A MULTICENTER, OPEN-LABEL EXTENSION STUDY TO EVALUATE THE LONG-TERM SAFETY AND TOLERABILITY OF LAMPALIZUMAB IN PATIENTS WITH GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION WHO HAVE COMPLETED A ROCHE-SPONSORED STUDY

Age-related macular degeneration (AMD) is the leading cause of irreversible
blindness in
people aged 50 years or older in the developed world. The majority of the
visual loss occurs in the advanced stage of AMD, which has two clinical forms:
a non-exudative form, geographic atrophy (GA) and an exudative or wet form. The
prevalence of GA increases exponentially with age and approximately quadruples
per decade beyond 50 years of age. The estimated prevalence of GA in
populations of European ancestry and those 70 years of age is 0.70% and rises
to 2.91% and 11.29% for those 80 years of age and 90 years of age, respectively.

GA causes progressive damage to the macula, the central region of the retina
(inside the eye), which is involved in seeing the fine details associated with
reading, driving, and recognizing faces. In the advanced stage of the disease,
GA results in severe central vision loss, which impairs performance of many
activities of daily living. The cause of AMD is not well understood. However,
recent scientific studies have found that people with specific inherited
(genetic) characteristics have an increased risk of AMD. Other scientific
studies also suggest that an increased activation of a specific part of your
immune system called the *alternative complement pathway* may be involved in
the disease.
Currently, there is no approved treatment for GA. Lampalizumab, the study
drug, is designed to slow down the activation of the alternative complement
pathway and is given by intravitreal (the route of administration) injection
into the eye.

Results from the Phase II Study CFD4870g provide evidence that lampalizumab may
slow the progression of GA and that lampalizumab administered as 10-mg ITV
injections monthly over 18 months demonstrates an acceptable safety and
tolerability profile in patients with GA secondary to AMD. The open label
Omaspect studie GX30191, will evaluate the long-term safety and tolerability of
10 mg lampalizumab administered by ITV injection to patients with GA secondary
to AMD who have completed study treatment and the Week 96 visit in one of the
parent studies (Study GX29176 or GX29815).
See protocol paragraphe 1.4 page 18.

See protocol chapter 1 page 16-18.

The primary objective of this study is to evaluate the long-term safety and
tolerability of ITV injections of 10 mg lampalizumab administered to patients
with GA secondary to AMD as assessed by the:
• Incidence and severity of ocular adverse events
• Incidence and severity of systemic (non-ocular) adverse events

EXPLORATORY OBJECTIVES
• GA area progression (as measured by fundus autofluorescence [FAF])
• Change in clinical outcomes (as outlined below)
• Correlation between GA area progression and change in clinical outcomes
The clinical and patient-reported outcomes (PROs) included in this study are the
following:
• Best corrected visual acuity (BCVA) score, as measured using the Early
Treatment
Diabetic Retinopathy Study (ETDRS) chart (at a starting distance of 4 meters)
• BCVA score, as measured using ETDRS chart at a starting distance of 4 meters
under low-luminance conditions
• Binocular and monocular reading speed, critical print size, and reading
acuity, as
assessed using the Minnesota Low-Vision Reading Test (MNRead) or by Radner
Reading Charts
• Patient-reported visual function, as assessed using the National Eye
Institute Visual
Functioning Questionnaire 25-item Version (NEI VFQ-25), particularly the NEI
VFQ-
25 composite score, the near activity subscale score, and the distance activity
subscale score
• Patient-reported functional reading independence, as assessed using the
Functional
Reading Independence (FRI) Index score
• In a selected subset of patients, macular functional response, as assessed by
mesopic microperimetry and measured by the number of scotomatous points and
change in macular sensitivity- NA for sites in The Netherlands

At the discretion of the Sponsor, additional assessments may be included in
this OLE (open label extention) study (Study GX30191), in which case a
supplemental assessment protocol will be provided.

PHARMACOKINETIC OBJECTIVES
The pharmacokinetic (PK) objective for this study is to observe the systemic
trough concentrations of 10 mg lampalizumab administered by ITV injections
through the analysis of the serum lampalizumab concentrations. The exploratory
PK objectives for this study are to observe the aqueous humor (optional sample)
concentrations of lampalizumab and to explore possible relationships between
lampalizumab PK, biomarkers, and clinically related endpoints.

IMMUNOGENICITY OBJECTIVES
The immunogenicity objective for this study is to evaluate the immune response
to
lampalizumab through the analysis of the incidence of anti-therapeutic
antibodies (ATAs)
during the study relative to the prevalence of ATAs at baseline.
The exploratory immunogenicity objective for this study is to evaluate
potential effects of
ATAs on the efficacy, safety, biomarker or PK endpoints.

BIOMARKER OBJECTIVE
The biomarker objective of this study is to explore the relationship of
biomarkers to each
other and to the endpoints in the study. These biomarkers include genetic
variants
identified in patients who completed the Phase III studies GX29176 and GX29185,
candidate anatomic biomarkers identified by spectral domain*optical coherence
tomography (SD-OCT), levels in the blood of proteins in the complement pathway,
and
molecular biomarkers measured in the optional aqueous humor sample. See the
separate patient information RCR and protocol appendix 19 page 125 and Schedule
of assessments appendix 1 pages 65-78.

