Characterisation of Audiological Outcomes With the Nucleus CI532 Cochlear Implant in Adult Subjects.
Phase: NA
Conditions: Hearing Loss
Sponsor: Cochlear

CLTD5626 CI532
audiological outcomes
APAC_CIP_review 
D748891 
Version: 6 
State: Approved (T+B) 
Approver: Mary-Beth Brinson (Mbbrinson)
Date : 31 Jul 2017 
Document Control Note: Hardcopies of this document 
are non-controlled unless the relevant Transmittal Advice 
Notification (TAN) information is stamped in the box below. 
Number of pages (include Coversheet): 40

 
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QMS Document No.: D748891 
CLTD5626 CI532 Audiological Outcomes Feasibility Clinical Investigation 
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Document Type: Clinical Investigation Plan 
 
CLINICAL INVESTIGATION PLAN (CIP) 
 
 
Characterisation of audiological outcomes with the Nucleus® CI532 
cochlear implant in adult subjects 
CHANGE1 Feasibility Study 
 
CLTD5626 
 
 
Date:  27 July 2017 
 
 
Authors: 
 
                                                                 
1 Clinical investigation title registered on ClinicalTrials.gov 

 
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Document Type: Clinical Investigation Plan 
Sponsor 
Cochlear Limited 
1 University Avenue, 
Macquarie University, 
NSW 2109 
Manufacturer 
Cochlear Limited 
1 University Avenue, 
Macquarie University, 
NSW 2109 
Principal Investigator(s)  
 
Assoc. Professor Robert Briggs 
Department of Otolaryngology     
Royal Victorian Eye and Ear Hospital 
32 Gisborne Street, 
East Melbourne 
Victoria 3002 
 
Professor Robert Cowan 
The HEARing CRC 
550 Swanston St 
Department of Audiology and Speech 
Pathology 
The University of Melbourne 
Carlton 
Victoria 3053 

 
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Document Type: Clinical Investigation Plan 
Clinical Research Organisation (or other 
institution involved) 
The HEARing CRC 
550 Swanston Street, 
Department of Audiology and Speech 
Pathology 
 
The University of Melbourne 
 
Carlton 3053 
 
 

 
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Document Type: Clinical Investigation Plan 
Sponsor, Principal Investigator and Clinical Research 
Organisation Signed Agreement 
Investigation Title 
Characterisation of audiological outcomes with the Nucleus® CI532 
cochlear implant in adult subjects 
Investigation 
Number 
CLTD5626 
Short Title 
CHANGE feasibility study 
 
Signature on behalf of Sponsor 
I agree with the content in this clinical investigation plan, including all appendices. 
Name 
Title 
Mary Beth Brinson 
 
Director of Quality, Regulatory and Clinical 
Signature 
Date 
(dd-mmm-yyyy) 
 
 
 
Signature of Principal Investigators 
I agree to the content of this clinical investigation plan, including all appendices. 
Name 
Title 
Robert Briggs 
 
Principal Investigator 
Signature 
Date 
(dd-mmm-yyyy) 
 
 
 
Name 
Title 
Robert Cowan 
 
Principal Investigator 
Signature 
Date 
(dd-mmm-yyyy) 
 
 
 

 
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Document Type: Clinical Investigation Plan 
Signature of Responsible Clinical Research Organisation 
I agree to the content of this clinical investigation plan, including all appendices, and 
undertake that the Clinical Research Organisation will conduct the research study in 
accordance with this plan. 
Name 
Title 
Robert Cowan 
 
Chief Executive Officer 
Signature 
Date 
(dd-mmm-yyyy) 
 
 
 

 
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Table of Contents 
1 
Clinical Investigation Synopsis ................................................................................................9 
2 
Identification and description of the investigational device ....................................................... 12 
3 
Justification for the design of the clinical investigation ............................................................. 14 
4 
Risks and benefits of the investigational device and clinical investigation ................................. 15 
4.1 
Anticipated clinical benefits.......................................................................................... 15 
4.2 
Anticipated adverse device effects ............................................................................... 15 
4.3 
Risks associated with participation in the clinical investigation ....................................... 16 
4.4 
Risk mitigation ............................................................................................................ 16 
4.5 
Risk-to-benefit rationale .............................................................................................. 17 
5 
Objectives and hypotheses ................................................................................................... 17 
5.1 
Objectives .................................................................................................................. 17 
5.1.1 
Primary objectives.......................................................................................... 17 
5.1.2 
Secondary objectives ..................................................................................... 17 
5.1.3 
Additional clinical measures............................................................................ 17 
5.2 
Hypotheses ................................................................................................................ 18 
6 
Claims and intended performance ......................................................................................... 18 
7 
Risks and anticipated device effects ...................................................................................... 18 
8 
Design of the clinical investigation ......................................................................................... 19 
8.1 
General ...................................................................................................................... 19 
8.2 
Endpoints ................................................................................................................... 19 
8.2.1 
Primary endpoints .......................................................................................... 19 
8.2.2 
Secondary endpoints...................................................................................... 20 
8.3 
Additional clinical measures ........................................................................................ 20 
8.3.1 
Device characteristics .................................................................................... 20 
8.3.2 
Electrode placement ...................................................................................... 20 
8.3.3 
Surgical questionnaire .................................................................................... 21 
8.4 
Equipment.................................................................................................................. 21 
8.5 
Investigation schedule................................................................................................. 21 
8.6 
Subjects ..................................................................................................................... 21 
8.6.1 
Inclusion Criteria ............................................................................................ 21 
8.6.2 
Exclusion Criteria ........................................................................................... 22 
8.6.3 
Number of subjects required ........................................................................... 22 
8.6.4 
Criteria and procedures for subject’s withdrawal or discontinuation ................. 23 
8.6.5 
Subject replacement ...................................................................................... 23 

 
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8.6.6 
Point of enrolment.......................................................................................... 23 
8.6.7 
Total expected duration of the clinical investigation .......................................... 24 
8.7 
Procedures ................................................................................................................ 24 
8.7.1 
Medical history (Pre-op) ................................................................................. 24 
8.7.2 
Audiogram (Candidacy, Activation, 3 months, 6 months and 12 months post-
activation) .................................................................................................................. 24 
8.7.3 
Speech recognition (Candidacy, 3, 6 and 12 months post-activation) ................ 25 
8.7.4 
Speech, Spatial, Qualities of Hearing scale – SSQ (Candidacy, 6 months post-
activation) .................................................................................................................. 26 
8.7.5 
Glasgow Benefit Inventory – GBI (6 months post-activation) ............................. 26 
8.7.6 
Video (Surgery) ............................................................................................. 26 
8.7.7 
Imaging:  X-ray and CT scan (Surgery) ........................................................... 26 
8.7.8 
Electrically evoked compound action potentials – ECAP (Surgery) .................... 26 
8.7.9 
Surgical questionnaire.................................................................................... 26 
8.7.10 
Activation (approximately 1 month post-surgery).............................................. 26 
8.7.11 
Acoustic Component Fitting (approximately 1 month post-surgery) ................... 27 
8.7.12 
Device characteristics (Activation, 3 months, 6 months and 12 months post-
activation) .................................................................................................................. 27 
8.7.13 
Safety ........................................................................................................... 27 
8.8 
Medical care post-investigation.................................................................................... 27 
8.9 
Monitoring Plan .......................................................................................................... 27 
9 
Statistical Considerations ..................................................................................................... 28 
9.1 
Missing Data .............................................................................................................. 29 
10 
Data Management ............................................................................................................... 29 
11 
Amendments to the CIP ....................................................................................................... 30 
12 
Deviations from the CIP........................................................................................................ 30 
13 
Device accountability............................................................................................................ 31 
14 
Statements of compliance..................................................................................................... 31 
14.1 Declaration of Helsinki and compliance with standards ................................................. 31 
14.2 Ethics Committee and Regulatory Authority Approval.................................................... 31 
15 
Informed consent process..................................................................................................... 32 
15.1 Obtaining informed consent......................................................................................... 32 
15.2 Data Privacy .............................................................................................................. 32 
16 
Reporting process for adverse events, adverse device effects and device deficiencies ............. 33 
16.1 Definitions .................................................................................................................. 33 
16.1.1 
Adverse event (AE) ....................................................................................... 33 
16.1.2 
Adverse device effect (ADE) .......................................................................... 33 

 
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16.1.3 
Device deficiency (DD)................................................................................... 33 
16.1.4 
Serious adverse event (SAE).......................................................................... 33 
16.1.5 
Serious adverse device effect (SADE)............................................................. 34 
16.1.6 
Unanticipated serious adverse device effect (USADE) ..................................... 34 
16.2 Reporting process for adverse events, adverse device effects and device deficiencies .... 34 
16.3 Data Monitoring Committee ......................................................................................... 34 
16.4 List of anticipated adverse events and anticipated adverse device effects ...................... 34 
17 
Incident reporting ................................................................................................................. 35 
17.1 Definition of Incident ................................................................................................... 35 
17.2 Reporting process....................................................................................................... 35 
18 
Vulnerable population ........................................................................................................... 35 
19 
Suspension or premature termination .................................................................................... 35 
20 
Publication Policy ................................................................................................................. 36 
21 
Change History .................................................................................................................... 36 
22 
Definitions............................................................................................................................ 37 
22.1 Definitions from ISO 14155:2011 ................................................................................. 37 
22.2 Other definitions ......................................................................................................... 38 
23 
Reference List...................................................................................................................... 39 
 
