Clinical trial NCT02745119
Conditions: Geographic Atrophy
Sponsor: Hoffmann-La Roche
Start date: 2016-07-21; Completion date: 2018-01-31
Enrollment: 994 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This multicenter open-label extension study is designed to evaluate the safety and tolerability of lampalizumab intravitreal injections in participants with GA secondary to age-related macular degeneration (AMD) who completed 96 weeks of treatment in Studies GX29176 (NCT02247479) or GX29185 (NCT02247531). The extension will enroll participants from the parent studies who received investigational lampalizumab, as well as lampalizumab-naive participants exposed to sham comparator. All participants will receive open-label lampalizumab in the present study.

Detailed description:

Arms: arm 1: Participants who received either lampalizumab or sham comparator every 4 weeks in one of the parent studies and completed the Week 96 visit will receive open-label lampalizumab as 10 milligrams (mg) via ITV injection, administered every 4 weeks. arm 2: Participants who received either lampalizumab or sham comparator every 6 weeks in one of the parent studies and completed the Week 96 visit will receive open-label lampalizumab as 10 mg via ITV injection, administered every 6 weeks.
Interventions: intervention 1: Lampalizumab
Intervention descriptions: intervention 1: Lampalizumab 10 mg will be administered every 4 or 6 weeks according to the frequency given during participation in the parent study.

Protocol documents:
Prot_SAP_000.pdf: 
 
Official Title: 
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 
NCT Number: 
NCT02745119 
Document Date: 
Protocol/Version 2: 11-July-2017 
 
 
 




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PROTOCOL AMENDMENT, VERSION 2:
RATIONALE
Changes to the protocol, along with a rationale for each change, are summarized below:

Section 3.1.3, Independent Data Monitoring Committee (iDMC), was added to 
monitor patients’ long-term safety.  This open-label study data will be reviewed by 
the iDMC along with data from the ongoing double-masked parent studies 
(i.e., GX29176 and GX29185).  This change was made following a recommendation 
to have an iDMC from an Ethics Committee and the Sponsor’s position that having 
all lampalizumab studies under a single iDMC would aid safety data interpretation.  
This information was also added to Section 5.1.

Information regarding lampalizumab’s formulation, packaging, storage, and handling 
as well as reconstitution and study treatment administration instructions were moved 
from Section 4.3.1 and Appendices 46 to the Pharmacy Manual to assist sites in 
locating necessary information promptly.

The Medical Monitor was changed for administrative reasons.  

Additional changes listed below have been incorporated for clarity and consistency, 
and to aid the transition of patients from the parent studies to this open-label 
extension study.  
–
Section 3.1.1 and Section 4.1 were updated to clarify procedures if images 
cannot be conducted at the Week 96 visit of the parent study.
–
In Section 4.4.1, prophylactic antibiotics were added to the permitted therapy list.
–
In Section 4.6.2, the study treatment discontinuation criteria were reorganized.
–
Section 5.1 was updated to clarify procedures if study treatment cannot be 
administered at a scheduled visit.
–
In Section 5.1.1, Table 1 was updated to clarify the dose-interruption, 
treatment-discontinuation, and study-withdrawal criteria language.
–
In Section 5.4.2, the reporting requirements for serious adverse events and 
adverse events of special interest during the transition period between the 
parent study and this extension study were clarified.
–
In Section 8.2, the phrase “patient’s legally authorized representative” was 
removed to clarify that the patient is required to sign the informed consent.

Revisions were made to update selected sections to match the Sponsor’s current 
model document text.
Additional minor changes have been made to improve clarity and consistency.  New 
information appears in italics.  This amendment represents cumulative changes to the 
original protocol.


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PROTOCOL AMENDMENT, VERSION 2:
SUMMARY OF CHANGES
GLOBAL CHANGES
The abbreviation “ITV” has been spelled out as “intravitreal” and the Medical Monitor 
was changed from 
, M.D. to 
, M.D. throughout the protocol.  The 
original Appendices 46 were removed, thus the numbering of appendices thereafter 
was updated.
PROTOCOL SYNOPSIS
The protocol synopsis has been updated to reflect the changes to the protocol, where 
applicable.
SECTION 1.3.3:  Phase II Study GX29455
Study GX29455 is a completed,an ongoing multicenter, randomized, single-masked, 
sham injection-controlled, Phase II study investigating the exposure response and safety 
of lampalizumab administered intravitreallyITV every 2 weeks or every 4 weeks (Q4W) 
for 24 weeks in patients with GA secondary to AMD.  The results of this study are 
pending.
SECTION 1.4:  STUDY RATIONALE AND BENEFITRISK ASSESSMENT
The OLE study, Study GX30191, will evaluate the long-term safety and tolerability of 
10 mg lampalizumab administered by intravitreal injection every 4 weeksQ4W or every 
6 weeks (Q6W) 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).
SECTION 3.1.1:  Overview of Study Design
If a site is not able to collect images during the Week 96 visit of the parent study, then 
the Day 1 visit study treatment will be interrupted, and the images will be collected as 
soon as possible and prior to the study treatment administration at the next study 
treatment visit (e.g., Week 4 or Week 6).  The reason for the study treatment 
interruption at the Day 1 visit will be recorded on the study treatment interruption 
electronic case report form (eCRF).
All patients enrolled in the extension study will have the first intravitreal ITV injection of 
lampalizumab administered by the investigator at the Day 1 visit, unless dose 
interruption is medically or otherwise justified by the investigator (see Section 5.1.1 and 
Table 1). by the investigator.  The lampalizumab injections should not be repeated 
earlier than 22 days from previous dosing;. Mmissed doses of study drug will not be 
made up. unless the missed dose is due to an unexpected issue, such as those listed in 
the following paragraph.  Patients’ self-administered anti-microbials pre- and 
post-injection may be used at the investigator’s discretion.


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All subsequent study treatment visits will be scheduled Q4W or Q6W (5 days), relative 
to Day 1 visit date, at which patients will have safety evaluations performed prior to 
receiving the study drug injection (see Appendix 1).  Patients will be contacted by site 
personnel 4 (2) days after each injection to elicit reports of decrease in vision, eye 
pain, unusual redness, or any other new ocular symptoms in the study eye.  If 
warranted, patients will be asked to return to the clinic as soon as possible for an 
unscheduled safety assessment visit (see Appendix 2).  Patients will be instructed to 
contact the investigator at any time if they have any health-related concerns.  If 
warranted, patients will be asked to return to the clinic as soon as possible for an 
unscheduled safety assessment visit (see Appendix 2).  If, during a scheduled visit, a 
site encounters an unexpected issue (e.g., the IxRS is not able to assign the study kit or 
there are any issues with a patient’s care),with the Medical Monitor’s permission, the 
patient’s study treatment may be administered within 3 working days of that visit.  The 
following assessments will be repeated on the day of the study treatment:  slit lamp 
examination, indirect ophthalmoscopy, and pre- and post treatment intraocular pressure 
(IOP) measurements (recorded on the scheduled visit electronic Case Report Form 
[eCRF] and dated with the actual administration date).
After the Day 1 visit, if a patient misses a study visit when ocular images are to be
obtained (see Appendix 1), the images must be obtained at the next scheduled study 
visit, if a patient attends it.
SECTION 3.1.3:  Data Monitoring Committee
An independent Data Monitoring Committee (iDMC) which is monitoring parent 
study will monitor safety and study conduct of this extension study on an ongoing 
basis as well.  Members of the iDMC will be external to the Sponsor and will follow a 
charter that outlines the iDMC roles and responsibilities.  The iDMC will meet 
approximately every 6 months (frequency adjustable as required) to evaluate the 
benefit-risk profile of lampalizumab treatment through reviewing both safety and 
efficacy data.  No formal interim efficacy/futility analysis is planned to be conducted by 
iDMC.  The iDMC may recommend stopping the study early for safety reasons.  
Further details can be found in the iDMC charter.
SECTION 4.1:  PATIENTS
If a site is not able to collect images during the Week 96 visit of the parent study, then 
the Day 1 visit study treatment will be interrupted, and the images will be collected as 
soon as possible and prior to the study treatment administration at the next study 
treatment visit (e.g., Week 4 or Week 6).  The reason for the study treatment 
interruption at the Day 1 visit will be recorded on the study treatment interruption 
eCRF.


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SECTION 4.1.1:  Inclusion Criteria
Patients must meet the following criteria for study entry:

For women of childbearing potential:  agreement to remain abstinent (refrain from 
heterosexual intercourse) or use contraceptive methods that result inwith a failure 
rate of 1% per year during the treatment period and for at least 30 days after the 
last dose of lampalizumab.
SECTION 4.3.1:  Lampalizumab Formulation, Packaging, Storage, and 
Handling
4.3.1.1 Lampalizumab Formulation
Lampalizumab drug product is provided as a sterile, white to off white, lyophilized 
powder in a 6 cc USP/European Pharmacopoeia (Ph. Eur.) Type 1 glass vial and is 
intended for ITV administration.  For the Phase III clinical studies, each glass vial 
contains a nominal 40 mg lampalizumab.  After reconstitution with Sterile Water for 
Injection (SWFI), the drug product is formulated as 100 mg/mL lampalizumab in 40 mM 
L histidine hydrochloride, 28 mM sodium chloride, 160 mM sucrose, 0.04% (w/v) 
polysorbate 20, pH 5.3.
Storage
Upon receipt of lampalizumab, vials should be refrigerated at 2C8C (36F46F) until 
use.  Lampalizumab vials should not be used beyond the expiration date provided by the 
manufacturer.  No preservative is used in lampalizumab drug product; therefore, the vial 
is intended for single use only.  Vial contents should not be frozen or shaken and should 
be protected from direct sunlight.  Within 2 hours following dose preparation
(reconstitution), lampalizumab should be administered; the prepared dose may be 
maintained at room temperature prior to administration.
For further details,Please see the Lampalizumab Investigator’s Brochure and/or for the 
lampalizumab clinical formulation.  See the Pharmacy BinderManual for additional 
specifics regarding the lampalizumab formulation, product packaging, storage, and 
handling.
SECTION 4.3.2:  Lampalizumab Dosage, Administration, and Compliance
SECTION 4.3.2.1:  Lampalizumab Dosage
A 10-mg dose of lampalizumab will be used in the extension study and will be 
administered by intravitrealITV injection to all enrolled patients either Q4W or Q6W 
during the treatment period (see Appendix 1 for the study flowchart).
The lampalizumab injections should not be repeated earlier than 22 days from previous 
dosing;. Mmissed doses of study drug will not be made up unless the missed dose is 
due to an unexpected issue, such as those listed in Section3.1.1.


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SECTION 4.3.2.2:  Administration
The detailed instructions for lampalizumab reconstitution with SWFI, USP/Ph. Eur., is 
required for preparation of the dose.  Sites will supply the SWFI.  Vials of lampalizumab 
are for single use only.  Vials used for one patient may not be used for any other patient.  
Detailed instructions for reconstitution of lampalizumab are provided in the 
Pharmacy Binder. 
Please refer to Appendix 4, Appendix 5, and Appendix 6 for detailed instructions on, for 
the pre-injection procedures, preparation and intravitrealITV administration of the study 
drug injection, and post-injection procedures for the study eye, respectively are provided 
in the Pharmacy Manual. 
SECTION 4.4.1:  Permitted Therapy
Of note, the following are examples of some common therapies that are permitted:

Prophylactic use of systemic antibiotics (e.g., for prevention of urinary tract 
infection [UTI]) should be discussed with Medical Monitor.
SECTION 4.5.2:  Medical History and Demographic Data
Medical history and demographic data were collected during the parent studies and will 
not need to be reobtainedobtained again during the OLE study.
SECTION 4.5.4.2:  Ocular Imaging and Microperimetry

FAF, SD-OCT, and NI images of both eyes (see Appendix 7, Appendix 8, and 
Appendix 9, respectively)
Note:  After enrollment, if a patient misses a study visit during which ocular 
images are scheduled to be taken, the images should be obtained at the next 
scheduled visit. , if a patient attends it.
SECTION 4.6.1:  Patient Discontinuation from Study
Only the section title was revised. 
SECTION 4.6.2:  Study Treatment Discontinuation
The investigator has the right toPatients must permanently discontinue a patient from 
the study treatment forif they experience any of the following:  

Any medical condition that the investigator or Sponsor determines may jeopardize 
the patient’s safety if he or she continues in theto receive study treatment

Pregnancy, 
The investigator has the right to discontinue a patient for reasons of non-compliance 
(e.g., missed doses and/or visits), if the patient becomes pregnant,) or if the investigator 
or Sponsor determines it is in the best interest of the patient.  The primary reason for the 
treatment discontinuation should be recorded on the appropriate eCRF.


