Restoration of central vision with the PRIMA System in Patients with Atrophic Age-Related Macular
Degeneration

The purpose of this study is to evaluate the safety and effectiveness of the
PRIMA bionic system (PRIMA system). The PRIMA system is a medical device
being developed for people with retinal degenerative conditions such as
atrophic age-related macular degeneration (or geographic atrophy). In this
disease the light sensitive cells in the middle area of the back of the eye are
degenerated, which leads to a loss of the central vision. As of today, this
disease represents an unmet medical need.
The PRIMA system aims to partially restore visual function by electrical
stimulation of the retina using stimulator surgically implanted under the
retina (subretinal). The subretinal implant attempts to partly replace the
degenerated photoreceptors associated with atrophic AMD.
Smaller studies have shown the initial safety of the device. However, this
study will be the first study to analyse the improvement in visual function
with the current version of the device in humans with a larger number of study
participants.

The objective of this study is to evaluate the efficacy and safety of the PRIMA
System in patients with atrophic AMD.

Eligible subjects will be implanted with the PRIMA Implant. The subjects will
be assessed with various visual function and functional vision tests at defined
timepoints throughout the clinical investigation with the PRIMA System (Implant
and Visual Processor).

The purpose of this study is to gather enough clinical data to support the
clinical evaluation required for the CE-mark. The data will also be used for
market approval in other countries including the USA.

The study is an open label, baseline-controlled, non-randomized, multi-centre,
prospective, single-arm, confirmatory
clinical investigation performed in several investigational sites in several
countries. After an initial evaluative and
training period, in which subjects will learn to use the device within a
controlled clinical environment, subjects will be
allowed to take the device at home and utilize it on their own environment.

The study is divided into 6 parts:

Part 1: Pre-implantation examination (eligibility assessments)
Subject be asked to undergo a series of pre-implantation examinations
approximately 4 weeks before the PRIMA implantation. These pre-implantation
exams can be spread over 3-5 days with several hours per day.

The following tests and assessments will be performed :
• A review of subject's medical history.
• A measurement of subject's eyesight done with a letter chart.
• A quality of life questionnaire composed of 28 questions
• An extensive medical examination of both eyes. These tests include taking
pictures of the inner eye using several modern imaging techniques which are not
invasive. Only one type of picture is minimally invasive as it requires a dye
to be injected in the arm through an IV line to see how blood is circulating
around subject's retina.

After the pre-implantation examination, if the subject meets all the
eligibility criteria, the study investigator will then
identify subject's weaker eye for implantation with the PRIMA implant.

Part 2: PRIMA implantation
The implantation of the PRIMA System is carried out under either local or
general anesthesia.

If subject does not already have an intraocular lens (IOL) in the study eye,
his/her natural lens will be removed and replaced with an artificial lens at
the same time as the implantation with the PRIMA implant. The vitreous (the
fluid in the eye) will be removed through very small holes made in the white of
the eye. A small area of the retina will then be lifted, and the Retinal
Implant placed underneath.

Following the placement of the Retinal Implant, the small area of the retina
that was lifted will then be reattached. The surgeon will then temporarily fill
the eye with silicone oil or gas. To avoid that the implant is moving after the
implantation the subject will be requested to stay in a specific position for
one hour or longer. If at the day after implantation it will be recognized that
the PRIMA implant moved under the retina and is no longer at the target
position, a reintervention to correct the position may be necessary.

Depending on whether the PRIMA implantation is carried out under local or
general anesthesia, the subject may be admitted to the clinic on the day of the
operation or the day before the operation. For monitoring and then discharged
in accordance with the clinical procedures and physicians* recommendations.

1 day and 1-week post-implantation ophthalmological exams (tonometry, slit lamp
and funduscopy) will be performed to examine subject's eye condition and
healing process. If the subject was already discharged from the clinic, she/he
will be asked to return for these examinations.

Part 3: Removal of silicone oil
If silicone oil was used during the implantation surgery, it will need to be
removed about 4 weeks after the implantation or at another time when the
healing process has ended. The silicone oil will be removed under anesthesia in
the operating room.

Part 4: Follow-up examinations
At 1, 3, 6, 9, 12, 18, 24, 30 and 36 months after implantation medical exams
and visual assessment tests will be done. These examinations consist of
procedures like those carried out during the pre-implantation examination. 3-5
days over several weeks will be required to do these examinations.

