
CIO 
Cisplatin-induced otoxicity 
CKD-EPI 
Chronic Kidney Disease Epidemiolog Collaboration equation for 
calculating creatinine clearance 
CL/F 
Apparent total clearance from plasma after oral administration 
Cmax 
Maximum observed plasma concentration 
CNS 
Central nervous system 
COVID-19 
Corona virus disease 2019 
CRO 
Clinical research organisation` 
CSR 
Clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DBP 
Diastolic blood pressure 
DPOAE 
Distortion product otoacoustic emissions 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
ECochG 
Electrocochleography 
EOS 
End of study visit 
ET 
Early termination visit 
FAS 
Full analysis set 
GCP 
Good Clinical Practice 
GGT 
Gamma-glutamyl transferase 
GMP 
Good Manufacturing Practice 


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HDPE 
High density polyethylene 
hERG 
Human ether-a-go-go gene 
HR 
Heart rate 
HREC 
Human Research Ethics Committee 
IC50 
Half maximal inhibitory concentration 
ICH 
International Conference on Harmonization 
IMP 
Investigational medicinal product 
INR 
International normalized ratio 
Investigator 
Principal Investigator or designated co- or sub-Investigator 
IRB 
Institutional Review Board 
IV 
Intravenous 
LDH 
Lactate dehydrogenase 
MDRD 
Modification of Diet in Renal Disease Study equation for 
calculating creatinine clearance 
MedDRA 
Medical Dictionary for Regulatory Activities 
MTD 
Maximum tolerated dose 
NOAEL 
No observed adverse event level 
PD 
Pharmacodynamic 
PICF 
Participant informed consent form 
PK 
Pharmacokinetics 
PN 
Preferred name 
PT 
Preferred term 
PTA 
Pure tone audiometry 
PTT 
Pure tone threshold 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SBP 
Systolic blood pressure 
SD 
Standard deviation 
SOA 
Schedule of Assessments 
SOC 
System organ class 
SSNHL 
Sudden sensorineural hearing loss 
SUSAR 
Suspected unexpected serious adverse reaction 
TEAE 
Treatment emergent adverse event 
T1/2 
Terminal half-life 
Tmax 
Time to maximum observed plasma concentration 


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WOCBP 
Woman of child-bearing potential 


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PROTOCOL APPROVAL/ SIGNATURES 
I approve the following protocol entitled “A Phase IIa, Multicenter, Randomized, 
Controlled, Open-label Study to Evaluate the Presence of SENS-401 in the Perilymph 
after 7 days of repeated oral administration in Adult Participants Scheduled for Cochlear 
Implantation”, Version 3.0 dated 08 February 2023. 
 
SPONSOR SIGNATURE 
 
 
Signature: 
Name: 
Role: 
Date: 


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PRINCIPAL INVESTIGATOR SIGNATURE 
 
A Phase IIa, Multicenter, Randomized, Controlled, Open-label Study to Evaluate the 
Presence of SENS-401 in the Perilymph after 7 days of repeated oral administration in 
Adult Participants Scheduled for Cochlear Implantation 
Version: 3.0 
 
Issue Date: 08 February 2023 
 
Principal Investigator Agreement 
 
I have read the above-mentioned protocol and am aware of my responsibilities as Principal 
Investigator for this study. As such, I agree to: 
- 
Personally supervise the conduct of this trial; 
- 
Conduct the trial in accordance with International Conference on Harmonization 
(ICH) E6 Good Clinical Practice: Consolidated Guidance (GCP), applicable 
regulatory requirements, and the protocol; 
- 
Comply with the procedures for data recording and reporting as required by the 
regulatory authorities and the Sponsor; 
- 
Permit monitoring, auditing, and inspection of study records as required by ICH 
GCP; 
- 
Retain the essential clinical study documents as required by ICH GCP, local 
regulatory requirements, and the Sponsor. 
 
 
Principal Investigator Signature: 
 
Principal Investigator Name: 
 
Date: 
 
/ 
/2023 














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3 STUDY OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary: 
 
x To detect the presence of SENS-401 in x Percentage of participants from Arm A 
with levels of SENS-401 in the 
perilymph 
above 
the 
Limit 
of 
Quantification on day of cochlear 
implant surgery after seven days of 
SENS-401. 
the 
perilymph 
of 
participants 
undergoing cochlear implant surgery 
after 7 days of oral administration of 
SENS-401. 
Secondary: 
 
x To 
measure 
the 
SENS-401 
concentrations in the perilymph and 
plasma of participants undergoing 
cochlear implant surgery after 7 days 
of oral administration of SENS-401. 
x SENS-401 perilymph concentration 
on day of cochlear implant surgery 
after seven days of SENS-401. 
x To 
compare 
the 
SENS-401 
concentrations 
in 
perilymph 
and 
plasma of participants undergoing 
cochlear implant surgery after 7 days 
of oral administration of SENS-401. 
x SENS-401 plasma concentration on 
day of cochlear implant surgery after 
seven days of SENS-401 
x To assess the efficacy of repeated oral 
administration with SENS-401 to 
protect against residual low frequency 
hearing loss in participants undergoing 
cochlear implant surgery at the Day 49 
visit and at EOS/ET. 
x Change of hearing threshold from 
baseline in the implanted ear at 500 Hz 
after 
repeated 
administration 
of 
SENS-401, as assessed by pure tone 
audiometry (PTA) at the Day 49 visit 
and at EOS/ET. 
 
x Change of hearing threshold from 
baseline in the implanted ear at 250 Hz 
and 
750 
Hz 
after 
repeated 
administration 
of 
SENS-401, 
as 
assessed by pure tone audiometry 
(PTA) at the Day 49 visit and at 
EOS/ET. 
x To assess the safety and tolerability of 
SENS-401 given for the whole 
duration of the study. 
x Incidence of treatment emergent AEs 
and SAEs in each participant until the 
end of their study participation. 
Exploratory: 
x To assess the efficacy of repeated oral In a subset of participants assessed by a 
neurophysiologist 
to 
have 
no 
electrophysiological evidence of basilar 
membrane fixation: 
administration with SENS-401 to 
protect against residual low frequency 
hearing loss in participants undergoing 
cochlear 
implant 
surgery; 
here 
performed on a subset of participants 


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Objectives 
Endpoints 
with no electrophysiological evidence 
of basilar membrane fixation as 
described in Section 6.4.2. 
x Change of hearing threshold from 
baseline in the implanted ear at 500 Hz 
after 
repeated 
administration 
of 
SENS-401, as assessed by pure tone 
audiometry (PTA) 
x Change of hearing threshold from 
baseline in the implanted ear at 250 Hz 
and 
750 
Hz 
after 
repeated 
administration 
of 
SENS-401, 
as 
assessed by pure tone audiometry 
(PTA). 
x To explore the correlation between 
biomarkers 
already 
pre-identified 
(e.g., prestin) or that will be identified 
in the future with clinical features of 
interest. 
x Serum/plasma 
concentrations 
of 
selected biomarkers at baseline (i.e., 
Day 1, and pre-dose for Arm A), at the 
Day 49 visit, and at EOS/ET. 


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4 INVESTIGATIONAL PLAN 
4.1 
DESCRIPTION OF OVERALL STUDY DESIGN AND PLAN 
This is a Phase IIa, open-label, randomized and controlled study in adult participants with 
preoperative threshold levels in the impaired ear demonstrating unaided audiometric 
WKUHVKROGRIG%RUEHWWHULHG% at 500 Hz), who meet the locally approved 
indication for, and have already consented to receiving, cochlear implant Cochlear™ 
Nucleus® C1622. This model is medically indicated, is an appropriate choice for the type 
of participant to be enrolled in this study, and ensures a homogenous study population. 
Study assessments are indicated in the Schedule of Assessments (SOA) Table 1 
(Section 1.3). 
After a screening period of 1 to 42 days (including informed consent to this study prior to 
the first screening assessment), 27 eligible participants will be randomized on Day 1 to 
either Arm A (18 participants treated with oral 43.5 mg SENS-401 twice daily for 7 weeks 
[one to two weeks before cochlear implant surgery and 5 to 6 weeks after]) or Arm B (9 
participants receiving no treatment with SENS-401). 
For participants in Arm A, twice-daily oral dosing with 43.5 mg SENS-401 will 
commence on Day 1 with cochlear implant surgery performed between Day 8 and Day 
14. If for any reason the surgery is delayed beyond Day 14 , the participant should cease 
taking SENS-401 and be withdrawn from the study (see Section 4.3.4). The participant 
may be screened again once a new date of surgery is identified (see Section 4.3.3). 
Blood and perilymph will be sampled from Arm A participants for measurement of SENS- 
401 on the day of the cochlear implant surgery (blood sampling pre-morning dose of 
SENS-401 and perilymph sampling during surgery). Data from ECochG during cochlear 
implant surgery will be obtained for both Arm A and Arm B participants. During electrode 
insertion, the Investigator may use ECochG if desired and/or their usual practice. After 
electrode insertion, an ECochG electrode sweep will be performed for all participants to 
generate exploratory study data. 
Arm A participants will continue to take SENS-401 twice daily including on day of 
surgery and until attending the Day 49 visit. Efficacy assessments including PTA and 
immittance audiometry, will be conducted with baseline assessments conducted during 
Screening and Day 1 pre-first dose. 
Participants randomized to Arm B on Day 1 will not take SENS-401 at any time, but will 
similarly undergo their planned cochlear implant surgery between Day 8 to 14 and return 
for the Day 49 visit. Arm B participants will undertake the same audiometric tests as Arm 
A participants in order to evaluate trends of efficacy, but will not be required to provide 
blood or perilymph samples for PK analysis on the day of cochlear implant surgery If the 
cochlear implant surgery is delayed beyond Day 14, participants will be withdrawn from 
the study but may be re-screened once the revised date of surgery is confirmed (see 
Sections 4.3.3 & 4.3.4). 
All participants will attend an EOS on Day 105 for final efficacy audiometric assessments. 
The Day 49 visit and EOS should ideally but not necessarily coincide with standard-of- 
care visits for switching on and programming of the cochlear implant respectively, for the 
convenience of the participant. Safety assessments according to the SOA will be 
performed at every site visit for all participants, and samples for exploratory biomarker 
analysis will be collected at baseline (Day 1), at the Day 49 visit, and at EOS . 


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The end of the study is defined as the date of the last visit of the last participant in the 
study or last scheduled procedure shown in the schedule of assessment for the last 
participant in the study globally. 
 
4.2 
DISCUSSION OF STUDY DESIGN INCLUDING CHOICE OF CONTROL 
GROUPS 
This study was designed to study mainly the trans-compartmental passage of SENS-401 
into the cochlea indicated by detection of SENS-401 in the perilymph (primary objective). 
Eighteen participants will be treated with SENS-401 for at least 7 days preceding the 
collection of perilymph. This sample size is generally considered to be large enough to 
provide robust information on this PK objective. Moreover, this type of PK study does 
not generally require blinding or a placebo control group. 
Participants will be randomized unblinded to a treated group (Arm A) and untreated 
control group (Arm B) for the efficacy analysis as a secondary objective. 
4.3 
SELECTION OF STUDY POPULATION 
4.3.1 Inclusion Criteria 
Potential participants must fulfil all of the following inclusion criteria to be eligible for 
the study: 
1. Adults aged from 18 years and older. 
2. Meets the locally approved indication for cochlear implantation with the Cochlear™ 
Nucleus® C1622 and has preoperative threshold levels in the impaired ear 
demonstrating unaided audiometric threshold of G%RUEHWWHULH dB) at 500 
Hz. The individual must have freely consented to the cochlear implant surgery before 
being offered to participate in the SENS-401-203 study. 
3. Signed and dated written informed consent. 
4. Females who have or may have male sexual partners must meet one of the following 
criteria at Screening: 
x Postmenopausal (defined as 12 consecutive months with no menses without an 
alternative medical cause), surgically sterile, or abstinent. 
or 
x A woman of childbearing potential (WOCBP) (any female who has experienced 
menarche and who is not permanently sterile or postmenopausal) practicing a 
method of highly effective birth control that is listed in Appendix 11.1 and is 
willing to continue to use highly effective contraception (as per Appendix 11.1) 
for the duration of study participation and for at least 30 days after the final dose 
of study drug. 
All WOCBP must have a negative serum pregnancy test at screening before the first 
dose of study drug is taken. Participants randomized to Arm B on Day 1 will not be 
required to further adhere to the contraception requirements of the study. 
Note: No contraception measures are needed for male participants, including those 
with pregnant or non-pregnant WOCBP partner. 
5. Vaccinated against coronavirus disease 2019 (COVID-19) per local vaccination 
schema requirement or previously contracted the disease and recovered within the last 
six months. 


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4.3.2 Exclusion Criteria 
Individuals will be excluded from the study if any of the following criteria apply: 
1. 0RGHUDWHWRVHYHUHUHQDOLPSDLUPHQWGHILQHGE\DFUHDWLQLQHFOHDUDQFHPOPLQ
(calculated with the Cockcroft-Gault formula for individuals <65 years old and with 
the the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine 
equation or the Modification of Diet in Renal Disease Study (MDRD) equation for 
LQGLYLGXDOV\HDUVROG 
2. Any condition that, in the opinion of the Investigator, may compromise the safety or 
compliance of the participant or would preclude the participant from successful 
completion of the study. 
3. Unable or unwilling to comply with the protocol requirements. 
4. Any therapy known as ototoxic (e.g. aminoglycosides, cisplatin, quinine etc.) at the 
current time or in the past 6 months prior to study inclusion. Loop diuretics at normal 
therapeutic doses are permitted. 
5. Known hypersensitivity, allergy or intolerance to the study medication or any history 
of severe abnormal drug reaction. 
6. Pregnant or breast-feeding. 
7. Treatment with any investigational agent within 4 weeks prior to screening or 5 half- 
lives of the investigational drug (whichever is longer). 
8. Either a history of significant arrhythmia, or a history of conditions known to increase 
the proarrhythmic risk (e.g., congestive heart failure, long QT Syndrome, 
hypokalemia). 
9. Radiological evidence of bony obliteration of the round window membrane on pre- 
operative high-resolution CT imaging of the temporal bone. 
10. Loss of cochlear fluid signals on pre-operative MRI imaging, suggestive of fibrosis or 
ossification of the cochlea. 
11. Any probihited concomitant therapy listed in the §5.8.1 Other prohibited concomitant 
therapies. 
4.3.3 Screen Failures 
Screen failures are participants who signed the PICF but are found to be ineligible for the 
study and are not randomized. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure participants to meet the Consolidated 
Standards of Reporting Trials publishing requirements and to respond to queries from 
regulatory authorities. The minimum information for screen failures includes signed 
PICF, demographics, reason for screen failure, eligibility criteria, and any serious adverse 
events. Screen failure information will be monitored and entered into the eCRF. 
Unscheduled visits may be planned to assess, confirm, and follow-up on out-of-range 
clinical laboratory test, vital sign, or ECG values that determine a volunteer’s eligibility, 
with each assessment to be repeated once only. The result of any re-test must be 
considered for volunteer eligibility and must be available prior to randomization. Findings 
made during unscheduled visits will be reported in the source document. 
Individuals who fail screening due to an underlying medical condition previously 
unknown to them (including COVID-19 but not including other acute self-limiting viral 
infections) will be provided with the appropriate referrals for guidance and counselling 
for their condition, if required. 


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Participants whose cochlear implant surgery is unavoidably delayed beyond Day 14 
(including after commencing study drug for Arm A participants) may be re-screened for 
the study once a new surgery date is confirmed, if they agree. This will be decided on a 
case-by-case basis after discussion between the Investigator, Sponsor and Medical 
Monitor. The participant should first be fully withdrawn from their first enrolment in the 
study, including attending an ET. The participant will then sign a new informed consent, 
be assigned a new participant number, and undergo all screening procedures again within 
the required timeframe. They should be made aware that they may be randomized to a 
different arm than previously. 
4.3.4 Withdrawal of Participants 
Withdrawal of consent is when a participant wishes to withdraw from further participation 
in the study in the absence of an Investigator-determined medical need to withdraw. 
Participants may withdraw from the study at any time upon request and irrespective of the 
reason. The Investigator will endeavour to obtain the reason for withdrawal, and if the 
participant gives a reason this will be recorded in the eCRF. The Investigator will ask the 
participant to attend an early termination visit (ET) where all procedures planned for EOS 
will be performed (see SOA Table 1). This includes audiometric testing and biomarker 
sampling if the participant agrees. 
If the participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. If a 
participant withdraws from the study, they may request destruction of any samples taken 
and not tested, and the Investigator must document this in the study site study records. 
The Investigator may also withdraw a participant from the study at any time for safety, 
behavioural, compliance or administrative reasons, including but not limited to: 
x Pregnancy in an Arm A female participant (must be withdrawn). Arm B participants 
may continue to participate if willing, if the Investigator permits, and if cochlear 
implant surgery proceeds (or has proceeded) as scheduled; 
x Significant non-compliance or major protocol deviation, including less than 70% 
compliance with study drug in the 3 days prior to cochlear implant surgery and less 
than 70% compliance in the entire dosing period prior to cochlear implant surgery; 
x Cochlear implant surgery is delayed beyond Day 14 (the participant must be 
withdrawn and study drug ceased if applicable). See Section 4.3.3 for possible re- 
screening of these participants; 
x Any clinical AE, laboratory abnormality or other medical condition or situation occurs 
that in the medical judgement of the Investigator would not be in the best interest of 
the person to continue to participate in the study. This includes serious and non-serious 
AEs regardless of relation to study drug (e.g., diagnosed with COVID-19); 
x An exclusion criterion newly develops or was not previously recognized that 
precludes the person from continuing to participate in the study; 
x Participating in any other investigational product study while enrolled in this study; 
x Death; 
x Other, such as termination of the study by the Sponsor. 
If a participant stops taking study drug after the cochlear implant surgery and before the 
Day 49 visit, they may continue to participate in study assessments at the scheduled 
timepoints if willing to do so. 