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Treatment discontinued patientsPatients who must discontinue treatment will not be 
replaced or allowed to restart the study treatment.  Any patient discontinued from study 
treatment will also be discontinued from the study and will not be allowed to re-enter the 
study; the patient will be encouraged to undergo a study early termination visit.
SECTION 5.1:  SAFETY PLAN
The incidence and characteristics of adverse events, serious adverse events, and 
laboratory abnormalities will be assessed as described within this protocol.  An iDMC 
will monitor patient safety and study conduct on an ongoing basis (see Section 3.1.3).  
The iDMC shares with the Sponsor the responsibility to monitor overall patient safety 
in relation to the IMP, lampalizumab.
SECTION 5.1.1:  Safety Procedures
Subheading was added. 
SECTION 5.1.2:  Dose-Interruption, Treatment-Discontinuation, and 
Study-Withdrawal Criteria
The following rows of Table 1 were revised as follows:
Table 1
Dose-Interruption, Treatment-Discontinuation, and 
Study-Withdrawal Criteria
Event
Dose-Interruption, Treatment-Discontinuation, and 
Study-Withdrawal Criteria
VA lossdecrease
Interrupt study treatment if there is a study
treatment-related decrease of 30 letters in BCVA in 
the study eye compared with the last assessment of 
BCVA prior to the most recent treatment.  Study 
treatment may be permitted subsequently as 
determined by the Sponsor and investigator.
Vitreous hemorrhage
Interrupt study treatment in the event of a vitreous 
hemorrhage in the study eye.  Study treatment may be 
permitted subsequently as determined by the Sponsor 
and investigator.
Active local or systemic infection
Interrupt study treatment if any of the following are 
present:  infectious conjunctivitis, infectious keratitis, 
infectious scleritis, or endophthalmitis in either eye; or 
if the patient is currently receiving systemic treatment 
for an active local or systemic infection.
Patients with endophthalmitis in the study eye will 
discontinue the study treatment and be withdrawn
from the study.
SECTION 5.2:  SAFETY PARAMETERS AND DEFINITIONS
Safety assessments will consist of monitoring and recording adverse events, including 
serious adverse events and adverse events of special interest, performing 


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protocol-specified safety laboratory assessments, and other protocol-specified tests that 
are deemed critical to the safety evaluation of the study.
SECTION 5.2.3:  Adverse Events of Special Interest (Immediately 
Reportable to the Sponsor)

Sight-threatening adverse events:  An adverse event is considered to be serious 
and sight threatening and should be reported expeditiously if it meets one or more of
the following criteria:
SECTION 5.3.1:  Adverse Events Reporting Period
After informed consent has been obtained but prior to initiationcompletion of study drug 
inthe Week 96 visit of the parent study and informed consent for the extension study, 
adverse events should be reported in the parent study.  Any adverse events or serious
has been obtained, any adverse events that are ongoing from or started after the Week 
96 visit of the parent study when study drug is initiated inshould be reported on the 
extension study should also be reported on the GX30191Adverse Event eCRF.
After initiation of study drug, All adverse events will be reported until at least 30 days 
after the last dose of study drug or the last study visit, whichever is later.  After this 
period, the investigator should report any serious adverse events that are believed to be 
related to prior study drug treatment (see Section 5.6).
SECTION 5.3.5.7:  Deaths
All deaths that occur during the protocol-specified adverse event reporting period (see 
Section 5.3.1), regardless of relationship to study drug, must be recorded on the 
Adverse Event eCRF and immediately reported to the Sponsor (see Section 5.4.2). This 
includes death attributed to progression of GA secondary to AMD.
Death should be considered an outcome and not a distinct event.  The event or condition 
that caused or contributed to the fatal outcome should be recorded as the single medical 
concept on the Adverse Event eCRF.  Generally, only one such event should be 
reported.  The term “sudden death” should be used only for the occurrence of an 
abrupt and unexpected death due to presumed cardiac causes in a patient with or 
without preexisting heart disease, within 1 hour after the onset of acute symptoms or, in 
the case of an unwitnessed death, within 24 hours after the patient was last seen alive 
and stable.  If the cause of death is unknown and cannot be ascertained at the time of 
reporting, “unexplained death” should be recorded on the Adverse Event eCRF.  If the 
cause of death later becomes available (e.g., after autopsy), “unexplained death” should 
be replaced by the established cause of death.  The term "sudden death" should not 
be used unless combined with the presumed cause of death (e.g., "sudden cardiac 
death").
If the death is attributed to progression of "GA secondary to AMD progression," 
geographic atrophy secondary to advanced macular degeneration progression should be 
recorded on the Adverse Event eCRF.  


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Deaths that occur after the adverse event reporting period should be reported as 
described in Section 5.6.
SECTION 5.3.5.9:  Lack of Efficacy or Worsening of Geographic Atrophy in 
Study Eye
Events that are clearly consistent with the expected pattern of progression of the 
underlying disease in the study eye should not be recorded as adverse events.  The 
expedited reporting requirements for sight-threatening events (listed in the Section 5.2.3) 
still apply to these unexpected changes in the study eye GA.
SECTION 5.4.1:  Emergency Medical Contacts
Medical Monitor Contact Information for Sites in North and South America
Medical Monitor/Roche Medical Responsible:
, M.D. (Primary)
Telephone No.:
Mobile Telephone No.:
SECTION 5.4.2.1:  Events That Occur prior to Study Drug Initiation
After informed consent has been obtained but prior to initiation of study drug in the 
extension study, sSerious adverse events and adverse events of special interest with 
onset prior to completion of the parent study the Week 96 visit of the parent study
should be reported in the parent study.  Any serious adverse events or adverse events 
of special interest that are ongoing from the parent study when study drug is initiated in 
the extension study should also be reported on the OLE eCRF  After .  completion of 
the Week 96 visit of the parent study the parent study Week 96 visit and an informed 
consent for the extension study has been obtained, the serious adverse events and 
adverse events of special interest that are ongoing or started after the Week 96 visit of 
the parent study the parent study Week 96 visit should be reported on the extension 
study eCRF.
SECTION 5.4.2.2:  Events That Occur after Study Drug Initiation
After initiation of study drug, sSerious adverse events and adverse events of special 
interest will be reported until at least 30 days after administration of the last dose of 
study drug or the last study visit, whichever is later.  Investigators should record all 
case details that can be gathered immediately (i.e., within 24 hours after learning of the 
event) on the Adverse Event eCRF and submit the report via the electronic data capture 
(EDC) system.  A report will be generated and sent to Roche Safety Risk Management 
by the EDC system.
SECTION 5.6:  POST STUDY ADVERSE EVENTS THAT OCCUR AFTER 
THE ADVERSE EVENT REPORTING PERIOD
Only the section title was revised. 


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SECTION 6.2:  SUMMARIES OF DEMOGRAPHIC AND BASELINE 
CHARACTERISTICS AND CONDUCT OF THE STUDY
Demographic and disease characteristics (such as GA area, BCVA, and VA under 
low-luminance conditions prior to enrollment) for patients enrolled in the extension study 
will be summarized in all patients and by treatment group in the parent study 
(Study GX29176 or Study GX29185).  Patient disposition and exposure to study drug 
(number of study treatments and duration of treatment) will be summarized in all 
patients and by treatment group in the parent study.
SECTION 6.3:  SAFETY ANALYSES
The safety analyses will include patients enrolled in this study who receive at least 
1 dose of study drug in all with patients and grouped according to treatment received in 
the parent study.
SECTION 6.4:  ANATOMIC AND CLINICAL OUTCOME ANALYSES
The anatomic and clinical outcome analyses will include all patients enrolled in this 
study who have received at least one dose of study drug.  The analyses will be 
summarized in all patients and by treatment group in the parent study had at least one 
assessment after the first dose of study drug, with patients grouped according to 
treatment received in the parent study.
SECTION 6.5:  PHARMACOKINETIC ANALYSES
The PK analyses will include all enrolled patients who have received at least one dose of 
study drug and have at least one serum sample.  The analyses will be summarized by 
treatment group in the parent study. with patients grouped according to treatment 
actually received and treatment received before being rolled to the study.  Serum 
concentrations of lampalizumab will be summarized descriptively.
SECTION 6.6:  IMMUNOGENICITY ANALYSES
The immunogenicity analyses will include patients with at least one predose (defined as 
prior to the first dose in the extension study for the prior sham patients, and prior to 
the first dose in the parent study for the prior lampalizumab patients)and one postdose 
ATA assessment.  The analysis will be summarized by treatment group in the parent 
study. with patients grouped according to treatment received (Q4W or Q6W) and to the 
treatment received in the parent study.
The number and proportion of ATA-positive and ATA-negative patients during this study 
will be summarized by treatment group.  The relationship between ATA status and the 
safety, efficacy, PK, and biomarker endpoints will be analyzed and reported descriptively 
in subgroup analyses.  Patients are considered to be ATA--positive if they are 
ATA-negative at baseline (defined as the last measurement prior to the first dose in the 
extension study for the prior sham patients, and the last measurement prior to the first 
dose in the Parent study for the prior lampalizumab patients) but develop an ATA 
response following study drug administration (i.e., treatment-induced ATA response) or if 


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they are ATA-positive at baseline and the titer of one or more post-baseline samples is 
at least 4-fold greater (i.e., 0.60 titer units) than the titer of the baseline sample (i.e., 
treatment-enhanced ATA response).  
SECTION 6.7:  HANDLING OF MISSING DATA
All efforts will be made to minimize missing data; no imputation will be performed for 
the missing data for the analyses.
SECTION 6.8:  OPTIONAL INTERIM ANALYSIS
No formal interim efficacy analysis is planned since all patients on this study will receive 
active lampalizumab treatment.Interim safety analyses will be conducted periodically by 
independent Data Monitoring Committee (iDMC) to monitor safety and study conduct 
of this extension study.  No formal interim efficacy/futility analyses are planned.  
Exploratory efficacy and/or safety analyses may be performed with interim data (e.g., to 
support regulatory submissions).
SECTION 8.2:  INFORMED CONSENT
The Consent Forms must be signed and dated by the patient or the patient’s legally 
authorized representative before his or her participation in the study.  The case history or 
clinical records for each patient shall document the informed consent process and that 
written informed consent was obtained prior to participation in the study.
A copy of each signed ICF must be provided to the patient or the patient’s legally 
authorized representative.  All signed and dated Consent Forms must remain in each 
patient’s study file or in the site file and must be available for verification by study 
monitors at any time.
APPENDIX 1:  Schedule of Activities
The schedule of activities has been revised to reflect the changes to the protocol.
SAMPLE INFORMED CONSENT FORM
None of the protocol revisions affected the Informed Consent Form; therefore, it was not 
updated.


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TABLE OF CONTENTS
PROTOCOL AMENDMENT ACCEPTANCE FORM .......................................... 18
PROTOCOL SYNOPSIS .................................................................................... 19
1.
BACKGROUND .......................................................................................... 26
1.1
Background on Geographic Atrophy Secondary 
to Age-Related Macular Degeneration .................................. 26
1.2
Background on Lampalizumab .............................................. 26
1.3
Ongoing Clinical Studies........................................................ 27
1.3.1
Phase III Studies GX29176 and GX29185 
(Chroma and Spectri) ............................................................ 27
1.3.2
Phase II Open-Label Extension Study GX28198 
(MAHALO OLE)..................................................................... 27
1.3.3
Phase II Study GX29455 ....................................................... 28
1.3.4
Prospective Epidemiological Studies GX29633 
and GX29639 (Proxima A and Proxima B) ............................ 28
1.4
Study Rationale and BenefitRisk Assessment..................... 28
2.
OBJECTIVES AND ENDPOINTS ............................................................... 29
2.1
Primary Objective .................................................................. 29
2.2
Exploratory Objectives........................................................... 29
2.3
Pharmacokinetic Objectives .................................................. 30
2.4
Immunogenicity Objectives.................................................... 30
2.5
Biomarker Objective .............................................................. 30
3.
STUDY DESIGN......................................................................................... 30
3.1
Description of the Study......................................................... 30
3.1.1
Overview of Study Design ..................................................... 30
3.1.2
Planned Total Sample Size ................................................... 32
3.1.3
Data Monitoring Committee................................................... 32
3.2
End of Study and Length of Study......................................... 32
3.3
Rationale for Study Design.................................................... 33
3.3.1
Rationale for Lampalizumab Dose and Schedule.................. 33
3.3.2
Rationale for Biomarker Assessments................................... 33
4.
MATERIALS AND METHODS .................................................................... 33


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4.1
Patients.................................................................................. 33
4.1.1
Inclusion Criteria.................................................................... 34
4.1.2
Exclusion Criteria................................................................... 35
4.2
Method of Treatment Assignment.......................................... 35
4.3
Study Treatment.................................................................... 35
4.3.1
Lampalizumab Formulation, Packaging, Storage, 
and Handling ......................................................................... 36
4.3.2
Lampalizumab Dosage, Administration, and 
Compliance............................................................................ 36
4.3.2.1
Dosage .................................................................................. 36
4.3.2.2
Administration........................................................................ 36
4.3.2.3
Compliance............................................................................ 36
4.3.3
Investigational Medicinal Product Accountability ................... 36
4.3.4
Post-Trial Access to Lampalizumab ...................................... 37
4.4
Concomitant Therapy ............................................................ 37
4.4.1
Permitted Therapy................................................................. 38
4.4.2
Excluded Therapy.................................................................. 38
4.5
Study Assessments ............................................................... 39
4.5.1
Informed Consent Forms....................................................... 39
4.5.2
Medical History and Demographic Data ................................ 39
4.5.3
Vital Signs.............................................................................. 39
4.5.4
Other Disease-Specific Assessments.................................... 39
4.5.4.1
Ocular Assessments.............................................................. 39
4.5.4.2
Ocular Imaging and Microperimetry....................................... 40
4.5.5
Laboratory and Other Biological Samples ............................. 41
4.5.6
Patient-Reported Outcomes .................................................. 42
4.5.7
Reading Speed Assessments................................................ 43
4.5.7.1
Minnesota Low-Vision Reading Test ..................................... 43
4.5.7.2
Radner Reading Charts......................................................... 43
4.5.8
Optional Samples for Roche Clinical Repository ................... 43
4.5.8.1
Overview of the Roche Clinical Repository............................ 43
4.5.8.2
Approval by the Institutional Review Board or 
Ethics Committee .................................................................. 44
4.5.8.3
Sample Collection.................................................................. 44