Table of Figures 
Figure 1: Left: The CI532 device (not to scale).  Right:  The EA32 electrode array loaded in the sheath 
(upper), advanced through the sheath, and with the sheath removed as in final situation (lower). ...12 
Figure 2: Speaker orientation for speech perception assessment ....................................................21 
 
Table of Tables 
Table 1: Investigation schedule .....................................................................................................11 
 

 
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1 CLINICAL INVESTIGATION SYNOPSIS 
Investigation title 
Characterisation of audiological outcomes with the Nucleus® CI532 
cochlear implant in adult subjects. 
Investigation number 
CLTD5626 
Short title 
CHANGE2 feasibility study 
Name of investigational 
device 
Approved Nucleus® CI532 cochlear implant 
Principal Investigators 
Associate Professor Robert Briggs 
Professor Robert Cowan 
Investigation start  
October 2015 
Total expected duration of 
the clinical investigation 
21 months 
Enrolment period 
6 months 
Expected duration per 
subject 
15 months/subject (upper estimate) 
Investigational design 
Prospective, single-centre, single arm with sequential enrollment. 
Number of subjects 
12 
Inclusion criteria 
1. Meet current cochlear implant indications at the implanting 
centre 
2. In addition to meeting current cochlear implant indications, 
subjects must also possess preoperative unaided hearing 
thresholds between 40 to 65 dB HL at 250 & 500Hz in the 
ear to be implanted. 
3. Fluent speaker in the local language used to assess clinical 
performance 
4. Eighteen years of age or older at the time of implantation 
with no upper age limit 
Exclusion criteria 
1. Evidence of hearing loss prior to 5 years of age. 
2. Sensorineural severe-to-profound hearing loss greater than 
20 years at 2 kHz and above. 
3. Simultaneous bilateral cochlear implantation or prior 
cochlear implantation in the ear to be implanted.  
4. Additional disabilities that may affect the subject’s 
participation or safety during the clinical investigation. 
5. Medical or psychological conditions that contraindicate 
undergoing general anaesthesia or surgery. 
6. Ossification, malformation or any other cochlear anomaly, 
such as common cavity, that might prevent complete 
                                                                 
2 CHaracterisation of Audiological outcomes with the Nucleus® CI532 cochlear implant in a Group of adult 
subjEcts. 

 
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insertion of the electrode array, as confirmed by medical 
examination. 
7. Hearing impairment due to lesion or neuropathy of the 
acoustic nerve, VIII nerve or central auditory pathway. 
8. Active middle-ear infection,  
9. Tympanic membrane perforation  
10. Unrealistic expectations on the part of the subject, 
regarding the possible benefits, risks, and limitations that 
are inherent to the surgical procedure(s) and prosthetic 
devices 
11. Unwillingness or inability of the candidate to comply with all 
investigational requirements. 
12. Patients with existing CSF shunts or drains, existing 
perilymph fistula, skull fracture or CSF leak. 
13. Patients with recurrent episodes of bacterial meningitis. 
Primary objectives 
1. Audiometric assessment post CI532 cochlear implantation 
2. Safety (monitoring of Adverse Events & Adverse Device 
Effects)  
Secondary objectives 
1. Patient reported outcome measures  
i) 
SSQ preoperatively and 6 months post-activation 
ii) GBI at 6 months post-activation 
Primary endpoints 
1. Report on the degree of hearing as measured by pure tone 
audiogram  
2. Report of clinical performance in quiet and noise 
3. Report of medical/surgical and device related adverse events 
compared to the current approved labelling with regard to type, 
frequency and seriousness. 
Secondary endpoints 
1. Report on Patient Reported Outcome Measures for SSQ (pre-
operatively to 6 months post-activation) and GBI (at 6 months 
post-activation) 
 

 
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Table 1: Investigation schedule 
Procedure 
Pre-op 
Surgery 
Activation 
3 months 
post-        
activation 
6 months 
post-        
activation 
12 months 
post-        
activation 
Medical history 
x 
 
 
 
 
 
Imaging (X-ray, cone beam CT) 
 
(x) 
(x) 
 
 
 
Intraoperative ECAP 
 
x 
 
 
 
 
Surgical Questionnaire 
 
x 
 
 
 
 
T/C Levels, Impedances 
 
 
x 
x 
x 
x 
Speech 
x 
 
 
x 
x 
x 
Audiogram 
x 
 
x 
x 
x 
x 
Aided Audiogram3 
x 
 
x 
x 
x 
x 
Tympanometry 
x 
 
x 
x 
x 
x 
SSQ 
x 
 
 
 
x 
 
GBI 
 
 
 
 
x 
 
Adverse Events and Device Deficiencies 
 
x 
x 
x 
x 
x 
                                                                 
3 Preoperative in both ears; postoperative in implanted ear only. 
 

 
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2 IDENTIFICATION AND DESCRIPTION OF THE INVESTIGATIONAL 
DEVICE 
Peri-modiolar electrodes such as the Contour Advance™ (CA) are designed to bring 
electrode contacts closer to the medial wall of the cochlea and so therefore closer to the 
spiral ganglion. Up until now these “pre-curved” electrodes have required a flexible metallic 
“stylet” to hold the electrode straight at the point of first introduction into the cochlea to avoid 
premature curling of the electrode.  It is recommended that the electrode is advanced off the 
stylet™ (AOS) so that it follows the trajectory of the basal turn of the cochlea due to its 
curved shape.  In this way contact with the lateral wall, which may produce trauma, may be 
avoided.  Necessarily the cross-sectional area of the CA is somewhat larger than what may 
be required for a non-stylet “straight” array and there is always some chance that the stiffer 
array-stylet combination could still produce trauma if deployment of the electrode is not well 
handled.  Either a classic insertion technique or a poorly-handled AOS technique may result 
in the electrode array dislocating between scala tympani and scala-media or scala-vestibuli, 
thus producing trauma to the interstitial membranes.  In addition an electrode array in scala 
vestibuli is at a greater distance from the stimulation target (spiral ganglion cells) compared 
to one in scala tympani – thus current paths to these cells may be irregular and stimulation 
will be less selective, potentially reducing performance (1). 
The device under investigation is the Nucleus® CI532 cochlear implant (Figure 1, left) which 
consists of a CI500 Series receiver/stimulator and a pre-curved, perimodiolar electrode array 
(EA32), which does not incorporate a lumen and stylet. Instead it has a thin electrode carrier 
which is introduced into the cochlea through a straightening sheath (Figure 1, right).  The 
CI532 cochlear implant is manufactured by Cochlear Ltd, Macquarie University, Australia.  
Cochlear has been manufacturing cochlear implants for over 30 years.  
 
Figure 1: Left: The CI532 device (not to scale).  Right:  The EA32 electrode array loaded in the 
sheath (upper), advanced through the sheath, and with the sheath removed as in final situation 
(lower). 
 

 
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As for the CA, the EA32 array must be orientated correctly so that its curvature is in the 
plane of the basal turn, with electrodes towards the modiolus, and the sheath must be 
immobile during this process.  The cross-sectional area of the EA32 is approximately 40% of 
that of the CA and thus it is overall less stiff than the CA; these two factors may allow the 
EA32 array to take up a position within scala tympani closer to the modiolus.  The sheath is 
removed and discarded once the electrode is fully inserted. 
The CI532 cochlear implant is a single use device intended for long term implantation under 
the skin in the mastoid region of either side of the head. Cochlear implantation can only be 
undertaken by an experienced surgical team, or under supervision of such a team.   
The CI532 cochlear implant will be used in the current clinical investigation in adults who 
meet current indications for cochlear implantation in Australia. As the clinical investigation 
aims to assess the degree of hearing preservation with the CI532 device, candidates who 
are at the upper range of pre-operative residual hearing (40 to 65 dB HL at 250 and 500 Hz) 
will be recruited to participate. 
 
The surgical approach will be cochlear implantation via posterior tympanotomy as described 
in the CI532 Physician’s Guide (2). The appearance of the RW and niche will be observed in 
order determine the choice of surgical approach and if necessary correctly position and drill a 
cochleostomy hole as mentioned in the Physician’s Guide.  Insertion of the array will be 
achieved using the advance-through-the-sheath technique described in the Physician’s 
guide. This ensures that intra-cochlear trauma is minimised and offers the potential for 
hearing preservation in as many cases as possible.   
The EA32 electrode (Figure 1, right) is placed into the cochlea and carries twenty-two 
electrode contacts.  In addition there are two extra-cochlear return electrode contacts; one is 
connected to the CI500 body via a lead wire and placed under the temporalis muscle and the 
other is an exposed area of the case of the CI500 (Figure 1, left). With each CI532 an 
additional cochleostomy sizing tool is provided.  The sizing tool allows verification of the size 
of the cochleostomy hole such that the guide tube (yellow/orange figure 1 right) may easily 
enter the cochleostomy hole but that the stopper cannot (2). 
The CI532cochlear implant has been approved by the TGA in April 2017.  Orders for devices 
will be placed in the Oracle system.  Devices are identified by unique serial numbers. 
This device when combined with the approved external Nucleus 6 Sound Processor (SP) 
(CP900 Series) provides electrical stimulation to the auditory nerve which can be interpreted 
as sound by the hearing impaired recipient. Biphasic current pulses at the electrode contacts 
are generated by the CI500-series receiver/stimulator which is controlled by the external 
Sound Processor via a transcutaneous radio link. 
Standard activation of the CI532 will be achieved using Custom Sound software running on a 
PC equipped with a Nucleus Pod programming interface.  A software key code will be 
provided to allow programming the investigational device.  Electrically-evoked Compound 
Action Potentials (ECAPs) may be measured using either Custom Sound or Custom Sound 
EP software during surgery. 