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The Investigator will continue to provide medical care for any SAEs with the participant’s 
permission, until symptoms resolve and/or the participant’s condition becomes stable. 
4.3.4.1 Replacement of Withdrawn/Discontinued Participants 
Participants who have signed the PICF but have not been randomized to treatment may 
be replaced. 
Participants who are randomized to treatment but withdraw or are withdrawn prior to 
cochlear implant surgery may be replaced on a case-by-case basis, in order to ensure 18 
participants take SENS-401 according to pre-defined compliance limits (see 
Section 5.1.1) and undergo cochlear implant surgery. The Investigator must confirm with 
the Sponsor before proceeding with replacement. 
Participants who are randomized to treatment and withdraw or are withdrawn from the 
study after cochlear implant surgery will not be replaced. 
4.3.5 Lost to Follow-Up 
A participant will be considered lost to follow-up if they repeatedly fail to attend 
scheduled visits and are unable to be contacted by the site. 
The following actions must be taken if a participant fails to return to the study site for a 
required study visit: 
x The study site must attempt to contact the participants and reschedule the missed visits 
as soon as possible and: 
o counsel the participant on the importance of maintaining the assigned visit 
schedule and returning dispensed study drug, and 
o acertain if the participant wishes to and/or should continue in the study. The reason 
will be reported to the Sponsor to identify a potential solution. 
x Before a participant is deemed lost to follow-up, the Investigator or designee must 
make every effort to regain contact with the participant (where possible, three (3) 
telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). 
x The study site must also contact the trusted person designated by the participant and 
the participant’s attending physician (e.g., general practitioner or local equivalent). 
x All attempts at contact must be documented in the participant’s medical record. 
If the participant continues to be unreachable, they will be considered to have withdrawn 
from the study. 
4.3.6 Study Discontinuation 
The Sponsor, Principal Investigator, approving EC/HREC, and regulatory authorities 
independently reserve the right to discontinue the trial at any time for safety or other 
reasons. Where practical, this will be done in consultation with the Sponsor and all parties 
notified in writing where applicable. The Sponsor and Principal Investigator will ensure 
that participants’ interest and safety are protected, and the Principal Investigator must 
review all participants and complete all records as required. 
4.3.7 Treatment Discontinuation – Safety Stopping Rules 
At study entry and prior to first dose of study drug, a full eligibility check will be 
performed. Participants who do not meet the study protocol inclusion/exclusion criteria 
will not be randomized or dosed. 


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Treatment will be discontinued for a participant’s safety if any of the following occur: 
x SAE considered related to study drug; 
x $GYHUVHHYHQWRI&7&$(*UDGHFRQVLGHUHGUHODWHGWRVWXG\GUXJDQGGLVFXVVHG
with Sponsor; 
x Pregnancy in an Arm A participant. 
Treatment may be discontinued for a participant’s safety if any of the following occur: 
x Clinically significant finding from 12-lead ECG (including but not limited to changes 
from baseline in QT interval corrected using Bazett’s formula [QTcB] or Fridericia’s 
formula [QTcF], as applicable) occurring after first dose: the Investigator will 
determine if the participant can continue in the study and if any change in participant 
management is required. This review of the ECG printed at the time of collection must 
be documented, and any new clinically relevant finding reported as an AE; 
x If a participant tests positive for COVID-19 after commencing study drug, the 
Investigator will decide if study drug should be discontinued (study visits/contact 
must remain virtual until participant permitted to attend study site according to local 
and institutional regulations and requirements). 
Temporary discontinuation of study drug (interruption) must be discussed on a case-by- 
case basis with the Sponsor and Medical Monitor. Rechallenge is not applicable for ECG 
abnormality but is applicable for renal/liver AEs if relevant laboratory results return to 
normal range (study drug may be restarted). 
Treatment will be suspended for all participants if clinical development of the study drug 
is suspended by the Sponsor. 
Treatment will only re-commence after timely appropriate safety review by the Sponsor 
Medical Director, Principal Investigator, and Study Medical Monitor, at a minimum. This 
process will be provided in advance in the Safety Plan. Extra internal or external experts 
may be consulted as necessary. 
4.3.8 Emergency Unblinding of Study Subjects 
The study is open-label and as such emergency unblinding is not applicable. 


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5 TRIAL INTERVENTIONS/TREATMENTS 
5.1 
INVESTIGATIONAL MEDICINAL PRODUCT (IMP) 
5.1.1 SENS-401 
SENS-401 ((R)-azasetron besylate) is the (R)-enantiomer of azesetron, a selective 5-HT3 
receptor antagonist. See Section 2.2 and the Investigator’s Brochure for further 
information. Participants will be randomized to treatment as per Section 5.10.1. 
Participants in Arm A only will take 43.5 mg SENS-401 (3 tablets) orally twice-daily 
(morning and evening) for a total of up to 56 days as follows: 
x 7 to 13 days prior to the day of cochlear implant surgery commencing Day 1. 
o Participants must be at least 70% compliant for at least the 3 days prior to cochlear 
implant surgery and for the morning dose on the day of surgery (i.e. no more than 
2 missing doses). 
x On the day of cochlear implant surgery, with first dose given after the plasma 
collection for PK and second dose in evening as scheduled. 
x For 42 to 56 days after day of cochlear implant surgery until attending the Day 49 
visit. 
o If cochlear implant surgery was performed between Day 9 to Day 14 no additional 
tablets will be dispensed and all participants will complete dosing when attending 
the Day 49 visit. 
Dosing Instructions: 
x During the course of the study, participants should not take SENS-401 within 2 hours 
of any meal/food (before or after). This fasting restriction must be strictly followed 
for the 3 days prior to cochlear implant surgery and for the morning dose on the day 
of surgery. 
x On Day 1, all participants should attend the study site in the morning ensuring that if 
randomized to Arm A they will adhere to the fasting restrictions outlined above. Once 
randomized, Arm A participants will take the first dose under supervision at the study 
site. 
x For each dose, participants will swallow three (3) tablets with a glass of water. 
x Tablets should be taken at approximately the same times (morning and evening) each 
day, with minimum of 8 hours and maximum of 16 hours between doses (i.e., 
approximately 12 hours between doses, e.g., 7AM and 7PM). 
x A dose will be considered to be missed if more than 16 hours since the last dose. 
Missed doses should be skipped and must not be taken as a double dose at the next 
dosing time. 
x If vomiting occurs, extra doses must not be taken. The participant should take the next 
dose as per the dosing schedule. In the event vomiting occurs within two hours post- 
drug intake in the three days before cochlear implant surgery, it is recommended that 
the participant contact the study site. 
Other Requirements: 
x Arm A participants must be advised to avoid skin exposure to strong sunlight and to 
wear sunglasses in bright sunlight for the duration of the study and for one (1) week 
after the last dose. 


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x Arm A participants will record each administration of IMP (date, time, number of 
tablets taken) and times of first and last meal per day in the study diary provided to 
them on Day 1, and will bring the completed diary and dispensed containers (even if 
empty) to each subsequent site visit for assessment of compliance. Study staff will 
transcribe drug administration details from the study diary into the eCRF. 
x Compliance: Participants must be at least 70% compliant with dosing for at least the 
3 days prior to cochlear implant surgery and for the morning dose on the day of surgery 
(i.e. no more than 2 missed doses), and no less than 70% compliant overall for the 
entire dosing period prior to cochlear implant surgery (i.e. no more than 4 missed 
doses if surgery occurred at Day 8, 5 if at Day 9 or 10, and 6 if at Day 11,..). If cochlear 
implant surgery is unavoidably rescheduled up to and including Day 14, participants 
will continue to take twice daily study drug without interruption as above until 
surgery. 
Total maximum number of scheduled doses: 84 to 112 (252 to 336 tablets total) 
5.2 
SELECTION OF DOSE IN THE STUDY 
See Section 2.3.2. 
5.3 
SELECTION AND TIMING OF DOSE FOR EACH PARTICIPANT 
See Sections 5.1 and 5.10.1. 
5.4 
DOSE INTERRUPTIONS AND REDUCTIONS 
No dose interruptions or reductions are permitted in the dosing period three days prior to 
cochlear implant surgery. Interruptions or reductions at other times pre-cochlear implant 
surgery will be evaluated as protocol deviations and discussed on a case-by-case basis. 
Decisions regarding dose interruptions or modifications after cochlear implant surgery 
will be made by the Investigator after discussing with the Medical Monitor based on the 
clinical evaluation of the participant. See Section 7.5.6 for instructions in the event of 
overdose. 
Treatment may be stopped by the Investigator and/or Sponsor if considered necessary for 
the safety of the participant(s) including as described in Section 4.3.7. If possible, the 
Investigator will discuss with the Medical Monitor before discontinuing treatment, and 
the Sponsor notified. 
5.5 
SUPPLY, PACKAGING AND LABELLING OF STUDY TREATMENTS 
The IMP will be manufactured and packaged according to Good Manufacturing Practice 
(GMP) and all local regulations, and supplied to the study sites with an acknowledgement 
of receipt form. The IMP will be labelled for clinical trial use in compliance with local 
regulatory requirements including Annex 13 of GMP where applicable. The certificate of 
analysis will be provided. 
SENS-401 is supplied for oral administration as 14.5 mg (10 mg free base) white, oval 
and film-coated tablets, debossed with ‘S401’ on one side. The tablets are packaged in 
high-density polyethylene (HDPE) bottles with intact induction seal and child-resistant 
closure (30 tablets per bottle). Formulation including excipients (methyl crystalline 
cellulose, starch, and magnesium stearate) is detailed in the Investigator’s Brochure. 
On Day 1, Arm A participants will be dispensed one kit each containing 12 bottles (360 
tablets in total) to ensure enough study drug for the entire dosing period. No additional 


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study drug will be dispensed in the event of permitted delay to the day of cochlear implant 
surgery. 
Supplies of the IMP will be shipped to the study sites prior to study start. 
5.6 
STORAGE OF STUDY TREATMENTS 
Refer to the Pharmacy Manual and Investigator’s Brochure for required storage and 
handling of the IMP. Prior to dispensing, the IMP must be stored in a secure and locked 
storage area with limited access, and under monitored, temperature-controlled conditions 
as required. 
Participants will be instructed to keep the IMP at room temperature (not exceeding 30ºC) 
out of reach of children. 
The Principal Investigator or appropriate delegate (e.g., Study/Site Pharmacist) are 
responsible for the correct storage and handling of the IMP while it is at site. Deviations 
from the storage requirements, including corrective actions, must be documented. 
5.7 
ACCOUNTABILITY, RECONCILIATION AND RETURN OF THE STUDY 
TREATMENTS 
The Investigator will ensure that: 
x The IMP is dispensed only to eligible participants randomized to Arm A in this study, 
and 
x Complete and current dispensing and inventory records are maintained. 
The site’s inventory/dispensing logs must record every episode of dispensing of IMP. The 
following information must be documented: 
x Date of receipt. 
x Number of tablets/containers received. 
x Batch number(s). 
x The identification of the participant to whom the tablets were dispensed. 
x The date(s), time and quantity dispensed to the volunteer. 
x The cumulative total of IMP at site. 
x Tablets and containers damaged, destroyed, or returned. 
The study monitor will perform drug accountability during routine, regular monitoring 
visits. Once the study has completed or been discontinued, final accountability and 
reconciliation will be performed. Any discrepancies will be investigated and the 
resolution documented. 
Participants will bring all IMP containers (even if empty) including unused IMP to study 
visits. Study staff will perform drug reconciliation with reference to the participant study 
diary on Day 8 and at the Day 49 visit. Compliance should be as described in 
Section 5.1.1. Any discrepancies will be documented and reasons clarified with the 
participant. All IMP container(s) and unused IMP will be retained at site at the Day 49 
visit for final monitoring. Study staff will also retain the participant diary at the Day 49 
visit and file as source document. 
All full, partially full, and empty containers of IMP must be returned to the Sponsor for 
destruction, after permission has been obtained from the Sponsor and final drug 
accountability has been performed by the study monitor. 


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5.8 
PROHIBITED CONCOMITANT THERAPY 
Any medication/therapy that is exclusionary for eligibility at Screening remains 
prohibited during the study (i.e., ototoxic therapies). Loop diuretics at normal therapeutic 
doses are permitted. Participants may be vaccinated during the study if necessary (e.g., 
COVID-19 vaccination or booster dose), but it is preferred if such vaccination(s) can be 
postponed until at least after the cochlear implant surgery. 
Corticosteroid use: Investigators will consult the separate guidance manual for cochlear 
implant surgery prepared for this study for permitted use of corticosteroids associated 
with the cochlear implant. 
Any use of concomitant medication (including vaccination) and/or treatment must be 
recorded by study staff in source document and the eCRF. Concomitant medication details 
should include at a minimum: name of medication, daily dosage, route of administration, 
duration of use (start/stop dates), and reason/indication for use. Concomitant medications 
for this study include all medications associated with the cochlear implant surgery (e.g., 
anaesthetic, pain relief). Concomitant treatment details should include at a minimum: 
treatment type, date, and reason/indication for use. 
5.8.1 Other prohibited concomitant therapies 
¾ Initiation of antidepressant treatment containing serotoninergic agents within the 
previous 24 hours due to the risk of serotoninergic syndrome. The following is a 
non-exhaustive list of serotoninergic agents: 
x Selective serotonin reuptake inhibitors (SSRIs), antidepressants such as 
citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline 
x Serotonin and norepinephrine reuptake inhibitors (SNRIs), antidepressants 
such as trazodone, duloxetine and venlafaxine 
x Bupropion, an antidepressant and tobacco-addiction medication 
x Tricyclic antidepressants, such as amitriptyline and nortriptyline 
x Monoamine 
oxidase 
inhibitors 
(MAOIs), antidepressants 
such 
as 
isocarboxazid and phenelzine 
x Anti-migraine medications such as triptans, carbamazepine and valproic acid 
x Pain medications such as opioid pain medications including codeine, fentanyl, 
hydrocodone meperidine, oxycodone and tramadol 
x Lithium, a mood stabilizer 
x Illicit drugs, including LSD, Ecstasy, cocaine and amphetamines 
x Herbal supplements, including St. John's wort, ginseng and nutmeg 
x Over-the-counter cough and cold medications containing dextromethorphan 
x Linezolid, an antibiotic 
x Ritonav, an anti-retroviral medication used to treat HIV/AIDS 
¾ Substrates of BCRP (breast cancer resistance protein) and transporter (see non- 
exhaustive below) 


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Transporter 
Gene 
Inhibitor 
P-gp 
ABCB1 
amiodarone, carvedilol, clarithromycin, dronedarone, 
itraconazole, lapatinib, lopinavir and ritonavir, propafenone, 
quinidine, ranolazine, ritonavir, saquinavir and ritonavir, 
telaprevir, tipranavir and ritonavir, verapamil 
BCRP 
ABCG2 
curcumin, cyclosporine A, eltrombopag 
OATP1B1, 
OATP1B3 
SLCO1B1, 
SLCO1B3 
atazanavir and ritonavir, clarithromycin, cyclosporine, 
erythromycin, gemfibrozil, lopinavir and ritonavir, rifampin 
(single dose), simeprevir 
OAT1, 
OAT3 
SLC22A6, 
SLC22A8 
p-aminohippuric acid (PAH), probenecid, teriflunomide 
MATE1, 
MATE2-K 
SLC47A1, 
SLC47A2 
cimetidine, dolutegravir, isavuconazole, ranolazine, 
trimethoprim, vandetanib 
¾ Calcineurin inhibitors (cyclosporine, and tacrolimus) 
 
 
Participants should discuss use of any other new concomitant medication with the 
Investigator, where possible, particularly if they have concerns about ototoxicity. 
5.9 
TREATMENT COMPLIANCE 
The first dose of study drug on Day 1 will be administered under supervision at the study 
site. Study staff will explain the required dosing regimen to the participant (see 
Section 5.1.1), and subsequent doses will be taken by the participant at home. In 
particular, study staff will emphasise treatment compliance for the period prior to and 
including the day of cochlear implant surgery as described in Section 5.1.1. Study staff 
will ask participants to retain all study drug bottles even if empty. 
Part A participants will record administration details including date and time, number of 
study drug tablets taken, and times of first and last meal, in the study diary issued on 
Day 1. The participant will bring the study diary and all study drug bottles (including if 
empty) to each subsequent visit (day of cochlear implant surgery and the Day 49 visit) for 
IMP reconciliation and compliance check as described in Section 5.7. 
5.10 MEASURES TO MINIMIZE BIAS 
5.10.1 Randomization Procedures 
Participants will be randomized to either Arm A or Arm B on Day 1: 
x Arm A: treated with SENS-401 as described in Section 5.1.1. Eighteen (18) 
participants will be randomized to Arm A. 
x Arm B: not treated with SENS-401 at any time. Nine (9) participants will be 
randomized to Arm B. 
Randomization will be according to a randomization schedule and plan prepared prior to 
study start. A Randomization Procedure document will be provided to the site by the 
Sponsor or CRO. 