Lampalizumab—F. Hoffmann-La Roche Ltd
14/Protocol GX30191, Version 2
4.5.8.4
Confidentiality........................................................................ 44
4.5.8.5
Consent to Participate in the Roche 
Clinical Repository................................................................. 45
4.5.8.6
Withdrawal from the Roche Clinical Repository..................... 46
4.5.8.7
Monitoring and Oversight....................................................... 46
4.6
Patient, Treatment, Study, and Site 
Discontinuation...................................................................... 46
4.6.1
Patient Discontinuation from Study........................................ 46
4.6.2
Study Treatment Discontinuation........................................... 47
4.6.3
Study and Site Discontinuation.............................................. 47
5.
ASSESSMENT OF SAFETY....................................................................... 48
5.1
Safety Plan ............................................................................ 48
5.1.1
Safety Procedures................................................................. 49
5.1.2
Dose-Interruption, Treatment-Discontinuation, 
and Study-Withdrawal Criteria............................................... 50
5.2
Safety Parameters and Definitions ........................................ 52
5.2.1
Adverse Events ..................................................................... 52
5.2.2
Serious Adverse Events (Immediately Reportable 
to the Sponsor)...................................................................... 53
5.2.3
Adverse Events of Special Interest (Immediately 
Reportable to the Sponsor).................................................... 54
5.3
Methods and Timing for Capturing and 
Assessing Safety Parameters................................................ 55
5.3.1
Adverse Event Reporting Period ........................................... 55
5.3.2
Eliciting Adverse Event Information....................................... 55
5.3.3
Assessment of Severity of Adverse Events ........................... 55
5.3.4
Assessment of Causality of Adverse Events ......................... 56
5.3.5
Procedures for Recording Adverse Events............................ 57
5.3.5.1
Diagnosis versus Signs and Symptoms................................. 57
5.3.5.2
Adverse Events That Are Secondary to 
Other Events.......................................................................... 58
5.3.5.3
Persistent or Recurrent Adverse Events................................ 58
5.3.5.4
Abnormal Laboratory Values ................................................. 58
5.3.5.5
Abnormal Vital Sign Values ................................................... 59
5.3.5.6
Abnormal Liver Function Tests.............................................. 60


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5.3.5.7
Deaths ................................................................................... 60
5.3.5.8
Preexisting Medical Conditions.............................................. 61
5.3.5.9
Worsening of Geographic Atrophy in Study Eye.................... 61
5.3.5.10
Hospitalization or Prolonged Hospitalization.......................... 61
5.3.5.11
Adverse Events Associated with an Overdose or 
Error in Drug Administration .................................................. 61
5.3.5.12
Patient-Reported Outcome Data ........................................... 62
5.4
Immediate Reporting Requirements from 
Investigator to Sponsor.......................................................... 62
5.4.1
Emergency Medical Contacts................................................ 62
5.4.2
Reporting Requirements for Serious Adverse 
Events and Adverse Events of Special Interest..................... 63
5.4.3
Reporting Requirements for Pregnancies.............................. 64
5.4.3.1
Pregnancies in Female Patients............................................ 64
5.4.3.2
Pregnancies in Female Partners of Male Patients................. 64
5.4.3.3
Abortions ............................................................................... 65
5.4.3.4
Congenital Anomalies/Birth Defects ...................................... 65
5.5
Follow-Up of Patients after Adverse Events .......................... 65
5.5.1
Investigator Follow-Up........................................................... 65
5.5.2
Sponsor Follow-Up ................................................................ 65
5.6
Adverse Events That Occur after the Adverse 
Event Reporting Period.......................................................... 65
5.7
Expedited Reporting to Health Authorities, 
Investigators, Institutional Review Boards, and 
Ethics Committees................................................................. 66
6.
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN....................... 66
6.1
Determination of Sample Size ............................................... 66
6.2
Summaries of Demographic and Baseline 
Characteristics and Conduct of the Study ............................. 66
6.3
Safety Analyses..................................................................... 66
6.4
Anatomic and Clinical Outcome Analyses ............................. 67
6.5
Pharmacokinetic Analyses..................................................... 67
6.6
Immunogenicity Analyses...................................................... 67
6.7
Handling of Missing Data....................................................... 68
6.8
Optional Interim Analysis....................................................... 68


Lampalizumab—F. Hoffmann-La Roche Ltd
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7.
DATA COLLECTION AND MANAGEMENT ............................................... 68
7.1
Data Quality Assurance......................................................... 68
7.2
Electronic Case Report Forms............................................... 68
7.3
Source Data Documentation.................................................. 69
7.4
Use of Computerized Systems .............................................. 69
7.5
Retention of Records............................................................. 70
8.
ETHICAL CONSIDERATIONS.................................................................... 70
8.1
Compliance with Laws and Regulations ................................ 70
8.2
Informed Consent.................................................................. 70
8.3
Institutional Review Board or Ethics Committee.................... 71
8.4
Confidentiality........................................................................ 72
8.5
Financial Disclosure .............................................................. 72
9.
STUDY DOCUMENTATION, MONITORING, AND 
ADMINISTRATION ..................................................................................... 72
9.1
Study Documentation ............................................................ 72
9.2
Protocol Deviations................................................................ 72
9.3
Site Inspections ..................................................................... 73
9.4
Administrative Structure......................................................... 73
9.5
Publication of Data and Protection of 
Trade Secrets........................................................................ 73
9.6
Protocol Amendments ........................................................... 74
10. REFERENCES ........................................................................................... 75
LIST OF TABLES
Table 1
Dose-Interruption, Treatment-Discontinuation, and 
Study-Withdrawal Criteria ........................................................... 51
Table 2
Adverse Event Severity Grading Scale ....................................... 56
Table 3
Causal Attribution Guidance ....................................................... 56


Lampalizumab—F. Hoffmann-La Roche Ltd
17/Protocol GX30191, Version 2
LIST OF APPENDICES
Appendix 1
Schedule of Assessments........................................................... 76
Appendix 2
Study Flowchart:  Unscheduled Safety Assessment Visit ........... 90
Appendix 3
Grading Scale for Assessment of Anterior Chamber Flare or 
Cells and Vitreous Cells.............................................................. 91
Appendix 4
Best Corrected Visual Acuity Testing.......................................... 93
Appendix 5
Low-Luminance Best Corrected Visual Acuity Testing................ 94
Appendix 6
Color Fundus Photography ......................................................... 95
Appendix 7
Fluorescein Angiography ............................................................ 96
Appendix 8
Fundus Autofluorescence ........................................................... 97
Appendix 9
Spectral Domain-Optical Coherence Tomography...................... 98
Appendix 10
Near-Infrared Imaging................................................................. 99
Appendix 11
Optional Mesopic Microperimetry (Selected Sites Only) ........... 100
Appendix 12
National Eye Institute Visual Functioning Questionnaire 
25-Item Version......................................................................... 101
Appendix 13
Functional Reading Independence Index.................................. 114
Appendix 14
Minnesota Low-Vision Reading Test......................................... 122
Appendix 15
Radner Reading Cards ............................................................. 125
Appendix 16
Biological Sample Collection and Shipping Instructions............ 128


Lampalizumab—F. Hoffmann-La Roche Ltd
18/Protocol GX30191, Version 2
PROTOCOL AMENDMENT ACCEPTANCE FORM
TITLE:
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
PROTOCOL NUMBER:
GX30191
VERSION NUMBER:
2
EUDRACT NUMBER:
2016-000423-13
IND NUMBER:
104996
TEST PRODUCT:
Lampalizumab (RO5490249)
MEDICAL MONITOR:
, M.D.
SPONSOR:
F. Hoffmann-La Roche Ltd
I agree to conduct the study in accordance with the current protocol.
Principal Investigator’s Name (print)
Principal Investigator’s Signature
Date
Please retain the signed original of this form for your study files.  Please return a copy of 
this form to the local study monitor. 


Lampalizumab—F. Hoffmann-La Roche Ltd
19/Protocol GX30191, Version 2
PROTOCOL SYNOPSIS
TITLE:
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
PROTOCOL NUMBER:
GX30191
VERSION NUMBER:
2
EUDRACT NUMBER:
2016-000423-13
IND NUMBER:
104996
TEST PRODUCT:
Lampalizumab (RO5490249)
PHASE:
IIIb
INDICATION:
Geographic atrophy
SPONSOR:
F. Hoffmann-La Roche Ltd
Objectives and Endpoints
Primary Objective
The primary objective of this study is to evaluate the long-term safety and tolerability of 
intravitreal injections of 10 mg lampalizumab administered to patients with geographic atrophy 
(GA) secondary to age-related macular degeneration (AMD) as assessed by the following:

Incidence and severity of ocular adverse events

Incidence and severity of systemic (non-ocular) adverse events
Exploratory Objectives
The exploratory objective of this study is to investigate the long-term efficacy of intravitreal 
injections of 10 mg lampalizumab as assessed by:

GA area progression (as measured by fundus autofluorescence)

Change in clinical outcomes (as outlined below) 

Correlation between GA area progression and change in clinical outcomes 
The clinical and patient-reported outcomes 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 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 


Lampalizumab—F. Hoffmann-La Roche Ltd
20/Protocol GX30191, Version 2

Patient-reported functional reading independence, as assessed using the Functional 
Reading Independence 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
At the discretion of the Sponsor, additional assessments may be included in this open-label 
extension (OLE) 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 intravitreal injections through the 
analysis of the serum lampalizumab concentrations.
The exploratory PK objectives for this study are to observe the aqueous humor 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, levels in the blood of 
proteins in the complement pathway, and molecular biomarkers measured in the optional 
aqueous humor sample.  
Study Design
Description of Study
Study GX30191 is a multicenter, open-label extension (OLE) study designed to evaluate the 
safety and tolerability of a 10-mg dose of lampalizumab administered by intravitreal injection to 
patients with GA secondary to AMD who have completed Study GX29176 or GX29185 
(henceforth referred to as the 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-naive (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, unless unmasking is 
permitted by the Sponsor.  In addition, the visual acuity (VA) examiner role will remain masked 
to the patients' study eye assignment.
Eligible patients who consent to participate in this extension study will be enrolled upon 
completion of the parent study (i.e., at the Week 96 visit) and study treatment. The 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; eligible patients will be enrolled using an interactive response system 
(IxRS). 
If a site is not able to collect images during the Week 96 visit of the parent study, then the 
Day 1 visit study treatment will be interrupted, and the images will be collected as soon as 
possible and prior to the study treatment administration at the next study treatment visit (e.g., 
Week 4 or Week 6).  The reason for the study treatment interruption at the Day 1 visit will be 
recorded on the study treatment interruption electronic case report form (eCRF).


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21/Protocol GX30191, Version 2
All patients from the parent studies who enroll in the OLE study will receive 10-mg intravitreal
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.  
That is, if a patient was originally randomized to the every 4 weeks (Q4W) arm in the parent 
study, the patient will remain on a Q4W schedule in the extension study.  Similarly, if a patient 
was originally randomized to the every 6 weeks (Q6W) arm in the parent study, the patient will 
remain on a Q6W schedule. 
All patients enrolled in the extension study will have the first intravitreal injection of 
lampalizumab administered by the investigator at the Day 1 visit, unless dose interruption is 
medically or otherwise justified by the investigator.  The lampalizumab injections should not be 
repeated earlier than 22 days from previous dosing. Missed doses of study drug will not be 
made up unless the missed dose is due to an unexpected issue, such as those listed in the 
following paragraph.  Patients’ self-administered anti-microbials pre- and post-injection may be 
used at the investigator’s discretion. 
All subsequent study treatment visits will be scheduled Q4W or Q6W (5 days), relative to 
Day 1 visit date, at which patients will have safety evaluations performed prior to receiving the 
study drug injection.  Patients will be contacted by site personnel 4 (2) days after each 
injection to elicit reports of decrease in vision, eye pain, unusual redness, or any other new 
ocular symptoms in the study eye.  If warranted, patients will be asked to return to the clinic as 
soon as possible for an unscheduled safety assessment visit.  Patients will be instructed to 
contact the investigator at any time if they have any health-related concerns.  If warranted, 
patients will be asked to return to the clinic as soon as possible for an unscheduled safety 
assessment visit.  If, during a scheduled visit, a site encounters an unexpected issue (e.g., the 
IxRS is not able to assign the study kit or there are any issues with a patient’s care), with the 
Medical Monitor’s permission, the patient’s study treatment may be administered within 3 
working days of that visit.  The following assessments will be repeated on the day of the study 
treatment:  slit lamp examination, indirect ophthalmoscopy, and pre- and post-treatment 
intraocular pressure (IOP) measurements (recorded on the scheduled visit electronic Case 
Report Form and dated with the actual administration date).
After the Day 1 visit, if a patient misses a study visit when ocular images are to be obtained, the 
images must be obtained at the next scheduled study visit, if a patient attends it.
Patients are not expected to attend their scheduled visits if there are extenuating circumstances 
justifying their inability to come to the clinic.   
Patients who discontinue from the study will be asked to return for an early termination visit after 
a minimum of 30 days has elapsed following their last study treatment for monitoring of adverse 
events and the early termination visit assessments.
A subset of the patients at selected sites may participate in a mesopic microperimetry 
assessment in order to evaluate macular functional response.  
An independent Data Monitoring Committee (iDMC), which is monitoring the parent 
studies, will monitor safety and study conduct of this extension study on an ongoing basis as 
well.
Number of Patients
Up to 1800 patients may be enrolled in the study at up to 300 sites located globally.
Target Population
Inclusion Criteria
Patients must meet the following criteria for study entry:

Willingness and ability to provide signed informed consent
Additionally, at U.S. sites, patients must provide Health Insurance Portability and 
Accountability Act authorization, and in other countries, as applicable according to 
national laws.