 
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The external envelope materials of the CI532, and sterile accessories, and the Nucleus 6 
CP900 Sound Processors are biocompatible according to applicable standards (i.e. ISO 
10993: 2009/AC: 2010).       
 
3 JUSTIFICATION FOR THE DESIGN OF THE CLINICAL 
INVESTIGATION 
A multi-centre clinical early feasibility trial was performed with 17 cases being implanted with 
version 1 of the electrode array/sheath assembly (3). Electrode tip fold-over was identified in 
32% of cases and due to this complication, 23% of cases received a commercial back-up 
device (CI24RE(CA) or CI512). Complications were related to device deficiencies and 
surgical protocol deviations. Hearing preservation was generally poor and most subjects lost 
their residual hearing in the implanted ear. The participants recruited for the early feasibility 
trial met current local indications for a conventional implant. The inclusion criteria specified 
an unaided hearing threshold in the ear to be implanted of equal to or better than 80 dB HL 
at 500Hz. Speech perception in quiet and noise significantly improved pre-operatively-to-
post-operatively. Follow-up of these cases is now more than 5 years with no device related 
adverse events reported – all devices remain functional and in place.  
Rotation of the electrode in the sheath may have contributed to the adverse device effects 
seen in the early feasibility trial and lead to further sheath design by Cochlear Limited. Most 
of the development focussed on the sheath until version 4 where the sheath to guide-tube 
assembly was reconfigured to further improve handling and visibility. In the intermediate 
designs tip folding occurrence was reduced by removing rotation and finally by modification 
of the slit in the sheath.  The slit allows the sheath to be removed after the electrode is fully 
deployed.  The final version improved the stability of the sheath especially when some 
bending of the array and sheath occurs.   
Pre-clinical testing with the CI532 was performed with four versions of the electrode-sheath 
assembly over four rounds of formal temporal bone trials. The temporal data on the EA32 
(using the latest sheath design) shows good perimodiolar position in a large majority of cases 
with a relatively low potential for intra-cochlear trauma shown by a scala dislocation rate of 
3.3%.  Once use errors were taken into account the tip fold-over rate was 3/110 or <3%.   
Currently, a multicentre clinical investigation is being undertaken to determine if a low rate of 
dislocation can be achieved in clinical cases.  Thirty-four adult candidates have been 
successfully implanted with the CI532 device (Melbourne, Las Palmas, Germany and 
Toulouse) with no scala dislocation. Anelectrode tip fold-over was reported for one 
participant in Freiburg which resolved with explantation of the CI532 and reimplantation with 
a CI512 device. All of the devices show good proximity to the modiolus from flat-panel 
volume computed tomography. Due to early success in the positioning of the CI532 device, 
further clinical evaluation is warranted to measure device performance in terms of hearing 
preservation in a clinical population with greater potential to preserve residual hearing.  
The primary objective of the clinical investigation is to assess the degree of hearing with the 
CI532 cochlear implant. In order to demonstrate the atraumatic nature of the electrode 
design and insertion technique, as well as the possibility of fitting of the acoustic component 

 
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postoperatively, the inclusion criteria has been structured to capture subjects who currently 
meet the clinical criteria for cochlear implantation but who also possess unaided audiometric 
thresholds between 40 to 65 dB HL at 250 and 500 Hz. The secondary objectives of this 
clinical investigation are to evaluate Patient Reported Outcomes (PRO) preoperatively to six 
months post-activation for the Speech Spatial and Quality of Hearing scale (SSQ) and the 
Glasgow Benefit Inventory (GBI) at six months post-activation    The outcomes from this 
feasibility study may be used to support the development of a randomised multi-centre 
clinical investigation evaluating the functional hearing preservation with the CI532 cochlear 
implant.   
4 RISKS AND BENEFITS OF THE INVESTIGATIONAL DEVICE AND 
CLINICAL INVESTIGATION 
4.1 Anticipated clinical benefits 
Analysis of the final positions of EA32 electrode in temporal bones, as reported above, 
revealed a low incidence of intra-cochlear trauma. The absence of dislocation is correlated 
with higher speech recognition scores (1, 4).  In addition, close proximity of the electrode 
array to the medial wall is correlated with higher speech recognition scores (1).  In both 
temporal bones and in the previous feasibility study the thinness of the pre-formed EA32 
array gave in most cases wrapping factors of ~0.5 as estimated from images of temporal 
bones – this is at the best-performing end of the distribution presented by Holden et al.(1).  
Therefore due to low potential for trauma and close proximity of electrode contacts to the 
modiolus we expect a high clinical benefit for patients from the CI532. 
4.2 Anticipated adverse device effects 
Subjects are exposed to the anticipated adverse device, and or procedure related effects 
associated with standard cochlear implant surgery and general anaesthesia. 
Adverse effects associated with cochlear implantation are: 
• 
Individuals are exposed to the normal risks associated with surgery and general 
anaesthesia. 
 
• 
The surgical procedure may result in infection or bleeding, numbness or stiffness 
about the ear, injury to or stimulation of the facial nerve, taste disturbance, dizziness, 
increased tinnitus, neck pain, or perilymph fluid leak. Inner ear fluid leak may result in 
meningitis. 
 
• 
The cochlear implant results in a palpable lump under the skin just behind the ear. 
The presence of a foreign body under the skin may cause irritation, inflammation or 
breakdown of the skin and, in some cases, extrusion of the device. The electrode 
array may migrate partially or completely out of the cochlea, resulting in decreased 
hearing ability. The electrode lead may perforate structures of the external ear, such 
as the tympanic membrane or canal wall. Misplacement of the electrode array may 
result in the perception of non-auditory sensations. Such complications may require 
additional medical treatment, surgery and/or removal of the device. 
 

 
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• 
Electrical stimulation may result in increased tinnitus, facial nerve stimulation, 
dizziness or pain. 
 
• 
Individuals who have residual hearing in the ear selected for the cochlear implant 
have a slightly greater risk of short-term postoperative dizziness than individuals with 
no residual hearing in that ear. 
 
• 
The long term effects of electrode insertion trauma or from chronic electrical 
stimulation are unknown. Such effects may include new bone growth in the cochlea 
or deterioration of the nerve cells. These effects may preclude replacement of the 
electrode array or may lead to eventual deterioration of cochlear response. 
 
• 
Failure of component parts (both external and internal) could result in the perception 
of an uncomfortably loud sound sensation or no sound. Failure of various component 
parts of the implanted device could require removal or replacement of the implant, or 
a reduction in the number of electrodes used. 
 
• 
Inserting the electrode into the cochlea may result in complete loss of residual 
hearing in the implanted ear. 
Residual risks for the investigational device compared to a similar device, such as the 
Nucleus CI512, relate to use errors which may increase the risk of tip fold-over.  It should be 
noted that tip folding is not unknown in similar pre-curved arrays or in straight arrays. The 
presence of a tip fold-over does not usually produce any clinical symptoms or adverse effect.  
However it is likely that the distribution of current produced by the electrode array would be 
perturbed such that performance outcomes could be limited (such as speech recognition 
scores). 
All residual risks for the investigational device will be described in the Patient Informed 
Consent (PIC) 
4.3 Risks associated with participation in the clinical investigation 
There are no anticipated adverse reactions specific to the investigational device other than 
those usually associated with cochlear implantation (as listed above) and concomitant 
medical treatments (2). 
4.4 Risk mitigation 
Tip fold-over of the array may necessitate re-implantation:  Tip fold-over is typically detected 
via imaging.  In this case the EA32 electrode may be removed from the cochlea, re-loaded 
and re-inserted or alternatively, the CI532 device may be removed completely and replaced 
with the Nucleus back-up device. 
More detail on device specific risks and how they are mitigated may be found in the 
Investigators Brochure (IB) and the Physician’s Guide (2). All surgeons will receive surgical 
training in the use and handling of the CI532 cochlear implant as part of study initiation. In 
addition, a Cochlear surgical support may be present during surgeries performed by the 
investigational site 

 
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4.5 Risk-to-benefit rationale 
The improved likelihood of correct scala tympani placement, increased proximity to the 
modiolus, and reduced potential for trauma for the CI532 may provide a better outcome for 
patients compared to the existing CI512 or CI24RE(CA) implants equipped with CA electrode 
arrays. 
Peri-operative X-ray and post-operative CT scans are used in a number of cochlear implant 
centres as a standard procedure in order to assess the quality of final electrode position.  
The peri-operative X-ray reduces the risk of leaving a very poorly placed array in situ (such 
as with tip fold-over).   
In conclusion, the risk benefit ratio of participating in this study is similar to the risk benefit 
ratio of receiving treatment with a conventional CI. 
5 OBJECTIVES AND HYPOTHESES 
5.1 
Objectives 
5.1.1 
Primary objectives 
The primary objectives for the clinical investigation are: 
1. To characterise audiometric outcomes post CI532 cochlear implantation in individuals 
who meet current indications for cochlear implantation but also have pre-operative 
hearing thresholds between 40 to 65 dB HL at 250 and 500 Hz of in the ear to be 
implanted. 
2. An assessment of medical/surgical and device related adverse events compared to the 
current approved labelling with regard to type, frequency and seriousness at six months 
post-activation to evaluate safety. 
5.1.2 
Secondary objectives 
The secondary objectives for the clinical investigation are of Patient Reported Outcomes 
(PRO): 
1. The Speech, Spatial and Qualities of Hearing scale (SSQ) (5) measures self-reported 
auditory disability across a variety of domains: the ability to hear speech in a range of 
competing contexts; the directional, distance and movement components of spatial 
hearing; and the quality of the listening experience.  
 