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5.10.2 Blinding 
The study is open-label and randomized, with Arm A receiving treatment with IMP and 
Arm B receiving no IMP treatment. See Section 4.2. 


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6 STUDY ASSESSMENTS AND PROCEDURES 
6.1 
STUDY CONDUCT SCHEDULE 
The schedules for all assessment and study activities are summarised in the Schedule of 
Assessments (SOA) provided in Table 1. Permitted visit windows are indicated in 
Section 6.1.8. All study assessments and procedures are as described in Sections 6.2 to 
6.5 and in Section 7. 
6.1.1 Screening Day -42 to Day -1 
x Voluntary, written informed consent using EC/HREC-approved PICF is required prior 
to any screening or study procedure as per Section 9.1.2. 
x Protocol waivers or exemptions are not permitted. 
x See SOA Table 1 for required assessments. 
x A 
thorough 
medical 
history, 
demographics, 
and 
prior 
and 
current 
medications/treamtents used within 3 months prior to screening will be recorded. 
x A screening log will be used to record suitable details of all screened individuals and 
to confirm eligibility or record reasons for screen failure as applicable. 
x All screening and eligibility evaluations (inclusion/exclusion criteria) must be 
completed and reviewed by the Investigator to confirm eligibility prior to 
randomization and first-dosing on Day 1. This must be clearly documented. 
x Re-testing of any screening parameters can be conducted once only. 
x Unscheduled visits and procedures for safety reasons are at the discretion of the 
Investigator and will be appropriately documented. 
6.1.2 Day 1 Randomization and First dose 
x See SOA Table 1 for required assessments. 
x All participants will attend the study site on Day 1 ensuring that if randomized to Arm 
A, they will adhere to the fasting restrictions described in Section 5.1.1. 
x Prior to randomization: 
o Testing for COVID-19 
o Check & record concomitant medications or treatments 
o Check & record AEs 
o Confirm eligibility 
x Eligible participants will be randomized to either Arm A or Arm B as per 
Section 5.10.1. 
x After randomization (and pre-firstdose for Arm A): 
o Hearing test PTA 
o Otoscopic examination 
o Immitance audiometry 
o Record AEs and concomitant medications/treatments at any time after 
randomization if required 
x For participants in Arm A only: 
o The first dose of study drug will be taken under supervision at the study site (see 
Section 5.1.1). 


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o Study drug will be dispensed to cover the entire dosing period and study diary 
provided. Study staff will explain: 
i) Dosing and storage instructions (see Section 5.1.1) 
ii) How to document study drug administration details (date, time, number of 
tablets taken, daily first and last meal times) and in the study diary. 
iii) Importance of treatment compliance, as described in Section 5.1.1. 
iv) To return for scheduled cochlear implant surgery. 
v) To bring the study diary and all study drug bottles (even if empty) to each 
study visit (including day of cochlear implant surgery) up to and including the 
Day 49 visit. 
o The participant will also be given information on who to contact in case of queries 
or concerns about the study drug and/or study. 
x For participants in Arm B: 
o No IMP will be dispensed 
o Study diary will not be provided. 
o The participant will also be given information on who to contact in case of queries 
or concerns about the study. 
6.1.3 Pre-implant Outpatient Period 
x Participants are not required to attend the study site between Day 1 and the day of 
cochlear implant surgery. 
x Arm A participants should continue to take study drug twice daily as per Section 5.1.1 
and document dosing information in the study diary. 
x Participants may contact the study site in case of queries or concerns. Unscheduled 
visits to the study site for study-related safety are at the discretion of the Investigator. 
All unscheduled study-related visits, assessments and any AEs will be documented 
and results entered into the eCRF. 
6.1.4 Day 8 to 14 Cochlear Implant Surgery 
See SOA Table 1 for required assessments. 
x Participants will attend the study site per Investigator decision (evening before or 
morning of surgery) for scheduled cochlear implant surgery as standard of care (see 
Section 6.5). Arm A participants will bring study drug containers and study diary for 
compliance check by study staff. Study staff will transcribe drug administration details 
from the study diary into the eCRF. Arm A participants: the morning dose of study 
drug will be taken as scheduled after the blood sample for PK is collected. The 
evening dose of SENS-401 should also be taken later as scheduled on the day of 
cochlear implant surgery. 
x Study staff will review the study diary for treatment compliance (Arm A only) and 
perform drug reconciliation. Study drug administration details will be transcribed into 
the eCRF as applicable. Any discrepancies between the study diary and the returned 
study drug will be discussed with the participant and documented. 
x Information on concomitant medication and AEs will be obtained from all participants 
and reported into the eCRF as required. 
x All medications used for cochlear implant surgery will be documented and reported 
into the eCRF as concomitant medications. 


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x Blood and perilymph samples will be collected from Arm A participants only (see 
above and Section 6.2) and ECochG performed for all participants (see Section 6.4.2) 
during the cochlear implant surgery. 
x Arm A participants will have their diaries and study drug returned to them to continue 
to record their study drug administration. 
x AEs and concomitant medications/treatments will be reported for all participants as 
required. 
x If unavoidable, cochlear implant surgery may be re-scheduled up to and including Day 
14. Arm A participants should continue to take twice-daily study drug without 
interruption until surgery. 
6.1.5 Post-implant Outpatient Period 
x Participants are not required to attend the site for study-related reasons after cochlear 
implant surgery until the Day 49 visit. 
x Arm A participants should continue to take study drug twice-daily as per Section 5.1.1 
and document administration information in their study diary. See Section 5.1.1 in the 
event of delayed cochlear implant surgery up to and including Day 14. 
x Participants may contact the study site in case of queries or concerns. Unscheduled 
visits to the study site for study-related safety are at the discretion of the Investigator. 
All unscheduled study-related visits, assessments and any AEs will be documented 
and results entered into the eCRF. 
6.1.6 Day 49 Visit 
All participants will attend the study site for a visit on Day 49. A visit window of ± 7 days 
is permitted. Arm A participants should continue to take study drug until attending the 
Day 49 visit. The visit should ideally but not necessarily coincide with a standard-of-care 
cochlear implant assessment visit. 
x Assessments are as indicated in SOA Table 1. 
x Arm A participants will return the following for final check of compliance and drug 
reconciliation: 
o Study diary (to be retained at site as source document). 
o All study drug containers (even if empty) and any unused study drug. 
x Study staff will transcribe drug administration details from the study diary into the 
eCRF. 
6.1.7 End of Study Visit (EOS) 
All participants will attend the study site for the EOS on Day 105. A visit window of ± 21 
days is permitted. The visit should ideally but not necessarily coincide with a standard- 
of-care cochlear implant assessment visit. 
x EOS/ET assessments are as indicated in SOA Table 1. 
x If required, ET assessments are as per EOS; At ET, audiometric testing and biomarker 
sampling should be performed if participant agrees. 
 
All the subjects receiving SENS-401 will have before EOS at least 4 weeks of follow-up 
after their last dose of SENS-401. 


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6.1.8
Permitted Visit Windows 
Table 4: Permitted Visit Windows
EOS = end of study visit
* Visit should ideally but not necessarily coincide with a standard-of-care cochlear implant assessment visit
6.2
PHARMACOKINETICS
6.2.1
Blood Sampling for SENS-401 Concentration
One blood sample of approximately 2.7 mL will be collected from Arm A participants
only for PK analysis prior to the morning dose of SENS-401 on the day of the cochlear 
implant surgery (see Section 5.1.1). Details including handling and preparation of samples 
is described in the study Laboratory Manual. The concentration of SENS-401 in samples 
will be measured using a partially-validated method. 
6.2.2
Perilymph Sampling for SENS-401 Measurement – Primary Endpoint
A sample that will allow storage of at least 1 μL of perilymph will be obtained from the 
round window during the cochlear implant surgery from Arm A participants only
(Section 6.5). Obtaining the sample and subsequent handling of the sample is described 
in the separate guidance manual for cochlear implant surgery prepared for this study. The 
concentration of SENS-401 in perilymph will be measured using a partially-validated 
method.
As this is for the primary endpoint, the Investigator must take care to ensure perilymph 
sampling is performed and handled correctly according to the manual provided. 
6.3
AUDIOMETRIC TESTING
6.3.1
Pure Tone Audiometry (PTA)
Pure tone audiometry (PTA) is a behavioural subjective test used to identify hearing 
threshold levels and will be performed according to standard AS ISO 8253-1:2010 
Acoustics – Audiometric test methods – Part 1: Pure-tone air and bone conduction 
audiometry. This test involves the peripheral and central auditory systems. Pure-tone 
thresholds (PTTs) indicate the softest sound audible to an individual at least 50% of the 
time. Hearing sensitivity is plotted on an audiogram displaying intensity as a function of 
frequency.
Pure-tone audiometry is a “gold” standard test to assess whether hearing acuity is normal 
or impaired. Air conduction hearing thresholds are measured for tonal stimuli at the range 
of frequencies from 0.125 kHz to 8 kHz with the use of headphones. Then, bone 
conduction hearing thresholds are measured for tonal stimuli at the range of frequencies 
from 0.25 to 4 kHz, with the use of a headband with oscillator. Hearing thresholds are 
measured in dB HL units. In sensorineural hearing loss both air conduction and bone 
conduction curves worsen, and no air–bone gap is present. If a Type B tympanogram
Visit
Permitted Window
Screening
Day -42 to Day -1 
Day 8 to 14 days
Up to and including Day 14
Day 49*
± 7 days
EOS*
± 21 days


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indicating presence of fluid in the middle ear is obtained at the time of audiometric testing 
(see Section 6.3.2), hearing threshold shift should be measured using bone conduction 
thresholds rather than air conduction thresholds. 
Frequencies specified for this study: 0.25, 0.5, 0.75, 1, 2, 3, and 4 kHz. 
Participant PTA will be performed at Screening, on Day 1 after randomization (prior to 
first dose of study drug for Arm A), at the Day 49 visit, and at EOS/ET for all participants 
(Arm A and Arm B). The PTA results will be recorded by the audiologist/operator on a 
form provided by the Sponsor for each participant’s assessment as described in the 
Investigator Manual. 
6.3.2 Immitance Audiometry 
Immitance audiometry evaluates middle ear function by three procedures: static 
immittance, tympanometry, and the measurement of acoustic reflex threshold sensitivity, 
and requires a small plastic probe to be placed in one or both ear canals for tympanometry. 
Tympanometry tests the condition of the middle ear and mobility of the eardrum 
(tympanic membrane) and the conduction bones by creating variations of air pressure in 
the ear canal. 
For this study, tympanometry will be performed at Screening, on Day 1 after 
randomization (prior to first dose of study drug for Arm A), at the Day 49 visit, and at 
EOS/ET for all participants (Arm A and Arm B). 
If a Type B tympanogram indicating presence of fluid in the middle ear is obtained at the 
time of audiometric testing (PTA; see Section 6.3.1), hearing threshold shift should be 
measured using bone conduction thresholds rather than air conduction thresholds. 
6.4 
EAR EXAMINATION 
6.4.1 Otoscopic Examination 
Participants will undergo an otoscopic examination by the Investigator at Screening, Day 
1 after randomization (prior to first dose of study drug for Arm A), at the Day 49 visit, 
and at EOS/ET, to examine the structure of the ear canal, tympanic membrane and the 
middle ear. Otoscopy is part of standard of care, to rule out possible outer-ear abnormality 
such as otitis media or tympanic perforation. 
The Investigator will document abnormalities found and indicate their clinical 
significance, or indicate the examination as normal. Clinically signicant abnormalities 
will be described into the eCRF. 
6.4.2 Electrocochleography 
Electrocochleography (ECochG) records electrical potentials generated in the inner ear 
and auditory nerve in response to acoustic sound stimulation.16 For this study’s 
exploratory objective, sites will use the Cochlear™ Research Platform System (software 
and hardware) according to the Cochlear™ Research Platform User Guide (Version 1.2). 
Study sites that are not already fully trained to use this technology will be provided with 
the system and trained by the local Cochlear Ltd representative. 
During cochlear implant surgery, surgeons will use the ECochG during electrode insertion 
according to their routine practice (if routinely used). For the study, the Investigator will 
record an electrode sweep in response to a 500 Hz acoustic stimulus presented at 108 dB 
HL at the end of each participant’s surgery (Arm A and Arm B). The anonymised csv 
file generated will be exported to the co-ordinating Investigator for analysis by a 


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designated Central Reader. Each Investigator will ensure that the anonymised csv file 
exported is identified only by participant number, and not by any other participant- 
identifying details (e.g., names, initials). Refer to the Investigator Manual (or relevant 
guidance manual as provided). 
Analysis by the Central Reader will report if there is evidence of basilar membrane 
fixation (yes/no), and if yes, on which electrode. Basilar membrane fixation (i.e., the 
electrode is touching the basilar membrane causing mechanical impairment) will be 
determined based on either (a) a latency shift of <0.05 msec from electrode 22 to 20 or 
(b) the maximum amplitude of the cochlear microphonic appearing on an electrode 
between 2 and 18. 
6.5 
COCHLEAR IMPLANT SURGERY 
Cochlear implant is a technological tool developed more than 40 years ago. Different 
surgical approaches have been adopted with cortical mastoidectomy–posterior 
tympanotomy being the most commonly followed technique. The one used within the 
framework of this protocol is standardized and will be described in a guideline which will 
be communicated to all the sites participating in this study. 
All participants were previously diagnosed to benefit from the Cochlear™ Nucleus® 
C1622 model. Cochlear implant surgery will be performed between Day 8 and Day 14. 
Immediately prior to insertion of the cochlear implant, perilymph will be sampled from 
the round window as per Section 6.2.2. The cochlear implant electrode will be performed 
via the round window, unless surgical considerations that arise during surgery dictate 
implantation via a cochleostomy or extended round window approach. Investigators will 
refer to the separate guidance manual for cochlear implant surgery prepared for this study. 
A blood sample for plasma PK analysis will also be collected on day of surgery as per 
Section 6.2.1. 
Intraoperative monitoring (electrocochleography and/or impedances) will be undertaken 
during electrode insertion, according to the routine practice of the Investigator. An 
electrode sweep will be performed with electrocochleography after completion of the 
surgery as per Section 6.4.2, to inform the study outcomes.The following information will 
be collected: 
x Electrode insertion depth (N electrodes outside cochlear) 
x Was surgery complicated or uncomplicated? 
o Please explain 
 
6.6 
BIOMARKERS 
Collection of samples for other biomarker research is also part of this study. Blood 
samples for biomarker research are required and will be collected from all participants 
(Arm A and Arm B) in this study on Day 1 (pre-dose for Arm A), at the Day 49 visit, and 
at EOS/ET as specified in the SOA Table 1. For each of these visits, approximately 8 mL 
from each participant will be required. 
Samples for biomarkers will be stored in a biobank. These may possibly be tested later to 
establish correlations between their levels and clinical features of interest . 
The accurate identification of biomarkers is not fully established yet. Some (e.g. Prestin) 
are foreseen as biomarkers of potential interest. Samples may be stored for a maximum 


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of 15 years (or according to local regulations) following the last participant’s last visit for 
the study at a facility selected by the Sponsor to enable further analysis of biomarker 
responses to SENS-401. 
Details regarding collection, storage, and handling of biomarker samples will be provided 
in an applicable laboratory or sample handling manual. 


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7 SAFETY ASSESSMENTS 
x The schedules for all safety assessments/activities are provided in the SOAs Table 1. 
x Protocol waivers or exemptions are not permitted. 
x All safety assessments may be conducted at unscheduled visits or timepoints if 
required for the participant’s safety at the discretion of the Investigator. Such visits 
and/or assessments will be documented and entered into the eCRF. 
x Re-testing of any screening parameters can be conducted once only. 
7.1 
PHYSICAL EXAMINATION 
A full physical examination will be performed by the Investigator at Screening, the Day 
49 visit, and at EOS/ET. 
Symptom-directed physical examination may be conducted during the study at the 
discretion of the Investigator if considered necessary for participant safety. 
All physical examination findings (normal/abnormal) must be recorded in source 
document and clinical significance of any abnormality provided by the Investigator and 
entered into the eCRF. 
See Section 6.4.1 for otoscopic examination. 
7.2 
VITAL SIGNS AND BODY MEASUREMENTS 
7.2.1 Vital Signs 
Vital signs will include systolic and diastolic blood pressure (BP; mmHg), heart rate (HR; 
beats per minute), respiratory rate (RR; breaths per minute) and body temperature (ºC). 
Body temperature method will be specified (e.g., tympanic, oral) and the same method 
should be used during the study. 
Vital signs will be measured at Screening, the Day 49 visit, and EOS/ET after participant 
is supine for at least 5 minutes. Vital signs may be measured at other timeponts during the 
study at the discretion of the Investigator, if considered necessary for participant safety. 
In source document, all measurements will be indicated as normal or abnormal, and the 
Investigator will indicate the clinical significance of abnormal results. All vitals signs 
values will be entered into the eCRF with clinical significance of abnormal results 
indicated. 
7.2.2 Body Measurements 
Height (cm) and weight (kg) will be measured at Screening only. It is not sufficient for 
the participant to provide this information without measurement. 
7.3 
12-LEAD ECGS 
Standard 12-lead ECGs will be recorded at Screening, the Day 49 visit, and at EOS/ET 
using a validated ECG device after participant is in supine position for at least 10 minutes. 
An ECG may be conducted at other times during the study at the discretion of the 
Investigator if considered necessary for participant safety. 
The ECG will include: date, time, participant number, signature of Investigator, and at 
least 3 complexes for each lead. The Investigator should document if normal, or indicate 
abnormalities and their clinical significance. 