Willingness and ability to undertake all scheduled visits and assessments


Lampalizumab—F. Hoffmann-La Roche Ltd
22/Protocol GX30191, Version 2

Previous enrollment in and completion of study treatment and the Week 96 visit of either 
Study GX29185 or Study GX29176, without early treatment discontinuation (lampalizumab 
or sham) 

For women of childbearing potential: agreement to remain abstinent (refrain from 
heterosexual intercourse) or use contraceptive methods with a failure rate of 1% per year 
during the treatment period and for at least 30 days after the last dose of lampalizumab.
A woman is considered to be of childbearing potential if she is postmenarcheal, has 
not reached a postmenopausal state (12 continuous months of amenorrhea with no 
identified cause other than menopause), and has not undergone surgical sterilization 
(removal of ovaries and/or uterus).
Examples of contraceptive methods with a failure rate of 1% per year include 
bilateral tubal ligation, male sterilization, established proper use of hormonal
contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and 
copper intrauterine devices.
The reliability of sexual abstinence should be evaluated in relation to the duration of 
the clinical trial and the preferred and usual lifestyle of the patient.  Periodic 
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and 
withdrawal are not acceptable methods of contraception.

For men:  agreement to remain abstinent (refrain from heterosexual intercourse) or use 
contraceptive measures, and agreement to refrain from donating sperm, as defined below:
With female partners of childbearing potential, men must remain abstinent or use a 
condom plus an additional contraceptive method that together result in a failure rate of 
1% per year during the treatment period and for at least 120 days after the last dose 
of study drug. Men must refrain from donating sperm during this same time period.
With pregnant female partners, men must remain abstinent or use a condom during 
the treatment period and for at least 120 days after the last dose of study drug to avoid 
exposing the embryo.
The reliability of sexual abstinence should be evaluated in relation to the duration of 
the clinical trial and the preferred and usual lifestyle of the patient.  Periodic 
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and 
withdrawal are not acceptable methods of contraception.

For patients participating in microperimetry (at selected sites only):  must have participated 
in the microperimetry testing during the parent study
Exclusion Criteria
Patients who meet any of the following criteria will be excluded from study entry:

Concurrent ocular conditions exclusion criterion
History of other ocular diseases that give reasonable suspicion of a disease or 
condition that contraindicates the use of lampalizumab or that might affect 
interpretation of the results of the study or that renders the patient at high risk of 
treatment complications

Concurrent systemic conditions exclusion criteria
History of other diseases, metabolic dysfunction, physical examination finding, or 
clinical laboratory finding that gives reasonable suspicion of a disease or condition that 
contraindicates the use of lampalizumab or that might affect interpretation of the 
results of the study or that renders the patient at high risk of treatment complications
Predisposition to or history of increased risk of infection (e.g., history of splenectomy 
or chronic immunosuppression)
Requirement for continuous use of any medications or treatments indicated in the 
“Excluded Therapy” section of the protocol
Pregnancy or lactation, or intention to become pregnant during the study
Women of childbearing potential must have a negative urine pregnancy test 
result at the Day 1 visit prior to initiation of study drug.


Lampalizumab—F. Hoffmann-La Roche Ltd
23/Protocol GX30191, Version 2
End of Study
The end of the study is defined as the date when the last patient, last visit occurs.  
Length of Study
The duration of the OLE study in each participating country will depend upon the health 
authority approval of lampalizumab in that country as well as the Sponsor’s discretion.  After 
completion of the phase III OLE study, patients will have access to post trial lampalizumab.
Investigational Medicinal Products
Test Product (Investigational Drug)
A 10 mg dose of lampalizumab will be used in the extension study and will be administered by 
injection to all enrolled patients either Q4W or Q6W during the treatment period.
The lampalizumab injections should not be repeated earlier than 22 days from previous dosing; 
missed doses of study drug will not be made up.
Statistical Methods
Safety Analyses
The safety analyses will include patients enrolled in this study who receive at least 1 dose of 
study drug in all patients and according to treatment received in the parent study. 
Verbatim descriptions of treatment-emergent adverse events will be coded, and their incidence 
will be summarized, as appropriate.  Separate summaries will be generated for serious adverse 
events, deaths, adverse events leading to discontinuation of study drug, and adverse events 
judged to be related to lampalizumab.  In addition, separate summaries will be prepared for 
systemic (non-ocular) and ocular adverse events.  Descriptive summaries will be generated for 
VA and IOP.  All patients will receive lampalizumab treatment in this study; therefore, caution 
must be taken when interpreting safety results as there is no inactive/sham treatment group for 
comparison.
Determination of Sample Size  
This study is open to all patients who complete study treatment and the Week 96 visit in parent 
Studies GX29176 and GX29185 and who meet the eligibility criteria.
Optional Interim Analysis
No formal interim efficacy analysis is planned since all patients on this study will receive active 
lampalizumab treatment.  Exploratory efficacy and/or safety analyses may be performed with 
interim data (e.g., to support regulatory submissions).


Lampalizumab—F. Hoffmann-La Roche Ltd
24/Protocol GX30191, Version 2
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
Abbreviation
Definition
ACP
alternative complement pathway
ALT
alanine aminotransferase
AMD
age-related macular degeneration
anti-VEGF
anti-vascular endothelial growth factor
AST
aspartate aminotransferase
ATA
anti-therapeutic antibody
BCVA
best corrected visual acuity
C3
complement component 3
CFB
complement factor B
CFD
complement factor D
CFH
complement factor H
CFI
complement factor I
CFP
color fundus photograph
CNV
choroidal neovascularization
EC
Ethics Committee
eCRF
electronic Case Report Form
EDC
electronic data capture
ELISA
enzyme-linked immunosorbent assay
ET
early termination
ETDRS
Early Treatment Diabetic Retinopathy Study
FA
fluorescein angiography
FAF
fundus autofluorescence
FDA
Food and Drug Administration
FRI
Functional Reading Independence
GA
geographic atrophy
GCP
Good Clinical Practice
HIPAA
Health Insurance Portability and Accountability Act
ICF
Informed Consent Form
ICH
International Conference on Harmonisation
iDMC
independent Data Monitoring Committee
IMP
investigational medicinal product
IND
Investigational New Drug
IOP
intraocular pressure
IRB
Institutional Review Board


Lampalizumab—F. Hoffmann-La Roche Ltd
25/Protocol GX30191, Version 2
Abbreviation
Definition
IxRS
interactive response system
logMAR
logarithm of the minimum angle of resolution
LPLV
last patient, last visit 
LL BCVA
low-luminance best corrected visual acuity
MNRead
Minnesota Low-Vision Reading Test
NEI VFQ-25
National Eye Institute Visual Functioning Questionnaire 25-item Version
NI
near-infrared
OLE
open-label extension
PD
pharmacodynamic
PK
pharmacokinetic(s)
PRO
patient-reported outcome
Q4W
every 4 weeks
Q6W
every 6 weeks
RCR
Roche Clinical Repository
RPE
retinal pigment epithelium
SD-OCT
spectral domainoptical coherence tomography
ULN
upper limit of normal
UTI
urinary tract infection
VA
visual acuity
VEGF
vascular endothelial growth factor


Lampalizumab—F. Hoffmann-La Roche Ltd
26/Protocol GX30191, Version 2
1.
BACKGROUND
1.1
BACKGROUND ON GEOGRAPHIC ATROPHY SECONDARY TO 
AGE-RELATED MACULAR DEGENERATION
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in 
people aged 50 years or older in the developed world (Friedman et al. 2004).  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), which is characterized by loss of 
choriocapillaris, retinal pigment epithelium (RPE), and photoreceptors; and an exudative 
or wet form, which is characterized by choroidal neovascularization (CNV) 
(Sunness et al. 1999b; Lindblad et al. 2009).  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 (Rudnicka et al. 2012).
In the early stages of GA, patients typically show minimal changes in central visual 
acuity (VA).  However, while central VA may not yet be affected, patients often still 
experience significant symptoms from visual dysfunction, such as dense parafoveal 
scotomas (e.g., leading to difficulties with face recognition), delayed dark adaptation, 
reduced contrast sensitivity, and a decrease in reading rate (Sunness et al. 1995, 
1996, 1999a).  In the later stages, as the GA lesion expands into the fovea, a profound 
decrease in central VA occurs leading to a decline in activities of daily living 
(Lindblad and Clemons 2005).  Moreover, GA is bilateral in most patients with advanced 
AMD (Sunness et al. 1999b; Lindblad et al. 2009).  As such, GA is a significant cause of 
both moderate and severe central visual loss.
Currently, there are no approved treatments to prevent the worsening of GA or the 
associated declines in visual function.  Consequently, a significant unmet need exists for 
the treatment of this serious condition. 
1.2
BACKGROUND ON LAMPALIZUMAB
The pathogenesis of AMD is complex and not well understood; however, genetics and 
environmental factors (such as smoking) as well as the alternative complement pathway 
(ACP) have all been implicated in AMD pathophysiology (de Jong 2006).  Increased 
activation of the ACP has been found in drusen, which are lipoproteinous depositions in 
the space between the RPE and Bruch’s membrane and a hallmark clinical observation 
associated with AMD.  Moreover, a role for ACP in AMD has been supported by human 
genetics (Yates et al. 2007; Scholl et al. 2008).  The largest study evaluating AMD 
genetics to date is a meta-analysis of 17,000 AMD cases and more than 60,000 controls 
that identified multiple genetic-risk loci, including four genes (complement factor H 
[CFH], complement factor B [CFB], complement factor I [CFI], and complement 
component 3 [C3]) in the ACP as confirmed genetic risk factors (Fritsche et al. 2013).


Lampalizumab—F. Hoffmann-La Roche Ltd
27/Protocol GX30191, Version 2
Complement factor D (CFD) is a highly specific chymotrypsin-like serine protease that 
plays a pivotal and rate-limiting role in the activation and amplification of the ACP.  The 
substrate for CFD, serine protease, factor B, is another alternative pathway.  Following 
cleavage by CFD, CFB converts into the proteolytically active factor Bb and initiates the 
ACP.
Lampalizumab is an antigen-binding fragment of a humanized monoclonal antibody 
directed against CFD.  Lampalizumab inhibits CFD-mediated cleavage of CFB, 
preventing activation of the ACP.  Lampalizumab is specific for the ACP and shows no 
inhibitory effect on classical complement pathway activation.  
By inhibiting ACP activity, lampalizumab may offer the potential to impede or arrest the 
progression of GA and vision loss.  Evidence for CFD in the pathogenesis of AMD 
include protection against oxidative-stressmediated photoreceptor degeneration in a 
murine model with genetic deficiency of factor D (Rohrer et al. 2007) and detection of 
increased systemic activation of complement components, including CFD, in the serum 
of patients with AMD compared with controls, suggesting that AMD may be a systemic 
disease with local manifestations in the aging macula (Scholl et al. 2008).
See the Lampalizumab Investigator’s Brochure for additional details on nonclinical and 
clinical studies.
1.3
ONGOING CLINICAL STUDIES
The safety and efficacy profile of lampalizumab as well as the natural history of GA have 
been and are continuing to be investigated in multiple trials.  A brief description of these 
ongoing studies is provided below.  
For more details about the safety and efficacy of lampalizumab in all clinical trials to date, 
please refer to the Lampalizumab Investigator’s Brochure.
1.3.1
Phase III Studies GX29176 and GX29185 (Chroma and Spectri)
Studies GX29176 and GX29185 are Phase III, multicenter, randomized, double-masked, 
sham-controlled studies evaluating the efficacy and safety of lampalizumab administered 
by intravitreal injections to patients with GA.  The studies are 96 weeks in duration and 
are ongoing.  Provided they meet the eligibility criteria, patients from either study who 
complete both study treatment and the study will be allowed to enroll in this open-label 
extension (OLE) study (GX30191). 
1.3.2
Phase II Open-Label Extension Study GX28198 (MAHALO OLE)
Study GX28198 is a multicenter, OLE study of the safety and tolerability of 
lampalizumab administered by intravitreal injection to patients with GA who have 
completed Study CFD4870g (a Phase Ib/II, randomized, single-masked, 
sham injectioncontrolled study of safety, tolerability, and evidence of activity of 
lampalizumab intravitreal injections in patients with GA) or Study GX29455 (a Phase II, 