2. The Glasgow Benefit Inventory (GBI) is a measure of patient reported benefit developed 
especially for otorhinolaryngological interventions (6).   
5.1.3 
Additional clinical measures 
5.1.3.1 
Electrode placement 
Electrode placement in the cochlea will be assessed by intra-operative lateral and modified 
Stenver’s view X-ray and post-operative cone beam CT imaging.   

 
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5.1.3.2 
Device characteristics 
Device characteristics (impedance, psychophysical T and C-levels and ECAP) will be 
collected via an anonymous cdx file. 
5.1.3.3 
Surgical questionnaire 
Surgical feedback on the usability and surgical outcomes with CI532 cochlear implant will be 
collected via a surgical questionnaire. 
5.2 
Hypotheses 
As this is a feasibility study, there is no formal hypothesis to be accepted or rejected on the 
basis of statistical analysis in the current clinical investigation.  
Individual outcomes will be compared, along with group effects, across pre- and 
postoperative test conditions for the speech perception outcomes. Adverse events will be 
summarized by event type, severity, seriousness, as well as relatedness to the device and 
implant procedure will be reported and tabulated.   
6 CLAIMS AND INTENDED PERFORMANCE 
The claims and intended performance of the investigational device that are to be verified are: 
1. The number and percentage of subjects who were able to be fit with the 
acoustic component postoperatively. 
2. Pre-to-post performance benefits with the CI532 cochlear implant for speech 
recognition. 
7 RISKS AND ANTICIPATED DEVICE EFFECTS 
For this clinical investigation, safety will be defined as freedom from device or procedure-
related adverse events. The risks and anticipated adverse device effects that are to be 
collected in the clinical investigation are: 
1. The number and percentage of subjects with electrode tip fold-overs as determined 
by X-ray. It is not intended that this data serve as a measure of treatment success 
since the focus of this study is hearing benefit. 
2. The number and percentage of subjects with electrode not fully within the scala 
tympani as determined by cone beam CT scan 
3. The number and percentage of subject with complete loss of hearing as compared to 
the Contour Advance electrode (CI512). 
 

 
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8 DESIGN OF THE CLINICAL INVESTIGATION 
8.1 
General 
The Implantation of the Cochlear™ Nucleus® CI532 in Adults feasibility study will be 
conducted as a single-site, prospective, single-arm clinical study, evaluating the safety and 
functionality of the Cochlear Nucleus CI532 cochlear implant in 12 subjects who meet current 
cochlear implant indications with low frequency unaided thresholds between 40 to 65 dB HL 
at 250 and 500 Hz. A single-subject repeated-measures analysis will be employed whereby 
subjects will act as their own controls. A single-subject research design is appropriate since it 
accommodates the heterogeneity that characterizes hearing-impaired populations. Blinding 
procedures are not appropriate for this trial design, as it is not possible to conceal the 
presence, or absence, of a cochlear implant from device recipients and/or Investigational 
device and comparator 
Subjects will be implanted with the investigational device, the Nucleus CI532 cochlear 
implant.  The device will be activated at approximately 3 – 4 weeks post-operatively 
according to the investigational sites standard clinical procedures.  Activation generally 
consists of determination of active electrodes via impedance measurements followed by the 
determination of subjective threshold (T) and comfortable (C) levels of stimulation (current 
amplitude) for each electrode.  The Nucleus CP900 Series Sound Processor, is programmed 
such that input sound frequencies are allocated across the electrode array with input sound 
intensities being converted to stimulation levels between Ts and Cs.  According to the 
postoperative audiogram, a subject may also receive the acoustic component. The acoustic 
component will be determined and fit according to commercial clinical recommendations and 
training. T and C-levels as well as use of the acoustic component may be re-determined at 
intervals after activation to take into account acclimatisation of the subject as well as 
postoperative hearing status 
This is a single-arm, single-centre investigation. The comparator device is the sponsor’s 
current commercially available pre-formed or peri-modiolar Contour Advance electrode which 
may be connected to the CI24RE “Freedom” receiver-stimulator electronics module or the 
later CI500 module.  There is no difference in electronic capability between the CI24RE and 
CI500; the difference lies in the form factor.  There is no proposed concurrent medical device 
or medication.  The investigational site may use systemic application of corticosteroids 
and/or antibiotics at time of surgery possibly followed by oral application according to clinical 
standard of care. 
8.2 
Endpoints 
8.2.1 
Primary endpoints 
The six month post-activation visit serves as the primary endpoint for data collection related 
to efficacy and safety outcomes post-CI532 implantation: 
1. Efficacy endpoints 

 
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1.1. Hearing in the implanted ear will be reported as the change in pure-tone air-
conduction thresholds (dB HL) pre-operatively to post-activation according to the 
Cochlear consensus  at six months post-activation and 12 months post-activation.  
Audiometric data will be summarized at each follow-up time point to assess any 
changes in hearing sensitivity and to characterize the impact of the procedure on 
hearing. 
To understand if measurable low frequency thresholds can be maintained with 
implantation using the CI532 cochlear implant and fit with the acoustic component 
1.2. Assessment of speech recognition in quiet will be measured using the CNC 
monosyllabic word test (7). Assessment of speech recognition in noise will be 
measured using sentences drawn from the Australian Sentence In Noise (AuSTIN) 
test (8) with speech-weighted noise (SWN) at a fixed +5 dB SNR.  
 
2. Safety endpoints 
 
2.1. Adverse events will be summarized by event type, severity, seriousness, as well as 
relatedness to the device and implant procedure will be reported and tabulated.  
 
2.2. Report of medical/surgical and device related adverse events compared to the 
current approved labelling with regard to type, frequency and seriousness. 
8.2.2 
Secondary endpoints 
The six month post-activation visit serves as the secondary endpoint for data collection 
related to Patient Reported Outcomes (PRO): 
1. Speech, Spatial and Qualities of Hearing scale (SSQ) 
The six month post-activation visit serves as the secondary endpoint for data collection 
related to self-reported auditory disability and quality assessment with the SSQ for the 
CI532 cochlear implant. 
2. Glasgow Benefit Inventory 
The six month post-activation visit serves as the secondary endpoint related to health 
utility data collection with the GBI for the CI532 cochlear implant. 
8.3 
Additional clinical measures 
8.3.1 
Device characteristics 
Report of device characteristics related to impedance, psychophysical T and C-levels and 
ECAP with the CI532 cochlear implant.  
8.3.2 Electrode placement 
Report of EA32 electrode placement as confirmed by X-ray (preferably a lateral or modified 
Stenver’s view). 

 
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8.3.3 
Surgical questionnaire 
Report on the usability and surgical outcomes with the CI532 cochlear implant as obtained 
via surgical questionnaire. 
8.4 
Equipment  
Speech perception performance in quiet will be assessed using a loud speaker configuration 
with the signal from the front (S0). Speech perception performance in noise will be assessed 
using a loud speaker configuration with signal from the front and noise from the implanted 
side (S0N90 or S0N270) as shown in Figure 2. 
 
Figure 2: Speaker orientation for speech perception assessment 
The loudspeakers are located at head height for a seated subject (reference point). The 
distance from the loudspeaker from the reference point is approximately one meter. There 
will be defined locations for the loudspeakers and subject within the test environment. Sound 
field calibration of the Average Sound Level (Leq) is performed prior to each visit using a 
sound level meter (SLM) using a dB A-weighting (dBA), slow time weighting. Calibration of 
the SLM will occur according to the centres’ current practise. 
8.5 
Investigation schedule 
The visit dates and measures to be applied are reported in the Investigation schedule in 
Table 1. 
8.6 
Subjects  
8.6.1 Inclusion Criteria 
1. Meet current cochlear implant indications at the implanting centre 
2. In addition to meeting current cochlear implant indications, subjects must also 
possess preoperative unaided hearing thresholds between 40 to 65 dB HL at 250 & 
500Hz in the ear to be implanted4 
3. Fluent5 speaker in the local language used to assess clinical performance 
                                                                 
4 If it is more than 90 days past the date of the Candidacy Evaluation, candidacy needs to be reconfirmed by 
repeating hearing threshold test measures at 250 and 500Hz. Any changes observed will need to be reviewed in 
consultation with the Sponsor prior to surgery occurring. 
or 
or 