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The Investigator’s medical opinion on clinical significance and automatic values will be 
recorded in the eCRF. 
7.4 
CLINICAL LABORATORY TESTS 
7.4.1 Safety Blood Tests – Chemistry and Haematology 
x Blood will be collected from all participants (Arm A and Arm B) at Screening, at the 
Day 49 visit, and EOS/ET for standard clinical laboratory safety tests conducted at the 
site’s local/preferred laboratory. 
x Participants are required to fast for at least 8 hours prior to collection of samples. 
x Clinical laboratory tests may be conducted at other times during the study at the 
discretion of the Investigator if considered necessary for participant safety. 
x Screening results must be available and reviewed to confirm eligibility prior to 
randomization on Day 1. 
x The Investigator will indicate the clinical significance of abnormal results. 
 
 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count 
RBC Indices: 
Mean corpuscular 
volume (MCV) 
Mean 
corpuscular 
hemoglobin 
(MCH) 
White Blood Cell Count with 
Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Red Blood Cell (RBC) 
Count 
Hemoglobin 
Hematocrit 
Clinical 
Chemistry 
Urea 
Potassium Aspartate 
Aminotransferase 
(AST)/ Serum 
Glutamic- 
Oxaloacetic 
Transaminase 
(SGOT) 
Total and direct 
bilirubin 
Creatinine and creatinine 
clearance GFR (calculated 
with the Cockcroft-Gault 
formula for subjects 
< 65 years old and CKD-EPI 
creatinine equation or with 
MDRD equation for subjects 
 65 years old; 
Sodium 
Alanine 
Aminotransferase 
(ALT)/ Serum 
Glutamic-Pyruvic 
Transaminase 
(SGPT) 
International 
normalized ratio 
(INR) 
Total Protein 
Glucose fasting 
Calcium 
Alkaline 
phosphatase 
 
NOTES: 
Abbreviations: CKD-EPI = chronic kidney disease epidemiology collaboration, GFR = glomerular 
filtration rate,MDRD = modification of diet in renal disease. 


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7.4.2 Pregnancy Testing 
A blood sample will be collected from all WOCBP at Screening for serum hCG pregnancy 
testing. Individuals will not be permitted to continue with the study if testing positive 
(screen failure). 
A urine sample will be collected from Arm A WOCBP at the Day 49 visit and at EOS/ET 
for hCG pregnancy testing. 
7.4.3 Testing for SARS-CoV-2 (COVID-19) 
For this study, participants will be tested via rapid antigen test for SARS-CoV-2 on Day 1 
prior to randomization. A positive result will constitute a screen failure, and the participant 
must not be randomized and must follow local regulatory requirements for receiving a 
positive rapid antigen test result for SARS-CoV-2. 
At all other times, study sites will follow their institutional and local regulatory 
requirements for screening/testing for COVID-19, and for handling of participants with 
signs and symptoms of COVID-19. Participants should not attend the study site if results 
of a COVID-19 test are still pending. Appropriate measures and procedures will be in 
place to ensure the safety of participants and study staff. The site visits scheduled for this 
study are the minimum required and cannot be conducted remotely. 
If a participant taking study drug tests positive for COVID-19 during the study (by 
polymerase chain reaction [PCR] test or rapid antigen testing), the Investigator will decide 
if the participant should discontinue study drug and how the follow-up visit and 
assessments can be performed. The participant must abide by local regulations and 
restrictions. 
7.5 
ADVERSE EVENTS (AES) 
The Principal Investigator or delegate and study site staff are responsible for detecting, 
recording and reporting events that meet the criteria and definition of adverse events as 
described below. Adverse events may be reported by the participant or observed by the 
Principal Investigator, delegate or other clinical site staff. When enquiring about AEs, the 
Investigator and study staff will take care to not introduce bias and will use open-ended 
and non-leading verbal questions. 
All AEs will be proactively followed at each subsequent visit or contact as medically 
indicated until the event has resolved, no further medically relevant information from the 
event can be expected and it is acceptable to discontinue follow-up of the event in the 
assessment of the Principal Investigator. The Principal Investigator should continue to 
follow up SAEs that were unresolved at the participant’s EOS/ET as long as medically 
required (resolution or stabilization), the event is otherwise explained, the participant is 
lost to follow-up or satisfactorily referred to a general practitioner or medical specialist as 
appropriate. The Sponsor or designee may request further measurements and/or 
evaluations (e.g., laboratory tests or investigations, histopatholigical examinations, or 
consultations with other health care professionals) to elucidate the nature of the AE or 
SAE as fully as possible. 
Adverse events will be recorded from the time of informed consent to study completion 
and entered into the eCRF. 


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Investigators are not obligated to seek AE or SAE information after the conclusion of 
study participation, however if the Investigator learns of any SAE (including death) at any 
time after a participant has been discharged from the study, and the Investigator considers 
the event to be reasonably related to the IMP or study participation, the Investigator must 
promptly notify the Sponsor or designee. 
If a participant dies during participation in the study or during a recognized follow-up 
period, the Investigator will provide the Sponsor or designee with a copy of any 
postmortem findings including histopathology. 
7.5.1 Definitions 
An adverse event (AE) is any untoward medical occurrence in a clinical trial participant 
administered a medicinal product, and that does not necessarily have a causal relationship 
with this treatment. 
Adverse events include, but are not limited to: 
x A new symptom, sign or medical condition 
x A disease or medical condition detected or diagnosed during the study even though it 
may have been present prior to the start of the study 
x An exacerbation of a pre-existing medical condition/disease 
x An increase in frequency or intensity of a pre-existing episodic disease or medical 
condition 
x Continuous persistent disease or symptoms present at the start of the study that worsen 
during the study 
x Signs, symptoms or the clinical sequelae of a suspected drug-drug interaction 
x Signs, symptoms or the clinical sequelae of a suspected overdose of either study drug 
or a concomitant medication. Overdose per se will not be reported as an AE/SAE 
unless it is an intentional overdose taken with possible suicidal/self-harming intent. 
Such overdoses should be reported regardless of sequelae. 
x ‘Lack of efficacy’ or ‘failure of expected pharmacological action’ per se will not be 
reported as an AE or SAE as such instances will be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting from 
lack of efficacy will be reported as AE or SAE if fulfilling the definition of AE/SAE 
(except for ‘loss of residual hearing’ as below). 
x A clinically significant abnormal assessment (e.g., change on physical examination, 
ECG finding) that was not present at the start of the study or worsened during the 
study 
x A clinically significant abnormal laboratory test result (e.g., CTCAE grade 2 or 
above), symptomatic or not, which: 
o Was not present at the start of the study, and/or 
o worsened during the study, and/or 
o led to the study drug dose being reduced, or 
o led to the study drug treatment being interrupted, or 
o led to the study drug treatment being permanently discontinued. 
Abnormal laboratory findings and other objective assessments should NOT be routinely 
captured and reported as AEs unless the following criteria are met: 


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x considered by the Investigator or Sponsor to be clinically significant or represent a 
clinically significance change from baseline, and/or 
x meets the criteria of serious for reporting as an SAE, and/or 
x associated with accompanying symptoms, and/or 
x requires additional diagnostic testing or medical/surgical interventions, and/or 
x leads to change in study drug dosing, or discontinuation from the study, significant 
additional concomitant medication or other therapy. 
The abnormal result/finding should then be documented and reported in the AE Section 
of the eCRF (see Section 7.5.4). 
Adverse events will not include: 
x A medical or surgical procedure such as surgery (including the scheduled cochlear 
implant surgery), endoscopy, tooth extraction or transfusion (although the condition 
that led to the procedure may be an AE); 
x A pre-existing disease or medical condition present at the start of the study that does 
not worsen (in intensity and/or frequency) during the study, except for loss of residual 
hearing (see below). This includes day-to-day fluctuations that do not worsen. 
x Any situation where an untoward medical occurrence has not occurred (e.g., 
hospitalization for cosmetic elective surgery or social admissions). 
x Any clinically significant abnormal laboratory findings or other safety assessment 
findings which are associated with the underlying disease/condition, unless judged by 
the Investigator to be more severe than expected for the participants condition. 
Untoward medical occurrences during or after the cochlear implant surgery (including if 
expected or known side-effects of the cochlear implant and/or surgery) will be reported 
as AEs. Any such AEs considered related to the cochlear implant or the surgery by the 
Investigator are defined as adverse device effects (ADEs). However, loss of residual 
hearing will not be recorded as an AE or ADE as it is part of the efficacy endpoint, unless 
it is considered to be an AE/ADE by the Investigator. 
7.5.2 Causal Relationship to Investigational Medicinal Product and Other Study 
Treatments/Procedures 
The Investigator is required to assess the causality for all AEs, and must indicate this in 
source document and eCRF. An adverse event with reasonable causal relationship to the 
IMP, cochlear implant (medical device), study sample collection procedure, or cochlear 
implant surgery means there is evidence or argument to suggest a causal relationship. The 
Investigator should also take into account any relevant information provided in documents 
including but not limited to the Investigator’s Brochure (for IMP), device instructions for 
use (cochlear implant), and/or study Laboratory Manual (study sample collection 
procedure). 
If considered related: 
x The temporal relationship between the event and the administration of the IMP (or 
cochlear implant, study sample collection, or cochlear implant surgery) is compelling 
and/or follows a known or suspected response pattern to that product/procedure, and 
the event cannot be explained by the participant’s medical condition, other therapies 
or accident. 
If considered not related: 


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x The event can be readily explained by other factors such as the participant’s 
underlying medical condition, concomitant therapy or accident and no plausible 
temporal or biologic relationship exists between the IMP (or cochlear implant, study 
sample collection, or cochlear implant surgery) and the event. 
7.5.3 Severity Grading of Adverse Events 
The severity of AEs will be recorded by the Investigator in accordance with the Common 
Terminology Criteria for Adverse Events (CTCAE) v5.0, published 27 November 2017. 
This guidance provides a common language to describe levels of severity, to analyse and 
interpret data, to scale the aggregate AE score, and to articulate the clinical significance 
of all AEs. 
If there is not CTCAE grading available for a specific AE, the severity of AEs will be 
graded as follows: 
x Grade 1: Mild; asymptomatic or mild symptoms, easily tolerated; clinical or 
diagnostic observations only; intervention not indicated. 
x Grade 2: Moderate; minimal, local or non-invasive intervention indicated (e.g., short 
course of antibiotics); discomfort enough for limiting age-appropriate instrumental 
activities of daily living. 
x Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalisation or prolongation of hospitalisation indicated; disabling/incapacitation; 
limiting self-care activities of daily living. 
x Grade 4: Life-threatening consequences/risk of death; urgent intervention indicated. 
x Grade 5: Death related to AE/fatal outcome. 
An AE that is assessed as severe is not the same as a serious AE. Severity is a category 
utilized for rating the intensity of an event and both AEs and SAEs can be assessed as 
severe. An AE is defined as ‘serious’ when it meets one of the pre-defined serious 
outcomes as described in Section 7.6.1. 
7.5.4 Documentation of Adverse Events 
The Principal Investigator or delegate is responsible for reviewing all documentation 
related to each AE, and for recording all relevant AE/SAE information in source 
document and in the CRF. The Principal Investigator or delegate will attempt to establish 
a diagnosis of the AE based on signs, symptoms and/or other clinical information, and 
where possible the diagnosis will be documented as the AE/SAE (and not individual signs 
or symptoms). 
The following information should be recorded for all AEs: 
x Description 
x Dates and times of onset and resolution 
x Seriousness 
x Severity 
o In the source data, the description of the AE will report the various severities 
observed over time. If the severity of an AE increases, separate AEs per severity 
grading will be recorded into the eCRF. 
o If the AE resolves and then reoccurs, then two AEs will be reported. 
x Action taken in response to the AE regarding IMP: 
o Interrupted, or 


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o Permanently discontinued, or 
o No action taken, or 
o Unknown/not applicable. 
x Outcome of AE: 
o Recovered/resolved, or 
o Recovering/resolving, or 
o Not recovered/not resolved, or 
o Recovered with sequelae/resolved with sequelae 
o Fatal 
o Unknown 
x Relationship to the: 
o IMP, 
o cochlear implant = medical device, 
o study sample collection procedure, and/or 
o cochlear implant surgery. 
7.5.5 Adverse Events of Special Interest 
Not applicable for this study. 
7.5.6 Treatment of Overdose 
Symptomatic overdose of IMP is an event suspected by the Principal Investigator or 
delegate, or notified by the participant. Overdose is defined as any dose greater than 
43.5 mg twice daily within a 24 hour period (±6 hours). Such an event should be reported 
promptly to the Sponsor as an SAE. Asymptomatic overdose will be reported as a standard 
AE. 
As there is no antidote for SENS-401, in cases of overdose intensive care admission 
should be considered according to clinical status, and treatment will be as standard for 
nonspecific drug intoxication. General support may include immediate gastric lavage 
within the first hour after intake to reduce the amount absorbed, continuous monitoring 
of vital signs, supportive care for cardiovascular function, respiratory aid in case of 
compromise, hydroelectrolyte balance, and other measures as clinically indicated. 
In the event of an overdose, the Investigator will: 
 Contact the Medical Monitor as soon as possible according to the level of medical 
emergency 
 Closely monitor the participant for any AE/SAE and laboratory abnormalities until 
SENS-401 can no longer be detected (at least 7 days) 
 Obtain a plasma sample for PK analysis within 7 days from the last dose of IMP 
if requested by the Medical Monitor. 
 Document the quantity of the excess dose as well as the duration of the overdose 
in the eCRF. 
Decisions regarding dose interruptions of modifications will be made by the Investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the 
participant. The Sponsor must be immediately notified of any instances of overdose and 
the protocol deviation must be thoroughly documented and reported per local regulations. 
An overdose or incorrect administration of a drug is not itself an AE, but may result in an 
AE(s). All AEs associated with an overdose or incorrect administration of a drug should 


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be recorded in the AE CRF. If the associated AE fulfills the serious criteria, the event 
should be reported as an SAE (see Section 7.6.3). 
7.6 
SERIOUS ADVERSE EVENTS (SAEs) 
7.6.1 Definitions of Serious Adverse Events (SAEs) 
A serious adverse event (SAE) is any AE that: 
1. Results in death, or 
2. Is life-threatening, and/or 
3. Requires inpatient hospitalisation or prolongs existing hospitalisation, and/or 
4. Results in persistent or significant disability or incapacity, and/or 
5. Is a congenital anomaly or birth defect, and/or 
6. Are important medical events that are not immediately life-threatening or do not 
result in death or hospitalization but may jeopardise the participant or may require 
intervention to prevent one of the other outcomes above should also be considered 
serious. Medical and scientific judgement should be exercised in deciding whether 
an AE should be classified as serious in these situations. Examples include: invasive 
or malignant cancers, intensive treatment in emergency room or at home for allergic 
bronchospasm, blood dyscrasias, or convulsions that do not result in hospitalization, 
or development of drug dependency or drug abuse. 
Note: 
x Life-threatening in the definition of an SAE refers to an event in which the participant 
was at risk of death at the time of the event. It does not refer to an event that 
hypothetically might have caused death if it were more severe. 
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at a hospital or emergency ward for observation 
and/or treatment that would have not been appropriate in the setting of a physician’s office 
or as an outpatient. Complications occurring during hospitalization are AEs and if meeting 
definition of serious (e.g., prolongs hospitalization) then the event is serious. When in 
doubt as to whether hospitalization occurred or was necessary, the AE should be 
considered serious. 
x Planned procedures (including cochlear implant surgery) that require admission to 
hospital or medical facility for this study, or any planned elective procedure that 
requires hospitalization, are not considered SAEs unless the underlying condition has 
worsened since the start of the study and/or the participant’s condition worsens after 
the procedure, resulting in extension of hospitalization or re-hospitalization, and/or 
other serious criteria are met. 
x The term disability means substantial disruption to a person’s ability to conduct 
normal life functions. It is not intended to include experiences of relatively minor 
medical significance such as uncomplicated headache, nausea, vomiting, diarrhoea, 
influenza, or accidental trauma (e.g., sprained ankle), which may interfere with or 
prevent everyday life function but do not constitute a substantial disruption. 
x If an event is not defined as an AE (see Section 7.5.1), it cannot be an SAE even if 
serious conditions are met. 