Part 5: Visual rehabilitation sessions
Objectives of the rehabilitation sessions
The aim of the low vision rehabilitation sessions is to customize the PRIMA
System to the subject, to train the subject to use the artificial vision and to
test the performance of the PRIMA System.

In the first sessions, the PRIMA Glasses will be customized to the size and
shape of subject's face, and the Projection Module will be moved to align the
infrared laser beam to the subjects pupil so that the stimulation pulses can
reach the retinal implant at the back of subject's eye. For this initial
fitting part, simple stimuli (for example, spots of light in different
positions of your visual field) will be exclusively generated by the computer.
The subject will be asked to describe details of her/his visual perceptions
such as perception location, size, shape, and color.

In later sessions, and for most of rehabilitation session, the images sent to
the implant will be captured from the real world through the camera on the
Projection Module.
Most of the rehabilitation sessions will be dedicated to the specific goals
subject aims to achieve with the PRIMA System, that will be discussed with the
subject at the beginning of the training program. Some sessions will be used to
train the subject for the endpoint testing and in some sessions, additional
tests will be performed to verify the system function, gather data and develop
additional tests to improve the system. The focus of additional tests will be
on daily living activities, central visual function, and the effect of
different stimulation parameters and image processing. Certain tests may be
developed during the study for research purposes. Some tests will be done with
the camera and some with artificial stimuli to assess the system performance
independently from the external environment and from the ability of the subject
to locate the patterns.

It is recommended to have frequent visual rehabilitation sessions in the
initial 12 months and then decrease the frequency. Rehabilitation sessions
typically last 2 to 4 hours, although subject may requests to finish earlier at
any time. A session may also be split into 2 days of 1-2 hours duration each.
The first visual rehabilitation session will take place between 3 to 5 weeks
after implantation surgery. The study team will be sure subject's healing is
sufficient and postoperative discomfort has resolved. If silicone oil was used
during the implantation, this session will take place approximately 1 week
after the silicone oil is removed. Over the course of the 36 months that
subject participates in the study, about 50-60 stimulation sessions will be
schedule.
Most of the rehabilitation sessions will take place at the clinical site or if
a third party is appointed to perform the rehabilitation session, these
sessions may take place in their locations. However, some sessions might be at
subject's home, if the subject allows it, or in outdoor environments to train
specific tasks such as reading street names. It may also be possible that
sessions at your home are conducted via a video conference, if allowed by the
subject.
Stimulation sessions may be recorded on video if allowed by the subject.

Independent home use
After a few fitting and training sessions, when subject's artificial vision
with the PRIMA System is optimized and she/he is able to use the PRIMA System
independently, the subject will be able to use the PRIMA System at home. The
clinical staff might give training exercises to perform at home to the subject,
and they will keep a record of subject's activities with the PRIMA System at
home.

Part 6: Study exit
Subject' study participation ends after 36months (-/+2m time window) after
implantation, when all required tests have been performed. The removal of the
retinal implant is not expected unless it is medically necessary.

The PRIMA system aims to partially restore visual function by electrical
stimulation of the retina using stimulator surgically implanted under the
retina (subretinal). The subretinal implant attempts to partly replace the
degenerated photoreceptors associated with atrophic AMD.

The primary procedural risks to subjects in this study are associated with the
surgical implantation of the device* these risks are associated with all
retinal surgeries. Pixium Vision*s PRIMA System and the corresponding surgical
method have undergone risk analysis in accordance with EN ISO 14971, IEC
60601-1,EN 60601-1-6 and EN 62366.
The following risks that were identified during the risk analysis, were found
to be acceptable in relation to benefit and are included within the clinical
investigation plan (CIP) and patient consent form as potential procedure
related risks.