 
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4. Eighteen years of age or older at the time of implantation with no upper age limit 
8.6.2 Exclusion Criteria 
1. Evidence of hearing loss prior to 5 years of age. 
2. Sensorineural severe-to-profound hearing loss greater than 20 years at 2 kHz and 
above 
3. Simultaneous bilateral cochlear implantation or prior cochlear implantation in the ear 
to be implanted.  
4. Additional disabilities that may affect the subject’s participation or safety during the 
clinical investigation. 
5. Medical or psychological conditions that contraindicate undergoing general 
anaesthesia or surgery. 
6. Ossification, malformation or any other cochlear anomaly, such as common cavity, 
that might prevent complete insertion of the electrode array, as confirmed by medical 
examination. 
7. Hearing impairment due to lesion or neuropathy of the acoustic nerve, VIII nerve or 
central auditory pathway. 
8. Active middle-ear infection,  
9. Tympanic membrane perforation  
10. Unrealistic expectations on the part of the subject, regarding the possible benefits, 
risks, and limitations that are inherent to the surgical procedure(s) and prosthetic 
devices 
11. Unwillingness or inability of the candidate to comply with all investigational 
requirements. 
12. Patients with existing CSF shunts or drains, existing perilymph fistula, skull fracture or 
CSF leak. 
13. Patients with recurrent episodes of bacterial meningitis 
8.6.3 Number of subjects required 
The protocol describes a feasibility study within a single site and a limited number of subjects 
(12 subjects) to characterise the audiological outcomes and the feasibility of fitting of the 
acoustic component postoperatively associated with the CI532 cochlear implant in adult 
cochlear implant candidates. As such, there have been no power or sample size estimations 
performed. It is estimated to take six months to recruit this number of subjects. The 
enrolment period will be extended if required.  
                                                                                                                                                                                                           
5 As judged by the investigator i.e. able to complete the speech perception assessment tasks and 
questionnaires. 

 
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8.6.4 Criteria and procedures for subject’s withdrawal or discontinuation 
Any subject may voluntarily discontinue the study at any time without prejudice. The 
Investigator may discontinue a subject from the study at any time if (s)he considers that 
remaining in the study compromises the subject’s health or the subject is not sufficiently 
cooperative. In either event, reason(s) for discontinuation should be recorded on a study 
withdrawal form, provided as part of the CRFs for the study.  Possible reasons for study 
discontinuation include the following: 
• 
AE necessitating discontinuation from the study 
• 
The subject is lost to follow-up 
• 
Voluntary decision to withdraw consent made by the subject6 
• 
Investigator decision7 
• 
Other reason 
In case of a subject lost-to-follow-up, the Investigator must attempt to contact the subject (or 
relative/family contact) by phone, email or letter at least three times. If attempts are 
unsuccessful, the ‘subject withdrawal’ form is to be completed in the study file and reported, 
as appropriate, in required reports to the Sponsor, EC and TGA. 
During surgery, an alternative device (e.g., CI522 or CI512) may be implanted in subjects 
where there are substantial difficulties with the CI532.  These subjects will continue the 
clinical investigation and their outcomes will be compared to those subjects who received the 
CI532 device. 
8.6.5 
Subject replacement 
The total number of subjects enrolled in the clinical investigation is 12. If a subject withdraws 
pre-operatively, they will be replaced by a newly recruited subject who meets the selection 
criteria for participation. 
8.6.6 Point of enrolment 
Subjects are recruited to the study by the investigators usually during the course of medical 
consultation.  Subjects will be sequentially enrolled once Cochlear Asia Pacific receives a 
properly executed Informed Consent form and has approved the preoperative candidacy 
evaluation in writing.  
                                                                 
6 Withdrawal of consent is defined as the subject’s voluntary decision to revoke consent to continue 
participation in the study. 
7 Subject withdrawal from the study is defined as an Investigator decision. The Investigator may elect to 
withdraw a subject from the study at any time if he/she considers that remaining in the study compromises the 
patient’s health or if the Investigator considers the subject lost to follow-up. 
 

 
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8.6.7 Total expected duration of the clinical investigation 
The total expected duration of the clinical investigation is 38 months. The total duration will 
be dependent on the ability to recruit the required number of subjects within the enrolment 
period.   
8.7 
Procedures 
8.7.1 Medical history (Pre-op) 
Information regarding subject hearing-history (e.g., etiology, onset of hearing loss, duration of 
severe-to-profound hearing loss, amplification use) will be obtained and reported on the 
respective case-report form.  In addition, patients will be carefully and extensively counseled 
to ensure that their expectations from cochlear implantation are reasonable and appropriate 
(as determined by the Investigator). 
8.7.2 Audiogram (Candidacy, Activation, 3 months, 6 months and 12 months 
post-activation) 
An unaided audiogram will be performed for both ears 8 at candidacy9, at initial activation, 
three, six and 12 months post-activation at the following pure-tone frequencies: 
Air conduction: 125, 250, 500, 750, 1000, 1500, 2000, 3000, 4000, 6000 & 8000 Hz  
Air conduction thresholds >80 dB HL at 125 Hz, >90 dB HL at 250 Hz, >100 dB at 8000 Hz 
and >120 dB for other test frequencies will be marked NR (no response).  
 
Bone conduction: 12510, 250, 500, 750, 1000, 1500, 2000, 3000, 4000 Hz 
Bone conduction thresholds >20 dB HL at 125 Hz, >30 dB HL at 250 Hz, >60 dB HL at 500 
Hz and >70 dB HL for other test frequencies will be marked NR (no response).  
Where the recipient reports feeling rather than hearing the acoustic stimuli, the threshold 
shall be recorded as vibrotactile (VT). 
An aided audiogram will be performed for both ears at candidacy, and the implanted ear at 
initial activation11, three, six and 12 months post-activation at the following frequencies using 
warble tones: 
 
Aided thresholds: 125, 250, 500, 750, 1000, 1500, 2000, 3000, 4000 Hz 
 
Tympanometry in each ear at each visit. 
                                                                 
8 The use of tube phones and appropriate masking of the non-test ear is required. 
9 If it is more than 90 days past the date of the Candidacy Evaluation, candidacy needs to be reconfirmed by 
repeating the air conduction hearing threshold test measure at 250 and 500Hz. Any changes observed will need 
to be reviewed in consultation with the Sponsor prior to surgery occurring. 
10 Bone conduction measures at 125 Hz are optional based on potential audiometric equipment limitations. 
11 Assessing aided thresholds after the initial activation will only be conducted if there is a shift in unaided 
hearing of more than 10 dB HL (for the better or worse) at two or more aidable frequencies. 

 
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8.7.2.1 
Determination of hearing preservation post CI532 implantation 
Unaided air conduction (AC) hearing thresholds will be reported for all participants at six 
months and twelve months post-activation to support the primary efficacy endpoint. 
The population implanted with the CI532 device (per protocol population) will be divided into 
two groups for analysis: 
1. Participants with a total hearing loss (no measureable AC threshold at audiometer 
limits at each frequency) 
2. Participants with preserved hearing (measureable AC threshold at 250, 500 and 750 
Hz) 
Hearing preservation post CI532 implantation will be considered to be functional hearing 
preservation as defined by the Cochlear consensus 12: 
i. 
Unaided AC hearing thresholds ≤ 70 dB HL at 250 Hz 
ii. 
Unaided AC hearing thresholds ≤ 90 dB HL at 500 Hz 
iii. 
Unaided AC hearing thresholds ≤ 90 dB HL at 750 Hz 
The number of participants with a total hearing loss, preserved hearing and preserved 
functional hearing post CI532 implantation will be reported for each frequency (250, 500 & 
750 Hz 13). 
8.7.3 Speech recognition (Candidacy, 3, 6 and 12 months post-activation) 
Speech recognition will be measured pre-operatively, 3, 6, 12 months post activation.  Pre-
operatively, speech recognition will be evaluated in the unilateral aided condition with the 
contralateral ear masked or plugged. Post-activation, the best unilateral listening condition 
will be evaluated; “Implant ear” using the acoustic component and/or the CI SP alone on one 
ear with the contra-lateral ear plugged or masked.  Post-activation speech recognition shall 
be evaluated with default Nucleus 6 input processing options (SCAN).  
Assessment of speech perception in quiet will be measured using two lists of CNC 
monosyllabic word test (7) at 60 dBA in the S0 speaker orientation (Figure 1).  
Assessment of speech understanding in noise will be measured using two lists drawn from 
the AuSTIN test (8) sentence lists spoken by a female talker at 60 dBA at a fixed +5 dB 
signal-to-noise ratio (SNR) in the S0N90 or S0N270 speaker orientation (Figure 1). The 
competing noise will be speech-weighted noise (SWN).  
No lists will be repeated for a given subject during the clinical investigation. 
Performance benefits are change in scores pre- to post-operatively: 
1. Gain in speech recognition in quiet (% correct) 
                                                                 
12 Cochlear clinical consensus for determination of residual hearing preservation (05/11/2015) 
13 The mean or median as statistically appropriate based on distribution of data. 