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8 STATISTICAL ANALYSES 
8.1 
SAMPLE SIZE 
Overall, for this study, 27 participants will be enrolled and randomized to either Arm A 
or Arm B on Day 1 in ratio 2:1 (18 participants in Arm A and 9 participants in Arm B). 
The sample size is not calculated based on statistical significance on any clinical efficacy 
parameters but on empirical considerations for the pharmacokinetic evaluation. Eighteen 
subjects are generally considered sufficient to characterise the PK of a small molecule. 
The purpose of the PK sampling is to determine if SENS-401 can be detected in the 
perilymph and to compare the levels of SENS-401 in two different body compartments 
and the overall safety profile. 
For efficacy, 27 participants are empirically expected to provide enough data to evaluate 
a trend of efficacy. 
Enough participants will be screened to randomize 27 participants. 
8.2 
GENERAL STATISTICAL APPROACH 
The following is an outline of the statistical methodology that will be used to report and 
analyse this study. A more detailed description will be provided in a separate Statistical 
Analysis Plan (SAP) that may include additional exploratory analysis not explicitly 
mentioned in the following sections. The SAP will be finalised prior to final database 
lock. Any significant changes to the analyses described in this protocol will be highlighted 
in the SAP and the clinical study report (CSR). 
The general analytical approach for all endpoints will be descriptive in nature. Unless 
otherwise stated, the following statistical approaches will be taken: 
Continuous variables: 
Descriptive statistics will include the number of non- 
missing values, mean, standard deviation (SD), median, 
minimum, and maximum. The minimum and maximum 
values will be presented to the same number of decimal 
places as recorded in the eCRF; mean, median and SD will 
be presented to one more decimal place than the raw data. 
Categorical variables: 
Descriptive statistics will include frequency counts and 
percentages per category. Percentages will be rounded to 
one decimal place, with the denominator being the number 
of participants in the relevant population with non-missing 
data. 
Imputation: 
No missing data will be imputed. 
Baseline: 
The baseline will be defined as the last available assessment 
prior to study drug administration. 
Confidence intervals (CIs):  If required, CIs will be two sided and will use 95% 
confidence levels. Any analyses requiring significance 
testing will use a two-sided test at the 5% significance level. 
Unscheduled assessments: 
Unscheduled visits will be excluded from visit-based 
summary tables. 
Early termination visits:  Assessments conducted at Early Termination will be 
excluded from visit-based summary tables. 


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8.3 
ANALYSIS SETS 
Two analysis datasets will be used for study analyses: Pharmacokinetics (PK) Set and Full 
Analysis Set (FAS). 
Additional study populations or subgroups may be detailed in the SAP. 
8.3.1 PK Set 
The PK Set will be comprised of all randomized participants who were at least 70% 
compliant with SENS-401 in the three (3) days prior to cochlear implant surgery and for 
the morning dose on the day of surgery and at least 70% compliant overall for the dosing 
period prior to surgery. 
8.3.2 Full Analysis Set (FAS) 
The FAS will be comprised of all randomised participants. Participants will be analysed 
according to the treatment received. 
8.4 
DEMOGRAPHICS AND BASELINE CHARACTERISTICS 
Demographics and baseline characteristic data will be summarised using the FAS. 
8.4.1 Demographics 
Demographic data will be listed for each participant and summarised descriptively by 
treatment group and overall. 
8.4.2 Medical History 
Medical history will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) and summarised by system organ class (SOC) and preferred term (PT), per 
treatment group and overall. 
8.4.3 Prior Medications 
Prior medications will be coded using WHODRUG and will be summarised by 
Anatomical Therapeutic Class (ATC) code and preferred name (PN), per treatment group 
and overall. 
Prior medications will be identified as medications commenced prior to the time of first 
study drug administration, regardless of whether the medication was continued after study 
drug administration. 
8.5 
PROTOCOL DEVIATIONS 
All protocol deviations will be listed using the FAS. 
Protocol deviations will be summarised by deviation type, per treatment group and 
overall. 
8.6 
PARTICIPANT DISPOSITION 
A listing of participant disposition, using the FAS, will present dates of informed consent, 
randomisation, treatment commencement, treatment completion, as well as reasons for 
treatment and study discontinuation. 
Participant disposition variables will be summarised per treatment group and overall. 
Early treatment and study discontinuation will also be detailed in a separate listing. 


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8.7 
TREATMENT COMPLIANCE 
All study drug administration data will be listed, using the PK Set. 
8.8 
PHARMACOKINETIC ENDPOINTS 
The PK analyses will be performed using the PK Set. 
8.8.1 Primary Endpoint 
The number and percentage of participants from Arm A with levels of SENS-401 in the 
perilymph above the Limit of Quantification on surgery day (visit 3) will be summarised. 
8.8.2 Secondary Endpoint 
SENS-401 concentration data will be listed for each participant from Arm A and 
summarised descriptively for plasma and perilymph. A paired t-test will be used to 
compare the SENS-401 concentrations in the perilymph and plasma if the data is normally 
distributed. If the data is not normally distributed, we will calculate medians (with their 
interquartile range [IQR]) and use the Wilcoxon signed ranks test. 
8.9 
EFFICACY ENDPOINTS 
8.9.1 Hearing threshold 
Change of hearing threshold from baseline in the implanted ear at 500 Hz, 250 Hz and 
750 Hz will be summarized as continuous variables by visit and treatment using simple 
descriptive statistics. 
Analysis of covariance model (ANCOVA) will be used to assess changes in the values 
from baseline at the Day 49 visit and at EOS/ET, comparing between treatment groups. 
The treatment group will be used as a fixed factor and the baseline as a covariate. 
 
8.9.2 Exploratory Endpoints 
8.9.2.1 Assessment of Basilar Membrane Fixation 
Participants who have impairment of the basilar membrane (IBM) as detected by the 
ECochG latency shift and/or mid peak amplitude will be listed, grouped by arm. 
The number and percentage of participants with IBM will be summarised by arm. 
8.9.2.2 Hearing threshold assessment excluding participants with IBM 
Supplementary analyses will be conducted, whereby the ANCOVA analysis and 
descriptive statistics to assess changes in hearing threshold from baseline, will be repeated 
excluding participants with IBM. 
8.9.2.3 Biomarker Analysis 
Biomarker exploratory analyses (if performed) will be described in the statistical analysis 
plan (SAP) finalized before database lock. 
8.10 SAFETY ENDPOINTS 
8.10.1 Adverse Events 
AEs will be coded using the current version of the Medical Dictionary for Regulatory 
Activities (MedDRA) by system organ class (SOC) and preferred term, classified from 
verbatim terms. 


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All AEs recorded during the study will be listed, grouped by participant and treatment 
group. The duration of AEs will be determined and included in the listings. 
A Treatment Emergent Adverse Event (TEAE) is defined as any untoward medical 
occurrence reported or observed after treatment administration. Conditions present before 
the first dose of study drug that increase in severity after the first study drug administration 
will also be considered TEAEs. Where an AE start date is partially or fully missing, and 
it is unclear as to whether the AE started after treatment administration, it will be assumed 
to be a TEAE. 
AEs will be summarized by the number of AEs and number and percentage of participants 
experiencing: 
x any AEs, 
x any severe and potentially life-threatening AEs, 
x any drug-related AEs, 
x any SAEs, 
x any drug-related SAEs, and 
x any AEs leading to study drug interruption. 
Adverse events will also be summarized by: 
1) system organ class and preferred term; 
2) system organ class, preferred term, and severity; and 
3) system organ class, preferred term, and relationship to study drug. 
If a participant experienced more than 2 AEs for a given preferred term, severity is defined 
by the most severe event and relationship to study drug is defined by the most related 
event. 
8.10.2 Vital Signs 
All vital sign data will be listed for all participants. For each parameter, observed values 
will be summarised descriptively per treatment group and overall. 
The incidence rates of clinically significant vital sign abnormalities will be summarized. 
8.10.3 Body Measurements 
Height (cm) and weight (kg) data will be listed for all participants. For each parameter, 
observed values will be summarised per treatment group and overall. 
8.10.4 Physical Examination 
Physical examination findings will be listed only. 
8.10.5 12-Lead ECG 
ECG data will be listed, with abnormal values and clinical significance flagged. All ECG 
variables will be summarised per treatment group and overall. 
8.10.6 Clinical Laboratory Tests 
All laboratory parameters will be listed with flags for values outside the reference ranges 
and values considered to be clinically significant. 
Each parameter will be summarised descriptively. 


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The number and percentage of participants with clinically meaningful laboratory test 
findings will also be summarized by treatment group. 
8.10.7 Pregnancy 
Pregnancy data will be listed only. 
8.10.8 Testing for SARS-CoV-2 (COVID-19) 
COVID-19 data will be listed only. 


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9 STUDY ADMINISTRATION 
9.1 
ETHICAL CONSIDERATIONS 
9.1.1 Ethical Principles 
This clinical study was designed and shall be implemented and reported in accordance 
with consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki, Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines, applicable ICH GCP Guidelines including the 
Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) dated 
09 November 2016, (for Australian sites) the National Statement on Ethical Conduct in 
Human Research, (2007 – updated 2018), and all applicable laws and regulations. 
9.1.2 Informed Consent 
Eligible participants may only be included in the study after providing voluntary, written 
(witnessed, where required by law or regulation), IRB/IEC/HREC-approved informed 
consent. Informed consent to participate in the study must be obtained according to GCP 
and local regulatory requirements before conducting any study-specific procedures (i.e., 
all of the procedures described in the protocol). The process of obtaining informed consent 
should be documented in the participant source documents, including stating that written 
informed consent was obtained before the participant was entered into the study and the 
date obtained, and a copy of the signed participant information and consent form (PICF) 
provided to the participant. 
If new information becomes available that may be relevant to the participant’s willingness 
to continue to participate in the study, a new PICF will be prepared and approved by the 
IEC/HREC. The study participants will be informed about the new information and re- 
consent obtained. Participants who are re-screened must sign a new PICF. 
9.1.3 Ethics Committee/Human Research Ethics Committee (HREC) Approval 
Before initiating a trial, the Investigator/institution will obtain written approval/favorable 
opinion from the EC/HREC for the trial protocol, written PICFs, PICF updates, 
participant recruitment procedures (e.g., advertisements) and any other written 
information to be provided to participants. 
The Investigator is responsible for ensuring that any necessary extensions or renewals of 
EC/HREC approval are obtained, and that EC/HREC approval of changes to the study 
such as protocol amendments, updated PICFs or other study documents is obtained prior 
to implementing the changes. The Investigator will also report promptly to the EC/HREC 
any new information that may adversely affect participant safety or study conduct, provide 
EC/HREC-requested reports or summaries, and notify the EC/HREC when the study has 
ended. 
9.2 
PROTOCOL ADHERENCE 
This protocol defines the study objectives, the study procedures, and the data to be 
collected on study participants. Additional assessments required to ensure safety of 
participants should be administered as deemed necessary on a case-by-case basis. In this 
instance, the Sponsor medical monitor must be advised before or as soon as possible after 
such assessments are conducted. 
Under no circumstances should an Investigator collect additional data or conduct any 
additional procedures for any research related purpose involving any investigational 


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drugs. Investigators will apply due diligence to avoid protocol deviations. If an 
Investigator feels a protocol deviation would improve the conduct of the study, this must 
be considered a protocol amendment and cannot be implemented unless such an 
amendment is agreed upon by the Sponsor and approved by the HREC. 
All protocol deviations will be recorded during the study, and listed in the clinical study 
report (CSR), including but not limited to the following deviation categories: 
x Informed consent 
x Eligibility 
x Visit not done 
x Visit performed out of window 
x Study procedure not done 
x Study procedure done out of window 
x Safety reporting 
x Investigational Product 
x Privacy and Data Protection 
x Concomitant Medication 
x Other (including disruptions to the trial due to COVID-19 that are not per protocol) 
Major protocol deviations may significantly impact the completeness, accuracy, and/or 
reliability of the study data or may significantly affect a participant’s rights, safety, or 
well-being. These include: 
x Participant entered the study even though they didn’t satisfy entry criteria; 
x Participant developed withdrawal criteria during the study but was not withdrawn; 
x Participant received the wrong treatment or incorrect dose; 
x Participant received an excluded concomitant medication. 
9.3 
PROTOCOL AMENDMENTS 
Any change or addition to the protocol can only be made in a written protocol amendment 
that must be approved by the Sponsor and the HREC prior to implementation. Only 
amendments that are intended to eliminate an apparent immediate hazard to participants 
may be implemented immediately, provided the Sponsor’s medical monitor is notified as 
soon as possible after the event and the reviewing HREC is subsequently notified. 
Notwithstanding the need for approval of formal protocol amendments, the Investigator 
is expected to take any immediate action required for the safety of any participant included 
in this study, even if this action represents a deviation from the protocol. In such cases, 
the Medical Monitor and Sponsor must be notified immediately. 
9.4 
DATA HANDLING AND RECORD KEEPING 
Participants will be assigned a unique identifier when participating in the study, and any 
participant datasets or records that are transferred to the Sponsor or CRO will be 
associated only with this identifier. Any other identifiable information about the 
participant, such as names, will not be transferred. The Principal Investigator will ensure 
procedures are in place to appropriately protect the confidentiality of the participant 
records and data, including adequate safeguards for digital/computer access by authorized 
personnel only. Participants will be informed that their personal study-related data will be 


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used by the Sponsor in accordance with local data protection law and that their medical 
records may be examined by auditors and regulatory agencies. 
Study-related participant data will be entered into electronic case report forms (eCRFs) 
by authorized study personnel, except for data that may be transmitted to the Sponsor or 
CRO electronically (such as laboratory data). Guidelines for completion of the eCRF 
including correction of entries and responding to data queries will be provided by the 
Sponsor or CRO. Data will be entered into the eCRF by authorized study personnel in a 
timely fashion and as requested by the study monitor. The Principal Investigator is 
responsible for i) ensuring that accurate source documents for all data entered into the 
eCRF are maintained at the study site, and ii) for verifying CRF data entries are accurate 
and correct by signing (electronically or physically) the eCRF after all queries have been 
resolved. Corrections to source document (whether paper or electronic) must have an audit 
trail (i.e., must not obscure or delete the original entry, and the date/time of correction and 
identity of the person making the correction must be clearly indicated). Participant study 
diaries are considered source document, and should be collected from the participant at 
EOS/ET for filing. 
All study documents including source documents and signed PICFs must be retained by 
the Principal Investigator for at least 15 years and according to local regulatory 
requirements. No study documents may be destroyed or transferred during the retention 
period without the Sponsor being directly notified in writing. 
9.5 
QUALITY CONTROL AND QUALITY ASSURANCE 
The Sponsor assumes accountability for actions delegated to other parties (including to 
the CRO). A risk-based approach to quality management will be applied to all stages of 
protocol development and study conduct to ensure protection of participants and 
reliability of trial results. The Sponsor or CRO maintains responsibility for quality 
assurance and for data management, with quality control applied to each stage of data 
handling to ensure reliability and correct processing. 
Prior to study start, the Investigator is required to sign a protocol signature page 
confirming his/her agreement to conduct the study in accordance with these documents 
and all of the instructions and procedures found in this protocol and to give access to all 
relevant data and records to the Sponsor-appointed monitors, auditors, Quality Assurance 
representatives, EC/HREC representatives, and regulatory authorities as required. If an 
inspection of the clinical site is requested by a regulatory authority, the investigator must 
inform the Sponsor immediately that this request has been made. 
Study monitors appointed by the Sponsor or CRO will conduct ongoing, regular visits to 
the study sites to verify the eCRF data is accurate and complete according to source 
documents, the safety and rights of participants are being protected, and that the study is 
being appropriately conducted according to the protocol, other study agreements, ICH 
GCP and local regulatory requirements. Monitoring visits may be conducted remotely if 
required due to the ongoing COVID-19 pandemic. Details will be provided in a 
Monitoring Plan. See also Section 9.4. 
After monitoring, the eCRF data will be validated by Sponsor-designated data 
management using a series of programmed checks and listing reviews according to 
relevant internal standard operating procedures (SOPs). Queries will be either 
automatically or manually generated and added to the eCRF to be resolved promptly by 
authorized site personnel. After all data discrepancies are resolved, medical coding 


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completed, serious adverse events (if any) reconciled with the CRF, and external data 
integrated, the database will be locked and provided to the Statistician for analysis. 
Data will be retained as required by ICH GCP and local regulatory requirements. 
9.6 
PUBLICATION POLICY 
Neither the complete nor partial results of the study achieved under this protocol, nor any 
of the information provided by the Sponsor for the purposes of performing the study, will 
be published, presented at scientific meetings, or otherwise passed on to any third party 
without the consent of the study Sponsor. Any Investigator involved with this study is 
obligated to provide the Sponsor with complete study results and all data derived from the 
study. 
Results of this trial will be submitted for publication and/or posted in a publicly accessible 
database of clinical trial results. 
9.7 
FINANCIAL DISCLOSURE 
Investigators will provide the Sponsor sufficient, accurate financial information as 
requested and according to local regulations, with information on financial interests to be 
provided during the study and for one (1) year after completion. This is to permit the 
Sponsor to submit complete and accurate financial certification or disclosure statements 
to regulatory authorities, where required. 