Potential risks from intraocular surgery (procedure related risks):
Occasionally:
• Active sub-macular choroidal neovascularization in study eye*
• Anatomical changes in the retina, RPE and/or choroid (e.g. fibrosis, schisis,
• intraretinal microcysts)*
• After cataract, posterior capsule opacification of the lens*
• Chronic hypotony leading to choroidal detachment or other complications*
• Choroid/Cornea/Iris/Retina damage*
• Corneal edema*
• Cell proliferation*
• Epithelial layer damage*
• Endophthalmitis*
• Eye pain or discomfort following surgery*
• Hypertonia*
• Impairment (temporary or permanent) of residual visual function*
• Infection*
• Opaque media after surgery*
• Peri-procedural problems typical of any major invasive eye operation*
• Prolonged or aborted surgical procedure*
• Retinal detachment*
• Risk of immediate re-intervention after the implantation surgery*
• Severe or non-severe ocular inflammation/irritation*
• Sympathetic ophthalmia*
• Vitreous hemorrhage*
Seldom:
• Adverse reactions and risks to general/local anesthesia.
The damaged retina includes macular edema/leakage of fluid and these risks
would be minimized by post-surgery anti-inflammatory eye drop medications as
part of the standard medical care. Cell proliferation includes epiretinal
membrane/pucker and in severe cases proliferative vitreoretinopathy (PVR).
Epithelial layer damage can include corneal abrasion.
Choroid/Cornea/Iris/Retina damage comprise for example choroidal hemorrhage,
punctuate keratitis, corneal epithelial effect, peripheral retinal tear and
choroidal detachment. Periprocedural problems typical for any major invasive
eye operation includes among others myodesopsia (or floater), sub-retinal
bleeding, remaining silicon oil/perfluorocarbon and sub-macular bubble of PFCL.
Severe or non-severe ocular inflammation/irritation involves for example eczema
of the eye lid. Risk of immediate re-intervention after implantation surgery
includes e.g. subretinal
chip displacement.
If a subject would develop an acute choroidal neovascular membrane (CNVM) after
PRIMA implantation and he or she would be eligible for a course if intravitreal
anti-VEGF per standard of care of the site, the subject can continue
participating in this clinical trial at the discretion of the study
investigator.
For the PRIMA implantation, the subject*s natural lens of the study eye, if
still present, will be removed and replaced with an intra ocular lens (IOL) in
the same procedure as the PRIMA procedure. This will be done since if not
already present, patients will very likely develop a cataract after
vitreoretinal surgery. There are potential risks related to phacoemulsification
and IOL placement for implanted subjects with a natural lens. These potential
risks can be inflammation or infection of the eye, bleeding in the eye,
swelling of the cornea, detachment of the retina, increased
pressure inside the eye, dislocation of the implanted lens, accumulation of
fluid in the retina, drooping eyelid, uncomfortable/painful eye, posterior
capsule opacity, light sensitivity.

The subjects participating in the study are severely visually impaired with
respect to the study eye. The eye with the worst visual acuity is planned to be
treated. Since most of the surgical risks are related to the study eye only,
the principal risk for the subject is damaging the remaining vision in the
implanted eye. While it is conceivable that more permanent damage could occur,
for example loss of an eye, the risk analysis predict that this is very
unlikely which is supported by the data from pre-clinical studies and from
feasibility clinical trial as far as this is possible with the limited number
of subjects.
There might procedural and device risks as well as disappointment risks for the
patients if the device failed to work.
However, the potential benefits of taking part justify undertaking these risk.
Furthermore, patient safety is put first at all times through assessments and
close follow ups.

The primary procedural risks to subjects in this study are associated with the
surgical implantation of the device*
these risks are associated with all retinal surgeries. Pixium Vision has taken
several measures to minimize subject risk. Only qualified trial investigators
trained in vitreoretinal surgery will carry out surgeries. Additionally, Pixium
Vision provides training to all study investigators including best practices
for surgical methods prior to the first implantation.

The following risks are related to the device: Ear pain and discomfort,nose
pain and discomfort, complications due to device explanation, impairment of
residual vision function, no increase of visual perception, damaged retina,
complications due to long term exposure to infrared light, epileptic seizure,
headache due to training and/or clinical testing, retinal or iris damage of a
tier user (patient's family etc) or intended user due to exposure to infrared
light of damaged external components, and Severe or non-severe tissue
necrosis. In addition to the above risks the subjects are counselled regarding
the risk of psychological stress.

Pixium Vision has developed the PRIMA retinal prosthesis with requisite
consideration to stimulation safety, material biocompatibility, surgical
implantation methods, as well as safety requirements.

For this study, only subjects with severe vision loss in the study eye of
logMAR 1.2 or worse are included. To minimize the risks for the subject, the
PRIMA device is implanted in the worse seeing eye. Therefore, the risk of
losing a significant component of a subject*s remaining functional vision is
low. Furthermore, it is reassuring that none of the subjects in the feasibility
clinical trial lost visual acuity in the study eye.

The start of the PRIMAvera clinical trial may fall in a time that is still
compromised by the COVID 19 pandemic. The
study will only start if the execution of the trial will be possible without
breaking national and regional regulations and
recommendations for protection of the individual person or to confine the
pandemic.

Patients are not obliged to take part in the study and can withdraw at any
point without any penalties.