 
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2. Gain in speech recognition in noise (% correct) 
8.7.4 Speech, Spatial, Qualities of Hearing scale – SSQ (Candidacy, 6 months 
post-activation) 
Subjective quality assessment will be measured using the SSQ preoperatively and again at 6 
months post-activation. The questionnaire will be completed during the visit by interview of 
the subject with the investigator.  
Subjective performance benefits are change in scores pre- to post-operatively: 
1. Gain in SSQ score (-10 to +10) 
8.7.5 
Glasgow Benefit Inventory – GBI (6 months post-activation) 
Health Utility assessment will measured using the GBI at six months post-activation. The 
questionnaire will be completed during the visit by interview of the subject with the 
investigator. 
Subjective performance benefits are change in scores pre- to post-operatively: 
1. GBI score (-100 to +100) 
8.7.6 Video (Surgery) 
Surgery may be recorded via a video camera connected to the surgeon’s microscope.   
8.7.7 Imaging:  X-ray and CT scan (Surgery) 
The presence of electrode tip fold-over may be detected intra-operatively via modified 
Stenver’s view X-ray, so that it may be corrected in-situ by removal and re-insertion of the 
electrode array.  If the folding persists the back-up device should be employed.  The correct 
positioning of the electrode within the scala will be assessed by post-operative cone beam 
CT scan. The resultant scan will be assessed post-operatively by the surgical team. 
8.7.8 
Electrically evoked compound action potentials – ECAP (Surgery)  
ECAP thresholds will be recorded using the AutoNRT algorithm in the CR220 Intra-operative 
Remote Assistant or Custom Sound EP software.  
8.7.9 
Surgical questionnaire 
Surgeons will complete the CI532 surgical questionnaire CRF to record the usability and 
surgical outcomes with the CI532 cochlear implant. 
8.7.10 Activation (approximately 1 month post-surgery) 
The CI532 cochlear implant will be activated with a commercially available Nucleus CP910 or 
CP920 Sound Processor and Custom Sound programming software as for recipients of 
existing devices.  This will take place approximately 3 – 4 weeks after surgery (plus/minus 2 
weeks). 

 
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Prior to activation of the sound processor, impedances and T/C levels will be determined.  
These data will be extracted from anonymized computer record files (“CDX”) produced by the 
Custom Sound software. 
Initially the default ACE sound coding strategy will be used with the parameters pulse rate 
900 pps per channel, 25 µs / phase, mode MP1+2, and 8 maxima.  These parameters may 
be adjusted afterward according to local procedures to improve subjective sound quality, if 
deemed necessary by the clinician.  The sound processor shall be programmed with the 
default Nucleus 6 input processing options (SCAN). Additional custom programs can be 
added to the sound processor in program slots 2, 3 & 4 as required. 
8.7.11 Acoustic Component Fitting (approximately 1 month post-surgery) 
In the event that a subject retains aidable hearing, they will be fitted with the Nucleus 6 
acoustic component (ACO). The ACO will be appropriately fit using the National Acoustics 
Laboratories’ hearing aid fitting strategy and assess the degree to which real-ear targets are 
met for each subject.  
8.7.12 Device characteristics (Activation, 3 months, 6 months and 12 months 
post-activation) 
Device characteristics will be recorded at every postoperative visit and maintained within the 
subject’s anonymous cdx. file (approximately one month post-surgery), at three, six and 12 
months post-activation.  
8.7.13 Safety 
The investigator will complete an Adverse Event (AE) CRF if any AE or Adverse Device 
Effect (ADE), or a Device Deficiency (DD) CRF if any DD is reported or observed for a 
subject during the investigation, even if they were acknowledged as risk factors in the Patient 
Informed Consent (PIC) form. 
8.8 
Medical care post-investigation 
Routine medical care from the implanting centre will be provided for the subjects after the 
clinical investigation has been completed. Subjects will be followed-up as per the centres’ 
standard procedures. 
8.9 
Monitoring Plan 
The sponsor will appoint a Study Monitor to perform regular visits at the study site, as 
defined in the study Monitoring Plan. Prior to the first subject enrolment an initiation visit will 
be performed by the Clinical Project Manager or delegate and the Study Monitor ensuring 
that assigned study personnel are familiar with this Clinical Investigation Plan and 
procedures and device handling, trained in GCP compliance, electronic CRF (eCRF) 
completion, AE reporting, and maintenance of study related documentation. 
The Study Monitor will ensure compliance with the clinical investigation plan and ISO14155, 
accurate data recording on the eCRFs, will raise data queries, will monitor recruitment rates 
and adherence to follow-up schedules. The Study Monitor will also check the upkeep of the 

 
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investigator file. The investigator shall permit and assist the Study Monitor to carry out 
verification of completed eCRFs against data in the source documents. 
Source documents are defined as any printed, optical or electronic document containing 
source data (hospital records, audiograms, speech test results, laboratory notes, device 
accountability records, radiographs, records kept at the investigational site) containing data 
necessary for the reconstruction and evaluation of the clinical investigation. The extent of 
source data verification is defined in the Monitoring Plan. The investigator shall provide all 
requested documentation in a timely and organized manner. 
The Study Monitor shall inform the Sponsor about any problems relating to facilities, 
technical equipment or medical staff at the study site. The Study Monitor shall provide the 
CPM with written reports, after each visit or contact with the investigational site. 
The investigator has to inform the Sponsor about any additional local requirements that may 
impact the work of a monitor especially if access to source data may be limited by local 
regulations. This is to ensure any necessary action to be taken before the study start to allow 
proper monitoring according to the ISO Standard. 
9 STATISTICAL CONSIDERATIONS 
All subjects who are recruited to the clinical investigation will constitute the intention-to-treat 
(ITT) population for the purposes of safety evaluation.  Only subjects implanted with the 
CI532 will be considered as the completed cases (CC) population and per protocol (PP) 
analysis of the primary endpoint will be performed.  
Where the CC population is insufficient, the sponsor reserves the right to ask the centres to 
recruit additional cases in order to reach the desired sample size of 12.  As this is a feasibility 
clinical investigation, there have been no formal power or sample size estimations performed 
for the primary objectives. 
To understand if measurable low frequency thresholds can be maintained with implantation 
using the CI532 cochlear implant and fit with the acoustic component: 
1. Audiometric data will be summarized at each follow-up time point to assess any changes 
in hearing sensitivity and to characterize the impact of the procedure on residual hearing.  
2. The degree of hearing will be reported and tabulated as the number of subjects who have 
measurable residual hearing post CI532 implantation. 
The number, severity and relationship of adverse events will be reported and tabulated. The 
rate of device-related adverse events will be compared to known rates of device-related 
adverse events for the commercially approved Nucleus cochlear implants. 
Pre- to post-operative gains in speech and SSQ scores will be tested using paired 
comparisons (Student’s t or non-parametric test if more appropriate).  GBI scores will be 
compared to a hypothesised mean score of 0 (no benefit). 
There are no pass/fail criteria to be applied to the results of the clinical investigation. 

 
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If required an interim analysis and report on three month speech and hearing threshold data 
will be provided for the purposes of submission to the TGA. 
The characteristics of the study group will be presented descriptively. Quantitative variables 
such as age will be presented with mean, standard deviation, median, minimum and 
maximum and 95% CI. Qualitative variables such as age or gender will be presented as 
percentages and observed frequencies. If differences in outcome are found for subgroups 
defined by baseline age or gender, analyses will be performed to explore the possible role of 
other baseline characteristics to explain the results. 
Supportive efficacy analyses will include analysis of individual data for all measures to 
establish the proportions of those subjects showing improvement, no change, and decrement 
in performance on the primary audiometry endpoint. 
9.1 
Missing Data  
All efforts will be put forth to ensure near complete follow-up, with particular focus on the 
assessment of the primary outcomes and occurrence of adverse events. A reminder of 
subject follow-up due date will be provided to participating centres to facilitate scheduling of 
the follow-up visit.  
In the event a subject is withdrawn prior to the six month post-activation assessment 
(audiometry), the analysis of the primary endpoint will involve imputing the data point 
captured (candidacy, activation or three months post activation) for the six month post-
activation assessment. The p-value for the primary statistical endpoints will be calculated 
using this imputation to understand the impact of missing data on the primary results. 
10 DATA MANAGEMENT 
Data collection is performed through electronic data capturing (EDC) on eCRFs. Site 
personnel will be trained on the completion of the eCRFs. Data validity has to be confirmed 
by the investigator through an electronic signature captured by the EDC system. Additional 
data is to be collected through the clinical fitting and electrophysiology software.  The file 
records should be anonymized and then identified using the study number and the patient’s 
study identifier (e.g. CLTD5626-MEL-01 3 month.cdx4). 
Surgical experiences will be collected in written form on questionnaire but in addition the 
investigator may provide a video recording of the surgery in DVD or other digital format (to be 
uploaded to the sponsor’s file server). Results from intra-operative X-rays can be 
summarized on the surgical questionnaire but the image or images should remain available 
for source verification.   
An additional eCRF will be provided for summary results obtained from post-operative CT 
scans.  However the anonymized raw image data will also be collected so that the results 
can be verified by the coordinating investigator and the consultant radiologist.  The data 
should be provided in a standard DICOM format on either machine readable disk (i.e. 
DVDRom) or uploaded to the sponsor’s file server.  The file folder should be identified using 
the patient’s study identifier (e.g. CLTD5626-MEL-01 CT scan). 