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randomized, single-masked, sham injection-controlled exposure-response study of 
intravitreal lampalizumab).  Study GX28198 is ongoing.
1.3.3
Phase II Study GX29455
Study GX29455 is a completed, multicenter, randomized, single-masked, sham 
injection-controlled, Phase II study investigating the exposure response and safety of 
lampalizumab administered intravitreally every 2 weeks or every 4 weeks (Q4W) for 
24 weeks in patients with GA secondary to AMD. The results of this study are pending.
1.3.4
Prospective Epidemiological Studies GX29633 and GX29639 
(Proxima A and Proxima B)
Studies GX29633 and GX29639 are ongoing multicenter, prospective, epidemiologic 
studies of the progression of GA secondary to AMD. Study GX29633 includes patients 
with bilateral GA secondary to AMD. Study GX29639 includes patients with unilateral 
GA secondary to AMD or patients with GA secondary to AMD in one eye and CNV 
(active or treated) secondary to AMD in the contralateral eye.  No study drug is 
administered in these studies.
1.4
STUDY RATIONALE AND BENEFITRISK ASSESSMENT
Results from the Phase II Study CFD4870g provide evidence that inhibition of the ACP
by lampalizumab may slow the progression of GA and that lampalizumab administered 
as 10-mg intravitreal injections monthly over 18 months demonstrates an acceptable 
safety and tolerability profile in patients with GA secondary to AMD (see Lampalizumab 
Investigator’s Brochure for further details on Study CFD4870g).  In addition, exploratory 
genetic analyses suggest that there may be a biomarker-defined population (CFI profile 
biomarker positive) that may have a more rapid progression of disease and potentially 
derive a greater efficacy benefit from lampalizumab than a group that is negative for the 
biomarker (CFI profile biomarker negative).
The OLE study, Study GX30191, will evaluate the long-term safety and tolerability of 
10 mg lampalizumab administered by intravitreal injection Q4W or every 6 weeks 
(Q6W) 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).  Study 
GX30191 will permit the evaluation of long-term safety and tolerability of lampalizumab 
in participants continuing from the active treatment arms.  In addition, this study will 
provide the opportunity for eligible patients from the sham treatment arms to 
receive lampalizumab.  
Specific objectives and corresponding endpoints for the study are outlined below.


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2.
OBJECTIVES AND ENDPOINTS 
2.1
PRIMARY OBJECTIVE
The primary objective of this study is to evaluate the long-term safety and tolerability of 
intravitreal injections of 10 mg lampalizumab administered to patients with GA 
secondary to AMD as assessed by the following:

Incidence and severity of ocular adverse events

Incidence and severity of systemic (non-ocular) adverse events
2.2
EXPLORATORY OBJECTIVES
The exploratory objective of this study is to investigate the long-term efficacy of 
intravitreal injections of 10 mg lampalizumab as assessed by:

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
At the discretion of the Sponsor, additional assessments may be included in this OLE 
study (Study GX30191), in which case a supplemental assessment protocol will be 
provided.


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2.3
PHARMACOKINETIC OBJECTIVES
The pharmacokinetic (PK) objective for this study is to observe the systemic trough 
concentrations of 10 mg lampalizumab administered by intravitreal injections through 
the analysis of the serum lampalizumab concentrations.
The exploratory PK objectives for this study are to observe the aqueous humor 
concentrations of lampalizumab and to explore possible relationships between 
lampalizumab PK, biomarkers, and clinically related endpoints.
2.4
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.
2.5
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.  
3.
STUDY DESIGN
3.1
DESCRIPTION OF THE STUDY
3.1.1
Overview of Study Design
Study GX30191 is a multicenter, open-label extension (OLE) study designed to evaluate 
the safety and tolerability of a 10-mg dose of lampalizumab administered by intravitreal
injection to patients with GA secondary to AMD who have completed Study GX29176 or 
GX29185 (henceforth referred to as the 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-naive 
(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, 
unless unmasking is permitted by the Sponsor.  In addition, the VA examiner role will 
remain masked to the patients' study eye assignment.


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Eligible patients who consent to participate in this extension study will be enrolled upon 
completion of the parent study (i.e., at the Week 96 visit) and study treatment.  The 
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 (see Sections 4.1.1 and 4.1.2); eligible 
patients will be enrolled using an interactive response system (IxRS). 
If a site is not able to collect images during the Week 96 visit of the parent study, then 
the Day 1 visit study treatment will be interrupted, and the images will be collected as 
soon as possible and prior to the study treatment administration at the next study 
treatment visit (e.g., Week 4 or Week 6).  The reason for the study treatment 
interruption at the Day 1 visit will be recorded on the study treatment interruption 
electronic case report form (eCRF).
All patients from the parent studies who enroll in the OLE study will receive 10-mg 
intravitreal 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.  That is, if a patient was originally randomized to the Q4W 
arm in the parent study, the patient will remain on a Q4W schedule in the extension 
study.  Similarly, if a patient was originally randomized to the Q6W arm in the parent 
study, the patient will remain on a Q6W schedule.  
All patients enrolled in the extension study will have the first intravitreal injection of 
lampalizumab administered by the investigator at the Day 1 visit, unless dose 
interruption is medically or otherwise justified (see Section 5.1.2 and Table 1) by the 
investigator.  The lampalizumab injections should not be repeated earlier than 22 days 
from previous dosing. Missed doses of study drug will not be made up unless the 
missed dose is due to an unexpected issue, such as those listed in the following
paragraph.  Patients’ self-administered anti-microbials pre- and post-injection may be 
used at the investigator’s discretion.
All subsequent study treatment visits will be scheduled Q4W or Q6W (5 days), relative 
to Day 1 visit date, at which patients will have safety evaluations performed prior to 
receiving the study drug injection (see Appendix 1).  Patients will be contacted by site 
personnel 4 (2) days after each injection to elicit reports of decrease in vision, eye 
pain, unusual redness, or any other new ocular symptoms in the study eye.  If 
warranted, patients will be asked to return to the clinic as soon as possible for an 
unscheduled safety assessment visit (see Appendix 2).  Patients will be instructed to 
contact the investigator at any time if they have any health-related concerns.  If, during a
scheduled visit, a site encounters an unexpected issue (e.g., the IxRS is not able to 
assign the study kit or there are any issues with a patient’s care), the patient’s study 
treatment may be administered within 3 working days of that visit.  The following 


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assessments will be repeated on the day of the study treatment:  slit lamp examination, 
indirect ophthalmoscopy, and pre-treatment intraocular pressure (IOP) measurements 
(recorded on the scheduled visit eCRF and dated with the actual administration date).
After the Day 1 visit, if a patient misses a study visit when ocular images are to be
obtained (see Appendix 1), the images must be obtained at the next scheduled study 
visit, if a patient attends it.
Patients are not expected to attend their scheduled visits if there are extenuating 
circumstances justifying their inability to come to the clinic.
Patients who discontinue from the study will be asked to return for an early termination 
visit after a minimum of 30 days has elapsed following their last study treatment for 
monitoring of adverse events and the early termination visit assessments (see 
Appendix 1).
A subset of the patients at selected sites may participate in a mesopic microperimetry 
assessment in order to evaluate macular functional response.  
3.1.2
Planned Total Sample Size
Up to 1800 patients may be enrolled in the study at up to 300 sites located globally.
3.1.3
Data Monitoring Committee
An independent Data Monitoring Committee (iDMC), which is monitoring the parent 
studies, will monitor safety and study conduct of this extension study on an ongoing 
basis as well.  Members of the iDMC will be external to the Sponsor and will follow a 
charter that outlines the iDMC roles and responsibilities.  The iDMC will meet 
approximately every 6 months (frequency adjustable as required) to evaluate the 
benefit-risk profile of lampalizumab treatment through reviewing both safety and 
efficacy data.  No formal interim efficacy/futility analysis is planned to be conducted by 
iDMC.  The iDMC may recommend stopping the study early for safety reasons.  
Further details can be found in the iDMC charter.
3.2
END OF STUDY AND LENGTH OF STUDY 
The end of the study is defined as the date when the last patient, last visit (LPLV) occurs.  
The duration of the OLE study in each participating country will depend upon the health 
authority approval of lampalizumab in that country as well as the Sponsor’s discretion.  
After completion of the Phase III OLE study, patients will have access to post-trial 
lampalizumab as outlined in the guidance in Section 4.3.4.


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3.3
RATIONALE FOR STUDY DESIGN
3.3.1
Rationale for Lampalizumab Dose and Schedule
The 10 mg lampalizumab monthly dosage was the dosing regimen that was found to be 
the most efficacious and was also well tolerated in the Phase II component of Study 
CFD4870g (see the Lampalizumab Investigator’s Brochure).
In the ongoing Phase III studies GX29176 and GX29185, both the 10 mg Q4W and 
10 mg Q6W dosing regimens are being evaluated. 
This OLE study, Study GX30191, will evaluate the long-term safety and tolerability of 
10 mg lampalizumab in patients who have completed study treatment and the Week 96 
visit in one of the parent studies (i.e., Studies GX29176 and GX29185).  Patients will 
continue on the same dosing regimen as they were assigned in the parent study.
3.3.2
Rationale for Biomarker Assessments
A biomarker plasma sample will be collected at the Day 1 visit of the study.  This sample 
will allow comparison of plasma biomarkers of the complement-pathway between the 
baseline sample collected in the parent study and a sample collected 2 years later (at 
entry into Study GX30191).  Evaluation of the longitudinal stability of plasma biomarkers 
will aid the understanding of relationships between these biomarkers and other 
biomarkers and endpoints in the study.
4.
MATERIALS AND METHODS
4.1
PATIENTS
All patients who have completed study treatment and the Week 96 visit of either parent 
study (Study GX29176 or GX29185) will be eligible to participate in this extension study.  
Patients who discontinued from study treatment early in the parent study, but remained 
in the study for safety evaluations, will not be eligible for this extension study. 
Written informed consent will be obtained prior to enrollment and the initiation of any 
study procedures for the extension study.  Day 1 of the extension study will occur on the 
same day as the Week 96 completion visit of the parent study, provided that the 
following inclusion and exclusion criteria are met.  If a patient misses the final Week 96 
visit in the parent study, participation in the extension study will be at the discretion of 
the Sponsor (and subject eligibility criteria).
Note:  Refer to Section 5.1.2 and Table 1 for the dose interruption and treatment 
discontinuation criteria.  The criteria need to be reviewed on Day 1 of the extension 
study to ascertain whether injection on Day 1 can proceed or needs to be interrupted.
If a site is not able to collect images during the Week 96 visit of the parent study, then 
the Day 1 visit study treatment will be interrupted, and the images will be collected as 
soon as possible and prior to the study treatment administration at the next study 


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treatment visit (e.g., Week 4 or Week 6).  The reason for the study treatment 
interruption at the Day 1 visit will be recorded on the study treatment interruption 
eCRF.
4.1.1
Inclusion Criteria
Patients must meet the following criteria for study entry:

Willingness and ability to provide signed informed consent
Additionally, at U.S. sites, patients must provide Health Insurance Portability 
and Accountability Act (HIPAA) authorization, and in other countries, as 
applicable according to national laws.

Willingness and ability to undertake all scheduled visits and assessments

Previous enrollment in and completion of study treatment and the Week 96 visit of 
either Study GX29185 or Study GX29176, without early treatment discontinuation 
(lampalizumab or sham) 

For women of childbearing potential:  agreement to remain abstinent (refrain from 
heterosexual intercourse) or use contraceptive methods with a failure rate of 1% 
per year during the treatment period and for at least 30 days after the last dose of 
lampalizumab.
A woman is considered to be of childbearing potential if she is postmenarcheal, 
has not reached a postmenopausal state (12 continuous months of 
amenorrhea with no identified cause other than menopause), and has not 
undergone surgical sterilization (removal of ovaries and/or uterus).
Examples of contraceptive methods with a failure rate of 1% per year include 
bilateral tubal ligation, male sterilization, established proper use of hormonal
contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, 
and copper intrauterine devices.
The reliability of sexual abstinence should be evaluated in relation to the 
duration of the clinical trial and the preferred and usual lifestyle of the patient.  
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation 
methods) and withdrawal are not acceptable methods of contraception.

For men:  agreement to remain abstinent (refrain from heterosexual intercourse) or 
use contraceptive measures and agreement to refrain from donating sperm, as 
defined below:
With female partners of childbearing potential, men must remain abstinent or 
use a condom plus an additional contraceptive method that together result in a 
failure rate of 1% per year during the treatment period and for at least 
120 days after the last dose of study drug. Men must refrain from donating 
sperm during this same time period.
With pregnant female partners, men must remain abstinent or use a condom 
during the treatment period and for at least 120 days after the last dose 
of study drug to avoid exposing the embryo.


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The reliability of sexual abstinence should be evaluated in relation to the 
duration of the clinical trial and the preferred and usual lifestyle of the patient.  
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation 
methods) and withdrawal are not acceptable methods of contraception.