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10 REFERENCES 
1. Hu BH, Henderson D, Nicotera TM. Involvement of apoptosis in progression of cochlear 
lesion following exposure to intense noise. Hear Res. 2002;166(1-2):62-71. 
2. Kujawa SG, Liberman MC. Adding insult to injury: cochlear nerve degeneration after 
"temporary" noise-induced hearing loss. J Neurosci. 2009;29(45):14077-85. 
3. Minami SB, Yamashita D, Schacht J, Miller JM. Calcineurin activation contributes to 
noise-induced hearing loss. J Neurosci Res. 2004;78(3):383-92. 
4. Uemaetomari I, Tabuchi K, Hoshino T, Hara A. Protective effect of calcineurin inhibitors 
on acoustic injury of the cochlea. Hear Res. 2005;209(1-2):86-90. 
5. Bas E, Martinez-Soriano F, Lainez JM, Marco J. An experimental comparative study of 
dexamethasone, melatonin and tacrolimus in noise-induced hearing loss. Acta 
Otolaryngol. 2009;129(4):385-9. 
6. Eshraghi AA, Nazarian R, Telischi FF, Rajguru SM, Truy E, Gupta C. The cochlear 
implant: historical aspects and future prospects. Anat Rec (Hoboken). 2012;295(11):1967- 
80. 
7. Clark G. The multi-channel cochlear implant: past, present and future perspectives. 
Cochlear Implants Int. 2009;10 Suppl 1:2-13. 
8. Patrick JF, Busby PA, Gibson PJ. The development of the Nucleus Freedom Cochlear 
implant system. Trends Amplif. 2006;10(4):175-200. 
9. Khoza-Shangase K, Gautschi-Mills K. Exploration of factors influencing the preservation 
of residual hearing following cochlear implantation. S Afr J Commun Disord. 
2019;66(1):e1-e7. 
10. Snels C, IntHout J, Mylanus E, Huinck W, Dhooge I. Hearing Preservation in Cochlear 
Implant Surgery: A Meta-Analysis. Otol Neurotol. 2019;40(2):145-53. 
11. Skarzynska MB, Skarzynski PH, Krol B, Koziel M, Osinska K, Gos E, Skarzynski H. 
Preservation of Hearing Following Cochlear Implantation Using Different Steroid 
Therapy Regimens: A Prospective Clinical Study. Med Sci Monit. 2018;24:2437-45. 
12. Kuthubutheen J, Smith L, Hwang E, Lin V. Preoperative steroids for hearing preservation 
cochlear implantation: A review. Cochlear Implants Int. 2016;17(2):63-74. 
13. Eshraghi AA, He J, Mou CH, Polak M, Zine A, Bonny C, Balkany TJ, Van De Water TR. 
D-JNKI-1 treatment prevents the progression of hearing loss in a model of cochlear 
implantation trauma. Otol Neurotol. 2006;27(4):504-11. 
14. El Kechai N, Agnely F, Mamelle E, Nguyen Y, Ferrary E, Bochot A. Recent advances in 
local drug delivery to the inner ear. Int J Pharm. 2015;494(1):83-101. 
15. Ritchie H ME, Rodes-Guirao L, Appel C, Giattino C, Ortiz-Ospina E, Hasell J, 
Macdonald B, Beltekian D, Roser M. Coronavirus Pandemic (COVID-19)2021 accessed 
03 January 2022. Available from: https://ourworldindata.org/covid-vaccinations. 
16. Bester CW, Campbell L, Dragovic A, Collins A, O'Leary SJ. Characterizing 
Electrocochleography in Cochlear Implant Recipients with Residual Low-Frequency 
Hearing. Front Neurosci. 2017;11:141. 


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11 APPENDICES 
11.1 HIGHLY EFFECTIVE METHODS OF CONTRACEPTION 
Female Participants (WOCBP only): 
The following methods of contraception can achive a failure rate of less than 1% per year 
when used consistently and correctly and are considered as highly effective birth control 
methods: 
x Combined (estrogen and progestogen containing) hormonal / contraception associated 
with inhibition of ovulation: 
o oral 
o intravaginal 
o transdermal 
x Progestogen-only hormonal contraception associated with inhibition of ovulation: 
o oral 
o injectable 
o implantable 
x Intrauterine device (IUD) 
x Intrauterine hormone-releasing system ( IUS) 
x Bilateral tubal occlusion 
x Vasectomised partner 
x Sexual abstinence 
Same-sex partner may also be considered an effective method of birth control for this 
study. 
Male Participants: 
No contraception measures are needed for male participants, including those with 
pregnant or non-pregnant WOCBP partner. 

SAP_001.pdf: 
Protocol Number: SENS-401-203 
Document Status: SAP v2.0 
03 July 2024 
CONFIDENTIAL 
Page 1 of 28 
Statistical Analysis Plan 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
A Phase IIa, Multicenter, Randomized, Controlled, Open-label Study to 
Evaluate the Presence of SENS-401 in the Perilymph after 7 days of 
repeated oral administration in Adult Participants Scheduled for 
Cochlear Implantation 
Protocol No.: SENS-401-203 
Product Code: SENS-401 
 
PREPARED FOR: Sensorion Australia Pty Ltd. 
Suite 2003, 109 Pitt Street 
Sydney, NSW 2000 
Australia 
 
PREPARED BY: 
 
 
 
DATE OF ISSUE: 
03 July 2024 
 
 
VERSION/STATUS: Version 2.0 
 
AUTHOR: 
 


Protocol Number: SENS-401-203 
Document Status: SAP v2.0 
03 July 2024 
CONFIDENTIAL 
Page 2 of 28 
Statistical Analysis Plan 
 
 
 
SAP APPROVAL 
 
By my signature, I confirm that this SAP has been reviewed and has been approved 
for use on the SENS-401-203 study: 
 
Name 
Title/ Company 
Signature 
Date 
 
 
SAP REVISION HISTORY 
 
 
Version 
Description/Updates 
Date 
1.0 
The sponsor approved first version of SAP 
and mock shells. 
02 May 2024 
2.0 
Efficacy analysis set was added and defined 
in the SAP. PK analysis set definition was 
revised for clarity. 
The CDISC section was removed as it was 
not required for this confirmed proof of 
concept study. 
The general analytical approach for 
continuous variables was updated to specify 
the presentation of decimal points in 
summary tables. 
Update to mock shells were made to reflect 
these changes. 
03 July 2024 


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Statistical Analysis Plan 
 
 
Table of contents 
1 
INTRODUCTION .................................................................................................................... 5 
2 
PROJECT OVERVIEW ............................................................................................................. 5 
2.1 
Study Design ............................................................................................................................... 5 
2.2 
SCHEMA ...................................................................................................................................... 6 
2.3 
SCHEDULE OF ASSESSMENTS ...................................................................................................... 7 
2.4 
Objectives ................................................................................................................................. 11 
2.5 
Endpoints .................................................................................................................................. 11 
2.6 
Sample Size ............................................................................................................................... 12 
2.7 
Treatment Assignment and Randomization .............................................................................. 12 
3 
STATISTICAL CONSIDERATIONS ........................................................................................... 13 
3.1 
General Analytical Approach ..................................................................................................... 13 
3.2 
Data Capture ............................................................................................................................. 13 
3.3 
Statistical Programming ............................................................................................................ 14 
4 
ANALYSIS SETS .................................................................................................................... 15 
4.1 
Analysis Set Descriptions ........................................................................................................... 15 
5 
PROTOCOL DEVIATIONS ...................................................................................................... 15 
5.1 
Data Lists ................................................................................................................................... 15 
5.2 
Analyses .................................................................................................................................... 15 
6 
PARTICIPANT DISPOSITION ................................................................................................. 16 
6.1 Data Lists ......................................................................................................................................... 16 
6.2 Analyses .......................................................................................................................................... 16 
6.3 Death ............................................................................................................................................... 16 
7 
DEMOGRAPHIC AND BASELINE INFORMATION................................................................... 17 
7.1 
Demographics ........................................................................................................................... 17 
7.2 
Medical and Surgical History ..................................................................................................... 17 
7.3 
Pregnancy Test .......................................................................................................................... 17 
7.4 
Eligibility .................................................................................................................................... 17 
7.5 
Hearing Loss History ................................................................................................................. 17 
7.6 
SARS-CoV-2 Screening ............................................................................................................... 17 
8 
TREATMENT EXPOSURE ...................................................................................................... 18 
8.1 
Study Drug Administration (Arm A only) ................................................................................... 18 
8.2 
Study Drug Reconciliation (Arm A only) .................................................................................... 18 
9 
PHARMACOKINETICS ENDPOINTS ....................................................................................... 19 
9.1 
Primary endpoint ...................................................................................................................... 19 
9.2 
Secondary endpoint .................................................................................................................. 19 
10 EFFICACY ENDPOINTS ......................................................................................................... 20 
10.1 
Hearing Threshold ..................................................................................................................... 20 
10.2 
Immittance Audiometry ............................................................................................................ 20 
10.3 
Exploratory ................................................................................................................................ 21 
11 SAFETY ................................................................................................................................ 23 
11.1 
Adverse Events .......................................................................................................................... 23 
11.2 
Prior and Concomitant Medications ......................................................................................... 24 
11.3 
Otoscopic Examination ............................................................................................................. 25 
11.4 
Electrocochleography (ECochG) ................................................................................................ 25 
11.5 
Cochlear Implant Surgery .......................................................................................................... 25 
11.6 
Laboratory Assessments ........................................................................................................... 25 


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Statistical Analysis Plan 
 
 
11.7 
Vital Signs .................................................................................................................................. 26 
11.8 
Physical Examination ................................................................................................................. 26 
11.9 
12-lead ECG ............................................................................................................................... 26 
12 CHANGES TO THE PLANNED ANALYSIS ............................................................................... 27 
13 INTERIM AND FINAL ANALYSIS ........................................................................................... 27 
14 SOFTWARE ......................................................................................................................... 27 
15 REFERENCES ....................................................................................................................... 28 


Protocol Number: SENS-401-203 
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Statistical Analysis Plan 
 
 
1 
INTRODUCTION 
The following Statistical Analysis Plan (SAP) provides the details of the planned statistical 
analyses of the data from the SENS-401-203 study. 
The planned analyses identified in this SAP will be included in clinical study reports (CSRs), 
regulatory submissions, or future manuscripts. In addition, post hoc exploratory analyses not 
identified in this SAP may be performed to further evaluate study data. Any post hoc analyses 
performed will be identified as such in the CSR. 
2 
PROJECT OVERVIEW 
2.1 
Study Design 
This is a Phase IIa, open-label, randomized and controlled study investigating repeated twice- 
daily administration of oral SENS-401 in adult participants with preoperative threshold levels 
LQWKHLPSDLUHGHDUGHPRQVWUDWLQJXQDLGHGDXGLRPHWULFWKUHVKROGRIG%RUEHWWHULH
dB) at 500 Hz), who meet the locally approved indication for, and have already consented to 
receiving, cochlear implant Cochlear™ Nucleus® C1622. 
After written informed consent is obtained and screening procedures completed, 27 eligible 
participants will be randomized on Day 1 to either Arm A or Arm B in ratio 2:1 (18 participants 
in Arm A and 9 participants in Arm B). Arm A participants will commence dosing with twice- 
daily oral 43.5 mg SENS- 401 for 7 to 13 days prior to their cochlear implant surgery scheduled 
from Day 8 to Day 14. Dosing will continue on the day of surgery. Arm B participants will not 
receive any treatment other than their scheduled cochlear implant surgery. All participants will 
undergo audiometric testing at screening and Day 1 (baseline). From Day 1, Arm A participants 
will record each administration of SENS-401 into a study diary. Blood and perilymph samples 
for determining SENS-401 concentration will be collected from Arm A participants only on the 
day of cochlear implant surgery (blood sampling before the morning dose of SENS-401 and 
perilymph sampling during the surgery). Electrocochleography will be performed for all 
participants (Arm A and Arm B) during cochlear implant surgery. All participants (Arm A and 
Arm B) will attend the Day 49 visit, when efficacy and safety assessments will be performed. 
Arm A participants will continue to take SENS-401 until this visit. All participants (Arm A and 
Arm B) will then return to the study site for the EOS on Day 105 for final safety and efficacy 
assessments. Blood samples for exploratory biomarker research will also be collected from all 
participants (Arm A and Arm B) on Day 1, Day 49 visit, and EOS. 
 
All the subjects receiving SENS-401 will have before EOS at least 4 weeks of follow-up after 
their last dose of SENS-401. 


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Statistical Analysis Plan
2.2
SCHEMA


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Statistical Analysis Plan 
 
 
2.3 
SCHEDULE OF ASSESSMENTS 
 
Study Period 
Screening 
Treatment Perioda 
Follow-up 
Period 
 
 
 
 
Implantb 
 
 
EOS/ETc 
Study day  
Day 1a 
 
Day 8b 
 
Day 49c 
Day 105 
Visit window 
D-42 to D-1  
 
Day 8 to 14  
± 7 days 
± 21 days 
Visit numberd 
1 
2 
Pre-implant 
Outpatient 
3 
Post-implant 
Outpatient 
4 
5 
Informed Consente 
X 
 
 
 
 
 
 
Demographics, medical history, prior medicine/treatment 
X 
 
 
 
 
 
 
Height (cm), weight (kg) 
X 
 
 
 
 
 
 
Physical examinationf 
X 
 
 
 
 
X 
X 
12-lead resting ECGg 
X 
 
 
 
 
X 
X 
Vital signs (SBP, DBP, HR, RR, Temp)h 
X 
 
 
 
 
X 
X 
Clinical Laboratory testing (haematology, chemistry)i 
X 
 
 
 
 
X 
X 
Pregnancy test for WOCBPj 
X 
 
 
 
 
X 
X 
Concomitant medication/treatmentsk 
X 
Xk 
 
X 
 
X 
X 
Inclusion and exclusion criterial 
X 
X 
 
 
 
 
 
Testing for COVID-19m 
 
X 
 
 
 
 
 
Biomarker blood samplingn 
 
Xn 
 
 
 
X 
X 
Randomization, dispensing of SENS-401 & diaryo 
 
X 
 
 
 
 
 
SENS-401 43.5 mg twice dailya (Arm A) 
 
X 
X 
X 
X 
X 
 


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Statistical Analysis Plan 
 
 
 
Study Period 
Screening 
Treatment Perioda 
Follow-up 
Period 
 
 
 
 
Implantb 
 
 
EOS/ETc 
Study day  
Day 1a 
 
Day 8b 
 
Day 49c 
Day 105 
Visit window 
D-42 to D-1  
 
Day 8 to 14  
± 7 days 
± 21 days 
Visit numberd 
1 
2 
Pre-implant 
Outpatient 
3 
Post-implant 
Outpatient 
4 
5 
Check study diary and perform drug reconciliationp 
 
 
 
X 
 
X 
 
SENS-401 plasma collectionq (Arm A) 
 
 
 
X 
 
 
 
SENS-401 perilymph collectionr (Arm A) 
 
 
 
X 
 
 
 
Hearing Test – PTA (0.125 to 4 kHz)s 
X 
Xs 
 
 
 
X 
X 
Otoscopic Examinations 
X 
Xs 
 
 
 
X 
X 
Immitance Audiometrys 
X 
Xs 
 
 
 
X 
X 
Cochlear Implant Surgeryt 
 
 
 
X 
 
 
 
Electrocochleographyu 
 
 
 
X 
 
 
 
AEs/ SAEsv 
 
Xv 
X 
X 
X 
X 
X 
ABBREVIATIONS: AE = adverse event; b.i.d. = twice daily; COVID-19 = coronavirus 2019; D = study day; DBP = diastolic blood pressure; ECG = electrocardiogram; EOS 
= end of study visit; ET = early termination visit; HR = heart rate; PTA = pure tone audiometry; RR = respiratory rate; SAE = serious adverse event; SBP = systolic blood 
pressure; Temp = temperature (ºCelcius); WOCBP = woman of child-bearing potential. 
a. 
All participants must attend Day 1 visit ensuring that if randomized to Arm A, they will adhere to the fasting restrictions. Only participants randomized to Arm A will be 
treated with study drug (see footnote [o]). On the morning of Day 1, Arm A participants will be dispensed one kit (12 bottles of 30 tablets each) and will take the first dose 
under supervision at the study site. Study staff will explain dosing and storage instructions and importance of treatment compliance (at least 70% compliance in the 3 days 
prior to cochlear implant surgery and for the morning dose on day of surgery [i.e. no more than 2 missed doses], and at least 70% compliant overall for the dosing period 
prior to surgery [i.e. no more than 4 missed doses if surgery occurred at Day 8, 5 if at Day 9 or 10, and 6 if at Day 11],…). Treatment period: Commencing Day 1, 43.5 mg 
oral SENS-401 will be administered twice-daily from 7 to 13 days (see also footnote [b]), on the day of cochlear implant surgery (morning dose after blood collection for 
PK), and twice-daily until attending the Day 49 visit. 