See for more information protocol chapter 2 page 19-20.

In this open label extension study, patients will receive lampalizumab by
intravitreal injection either every 4 weeks (Q4W) or every 6 weeks (Q6W).
Lampalizumab is an experimental drug, which means that health authorities have
not approved lampalizumab for the treatment of GA.

Omaspect is a multicenter, open-label extension study to evaluate the long-term
safety and tolerability of lampalizuman in patients with geographic atrophy
secondary to age-related macular degeneration who have completed a
roche-sponsored study (GX29176 Chroma or GX29185 Spectri, named parent
studies). Patients in the parent studies who discontinued from study treatment
prior to completion of the 96-week treatment period are not eligible for
enrollment in this extension study. The extension study will enroll two groups
of patients from the parent studies: patients previously exposed to
lampalizumab as well as patients who are lampalizumab-naïve (i.e., received
sham during a parent study). Although this extension study is open-label,
patients will remain masked to their previous treatment assignment in the
parent study. Week 96 visit will serve as the final visit for the parent study
and the Day 1 visit for the extension study (i.e., the two visits will be
conducted on the same day). Patients must satisfy all eligibility criteria at
the Day 1 visit. All patients from the parent studies who enroll in the OLE
study will receive 10-mg ITV injections of lampalizumab. The study eye for the
extension study will be the same eye that received lampalizumab or sham
administrations in the parent study; only the study eye will receive
administration of lampalizumab in this extension study. Dosing frequency in
this extension study will remain consistent with the original dosing schedule
in the parent study: thus either on the Q4W (± 5 days) schedule or the Q6W
schedule (± 5 days).

See protocol chapter 3, pages 20-22.

Patients that are participating are being treated with lampalizumab in a Q4W or
Q6W dosing schedule.

The patient may have side effects from the drugs or procedures used in this
study. Side effects can vary from mild to very serious and may vary from
person to person. Everyone taking part in the study will be watched carefully
for any side effects. However, Roche, the study doctor, and other doctors do
not know all of the side effects that could occur. The study doctors may give
the patient drugs to help lessen side effects, and the patient may need to
temporarily or permanently stop taking lampalizumab. Many side effects go away
soon after you stop what is causing them. In some cases, side effects can be
serious and may be long lasting or may never go away. There may even be a risk
of death.
In a completed study, patients with GA received injections either monthly or
every other month in an 18-month treatment period. The experience in that
study suggests the administration of lampalizumab injections over time was well
tolerated. Potential side effects of the study drug and related procedures are
described below.

SIDE EFFECTS KNOWN TO BE ASSOCIATED WITH LAMPALIZUMAB AND/OR EYE INJECTION
There are events that have been reported by a small number of patients after
the use of lampalizumab in previous clinical trials. These events, which have
been seen with other injections into the eye, have also been seen with the use
of lampalizumab. The frequencies listed below are based on use of lampalizumab
in a total of 147 patients, who were enrolled in prior clinical trials.
Very Common (Occurring in at least 1 in 10 patients treated):
• Bleeding of the thin membrane covering the white of the eye and inner lid,
• Temporary increase in the pressure in the eye
• Eye pain

Common (Occurring in at least 1 in 100 to 1 in 10 patients treated):
• Eye irritation
• Swelling of the thin membrane covering the white of the eye and inner lid
• Feeling that there is something in the eye

Uncommon (Occurring in at least 1 in 1000 to 1 in 100 patients treated):
• A serious eye infection called endophthalmitis


SIDE EFFECTS POTENTIALLY ASSOCIATED WITH LAMPALIZUMAB AND/OR EYE INJECTION
EYE-RELATED COMPLICATIONS
There is a chance that the patients vision may worsen, which may result from
progression of the eye disease, as a side effect of the study drug injections
or for other reasons. The study drug may have the potential to cause
inflammation in the eye, which may be experienced as redness, swelling, or pain
in the eye. This inflammation may not be related to bacteria. The study drug
may also increase the risk of having certain types of bacterial infections
inside the eye; however, this risk has not been observed in previous animal or
human studies with the study drug to date.
The injection of study drug into the eye also has the potential to cause side
effects. These events include separation of the retina from the underlying
pigment cell layer or a cloudiness of the eye lens (cataract) or temporary loss
of vision due to an increase in the pressure within the eye. In a few
patients, release of ocular fluid by a needle was necessary to reduce the eye
pressure and resolve the temporary vision loss.
The patient may experience side effects from the drugs or procedures used in
this study. These may be associated with the use of lampalizumab, eye
injection, drug-drug interaction, allergic reactions, possible risk and
discomfort associated with drawing blood, risks of fluorescein angiography,
bleeding associated with the use of blood-thinning medications, possible risks
associated with loss of privacy and reproductive risks. These are described in
the subject information leaflet.
See for (potential) side-effects the subject information leaflet and the IB.