For patients participating in microperimetry (at selected sites only):  must have 
participated in the microperimetry testing during the parent study
4.1.2
Exclusion Criteria
Patients who meet any of the following criteria will be excluded from study entry:

Concurrent ocular conditions exclusion criterion
History of other ocular diseases that give reasonable suspicion of a disease or 
condition that contraindicates the use of lampalizumab or that might affect 
interpretation of the results of the study or that renders the patient at high risk 
of treatment complications

Concurrent systemic conditions exclusion criteria
History of other diseases, metabolic dysfunction, physical examination finding, 
or clinical laboratory finding that gives reasonable suspicion of a disease or 
condition that contraindicates the use of lampalizumab or that might affect 
interpretation of the results of the study or that renders the patient at high risk 
of treatment complications
Predisposition to or history of increased risk of infection (e.g., history of 
splenectomy or chronic immunosuppression)
Requirement for continuous use of any medications or treatments indicated in 
the “Excluded Therapy” section of the protocol (see Section 4.4.2)
Pregnancy or lactation, or intention to become pregnant during the study
Women of childbearing potential must have a negative urine pregnancy 
test result at the Day 1 visit prior to initiation of study drug.
4.2
METHOD OF TREATMENT ASSIGNMENT 
This is an open-label study.  All patients enrolled in the extension study will receive 
10 mg intravitreal injections of lampalizumab Q4W or Q6W.  
A patient must satisfy all eligibility criteria (see Sections 4.1.1 and 4.1.2) at the Day 1 
visit (first study treatment) and sign informed consent for enrollment.  All patients 
enrolled will receive lampalizumab treatment at the same dosing frequency as their 
originally assigned dosing frequency in the parent study.
4.3
STUDY TREATMENT 
The investigational medicinal product (IMP) for this study is lampalizumab.


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4.3.1
Lampalizumab Formulation, Packaging, Storage, and Handling
Please see the Lampalizumab Investigator’s Brochure for the lampalizumab clinical 
formulation.  See the Pharmacy Manual for additional specifics regarding the 
lampalizumab formulation, product packaging, storage, and handling.
4.3.2
Lampalizumab Dosage, Administration, and Compliance
4.3.2.1
Dosage
A 10-mg dose of lampalizumab will be used in the extension study and will be 
administered by intravitreal injection to all enrolled patients either Q4W or Q6W during 
the treatment period (see Appendix 1 for the study flowchart).
The lampalizumab injections should not be repeated earlier than 22 days from previous 
dosing. Missed doses of study drug will not be made up unless the missed dose is due 
to an unexpected issue, such as those listed in Section 3.1.1.
4.3.2.2
Administration
The detailed instructions for lampalizumab reconstitution for the pre-injection procedure, 
intravitreal administration, and post-injection procedure for the study eye are provided 
in the Pharmacy Manual. 
Guidelines for treatment interruption or discontinuation are provided in Section 5.1 and 
Table 1.
Any overdose or incorrect administration of study drug should be noted on the 
Study Drug Administration eCRF.  Adverse events associated with an overdose or 
incorrect administration of study drug should be recorded on the Adverse Event eCRF. 
4.3.2.3
Compliance
This study will be conducted in accordance with the U.S. Food and Drug Administration 
(FDA) regulations; the International Conference on Harmonisation (ICH) E6 Guideline for 
Good Clinical Practice (GCP); and applicable local, state, and federal laws, as well as 
other applicable country laws.
4.3.3
Investigational Medicinal Product Accountability
All IMPs required for completion of this study (lampalizumab) will be provided by the 
Sponsor.  The study site will acknowledge receipt of IMPs, using the IxRS to confirm the 
shipment condition and content.  Any damaged shipments will be replaced.
IMPs will either be disposed of at the study site according to the study site’s institutional 
standard operating procedure or will be returned to the Sponsor with the appropriate
documentation.  The site’s method of IMP destruction must be agreed to by the Sponsor.  
The site must obtain written authorization from the Sponsor before any IMP is destroyed, 
and IMP destruction must be documented on the appropriate form.


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Accurate records of all IMPs received at, dispensed from, returned to, and disposed of 
by the study site should be recorded on the Drug Inventory Log.
4.3.4
Post-Trial Access to Lampalizumab
The Sponsor will offer post-trial access to the study drug (lampalizumab) free of charge 
to eligible patients in accordance with the Roche Global Policy on Continued Access to 
Investigational Medicinal Product, as outlined below.
A patient will be eligible to receive study drug after completing the study if all of the 
following conditions are met:

The patient has a sight-threatening or severe medical condition and requires 
continued study drug treatment for his or her well-being.

There are no appropriate alternative treatments available to the patient.

The patient and his or her doctor comply with and satisfy any legal or regulatory 
requirements that apply to them.
A patient will not be eligible to receive study drug after completing the study if any of the 
following conditions are met:

The study drug is commercially marketed in the patient's country and is reasonably 
accessible to the patient (e.g., is covered by the patient's insurance or would not 
otherwise create a financial hardship for the patient).

The Sponsor has discontinued development of the study drug or data suggest that 
the study drug is not effective for GA.

The Sponsor has reasonable safety concerns regarding the study drug as treatment 
for GA.

Provision of study drug is not permitted under the laws and regulations of the 
patient's country.
The Roche Global Policy on Continued Access to Investigational Medicinal Product is 
available at the following Web site:
http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf
4.4
CONCOMITANT THERAPY
Patients who use other maintenance therapies should continue their use.  Patients 
required to use medications that are prohibited will not be eligible for enrollment or 
continuation in the study (see Section 4.4.2).
Concomitant therapy includes any prescription drugs or over-the-counter preparations 
other than protocol-specified procedural medications (e.g., dilating drops) and pre- and 
post-study treatment medications (e.g., proparacaine or anti-microbials [if applicable]) 
used by a patient from the time of study enrollment at the Day 1 visit through the 
conclusion of the patient’s study participation or early termination visit.  All concomitant 


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medications should be reported to the investigator and recorded on the Concomitant 
Medications eCRF log except for Lucentis® for treatment of either eye (if applicable), 
which will have a separate eCRF log.  
4.4.1
Permitted Therapy 
Patients required to use medications that are prohibited (see Section 4.4.2) will not be 
eligible for the study or continuation of the study.  Of note, the following are examples of 
some common therapies that are permitted:

Onset of ocular hypertension or glaucoma in either eye during a patient’s study 
participation should be treated as clinically indicated.

Onset of cataract or posterior capsular opacification in either eye during the patient’s 
study participation may be treated as clinically indicated.  Dose interruption criteria 
(see Section 5.1.2 and Table 1) may apply with cataract surgery.

Short-term use of topical corticosteroids may be administered (e.g., after cataract 
surgery, yttrium aluminum garnet capsulotomy, or peripheral iridotomy).

At the discretion of the investigator, patients may be treated with Lucentis if they are 
diagnosed with an ocular condition in either eye for which Lucentis is approved in 
the patient’s country.  Consult the region-specific Lucentis prescribing information 
for dosing, frequency, and administration guidance. 
Note:  If, in the opinion of the investigator, treatment with Lucentis should be 
given (in either eye) at the same visit during which study treatment will be 
administered, treatment with Lucentis must be administered first.  Following this, 
the safety assessments (including IOP check) must be performed prior to 
calling IxRS for the study treatment kit assignment and prior to lampalizumab 
injections.  Individual trays and separate sterile preparation must be prepared 
and separately performed for each treatment.   

Oral corticosteroids at doses 10 mg/day of prednisone or equivalent may be 
administered.  The dose-holding criteria apply to doses 10 mg/day (see 
Section 5.1.2 and Table 1). 

Prophylactic use of systemic antibiotics (e.g., for prevention of urinary tract 
infection [UTI]) should be discussed with Medical Monitor.
4.4.2
Excluded Therapy
At the discretion of the investigator, patients may continue to receive medications and 
standard treatments administered for other conditions.  However, the following 
medications and treatments are prohibited from use during a patient’s study treatment, 
and patients discontinue the study drug and the study to receive these therapies:

Investigational therapy other than study drug

Systemic anti-vascular endothelial growth factor (anti-VEGF) agents

Intravitreal anti-VEGF agents (other than Lucentis) in either eye

Intravitreal, subtenon, or chronic topical (ocular) corticosteroids in study eye 


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
Systemic or intravenous immunomodulatory therapy (e.g., azathioprine, 
methotrexate, mycophenolate mofetil, cyclosporine, cyclophosphamide, antitumor 
necrosis factors, eculizumab)

Treatment with Visudyne® in study eye

Other experimental therapies (except those with vitamins and minerals)
4.5
STUDY ASSESSMENTS 
Please see Appendix 1 for the schedule of assessments performed during the study.
4.5.1
Informed Consent Forms
Written informed consent for participation in the study must be obtained before 
performing any study-related procedures.  Informed Consent Forms (ICFs) for enrolled 
patients will be maintained at the study site.
At the sites where investigator intends to ask his/her patients to self-administer 
antimicrobials pre- and post-injection, the ICF needs to be signed at an earlier date (e.g., 
Week 90 or 92 visit in parent study) in order to allow the ICF to be in place prior to the 
patient receiving pre-injection antimicrobials.  In addition, during the Week 96 visit, if the 
ICF is signed prior to completion of the Week 96 assessments of the parent study, then 
the Week 96 parent study blood draws and the Day 1 OLE blood draw can be performed 
at the same time.
All parent-study Week 96 evaluations must be completed and reviewed to confirm that 
patients meet all eligibility criteria prior to enrollment at the Day 1 visit in this extension 
study.  The investigator will maintain a log to record details of all patients who sign the 
ICF to confirm patient’s eligibility or ineligibility to be enrolled in the study as applicable. 
4.5.2
Medical History and Demographic Data
Medical history and demographic data were collected during the parent studies and will 
not need to be obtained again during the OLE study.
4.5.3
Vital Signs
Vital signs will be collected at the early termination visits and will include measurements 
of temperature, respiratory rate, pulse rate, and systolic and diastolic blood pressure 
while the patient is in a seated position after resting for 5 minutes.
4.5.4
Other Disease-Specific Assessments 
4.5.4.1
Ocular Assessments
Ocular assessments include the following:

BCVA on ETDRS chart at a starting distance of 4 m (perform prior to dilating eyes; 
see Appendix 4)

BCVA assessed by ETDRS chart at a starting distance of 4 m (perform prior to 
dilating eyes; see Appendix 5) under low luminance conditions


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
MNRead charts (see Appendix 14 for details on specific countries where test will be 
administered) or Radner Reading Charts (see Appendix 15 for details on specific 
countries where test will be administered; perform prior to dilating eyes).  The test 
will be administered first monocularly (right/left eye) and then binocularly (both eyes).

Pre-injection IOP measurement for both eyes (perform prior to dilating eyes; the 
method used for this assessment must remain consistent throughout the study)

Slit-lamp examination (for the definition of ocular inflammation, see Section 5.3.5; 
for inflammation grading scales, see Appendix 3)

Dilated binocular indirect ophthalmoscopy

Finger-counting, hand-motion, or light-perception tests performed by the investigator 
within 15 minutes post-injection for the study eye only.  A finger-counting test will be 
conducted for each patient by the physician within 15 minutes following study 
treatment; hand-motion and light-perception tests will be performed when necessary.  

Following the study treatment, IOP will be measured between 30 and 50 minutes 
after study treatment by qualified site staff (except for the VA examiner) for the study 
eye only; if the IOP is increased by 10 mmHg from the pre-injection IOP value, 
IOP will be measured again at 6080 minutes post-injection.  If there are no safety 
concerns, the patient will be permitted to leave the clinic.  If the IOP value is of 
concern to the investigator, the patient will remain in the clinic and will be managed 
in accordance with the investigator’s clinical judgment.  Both the last post-injection 
IOP measured prior to any intervention for increased IOP (if applicable) and the last 
post-intervention IOP value (if applicable) will be recorded on the appropriate eCRF.  
If applicable, an Adverse Event eCRF should also be completed (see Section 5.2.1). 
Note:  If the study eye is treated with a Lucentis injection during the same visit 
that study treatment is administered, the treatment with Lucentis must be 
performed first.  The post-Lucentis treatment IOP is to be measured and 
recorded on the eCRF, irrespective of the subsequent study treatment 
administration.
4.5.4.2
Ocular Imaging and Microperimetry
The central reading center will provide sites with the central reading center’s manual and 
training materials for specified study ocular images and microperimetry (at selected 
sites).  Before any study images and microperimetry are obtained, site personnel, test 
images, systems, and software (where applicable) will be certified/validated by the 
reading center as specified in the central reading center manual.  
“Grandfathering” certifications for personnel and equipment from the parent studies will 
be allowed according to central reading center’s guidelines.  
All ocular images and microperimetry results will be obtained by trained site personnel at 
the study sites and forwarded to the central reading center for independent analysis 
and/or storage (see Appendix 6, Appendix 7, Appendix 8, Appendix 9, Appendix 10, and 
Appendix 11).