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Statistical Analysis Plan 
 
 
b. All participants will undergo cochlear implant surgery between Day 8 and 14 as indicated in footnote [t]. Participants must have consented to cochlear implant surgery 
prior to being approached for this study. 
c. All participants will attend the study site for the Day 49 visit (Arm A participants will continue to take study drug until attending this visit) and for the EOS. Arm A 
participants will return all study drug containers (even if empty) and any unused study drug at the Day 49 visit. Both visits should ideally but not necessarily coincide with 
standard-of-care cochlear implant assessment visits. If a participant withdraws or is withdrawn from the study, they will be asked to attend an early termination (ET) visit 
with the same procedures as EOS, including audiometric testing and biomarker sampling if willing. Visit windows: Day 49 visit ± 7 days; EOS: Day 105 ± 21 days. 
d. All participants will attend the study site for 5 visits as indicated and will be advised to contact the study site during outpatient periods if they have queries or concerns. 
Such contact will be documented. Unscheduled visits for study-related safety are at the discretion of the Investigator and will be documented in source document and in 
the eCRF. 
e. 
Voluntary, signed, informed consent on forms approved by the Ethics Committee is required prior to the first screening assessment. 
f. 
Physical examination will be conducted by the Investigator (physician). Unscheduled symptom-directed physical examination during the study are at the discretion of the 
Investigator if required for safety. 
g. Single 12-lead ECG will be performed after participant supine for at least 10 minutes. Unscheduled ECGs during the study are at the discretion of the Investigator if 
required for safety. 
h. Vital signs will be measured after the participant is supine for at least 5 minutes. Unscheduled vital signs during the study are at the discretion of the Investigator if 
required for safety. 
i. 
Fasting blood samples will be collected from all participants (Arm A and Arm B) for haematology and chemistry (fasted for at least 8 hours). Unscheduled samples collected 
for clinical laboratory testing during the study are at the discretion of the Investigator if required for safety. 
j. 
Blood samples will be collected from all WOCBP for serum pregnancy testing (human chorionic gonadotropin [hCG]) at screening, and urine samples collected from 
Arm A WOCBP only for pregnancy testing (hCG) at the Day 49 visit and EOS. 
k. All concomitant medications and treatments will be documented and entered into the eCRF. On Day 1: to be checked before randomization with any concomitant 
medication/treatment required on Day 1 after randomization also recorded. 
l. 
Eligibility for all participants must be confirmed prior to randomization and first dose on Day 1. 
m. Participants will be tested for SARS-Cov-2 (COVID-19) on Day 1 prior to randomization. If positive, the participant will be deemed a screen failure and must not be 
randomized. Any other COVID-19 screening or testing will be as per Institutional and local regulatory guidelines and requirements. 
n. Blood samples will be collected from all participants (Arm A and Arm B) for biomarker research. On Day 1: to be collected after randomization for both Arm A (pre-first 
dose) and Arm B participants. 
o. In the morning of Day 1 after confirming eligibility, participants will be randomized pre-dose to either Arm A or Arm B. Arm A will be dispensed SENS-401 kit and study 
diary (see footnote [p]) on Day 1 and treated with SENS-401 as per footnote (a). Arm B (control group) will not be treated with SENS-401 at any time. The study is open- 
label and there is no placebo treatment. 


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Statistical Analysis Plan 
 
 
p. Study staff will give Arm A participants a paper study diary on Day 1 and will explain how to record times and dates of study drug administration including number of 
tablets taken (daily first and last mealtimes will also be recorded). Participants will be reminded to bring the study diary and unused study drug with all empty or full bottles 
to subsequent site visits, at which study staff will review the study diary for treatment compliance and perform drug reconciliation. Study staff will transcribe drug 
administration details from the study diary into the eCRF. The study diary and study drug will be returned to the participant on Day 8 and reminded to return both (including 
empty bottles) at the visit on Day 49. The diary will be considered a source document and study staff will retain the diary at the Day 49 visit. 
q. One blood sample will be taken from Arm A participants only prior to the morning dose on the day of cochlear implant surgery to determine SENS-401 plasma 
concentration. Blood samples are not required from Arm B participants on Day 8. 
r. 
During the cochlear implant surgery, one (1) perilymph sample of at least 1 μL will be collected from Arm A participants only to determine SENS-401 concentration. 
Perilymph samples are not required from Arm B participants. 
s. 
At Screening, on Day 1, on Day 49, and EOS, audiometric assessments will be conducted for all participants (Arm A and Arm B). On Day 1: to be conducted after 
randomization for both Arm A participants (pre-first dose) and Arm B participants. On Day 49 and EOS: to be conducted with the Cochlear™ Nucleus® C1622 turned 
off. 
t. 
Cochlear implant surgery will be performed as standard of care using model Cochlear™ Nucleus® C1622. 
u. Electrocochleography will be performed during cochlear implant surgery for all participants (Arm A and Arm B). 
v. Adverse events will be recorded throughout the study from the time of informed consent for all participants (Arm A and Arm B). On Day 1: to be checked before 
randomization and any AEs experienced on Day 1 post-randomization also recorded. 


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Statistical Analysis Plan 
 
 
 
2.4 
Objectives 
2.4.1 Primary objective 
x 
To detect the presence of SENS-401 in the perilymph of participants undergoing 
cochlear implant surgery after 7 days of oral administration of SENS-401.
2.4.2 Secondary objective(s) 
x 
To measure the SENS-401 concentrations in the perilymph and plasma of 
participants undergoing cochlear implant surgery after 7 days of oral administration 
of SENS-401.
x 
To compare the SENS-401 concentrations in perilymph and plasma of participants 
undergoing cochlear implant surgery after 7 days of oral administration of SENS- 
401.
x 
To assess the efficacy of repeated oral administration with SENS-401 to protect 
against residual low frequency hearing loss in participants undergoing cochlear 
implant surgery at the Day 49 visit and at EOS.
x 
To assess the safety and tolerability of SENS-401 for the whole duration of the 
study.
2.4.3 Exploratory objective(s) 
 
x 
To assess the efficacy of repeated oral administration with SENS-401 to protect against 
residual low frequency hearing loss in participants undergoing cochlear implant surgery 
and with no electrophysiological evidence of basilar membrane fixation.
x 
To collect and store a biobank of plasma and serum to be able if necessary and possible 
to explore the correlation between biomarkers already pre-identified (e.g., prestin) or that 
will be identified in the future with clinical features of interest.
2.5 
Endpoints 
2.5.1 Primary Endpoints 
x 
Percentage of participants from Arm A with levels of SENS-401 in the perilymph above 
the Limit of Quantification on day of cochlear implant surgery after seven days of SENS- 
401.
2.5.2 Secondary Endpoints 
2.5.2.1 Pharmacokinetic Endpoints 
x 
SENS-401 perilymph concentration on day of cochlear implant surgery after seven days 
of SENS-401
x 
SENS-401 plasma concentration on day of cochlear implant surgery after seven days of 
SENS-401.
2.5.2.2 Efficacy Endpoints 
x 
Change of hearing threshold from baseline in the implanted ear at 500 Hz after repeated 
administration of SENS-401, as assessed by pure tone audiometry (PTA) at the Day 49 
visit and at EOS.


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Statistical Analysis Plan 
 
 
x 
Change of hearing threshold from baseline in the implanted ear at 250 Hz and 750 Hz 
after repeated administration of SENS-401, as assessed by pure tone audiometry (PTA) 
at the Day 49 visit and at EOS.
2.5.2.3 Safety Endpoints 
Safety endpoints will include evaluation of the following: 
x 
Incidence, severity and relationship of treatment emergent adverse events (AEs) and 
serious AEs.
x 
Change from baseline in vital signs.
x 
Change from baseline in 12-lead ECG parameters.
x 
Change from baseline in clinical laboratory parameters (serum chemistry, hematology, 
coagulation).
 
2.5.2.4 Exploratory Endpoints 
¾ In 
a subset 
of participants 
assessed 
by a neurophysiologist 
to have 
no 
electrophysiological evidence of basilar membrane fixation:
x 
Change of hearing threshold from baseline in the implanted ear at 500 Hz after repeated 
administration of SENS-401, as assessed by pure tone audiometry (PTA) 
x 
Change of hearing threshold from baseline in the implanted ear at 250 Hz and 750 Hz 
after repeated administration of SENS-401, as assessed by pure tone audiometry (PTA). 
 
¾ Serum/plasma concentrations of selected biomarkers at baseline (i.e., Day 1, and pre- 
dose for Arm A), at the Day 49 visit, and at EOS.
 
2.6 
Sample Size 
Overall, for this study, 27 participants will be enrolled and randomized to either Arm A or Arm B 
on Day 1 in ratio 2:1 (18 participants in Arm A and 9 participants in Arm B). 
The sample size is not calculated based on statistical significance on any clinical efficacy 
parameters but on empirical considerations for the pharmacokinetic evaluation. Eighteen 
subjects are generally considered sufficient to characterize the PK of a small molecule. The 
purpose of the PK sampling is to determine if SENS-401 can be detected in the perilymph and 
to compare the levels of SENS-401 in two different body compartments and the overall safety 
profile. 
For efficacy, 27 participants are empirically expected to provide enough data to evaluate a trend 
of efficacy. 
Enough participants will be screened to randomize 27 participants. The expected power and 
precision related to this sample size is further discussed for both the main endpoint and the 
secondary endpoint in sections 9 and 10. 
 
2.7 
Treatment Assignment and Randomization 
All participants will be randomized as detailed in the randomization plan. Overall, for this study, 
27 participants will be enrolled and randomized to either Arm A or Arm B on Day 1 in ratio 2:1: 
x 
Arm A: treated with SENS-401. Eighteen (18) participants. 
x 
Arm B: not treated with SENS-401. Nine (9) participants. 


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Statistical Analysis Plan 
 
 
3 
STATISTICAL CONSIDERATIONS 
3.1 
General Analytical Approach 
Data analysis will be performed according to 
 Standard 
Operating Procedures (SOPs). 
 
The general analytical approach for all endpoints will be descriptive in nature. 
Unless otherwise stated, the following statistical approaches will be taken: 
Continuous variables: 
Descriptive statistics will include the number of non-missing values, 
mean, standard deviation (SD), median, minimum, and maximum. 
The minimum and maximum values will be presented to the same 
number of decimals as recorded in the raw data. The mean and 
median will be presented to one more decimal place than the raw 
data and SD will be presented to two decimal places more than the 
raw data. 
 
Categorical variables: 
Descriptive statistics will include frequency counts and 
percentages per category. Percentages will be rounded to one 
decimal place, with the denominator being the number of 
participants in the relevant population. 
Imputation: 
No imputation will be performed for missing data. 
 
Baseline: 
Baseline will be defined as the last available assessment prior 
randomization, excluding the audiogram values. For the 
audiogram values, the baseline will be determined based on 
the data collected on Day 1 after randomization of study 
participants. 
Unscheduled visits 
Unscheduled visits will be excluded from visit-based summary 
tables, but will be included in data listings. 
Early termination visits 
Early termination visits will be excluded from visit-based 
summary tables but will be included in data listings. 
 
3.2 
Data Capture 
3.2.1 Database 
The primary method of data collection is via the study database, developed within the third 
party validated, 21 CFR Part 11 compliant, technology solution 
. The 
database has been designed based on the final protocol, the system/core configuration, 
electronic Case Report Form (eCRF) specifications and/or mock eCRF and consistency check 
specifications. 
Data will be entered directly into the EDC system. Site-collected data will be entered directlyfrom 
source notes at the site and will be verified by Clinical Research Associates (CRAs) to ensure 
data integrity. 
Refer to the Data Management Plan for further details. 


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Statistical Analysis Plan 
 
 
3.2.2 Third Party Data 
3.2.2.1 Safety & PD Laboratory 
Bioanalytical data will be received from 
 as specified in the Data Transfer 
Agreement (DTA). Data transfers will be reconciled against the CRF data. 
The central reading of electrocochleography results will be sent back to the clinical site that 
will directly enter the data into the EDC system. 
The final data transfer(s) will be incorporated into the End of Study analysis once the final 
transfer has been received, reconciled and all issues are considered resolved. 
 
No unit conversion of laboratory data is planned. 
 
3.3 
Statistical Programming 
 
3.3.1 Change from Baseline 
Absolute Change from Baseline will be calculated as: 
Change from baseline = postbaseline value - baseline value 
 
3.3.2 Listings, Tables and Figures 
Listings, tables and figures will be delivered as individual .RTF files in accordance with the 
mock listings, tables and figures. 
Data listings will present all data, with participants grouped by the treatment arm. These are 
typically sorted by arm treatment, participant ID, and date/time of assessment. 
 
Tabulations will summarize data by treatment arm, and total. 
Tables are planned to be presented as: 
Arm A 
(N=X) 
Arm B 
(N=X) 
Overall 
(N=X) 
 
 
Where Arm A: treated with SENS-401; and Arm B: not treated with SENS-401 


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Statistical Analysis Plan 
 
 
4 
ANALYSIS SETS 
Two analysis datasets will be used for study analyses: Pharmacokinetics (PK) Set and Full 
Analysis Set (FAS). 
Additional study populations or subgroups of interest may be required as part of post-hoc 
analyses. These will be detailed in the CSR. 
The number and percentage of participants in each analysis set will be summarized. 
4.1 
Analysis Set Descriptions 
4.1.1 
PK Set 
The PK set consists of study participant for whom perilymph and/or plasma was analysed. 
4.1.2 
FAS Set 
The FAS will be comprised of all randomized participants. A randomized participant is 
defined as having a profile deemed suitable for participation in the study by the 
investigator, based on adherence to all eligibility criteria, which allowed the study 
participant to be randomly allocated to either Arm A or B. Participants will be analyzed 
according to the treatment received. 
 
4.1.3 Efficacy Set 
The efficacy set will consist of all FAS participants who have at least hearing threshold 
parameter data at Baseline and Day 49. 
5 
PROTOCOL DEVIATIONS 
Analysis Set: FAS 
 
5.1 
Data Lists 
All protocol deviations will be listed, grouped by the treatment arm. 
5.2 
Analyses 
 
The protocol deviation summary table will include: 
x 
The total number of minor protocol deviations 
x 
The total number of major protocol deviations 
x 
The number of participants who reported at least one minor protocol deviation 
x 
The number of participants who reported at least one major protocol deviation 


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Statistical Analysis Plan 
 
 
6 
PARTICIPANT DISPOSITION 
Analysis Set: All participants 
 
6.1 Data Lists 
 
A listing of subject disposition will present: 
x 
Date of informed consent 
x 
Date of randomization 
x 
Date of first treatment 
x 
Date of last treatment 
x 
Date of completion / early withdrawal 
x 
Primary reason for early withdrawal 
6.2 Analyses 
The participant disposition summary table will include: 
x 
Number of participants consented 
x 
Number of participants screened 
x 
Number of participants randomized 
x 
Number of participants eligible for PK set 
x 
Number of participants eligible for FAS set 
x 
Number of participants eligible for Efficacy set 
x 
Number of participants who received at least one dose of study drug (Arm A only) 
x 
Number of participants who had the Cochlear Implant Surgery 
x 
Number of participants withdrawn from the study early 
x 
Reason for early study withdrawal 
x 
Number of participants completing study 
 
 
6.3 Death 
Death-related details will be listed only if deaths occur. 


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Statistical Analysis Plan 
 
 
7 
DEMOGRAPHIC AND BASELINE INFORMATION 
Analysis Set: FAS except for Eligibility where all subjects are included. 
7.1 
Demographics 
7.1.1 Parameters 
x 
Age (years) 
x 
Sex 
x 
Childbearing potential 
x 
Menopause status 
x 
Body Measurements 
• 
Height 
• 
Weight 
7.1.2 Biostatistical methods 
 
7.1.2.1 Data Lists 
Demographic data will be listed for each participant. 
 
7.1.2.2 Analyses 
Demographic data will be summarized using descriptive statistics, tabulated by the treatment 
arm. 
7.2 
Medical and Surgical History 
Medical and surgical history will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA®) and summarized by system organ class (SOC) and preferred term (PT), by 
treatment arm and overall. Data on history will also be presented in listings. 
7.3 
Pregnancy Test 
Pregnancy test data will be listed for all women of childbearing potential. 
7.4 
Eligibility 
All eligibility data will be listed (include all participants). 
 
7.5 
Hearing Loss History 
 
7.5.1 Data Lists 
Hearing loss history will be listed for each participant by the treatment arm. 
 
7.5.2 Analyses 
Hearing loss history will be summarized using descriptive statistics, tabulated by the treatment 
arm. 
 
7.6 
SARS-CoV-2 Screening 
Any SARS-CoV2 screening results will be listed. 


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Statistical Analysis Plan 
 
 
8 
TREATMENT EXPOSURE 
Analysis Set: FAS 
 
8.1 
Study Drug Administration (Arm A only) 
 
The diary data will be listed. 
 
8.2 
Study Drug Reconciliation (Arm A only) 
8.2.1 Data Lists 
 
Study drug reconciliation will be listed, including data on: 
x 
Study drug dispensation date 
x 
Number of tablets dispensed 
x 
Study drug return date 
x 
Number of tablets taken 
x 
Number of tablets returned 
x 
IMP compliance  70% in the 3 days prior to surgery 
x 
IMP compliance  70% for dosing period prior to surgery 
x 
IMP compliance  70% during the entire treatment period 
x 
IMP compliance at 100% in the 3 days prior to surgery 
 
8.2.2 Analyses 
Treatment exposure will be summarized as: 
x 
Total Number of tablets 
x 
Number of participants with IMP compliance  70% in the 3 days prior to surgery 
x 
Number of participants with IMP compliance  70% Dosing Period Prior to Surgery 
x 
Number of participants with IMP compliance  70% during the entire treatment period 
x 
Number of participants with IMP compliance at 100% in the 3 days prior to surgery 
x 
Duration of exposure: Date of last dose - date of first dose + 1 


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Statistical Analysis Plan 
 
 
9 
PHARMACOKINETICS ENDPOINTS 
 
Analysis Set: PK Set (Arm A only) 
 
9.1 
Primary endpoint 
 
9.1.1 
Data Lists 
 
Data on sample collections before Cochlear implant surgery and on the surgery, will be listed, 
including: 
x 
Date of perilymph sample collection 
x 
Time of perilymph sample collection 
x 
If surgery was complicated 
x 
Date / Time of last drug intake before plasma sample collection 
x 
Date / Time of plasma sample collection 
x 
Time lapse between last drug intake and perilymph sample collection 
9.1.2 
Analyses 
 
The number and percentage of participants from Arm A with levels of SENS-401 in the 
perilymph above the Limit of Quantification will be summarized. 
9.2 
Secondary endpoint 
 
9.2.1 
Data Lists 
 
The evaluation of the secondary endpoints will be purely descriptive. It will involve listing the 
concentrations of SENS401 obtained in the plasma and in the perilymph for each participant in 
Arm A. 