 
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Electronically captured data on e-CRFs are stored in a SQL database located on a server at 
Cochlear Limited. 
eCRFs are reviewed by Data Management and electronic data clarification forms (eDCFs) 
are generated for data inconsistencies, which are sent to the investigational site. EDC has 
built-in edit checks and generates data clarification forms automatically. In addition, the 
clinical project manager (CPM) may review the data from a medical and scientific perspective 
and create DCFs where appropriate. Responses to eDCFs are entered in EDC. 
The EDC system is a product that has been verified and validated extensively by the vendor. 
The installation of the system within Cochlear has been validated by the sponsor. Study 
specific implementations are validated by Data Management and consist of verification that 
all required items are included, validity of edit checks and appropriate functionality of 
conditional fields. The EDC system can only be accessed by those that have been allocated 
their individual account, which are personal of the investigational sites, CPMs, Study 
Monitors and Data Management. Upon request investigators will be provided with site 
specific data (e.g. on a CD-ROM) for national and site specific archiving requirements. 
After the final clinical investigation report (CIR) has been approved the data are maintained 
with the trial master file at the sponsor’s site. The data are stored for a period of 15 years. 
Source data collection is performed on paper Case Report Forms (CRFs). Site personnel will 
be trained on the completion of the CRFs. Data validity has to be confirmed by the 
investigator through a signature. In addition, data can be collected through the clinical fitting 
and electrophysiology software and through x- rays. 
Original completed CRFs are collected by Cochlear. CRFs are entered in a suitable 
database after review by the Investigation Monitor. The Clinical Project Manager may review 
data from a medical and scientific perspective and create Data Clarification Forms (DCFs) 
where appropriate. In case of DCFs the investigator should respond within the time windows 
as agreed upon. Responses to DCFs are entered in the database by Cochlear. Copies of 
completed CRFs and DCFs will remain at the investigator site.  
11 AMENDMENTS TO THE CIP 
No changes in the CIP or investigation procedures shall be effected without mutual 
agreement of the Principal Investigators and the Sponsor. Changes related to the scientific 
intent of the study shall be documented in the CIP and requires signatures from the sponsor 
and the coordinating investigator. Such changes will require notification to the Ethics 
Committee by the Principal investigator (and the TGA by the sponsor – if applicable).  
12 DEVIATIONS FROM THE CIP 
The investigator is not allowed to deviate from the CIP except under emergency 
circumstances to protect the rights, safety and well-being of the subjects. Such deviation 
shall be documented and reported to the sponsor and the EC as soon as possible.  

 
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13 DEVICE ACCOUNTABILITY 
Investigational devices will be shipped with individual registrations cards indicating the study 
number. Devices should be registered by the clinic according to usual practice.  In addition 
the clinic is asked to return a copy of the completed registration card to: 
  
14 STATEMENTS OF COMPLIANCE 
14.1 Declaration of Helsinki and compliance with standards 
The clinical investigation shall be conducted in accordance with the ethical principles that 
have their origin in the Declaration of Helsinki (2013), the ISO 14155:2011 Standard and any 
regional or national regulations, as appropriate. 
14.2 Ethics Committee and Regulatory Authority Approval 
The clinical investigation shall not commence prior to the written favourable opinion or 
approval from the Ethics Committee (EC) and or TGA (if appropriate) is obtained.  
The Principal Investigator or sponsor shall submit the final approved version of the CIP, the 
approved PIC and all subsequently approved documents to the EC and the TGA.  A copy of 
the EC and the TGA approval shall be provided to the sponsor if not directly communicated.  
The Principal Investigator or sponsor shall forward any amendment made to the approved 
PIC any other written information to be provided to the subject for review and approval by the 
sponsor prior to submission to the EC.  
The Principal Investigator or sponsor shall continue the communication with the EC and the 
TGA as required by national regulations, the clinical investigational plan or the responsible 
TGA.  
Any additional requirements imposed by the EC and the TGA shall be followed. 
The Principal Investigator or sponsor shall submit the appropriate documentation if any 
extension or renewal of the EC and the TGA approvals are required. In particular substantial 
amendments to the CIP, the PIC, or other written information provided to subjects shall be 
approved in writing by the EC and the TGA. 
The Principal Investigator or sponsor will report to the EC and the TGA any new information 
that may affect the safety of the subjects or the conduct of the clinical investigation. The 
investigator shall send written status summaries of the investigation to the EC and the TGA 
regularly as per local requirements. 
Upon completion of the clinical investigation, the Principal Investigator or sponsor shall 
provide the EC and the TGA with a brief report of the outcome of the clinical investigation as 
per local requirements. 
The clinical investigation is covered by clinical trial insurance meeting Australian 
requirements. 

 
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15 INFORMED CONSENT PROCESS 
15.1 Obtaining informed consent 
The investigator shall obtain written informed consent using an approved Patient Informed 
Consent Form (PIC) from the subject prior to any clinical investigation related examination or 
activity. The rationale for and the details, aims and objectives of the investigation, the risks 
and benefits and alternative treatments, and the extent of the subject’s involvement shall be 
explained. Ample time shall be provided for the subject to inquire about details of the clinical 
investigation and to decide whether to participate. All questions about the clinical 
investigation shall be answered to the satisfaction of the subject or the subject’s legally 
acceptable representative. Subjects shall not be coerced or unduly influenced to participate 
or to continue to participate in a clinical investigation. 
Each subject and the person who conducted the informed consent discussion shall sign and 
date two original versions of the PIC. Where required, a witness shall sign and personally 
date the PIC. 
One original signed PIC shall be given to the subject. The other original signed PIC shall be 
archived in the Investigator’s File at the investigational site, according to the requirements of 
the country’s health regulations, but for a minimum of 15 years after completion of the clinical 
investigation.  
The subject or the subject’s legally acceptable representative shall be informed in a timely 
manner if new information becomes available that may be relevant to the subject’s 
willingness to continue participation in the clinical investigation. The communication of this 
information shall be documented. 
In circumstances where the subject is unable to give informed consent (e.g. surgical 
complications requiring the use of a back-up device), the informed consent of the subject’s 
legally authorized representative, if present, shall be requested. 
15.2 Data Privacy 
Subjects will be identified on CRFs or similar documents (for example, questionnaires) by a 
unique subject identification code. Completed CRFs or similar documents are confidential 
documents and will only be available to the Sponsor and their representatives, the 
investigator, the investigational statistician, and if requested to the Ethics Committee and 
TGA.  
The investigator and site staff will not include the name of any subject in any CRF or other 
forms, electronic files, imaging items (for example, X-ray, CT scan), publication, or 
submission to a regulatory authority; will not otherwise disclose the identity of any subject; 
and, in any CRF, will refer to each subject by their identification code. The Patient ID log 
CRF is explicitly excluded from this requirement. 

 
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16 REPORTING PROCESS FOR ADVERSE EVENTS, ADVERSE DEVICE 
EFFECTS AND DEVICE DEFICIENCIES 
16.1 Definitions 
All definitions are according to the EN ISO 14155:2011 standard. 
16.1.1 Adverse event (AE) 
Any untoward medical occurrence, unintended disease or injury, or untoward clinical signs 
(including abnormal laboratory findings) in subjects, users or other persons whether or not 
related to the investigational medical device.  
NOTE 1 This definition includes events related to the investigational medical device or the 
comparator. 
NOTE 2 This definition includes events related to the procedures involved.   
NOTE 3 For users and other persons, this definition is restricted to events related to 
investigational medical devices. 
16.1.2 Adverse device effect (ADE) 
Adverse device effect is an adverse event related to the use of an investigational medical 
device. 
NOTE 1 This includes any adverse event resulting from insufficiencies or inadequacies in the 
instructions for use, the deployment, the implantation, the installation, the operation, or any 
malfunction of the investigational medical device. 
NOTE 2 This definition includes any event resulting from use error or from intentional misuse 
of the investigational medical device. 
16.1.3 Device deficiency (DD) 
A device deficiency is an inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety or performance. 
NOTE Device deficiencies include malfunctions, use errors, and inadequate labelling. 
16.1.4 Serious adverse event (SAE) 
A serious adverse event is any adverse event that: 
1) led to a death, 
2) led to a serious deterioration in the health of the subject that either resulted in 
a) a life-threatening illness or injury, or 
b) a permanent impairment of a body structure or a body function, or 
c) in-patient hospitalization or prolonged hospitalization, or 
d) medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function, 

 
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3) led to foetal distress, foetal death or a congenital abnormality or birth defect 
NOTE Planned hospitalization for a pre-existing condition, or a procedure required by the 
CIP, without serious deterioration in health, is not considered a serious adverse event. 
16.1.5 Serious adverse device effect (SADE) 
A serious adverse device effect is an adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event. 
16.1.6 Unanticipated serious adverse device effect (USADE) 
An unanticipated serious adverse device effect is a serious adverse device effect which by its 
nature, incidence, severity or outcome has not been identified in the risk analysis report (for 
the investigational device or its comparator). 
16.2 Reporting process for adverse events, adverse device effects 
and device deficiencies 
The investigator shall report all adverse events and adverse device effects and device 
deficiencies without delay to the sponsor. 
Name of contact person of the sponsor 
 
Phone number (business hours) 
 
Phone number (after hours) 
 
E-mail 
 
If applicable: the sponsor is responsible to report all SAEs, SADEs and USADEs to the EC 
and the TGA in the clinical investigation in accordance with local regulations. 
The investigator has to report all AEs, SAEs, SADEs and USADEs to the EC and the TGA (if 
applicable) using the applicable report form as per Australian requirements.  
Subjects shall be carefully monitored during the clinical investigation for potential adverse 
events and shall be routinely questioned about adverse events at investigation visits. For all 
adverse events, information obtained by the investigator shall be recorded in the Adverse 
Event CRF. The investigator shall attempt to assess the relationship between the 
investigational device and the adverse event.  
16.3 Data Monitoring Committee 
No DMC will be established. 
16.4 List of anticipated adverse events and anticipated adverse 
device effects 
For this clinical investigation the listed items in Section 4 of this CIP are anticipated Adverse 
Device Effects. 
Medical occurrences that are related to pre-existing conditions (e.g. diabetes, cardiac 
problems) are considered as unexpected adverse events in the frame of the clinical 
investigation. 