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An independent review of digital color fundus photographs (CFPs); FAF, near-infrared 
(NI), and SD-OCT images (including exploratory anatomic biomarker studies); and 
fluorescein angiography (FA) will be performed at a central reading center to provide an 
objective analysis of these assessments.  The central reading center evaluation will be 
performed by graders and retinal specialists experienced in the conduct of AMD clinical 
trials.  For further details, please refer to the central reading center’s manual. 
Ocular images obtained include the following:

Stereoscopic, digital CFPs of both eyes (see Appendix 6) 

FAs of both eyes (performed after laboratory samples are obtained; see Appendix 7)

FAF, SD-OCT, and NI images of both eyes (see Appendix 8, Appendix 9, and 
Appendix 10, respectively)
Note:  After enrollment, if a patient misses a study visit during which ocular 
images are scheduled to be taken, the images should be obtained at the next 
scheduled visit, if a patient attends it.
Additional details on obtaining these images are included in the Central Reading 
Center manual.
4.5.5
Laboratory and Other Biological Samples
At the scheduled visit, specimens should be collected prior to study eye treatment and 
FA assessments (if applicable).  Fasting is not required prior to specimen collection.  
Specimens will be forwarded to the central laboratory, where they will be analyzed or 
forwarded to the Sponsor or its designee for analysis and/or storage.  
The following assessments will be performed:

Urine pregnancy test (performed at the site) prior to each study treatment for women 
of childbearing potential, including those who have had tubal ligation  
If positive, collect blood sample for the serum pregnancy test and forward to 
central lab for analysis.  If the serum pregnancy test is positive, discontinue the 
patient from study treatment. 

Measurement of anti-lampalizumab antibodies in serum samples

Measurement of lampalizumab concentration in serum samples

Measurement of lampalizumab and CFD levels in optional anterior chamber 
(aqueous humor) paracentesis samples in order to assess PK and 
pharmacodynamic (PD) relationships

Assessment of measures of the complement pathway in plasma samples
The following assessments will be performed only at the early termination visit:

Urinalysis:  specific gravity, pH, blood, protein, ketones, glucose, bilirubin, 
urobilinogen, and microscopic examination (if any of the preceding urinalysis tests, 
other than glucose and ketones, are abnormal)


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
Hematology:  hemoglobin, hematocrit, quantitative platelet count, red blood cell 
counts, white blood cell counts, and differentials, including neutrophils, bands, 
lymphocytes, basophils, eosinophils, and monocytes (absolute)

Chemistry panel (serum or plasma):  sodium, potassium, chloride, bicarbonate, 
glucose, blood urea nitrogen, creatinine, calcium, phosphorus, total and direct 
bilirubin, total protein, albumin, aspartate aminotransferase (AST), alanine 
aminotransferase (ALT), lactate dehydrogenase, alkaline phosphatase, and uric 
acid

Coagulation:  activated partial thromboplastin time and prothrombin time
The samples (except those for hematology, serum chemistry, urinalysis, coagulation, 
and serum and urine pregnancy tests that will be destroyed after their analysis during 
the study) will be stored for up to 5 years after the date of final closure of the associated 
clinical database.
In addition, remainders of serum PK, serum ATAs, biomarker plasma, and aqueous 
humor samples will be stored for up to 15 years after the date of the final closure of the 
associated clinical database if the patient gave specific Roche Clinical Repository (RCR) 
consent for them to be stored for optional research (see Appendix 16).
Drug concentration will be determined in serum using an enzyme-linked immunosorbent 
assay (ELISA) method.  ATAs will be detected in serum using a bridging ELISA.
4.5.6
Patient-Reported Outcomes
PROs (i.e., the NEI VFQ-25 and the FRI Index) will be collected via 
interviewer-administered questionnaires to help characterize the clinical profile of 
lampalizumab from the patient’s perspective. 
The questionnaires will be translated as required to different languages.  The 
questionnaires will be administered by the site staff (except for the VA examiner) prior to 
any other study visit assessments being performed on that day. 
The National Eye Institute Visual Functioning Questionnaire 25-Item 
Version
The NEI VFQ-25 is a 25-item, interviewer-administered assessment of visual functioning 
(see Appendix 12).  The appendix items for the near and distance domains will also be 
included (an additional three items for each domain).  It is scored on a scale of 0100, 
with higher scores indicating better visual function.  It has a composite score and 
12 domains: general health, general vision, ocular pain, near activities, distance 
activities, social functioning, mental health, role difficulties, dependency, driving, color 
vision, and peripheral vision.  It does not have a specified recall period.


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The Functional Reading Independence Index
The FRI Index is an interviewer-administered assessment of functional reading 
independence containing seven items on performance of activities of daily living that 
require reading and follow-up items on compensating mechanisms, adjustments, and 
assistance required for each activity (see Appendix 13).  The mean FRI Index score is a 
continuous score ranging from 1 to 4, with a higher score representing higher functional 
reading independence.  A categorical FRI level score may also be computed, with 
scores of 1unable to do, 2help some or most of the time, 3moderately independent, 
and 4totally independent.  The FRI Index has a specified recall period of 7 days.
4.5.7
Reading Speed Assessments
Reading function will be assessed using one of two validated and widely used tests prior 
to eye dilation:  the MNREAD or the Radner Reading Charts.  Test selection is based on 
language availability (see Appendix 14 and Appendix 15, respectively, for details on 
specific countries where each test will be administered).  The test will be administered to 
patients first monocularly (right/left eye) and then binocularly (both eyes), prior to 
dilation.  From each test, scores will be derived for maximum reading speed (words per 
minute), critical print size (logarithm of the minimum angle of resolution [logMAR]), and 
reading acuity (logMAR).  For maximum reading speed, a higher score indicates better 
reading function.  For critical print size and reading acuity, a lower score indicates better 
reading function.
4.5.7.1
Minnesota Low-Vision Reading Test
The MNRead acuity cards are continuous-text reading cards, with 19 highly 
comparable sentences in terms of number of words, word length, position of words, and 
reading level.  The print sizes are scaled logarithmically.  The test is performed under 
standardized conditions, and speed and accuracy are recorded on a worksheet.
4.5.7.2
Radner Reading Charts
Radner Reading Charts are also continuous-text reading cards available in numerous 
languages.  Each card has 24 highly comparable sentences in terms of number of 
words, word length, position of words, and reading level. The print sizes are scaled 
logarithmically.  The test is performed under standardized conditions, and speed and 
accuracy are recorded on a worksheet.
4.5.8
Optional Samples for Roche Clinical Repository
4.5.8.1
Overview of the Roche Clinical Repository
The RCR is a centrally administered group of facilities used for the long-term storage of 
human biologic specimens, including body fluids, solid tissues, and derivatives thereof 
(e.g., DNA, RNA, proteins, peptides).  The collection and analysis of RCR specimens will 
facilitate the rational design of new pharmaceutical agents and the development of 
diagnostic tests, which may allow for individualized drug therapy for patients in the future.


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Specimens for the RCR will be collected from patients who give specific consent to 
participate in this optional research.  RCR specimens will be used to achieve the 
following objectives:

To study the association of biomarkers with efficacy, adverse events, or 
disease progression

To increase knowledge and understanding of disease biology

To study drug response, including drug effects and the processes of drug absorption 
and disposition

To develop biomarker or diagnostic assays and establish the performance 
characteristics of these assays
4.5.8.2
Approval by the Institutional Review Board or 
Ethics Committee
Collection and submission of biological samples to the RCR is contingent upon the 
review and approval of the exploratory research and the RCR portion of the ICF by each 
site's Institutional Review Board or Ethics Committee (IRB/EC) and, if applicable, an 
appropriate regulatory body.  If a site has not been granted approval for RCR sampling, 
this section of the protocol (Section 4.5.8) will not be applicable at that site.
4.5.8.3
Sample Collection
The following samples will be collected for research purposes, including, but not limited 
to, research on dynamic (non-inherited) biomarkers associated with AMD and related 
diseases, lampalizumab, and signaling pathways related to AMD and the complement 
pathway:

Residual aqueous humor sample

Residual biomarker plasma sample

Residual serum PK sample

Residual serum ATA sample
For all samples, dates of consent should be recorded on the associated RCR page of 
the eCRF.  For sampling procedures, storage conditions, and shipment instructions, see 
the laboratory manual.  
RCR specimens will be destroyed no later than 15 years after the date of final closure of 
the associated clinical database.  The RCR storage period will be in accordance with the 
IRB/EC-approved ICF and applicable laws (e.g., health authority requirements).
4.5.8.4
Confidentiality
Confidentiality for All RCR Specimens
Specimens and associated data will be labeled with a unique patient identification 
number.


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Patient medical information associated with RCR specimens is confidential and may be 
disclosed to third parties only as permitted by the ICF (or separate authorization for use 
and disclosure of personal health information) signed by the patient, unless permitted or 
required by law.
Data generated from RCR specimens must be available for inspection upon request by 
representatives of national and local health authorities and Roche monitors, 
representatives, and collaborators, as appropriate.
Data derived from RCR specimen analysis for individual patients will generally not be 
provided to study investigators unless a request for research use is granted.  The 
aggregate results of any research conducted using RCR specimens will be available in 
accordance with the effective Roche policy on study data publication.
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of the RCR data will become and remain the exclusive and unburdened property 
of Roche, except where agreed otherwise.
Additional Confidentiality for Specimens Used for Genetic Research
Given the sensitive nature of genetic data, Roche has implemented additional processes 
to ensure patient confidentiality for RCR specimens collected for genetic research.  
Upon receipt by the RCR, specimens for genetic research are “double-coded” by 
replacing the patient identification number with a new independent number.  Data 
generated from the use of these specimens and all clinical data transferred from the 
clinical database and considered relevant are also labeled with this same independent 
number.  A “linking key” between the patient identification number and this new 
independent number is stored in a secure database system.  Access to the linking key is 
restricted to authorized individuals and is monitored by audit trail.  Legitimate operational 
reasons for accessing the linking key are documented in a standard operating procedure.  
Access to the linking key for any other reason requires written approval from the Pharma 
Repository Governance Committee and Roche's Legal Department, as applicable.
4.5.8.5
Consent to Participate in the Roche Clinical Repository
The ICF will contain a separate section that addresses participation in the RCR.  The 
investigator or authorized designee will explain to each patient the objectives, methods, 
and potential hazards of participation in the RCR.  Patients will be told that they are free 
to refuse to participate and may withdraw their specimens at any time and for any 
reason during the storage period.  A separate, specific signature will be required to 
document a patient's agreement to provide optional RCR specimens.  Patients who 
decline to participate will not provide a separate signature.
The investigator should document whether or not the patient has given consent to 
participate by completing the RCR Research Sample Informed Consent eCRF.


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In the event of an RCR participant's death or loss of competence, the participant's 
specimens and data will continue to be used as part of the RCR research.
4.5.8.6
Withdrawal from the Roche Clinical Repository
Patients who give consent to provide RCR specimens have the right to withdraw their 
specimens from the RCR at any time for any reason.  If a patient wishes to withdraw 
consent to the testing of his or her specimens, the investigator must inform the Medical
Monitor in writing of the patient's wishes through use of the RCR Subject Withdrawal 
Form and, if the trial is ongoing, must enter the date of withdrawal on the RCR Research 
Sample Withdrawal of Informed Consent eCRF.  The patient will be provided with 
instructions on how to withdraw consent after the trial is closed.  A patient's withdrawal 
from Study GX30191 does not, by itself, constitute withdrawal of specimens from the 
RCR.  Likewise, a patient's withdrawal from the RCR does not constitute withdrawal from 
Study GX30191.
4.5.8.7
Monitoring and Oversight
RCR specimens will be tracked in a manner consistent with GCP by a quality-controlled, 
auditable, and appropriately validated laboratory information management system, to 
ensure compliance with data confidentiality as well as adherence to authorized use of 
specimens as specified in this protocol and in the ICF.  Roche monitors and auditors will 
have direct access to appropriate parts of records relating to patient participation in the 
RCR for the purposes of verifying the data provided to Roche.  The site will permit 
monitoring, audits, IRB/EC review, and health authority inspections by providing direct 
access to source data and documents related to the RCR samples.
4.6
PATIENT, TREATMENT, STUDY, AND SITE DISCONTINUATION
Patients withdrawn from the study will be asked to return for an early termination 
evaluation after a minimum of 30 days has elapsed following their last study treatment 
for monitoring of adverse events and assessments listed for the early termination visit 
(see Appendix 1).  The reason for the patient’s discontinuation from the study should be 
recorded on the appropriate eCRF.  Discontinued patients will not be replaced or 
allowed to re-enter the study.
4.6.1
Patient Discontinuation from Study
Patients have the right to voluntarily withdraw from the study at any time for any reason.  
In addition, the investigator has the right to withdraw a patient from the study at any time.  
Reasons for withdrawal from the study may include, but are not limited to, the following:

Patient withdrawal of consent at any time

Any medical condition that the investigator or Sponsor determines may jeopardize 
the patient’s safety if he or she continues in the study

Investigator or Sponsor determines it is in the best interest of the patient

Patient non-compliance, defined as missed doses and visits


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If a patient misses more than three consecutive doses of study treatment within any 
6-month treatment period, the investigator and the Sponsor may consider withdrawing 
the patient from the study.
Every effort should be made to obtain information on patients who are discontinued from 
the study.  The primary reason for discontinuation from the study should be documented 
on the appropriate eCRF.
If a patient discontinues from the study but has not withdrawn informed consent, the site 
should make every effort to continue to follow-up on serious adverse events, deaths, and 
adverse events of special interest in these patients.  In order to avoid loss to follow-up, 
the investigator should ask the patient at the study start for the contact details of a 
relative or friend who may be contacted in case the patient cannot be reached.  However, 
patients will not be followed for any reason after consent has been withdrawn.  Patients 
who discontinue from the study will not be replaced.
4.6.2
Study Treatment Discontinuation
Patients must permanently discontinue study treatment if they experience any of the 
following:  

Any medical condition that the investigator or Sponsor determines may jeopardize 
the patient’s safety if he or she continues to receive study treatment

Pregnancy
The investigator has the right to discontinue a patient for reasons of non-compliance 
(e.g., missed doses and/or visits) or if the investigator or Sponsor determines it is in the 
best interest of the patient.  The primary reason for the treatment discontinuation should 
be recorded on the appropriate eCRF.
Patients who must discontinue treatment will not be replaced or allowed to restart the 
study treatment.  Any patient discontinued from study treatment will also be discontinued 
from the study and will not be allowed to re-enter the study; the patient will be 
encouraged to undergo a study early termination visit.
4.6.3
Study and Site Discontinuation
The Sponsor has the right to terminate this study at any time.  Reasons for terminating 
the study may include, but are not limited to, the following:

The incidence or severity of adverse events in this or other studies indicates a 
potential health hazard to patients.