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Statistical Analysis Plan 
 
 
10 EFFICACY ENDPOINTS 
 
Analysis Set: FAS Set 
 
10.1 Hearing Threshold 
 
10.1.1 Data Lists 
 
Hearing threshold values for each patient, as assessed by bone and air conduction pure tone 
audiometry (PTA), will be listed at frequencies 125 to 4kHz (air) and 250 to 4kHz (bone), by 
treatment arm and timepoint. 
 
For each participant, a 3-frequency average of the hearing threshold values (250-500-750 Hz) 
will be calculated and listed by treatment arm and timepoint. For each timepoint, if there is a 
missing hearing threshold value at any of these 3 frequencies, the average will not be 
calculated. 
 
10.1.2 Analyses 
 
Analyses will be conducted on air conduction hearing threshold results only and not on bone 
conduction hearing threshold results. 
10.1.2.1 Hearing Threshold by Air Conduction PTA – Covariance Analysis 
 
Change of hearing threshold from baseline in the implanted ear at 250 Hz, 500 Hz and 750 
Hz will be summarized as continuous variables by visit and treatment arm using simple 
descriptive statistics. 
 
Change from baseline of the average hearing threshold values for frequencies 250-500-750 
Hz will be summarized as continuous variables by visit and treatment arm using simple 
descriptive statistics. 
 
Some threshold results are recorded as “No response” or “Vibrotactile only”. A “No response” 
and “Vibrotactile only” result is never to be considered a threshold. Therefore 5 dB will be added 
to each threshold value associated to a “No response” or “Vibrotactile only” result (Sijgers et al., 
2023). 
Analysis of covariance model (ANCOVA) will be used to assess changes in the values from 
baseline at the Day 49 visit and at EOS, comparing between treatment groups. The treatment 
group will be used as a fixed factor and the baseline as a covariate. If baseline is not available 
at a frequency, the post-baseline value will be excluded from the descriptive table and the 
ANCOVA for that frequency. For the average of the 3 frequencies, if there is a missing value 
at one of the 3 frequencies, the participant will be excluded from the descriptive table and the 
ANCOVA. 
 
10.2 Immittance Audiometry 
 
Immittance audiometry assessment data will be listed for each participant by treatment arm 
and timepoint. 


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Statistical Analysis Plan 
10.3 Exploratory 
10.3.1 Hearing Preservation 
Hearing preservation will be calculated for each participant by treatment arm at baseline, Day 
49, and Day 105. This will be done at measured frequencies 125, 250, 500 and 750 Hz, as 
well as using the average of 125 to 750 Hz and 250 to 750 Hz. 
The degree of hearing preservation will be quantified using the Hearing Preservation 
Classification System technique (Skarzynski et al). 
The Hearing Preservation Classification System defines four categories of hearing preservation 
(HP)%: 
x
Category HP1 is complete or near complete preservation.
with a HP of more than 75%.
x
Category HP2 is partial preservation with a HP of 25 to 75%.
x
Category HP3 is minimal HP with a HP 0 to 25%.
x
Category HP4 is loss of hearing/no hearing when no measurable
hearing is preserved.
+HDULQJ3UHVHUYDWLRQ+3 37$SRVWRSHUDWLYH37$EDVHOLQH37$PD[37$EDVHOLQH
100 
Where: 
o
PTA baseline is pure tone average measured preoperatively.
o
PTA postoperative is pure tone average measured postoperatively.
o
PTA max is the maximal sound intensity at the frequency.
For frequency 125 Hz, PTA max = 90 dB HL Æ PTA postoperative upper limit = 90 dB HL 
For frequency 250 Hz, PTA max = 105 dB HL Æ PTA postoperative upper limit = 105 dB HL 
For frequency 500 Hz, PTA max = 110 dB HL Æ PTA postoperative upper limit = 110 dB HL 
For frequency 750 Hz, PTA max = 120 dB HL Æ PTA postoperative upper limit = 120 dB HL 
For the average frequencies from 125-750 Hz: 
o
PTA baseline is the average dB HL across the 4 frequencies.
o
PTA postoperative is the average dB HL across the 4 frequencies.
o
PTA max is the average of the 4 maximums: (90+105+110+120/4)
For the average 250 – 750 Hz: 
o
PTA baseline is the average dB HL across the 3 frequencies.
o
PTA postoperative is the average dB HL across the 3 frequencies.
o
PTA max is the average of the 3 maximums: (105+110+120/3)
The HP outcomes will be listed for each participant by treatment arm, by individual frequency 
(125 – 750 Hz), by 4-frequency average (125-750 Hz), by 3-frequency average (250 – 750 Hz) 
and by timepoint. 
The HP outcomes will be summarized by visit and by percentage of participants per treatment 
arm for each category of hearing preservation. There will be a summary table per individual 


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Statistical Analysis Plan 
 
 
frequency (125 – 750 Hz), a second per 4-frequency average (125-750 Hz), and a third per 
3-frequency average (250 – 750 Hz). 
 
If the PTA baseline is not available at one of the 3 (250-750 Hz) or 4 (125-750 Hz) frequencies, 
the participant will be excluded from the summarized tables of the 3 or 4-frequency average. 
 
10.3.2 Assessment of Basilar Membrane Fixation 
 
Participants who have impairment of the basilar membrane (IBM) as detected by the ECochG 
latency shift and/or mid peak amplitude will be listed, grouped by treatment arm. 
The number and percentage of participants with IBM will be summarized by treatment arm. 
 
10.3.3 Hearing Threshold assessment excluding participants with IBM 
 
Supplementary analyses will be conducted, whereby the ANCOVA analysis and descriptive 
statistics to assess changes in hearing threshold from baseline, will be repeated excluding 
participants with IBM. 
 
 
10.3.4 A Biomarker Analysis 
 
Biomarker exploratory analyses will not be performed presently and serum/plasma samples will 
be stored for biobank. If performed, analysis plan will be documented separately from this SAP. 


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Statistical Analysis Plan 
 
 
11 SAFETY 
Analysis Set: FAS Set 
 
11.1 Adverse Events 
 
11.1.1 Definition of Variables 
 
x 
An adverse event (AE) is any untoward medical occurrence in a clinical trial participant 
administered a medicinal product, and that does not necessarily have a causal 
relationship with this treatment. 
 
x 
A serious adverse event (SAE) is any AE that results in death, or is life-threatening, 
and/or requires inpatient hospitalization or prolongs existing hospitalization, and/or 
results in persistent or significant disability or incapacity, and/or is a congenital 
anomaly or birth defect. Important medical events that are not immediately life- 
threatening or do not result in death or hospitalization but may jeopardize the 
participant or may require intervention to prevent one of the other mentioned 
outcomes should also be considered as SAEs. 
x 
A Treatment Emergent Adverse Event (TEAE) is defined as any untoward medical 
occurrence reported or observed after treatment administration. Conditions present 
before the first dose of study drug that increase in severity after the first study drug 
administration will also be considered TEAEs. Where an AE start date is partially or 
fully missing, and it is unclear as to whether the AE started after treatment 
administration, it will be assumed to be a TEAE. 
11.1.2 Biostatistical methods 
AEs will be coded using MedDRA. The MedDRA version used will be displayed in the output 
footer. 
11.1.3 Data Lists 
 
All AEs recorded during the study will be listed, grouped by participant and treatment arm. 
 
11.1.4 Analyses 
 
An overview summary table of AEs will be provided by treatment arm including: 
Number of participants reporting at least one of the following: 
x 
AE 
x 
Grade 3+ AE 
x 
Related AE (to study drug treatment, sample collection procedure, Cochlear implant 
surgery and implant) 
x 
Serious AE 
x 
Serious and study drug-related AE 
x 
Serious and sample collection procedure related AE 
x 
Serious and Cochlear implant surgery related AE 
x 
Serious and Cochlear implant related AE 
Number of participants discontinued from study drug treatment due to an AE 
Number of participants interrupted from study drug treatment due to an AE 


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Document Status: SAP v2.0 
03 July 2024 
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Statistical Analysis Plan 
 
 
Number of participants withdrawn from the study due to an AE 
Number of deaths 
 
A similar overview summary table will be provided for the TEAE for arm A participants only. 
The following summary tables will be provided for TEAEs for participants in arm A. 
x 
TEAEs by SOC and PT 
x 
Serious TEAEs by SOC and PT 
x 
Grade 3 or greater TEAEs by SOC and PT 
x 
Study drug related TEAEs by SOC and PT 
x 
TEAEs by SOC, PT and maximum severity 
x 
TEAEs related to the study sample collection procedure by SOC and PT 
x 
TEAEs related to Cochlear implant surgery by SOC and PT 
x 
TEAEs related to Cochlear implant by SOC and PT 
For the TEAE summaries, participants who experience the same TEAE more than once, the 
participant will be counted only once for that event within each category (PT, SOC or overall). 
If a participant experiences multiple occurrences of the same TEAE with different relationship 
categories, the participant will be counted once as a relationship category of Related. 
 
If a participant experiences multiple occurrences of the same TEAE with different intensity 
toxicity grades, the participant will be counted once for the maximum (most severe) toxicity 
grade. TEAEs with a missing intensity will be presented in the summary table with a toxicity 
grade of Missing. Grade 3 or greater is defined as Grade 3, Grade 4, Grade 5, or Missing. 
11.2 Prior and Concomitant Medications 
 
11.2.1 Definition of Variables 
 
x 
Prior medications will be identified as medications commenced prior to randomization, 
regardless of when it ended.
x 
Concomitant medications will be defined as any medication that is taken at or after 
randomization, regardless of when it started. All medications used for cochlear implant 
surgery will be documented and reported into the eCRF as concomitant medications. 
If a medication has a missing or partial missing start/end date or time and it cannot be 
determined whether it was taken before initial treatment or concomitantly, it will be 
considered as both prior and concomitant.
11.2.2 Biostatistical methods 
Medications will be coded using the World Health Organization Drug Dictionary (WHODrug). 
The WHODrug version used will be displayed in the output footer. Prior and concomitant 
medications will be presented in separate listings and tables. 
 
All prior and concomitant medications will be listed separately. 
 
Prior and concomitant medication summaries will be presented in separate tabulations by 
treatment arm, with data summarized by ATC Level 3 and Preferred Name. 


Protocol Number: SENS-401-203 
Document Status: SAP v2.0 
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CONFIDENTIAL 
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Statistical Analysis Plan 
 
 
11.3 Otoscopic Examination 
 
Otoscopic assessment data will be listed for each participant by treatment arm and timepoint. 
11.4 Electrocochleography (ECochG) 
 
11.4.1 Data Lists 
 
ECochG assessment data will be listed for each participant by treatment arm and timepoint. 
 
11.4.2 Analyses 
The number of participants with Impairment of the Basilar Membrane (IBM) will be summarized 
by the treatment arm. 
 
11.5 Cochlear Implant Surgery 
Cochlear implant surgery data will be listed for each participant by the treatment arm. 
 
11.6 Laboratory Assessments 
Data for each of the assessments below will be presented in listings: 
11.6.1 Parameters 
 
HAEMATOLOGY 
CHEMISTRY 
Hemoglobin 
Sodium 
Hematocrit 
Potassium 
Red Blood Cell (RBC) Count 
Calcium 
Mean corpuscular volume (MCV) 
Creatinine 
Mean corpuscular hemoglobin (MCH) 
Creatinine clearance GFR (calculated with the Cockcroft-Gault 
formula 
White Cell Count 
Urea 
Neutrophils 
Total Protein 
Lymphocytes 
Alkaline Phosphatase (ALP) 
Monocytes 
Alanine-aminotransferase (ALT) / ALT)/ Serum Glutamic-Pyruvic 
Transaminase (SGPT) 
Eosinophils 
Aspartate-aminotransferase (AST) / Serum Glutamic-Oxaloacetic 
Transaminase (SGOT) 
Basophils 
Total Bilirubin 
Platelet Count 
Direct Bilirubin 
 
Glucose Fasting 
 
International normalized ratio (INR) 
CKD-EPI = chronic kidney disease epidemiology collaboration, GFR = glomerular filtration rate, 
MDRD = modification of diet in renal disease. 
Creatine Clearance conversion: ml/min = (ml/min/1.73m2 value * BSA) / 1.73 m2 
with BSA = 0.007184 * Height (cm) 0.725 * Weight (kg) 0.425. 
11.6.2 Biostatistical methods 
 
11.6.3 Data Lists 
All laboratory parameters will be listed with flags for values the reference ranges and values 
considered to be clinically significant. 


Protocol Number: SENS-401-203 
Document Status: SAP v2.0 
03 July 2024 
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Statistical Analysis Plan 
 
 
11.6.4 Analyses 
 
Observed values (including change from baseline) will be summarized descriptively for 
hematology and chemistry parameters at baseline and each post-baseline scheduled visit. 
Both parameters will be presented categorically (Normal, Abnormal Not Clinically Significant 
(NCS), Abnormal Clinically Significant (CS)) at baseline and each post-baseline scheduled 
visit. Tables will be presented by the treatment arm. 
 
11.7 Vital Signs 
11.7.1 Parameters 
x 
Systolic Blood Pressure (mmHg) 
x 
Diastolic Blood Pressure (mmHg) 
x 
Heart Rate (beats per minute) 
x 
Respiration rate (breaths per minute) 
x 
Temperature (°C) 
11.7.2 Biostatistical methods 
Vital sign parameters will be listed for each participant by treatment arm and timepoint, and 
assessment date/time, with abnormal values flagged. 
 
11.8 Physical Examination 
11.8.1 Parameters 
x 
General appearance 
x 
Neurological System 
x 
HEENT (Head, Eyes, Ears, Nose, Throat) 
x 
Skin 
x 
Blood and Lymphatic 
x 
Cardiovascular System 
x 
Respiratory System 
x 
Musculoskeletal System 
x 
Neck (including Thyroid) 
x 
Renal System 
x 
Gastrointestinal System 
11.8.2 Biostatistical methods 
Physical examination data will be listed for all abnormal clinical assessments. 
11.9 12-lead ECG 
11.9.1 Parameters 
x 
PR interval (msec) 
x 
QT interval (msec) 
x 
QRS duration (msec) 
x 
QTcF Interval (msec) 
x 
QTcB Interval (msec) 
x 
Ventricular rate (bpm) 
x 
Overall ECG assessment: 
o ECG status (Normal, Abnormal), including specified abnormality. 
o Clinical significance 


Protocol Number: SENS-401-203 
Document Status: SAP v2.0 
03 July 2024 
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Statistical Analysis Plan 
 
 
11.9.2 Biostatistical methods 
11.9.3 Data Lists 
ECG data will be listed for all participants and time points per treatment arm. 
 
11.9.4 Analyses 
 
Parameters will be presented categorically (Normal, Abnormal Not Clinically Significant 
(NCS), Abnormal Clinically Significant (CS)) at baseline and each post-baseline scheduled 
visit. Tables will be presented by the treatment group. An additional table will present the 
frequencies of participants who fulfill the following prolongation (change from baseline) 
criteria, considering all scheduled and non-scheduled visit data: 
• 
QTcB prolongation >30 
• 
QTcF prolongation >30 
• 
QTcB prolongation >60 
• 
QTcF prolongation >60 
• 
QTcB>450 msec for males 
x 
QTcF >450 msec for males 
• 
QTcB >470 msec for females 
• 
QTcF >470 msec for females 
 
 
12 CHANGES TO THE PLANNED ANALYSIS 
Baseline definition will be the last available assessment prior to randomization, not prior to study 
drug administration as defined in the protocol. 
Descriptive statistics will be rounded to one decimal place, except for SD which will be reported 
to two decimal places. This differs to reporting the minimum and maximum values to the same 
number of decimal places as recorded in the eCRF; mean, median and SD to one more decimal 
place than the raw data, as reported in the protocol. 
 
Prior medications will be identified as medications commenced prior to randomization, 
regardless of when it ended, not prior to first administration of study drug as stated in protocol. 
Concomitant medications will be defined as any medication that is taken at or after 
randomization, regardless of when it started. Not clearly stated in protocol. 
Evaluation of the SENS-401 concentration data will be done descriptively and not by applying a 
paired t-test as mentioned in the protocol. 
Any changes in the analyses from the SAP will be described fully in the CSR. 
 
13 INTERIM AND FINAL ANALYSIS 
There will be no Interim analysis. A data review will be conducted. 
 
14 SOFTWARE 
SAS® Version 9.4 will be used to perform the statistical analyses. Any other software used to 
analyze data (including PK) will be noted in the CSR. 


Protocol Number: SENS-401-203 
Document Status: SAP v2.0 
03 July 2024 
CONFIDENTIAL 
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Statistical Analysis Plan 
 
 
15 REFERENCES 
1) SENS-401-203_Protocol_Clean_V3.0_08 February 2023_Signed.pdf 
2) Sensorion, SENS-401-203_3.1_Annotated.pdf 
3) S. Bourn et al. Hearing Preservation in Elderly Cochlear Implant Recipients. 2020 
4) H. Skarzynski et al. Towards a Consensus on a Hearing Preservation Classification 
System. 2013 
5) Sijgers et al. Classification of Acoustic Hearing Preservation After Cochlear Implantation 
Using Electrocochleography. 2023