 
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17 INCIDENT REPORTING 
In cases where the investigational devices are commercially released products (Nucleus 6 
System), the Principal Investigator shall report all adverse events to the EC and the TGA 
according to governing regulations supplementary to reporting these adverse events to the 
sponsor.  
The sponsor shall report adverse events which classify as reportable events to the TGA. 
17.1 Definition of Incident 
Any malfunction or deterioration in the characteristics and/or performance of a device, as 
well as any inadequacy in the labelling or the instructions for use which, directly or indirectly, 
might lead to or might have led to the death of a subject, or USER or of other persons or to a 
serious deterioration in their state of health. 
17.2 Reporting process 
The investigator shall report all incidents without undue delay to the sponsor and the national 
competent authority following MEDDEV 2.12-1 rev. 8 (and higher): 
Name of contact person of the sponsor 
 
Phone number (business hours) 
 
Phone number (after hours) 
 
E-mail 
 
The Sponsor shall assess all reported incidents with the investigator, co-ordinate appropriate 
actions, if required, and provide the TGA with a final report.  
Appropriate treatment of the subject shall be initiated but the investigation follow up shall 
continue when ethical.  
The investigator shall report all incidents to the EC using the applicable report form as per 
national requirement.  
18 VULNERABLE POPULATION 
Not applicable for this clinical investigation. 
19 SUSPENSION OR PREMATURE TERMINATION 
The Sponsor will withdraw from sponsorship of the clinical investigation if: 
1) major non-adherence to the CIP is occurring 
2) it is anticipated that the subject recruitment will not be adequate to meet the objectives of 
the clinical investigation 
Should the sponsor withdraw from sponsorship of the clinical investigation, the sponsor will 
continue sponsorship for the subjects already recruited into the investigation. Subject follow-
up will occur as per the clinic’s standard procedures. 

 
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An ongoing clinical investigation can be discontinued in case of: 
4) device failure 
5) serious or intolerable adverse device effect, leading to the explant or discontinued use of 
the device 
6) subject’s death 
7) investigator’s decision 
8) subject’s decision 
20 PUBLICATION POLICY 
It is planned to generate a joint publication by the Principal Investigator and the sponsor. The 
responsibility for writing the publication is with the Principal Investigator (to be discussed and 
agreed prior to investigation start). In case of multi-centre investigation, the authorship will be 
based on contribution of complete datasets and contribution to paper preparation according 
to the rules of the journal chosen for publication. The joint publication shall be reviewed by 
the sponsor at least 30 days in advance to any release of publication. If the publication 
contains information that the sponsor at his discretion finds worth protecting in the form of a 
patent or trademark etc., the sponsor has the right to delay the publication or presentation for 
90 days.  
Following acceptance of the joint paper, the investigators will be able to publish as they wish. 
The publishing investigator will provide the sponsor with a manuscript copy of the abstract 
and paper at least 30 days in advance of publication or presentation. If the publication 
contains information that the sponsor at his discretion finds worth protecting in the form of a 
patent or trademark etc., the sponsor has the right to withhold the publication or presentation 
for 90 days. 
21 CHANGE HISTORY 
Version 
Change 
Author 
Date 
1.0 
Introduction of document 
M. Knight & C. 
Morgan 
24/8/2015 
2.0 
Modification of exclusion criteria #2, removal of 
exclusion criteria #3, addition of speech in noise 
test condition (+5 dB SNR), test level changed to 
60 dBA for quiet and noise. 
M. Knight 
9/11/2015 
3.0 
Removal of +10 dB SNR test condition for 
AuSTIN test (pg.20), correction of inclusion 
criteria #1 & #2 order (pg.21,)  
M. Knight 
16/12/2015 
4.0 
Removal of intraoperative electrophysiology 
testing from CIP for alignment with US CI532 
clinical investigation. Replacement of HEARRING 
consensus with Cochlear consensus for 
determination of hearing preservation. 
M. Knight 
15/03/2016 

 
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Version 
Change 
Author 
Date 
5.0 
Updated CIP after TGA approval of CI532 
cochlear implant. Updated investigation duration 
to align with enrolment period extensions. 
Note: This version not submitted to HREC 
M. Knight 
24/04/2017 
6.0 
Returned investigation duration and recruitment 
period dates in synopsis to original dates. 
Improved formatting in Section 8.2.7.1 
M. Knight 
27/07/2017 
22 DEFINITIONS 
22.1 Definitions from ISO 14155:2011 
Term 
Description 
Adverse event (AE) 
Any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) in subjects, 
users or other persons whether or not related to the investigational medical 
device. 
NOTE 1 This definition includes events related to the investigational medical 
device or the comparator 
NOTE 2 This definition includes events related to the procedures involved.   
NOTE 3 For users and other persons, this definition is restricted to events 
related to investigational medical devices. 
Adverse device effect 
(ADE) 
Adverse device effect is an adverse event related to the use of an 
investigational medical device. 
Note to the author:  
NOTE 1 This includes any adverse event resulting from insufficiencies or 
inadequacies in the instructions for use, the deployment, the implantation, 
the installation, the operation, or any malfunction of the investigational 
medical device. 
NOTE 2 This definition includes any event resulting from use error or from 
intentional misuse of the investigational medical device. 
Device deficiency (DD) 
A device deficiency is an inadequacy of a medical device with respect to its 
identity, quality, durability, reliability, safety or performance. 
NOTE Device deficiencies include malfunctions, use errors, and inadequate 
labelling. 
Incident 
Any malfunction or deterioration in the characteristics and/or performance of 
a device, as well as any inadequacy in the labelling or the instructions for 
use which, directly or indirectly, might lead to or might have led to the death 
of a subject, or USER or of other persons or to a serious deterioration in 
their state of health. 

 
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Term 
Description 
Serious adverse event 
(SAE) 
A serious adverse event is any adverse event that: 
a) led to a death, 
b) led to a serious deterioration in the health of the subject that either 
resulted in 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, or 
3) in-patient hospitalization or prolonged hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function, 
c) led to foetal distress, foetal death or a congenital abnormality or birth 
defect 
NOTE Planned hospitalization for a pre-existing condition, or a procedure 
required by the CIP, without serious deterioration in health, is not 
considered a serious adverse event. 
Serious adverse device 
effect (SADE) 
A serious adverse device effect is an adverse device effect that has resulted 
in any of the consequences characteristic of a serious adverse event. 
Unanticipated serious 
adverse device effect 
(USADE) 
An unanticipated serious adverse device effect is a serious adverse device 
effect which by its nature, incidence, severity or outcome has not been 
identified in the risk analysis report (for the investigational device or its 
comparator). 
22.2 Other definitions 
Term 
Description 
CA 
Competent Authority 
CER 
Clinical Evaluation Report 
EC 
Ethics Committee 
IB 
Investigator’s brochure is a compilation of the current clinical and non-
clinical information on the investigational device(s) relevant to the clinical 
investigation. 
ITT analysis 
The comparison of the treatment groups for all subjects as originally 
allocated after randomisation to avoid bias. 
PASS 
Post-authorization safety studies mandated by medical device regulators  
PIC 
Patient Informed Consent form 
PIL 
Principal Investigator List 
PMS 
Post-market surveillance studies 
PP analysis 
The comparison of treatment groups that includes only those subjects who 
completed the treatment originally allocated according to the protocol (i.e. a 
complete dataset). This form of analysis is open to bias is it does not 
include comparison of treatment groups for all subjects enrolled into the 
investigation.  
 

 
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23 REFERENCE LIST 
 
1. 
Holden LK, Finley CC, Firszt JB, Holden TA, Brenner C, Potts LG, et al. Factors 
affecting open-set word recognition in adults with cochlear implants. Ear Hear. 
2013;34(3):342-60. 
2. 
Cochlear. CI532 Physician's Guide. 
3. 
Knight M, Killian M. Clinical evaluation of the Modiolar Research Array Cochlear 
Implant. 2015  Contract No.: 343015. 
4. 
Aschendorff A, Kromeier J, Klenzner T, Laszig R. Quality control after insertion of the 
nucleus contour and contour advance electrode in adults. Ear Hear. 2007;28(2 Suppl):75S-
9S. 
5. 
Gatehouse S, Noble W. The Speech, Spatial and Qualities of Hearing Scale (SSQ). 
Int J Audiol. 2004;43(2):85-99. 
6. 
Robinson K, Gatehouse S, Browning GG. Measuring patient benefit from 
otorhinolaryngological surgery and therapy. Ann Otol Rhinol Laryngol. 1996;105(6):415-22. 
7. 
Peterson GE, Lehiste I. Revised CNC lists for auditory tests. J Speech Hear Disord. 
1962;27:62-70. 
8. 
Dawson PW, Hersbach AA, Swanson BA. An adaptive Australian Sentence Test in 
Noise (AuSTIN). Ear Hear. 2013;34(5):592-600.