Patient enrollment is unsatisfactory.

Data recording is inaccurate or incomplete.
The Sponsor will notify the investigator if the Sponsor decides to discontinue the study.  


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The Sponsor has the right to close a site at any time.  Reasons for closing a site may 
include, but are not limited to, the following:

Excessively slow recruitment

Poor protocol adherence

Inaccurate or incomplete data recording

Non-compliance with the ICH guideline for GCP

No study activity (i.e., all patients have completed the study and all obligations have 
been fulfilled)
5.
ASSESSMENT OF SAFETY
5.1
SAFETY PLAN
Lampalizumab is not an approved drug and is currently in clinical development.  Thus, 
the full safety profile is not completely known at this time.  The safety plan for patients in 
this study is based on clinical experience with lampalizumab in completed and ongoing 
studies.  The safety plan for this study is designed to help minimize patient risk and will 
include specific monitoring assessments as detailed below.  The incidence and 
characteristics of adverse events and serious adverse events will be assessed as 
described in this protocol.  Detailed ocular examinations, including indirect 
ophthalmoscopy and slit-lamp examination, will be performed throughout the study.
Potential ocular safety issues currently thought to be associated with the route of 
administration or pharmacology of lampalizumab include decreased BCVA, conjunctival 
hemorrhage, ocular inflammation (see Section 5.3.5 and Appendix 3 for anterior 
chamber and vitreous inflammation grading scales), intraocular infection 
(endophthalmitis), transient and/or sustained elevation of IOP, transient vision loss,
cataract development or progression, retinal or vitreous hemorrhage, and retinal break 
or detachment.  The occurrence of all adverse events (serious and non-serious) and 
pregnancies will be recorded for the duration of this study.
Systemic levels of lampalizumab following multiple intravitreal administrations are 
anticipated to be low. Systemic side effects of lampalizumab are not anticipated based 
on nonclinical data and clinical studies conducted to date, but are possible.  As part of 
the safety plan, aggregate adverse event reports will be reviewed periodically to assess 
for potential systemic safety effects, such as cardiovascular events, neoplasms, or 
alteration in immune function (e.g., reports of infections to encapsulated bacteria, such 
as Neisseria meningitidis, Streptococcus pneumonia, and Haemophilus influenza).
The incidence and characteristics of adverse events, serious adverse events, and 
laboratory abnormalities will be assessed as described within this protocol.  An iDMC 
will monitor patient safety and study conduct on an ongoing basis (see Section 3.1.3). 
The iDMC shares with the Sponsor the responsibility to monitor overall patient safety 
in relation to the IMP, lampalizumab.


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Patients will be contacted by study site personnel 4 (2) days after each injection to elicit 
reports of any decrease in vision, eye pain, unusual redness, or any other new ocular 
symptoms in the study eye.  At the sites where the investigator’s decision is for the 
patients to take pre- and post-injection anti-microbials, the patients will also be asked 
whether they have taken the prescribed, self-administered, pre- and post-injection 
anti-microbials.  Patients will be instructed to contact the investigator at any time if they 
have any health-related concerns.  If warranted, patients will be asked to return to the 
clinic as soon as possible for an unscheduled safety assessment visit (see Appendix 2).
5.1.1
Safety Procedures
A finger-counting test will be conducted for each patient by the physician within 
15 minutes following study treatment; hand-motion and light-perception tests will be 
performed when necessary.  Following the study treatment, IOP will be measured 
between 30 and 50 minutes after study treatment by the site staff for the study eye only; 
if the IOP is increased by 10 mmHg from the pre-injection IOP value, IOP will be 
measured again at 6080 minutes post-injection.  If there are no safety concerns, the 
patient will be permitted to leave the clinic.  If the IOP value is of concern to the 
investigator, the patient will remain in the clinic and will be managed in accordance with 
the investigator’s clinical judgment.  Both the last post-injection IOP measured prior to 
any intervention for increased IOP (if applicable) and the last post-intervention IOP value 
(if applicable) will be recorded on the appropriate eCRF.  If applicable, an Adverse Event 
eCRF should also be completed (see Section 5.2.1). 
If the study eye is treated with a Lucentis injection during the same visit that study 
treatment is administered, the treatment with Lucentis has to be performed first.  Please 
measure and record the post-Lucentis treatment IOP value on the eCRF, irrespective of 
the subsequent study treatment administration.
Detailed ocular examinations, including indirect ophthalmoscopy and slit-lamp 
examination, will be performed throughout the study.  Blood samples will be obtained 
from all patients at selected timepoints in order to measure serum lampalizumab 
concentrations and levels of antibodies to lampalizumab and other biomarkers (see 
Appendix 1).  The optional aqueous humor samples will be obtained from the patients 
who consent to this procedure and sample collection.
Patients discontinued from the study will be asked to return for early termination visit 
assessments after a minimum of 30 days has elapsed following the last study treatment 
visit (see Appendix 1).  The visit will include assessment of all adverse events (serious 
and non-serious; ocular and non-ocular).  Serious adverse events will be reported in 
compliance with GCP guidelines.


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5.1.2
Dose-Interruption, Treatment-Discontinuation, and 
Study-Withdrawal Criteria
Study-treatment interruption, discontinuation of study treatment, and patient withdrawal 
from the study due to adverse events will be determined using the criteria listed in 
Table 1.  If any of these criteria are met, treatment will be interrupted (or discontinued, if 
applicable) and will not be resumed earlier than the next scheduled study visit.  The 
reason for study-treatment interruption or discontinuation should be recorded on the 
Study Drug Interruption eCRF and, if applicable, on the Adverse Event eCRF.
If a patient misses more than three consecutive doses of study treatment within any 
6-month treatment period, the investigator and the Sponsor may consider withdrawing 
the patient from the study.


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Table 1
Dose-Interruption, Treatment-Discontinuation, and 
Study-Withdrawal Criteria
Event
Dose-Interruption, Treatment-Discontinuation, and 
Study-Withdrawal Criteria
Intraocular inflammation
Interrupt study treatment if intraocular inflammation 
(iritis, iridocyclitis, or vitritis) is 1in the study eye 
(see the grading scales of intraocular inflammation in 
Section 5.3.5 and Appendix 3).  
Patients with 3intraocular inflammation will 
discontinue study treatment and will be withdrawn
from the study.
VA decrease
Interrupt study treatment if there is a study
treatment-related decrease of 30 letters in BCVA in 
the study eye compared with the last assessment of 
BCVA prior to the most recent treatment.  Study 
treatment may be permitted subsequently as 
determined by the investigator.
Elevated IOP
Interrupt study treatment if IOP in the study eye is
30 mmHg.  Treatment may be permitted when IOP 
has been lowered to 30 mmHg, either spontaneously 
or by treatment, or as determined by the investigator.
Vitreous hemorrhage
Interrupt study treatment in the event of a vitreous 
hemorrhage in the study eye.  Study treatment may be 
permitted subsequently as determined by the 
investigator.
Rhegmatogenous retinal break
Interrupt study treatment if a retinal break is present in 
the study eye.  Study treatment may be resumed no 
earlier than 30 days after successful laser retinopexy 
as determined by the investigator.
Rhegmatogenous retinal detachment or 
macular hole
Discontinue study treatment and withdraw the patient 
from the study if rhegmatogenous retinal detachment 
or Stage 3 or 4 macular hole is observed.
Central serous retinopathy
Interrupt study treatment if serous retinopathy is 
present in the study eye.  Study treatment may be 
resumed upon resolution.


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Table 1
Dose-Interruption, Treatment-Discontinuation, and 
Study-Withdrawal Criteria (cont.)
Event
Dose-Interruption, Treatment-Discontinuation, 
Study-Withdrawal Criteria
Active infection
Interrupt study treatment if any of the following are 
present:  infectious conjunctivitis, infectious keratitis, 
infectious scleritis, or endophthalmitis in either eye; or 
if the patient is currently receiving systemic treatment 
for an active infection.
Patients with endophthalmitis in the study eye will 
discontinue the study treatment and be withdrawn
from the study.
Cataract surgery in study eye
Interrupt study treatment after cataract surgery in study 
eye.  Study treatment may be resumed no earlier than 
30 days after an uncomplicated cataract surgery and 
no evidence of post-operational inflammation.  For 
cataract surgery with complications, study treatment 
may be permitted as determined by the Sponsor and 
investigator.
Oral corticosteroids (prednisone 
10 mg/day or equivalent)
Interrupt study treatment.  Study treatment may be 
resumed when oral corticosteroids dosing is 
prednisone 10 mg/day or equivalent.
IV corticosteroids
Interrupt study treatment.  Study treatment may be 
resumed when the patient has finished IV 
corticosteroid course and oral corticosteroid dosing is 
prednisone 10 mg/day or equivalent.
BCVAbest corrected visual acuity; IOPintraocular pressure; IVintravenous; VAvisual 
acuity.
5.2
SAFETY PARAMETERS AND DEFINITIONS
Safety assessments will consist of monitoring and recording adverse events, including 
serious adverse events and adverse events of special interest, performing 
protocol-specified safety laboratory assessments, and other protocol-specified tests that 
are deemed critical to the safety evaluation of the study.
Certain types of events require immediate reporting to the Sponsor, as outlined in 
Section 5.4.
5.2.1
Adverse Events
According to the ICH guideline for GCP, an adverse event is any untoward medical 
occurrence in a clinical, investigational, patient-administered pharmaceutical product, 
regardless of causal attribution.  An adverse event can therefore be any of the following:

Any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a medicinal product, 
whether or not considered related to the medicinal product


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
Any new disease or exacerbation of an existing disease (a worsening in the 
character, frequency, or severity of a known condition), except as described in 
Section 5.3.5.9

Recurrence of an intermittent medical condition (e.g., headache) not present 
at baseline

Any deterioration in a laboratory value or other clinical test (e.g., electrocardiogram, 
X-ray) that is associated with symptoms or leads to a change in study treatment or 
concomitant treatment or discontinuation from study drug

Adverse events that are related to a protocol-mandated intervention, including those 
that occur prior to study drug administration (e.g., screening invasive procedures, 
such as biopsies)
5.2.2
Serious Adverse Events (Immediately Reportable to 
the Sponsor)
A serious adverse event is any adverse event that meets any of the following criteria:

Is fatal (i.e., the adverse event actually causes or leads to death)

Is life threatening (i.e., the adverse event, in the view of the investigator, places the 
patient at immediate risk of death)
This does not include any adverse event that had it occurred in a more severe 
form or was allowed to continue might have caused death.

Requires or prolongs inpatient hospitalization (see Section 5.3.5.10)

Results in persistent or significant disability/incapacity (i.e., the adverse event 
results in substantial disruption of the patient’s ability to conduct normal life 
functions)

Is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to 
study drug

Is a significant medical event in the investigator's judgment (e.g., may jeopardize the 
patient or may require medical/surgical intervention to prevent one of the outcomes 
listed above)
The terms “severe” and “serious” are not synonymous.  Severity refers to the intensity of 
an adverse event (e.g., rated as mild, moderate, or severe; see Section 5.3.3); the event 
itself may be of relatively minor medical significance (such as severe headache without 
any further findings).
Severity and seriousness need to be independently assessed for each adverse event 
recorded on the eCRF.
Serious adverse events are required to be reported by the investigator to the Sponsor 
immediately (i.e., no more than 24 hours after learning of the event; see Section 5.4.2 for 
reporting instructions).


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5.2.3
Adverse Events of Special Interest (Immediately Reportable to 
the Sponsor)
Adverse events of special interest are required to be reported by the investigator to the 
Sponsor immediately (i.e., no more than 24 hours after learning of the event; see 
Section 5.4.2 for reporting instructions).  Adverse events of special interest for this study 
include the following:

Cases of potential drug-induced liver injury that include an elevated ALT or AST in 
combination with either an elevated bilirubin or clinical jaundice, as defined by 
Hy’s law (see Section 5.3.5.6)

Suspected transmission of an infectious agent by the study drug, as defined below
Any organism, virus, or infectious particle (e.g., prion protein transmitting 
transmissible spongiform encephalopathy), pathogenic or non-pathogenic, is 
considered an infectious agent.  A transmission of an infectious agent may be 
suspected from clinical symptoms or laboratory findings that indicate an 
infection in a patient exposed to a medicinal product.  This term applies only
when a contamination of the study drug is suspected.

Adverse events resulting from medication error
Examples of medication errors include, but are not limited to, overdose, 
incorrect dose, incorrect route, incorrect drug, incorrect administration, or 
incorrect kit.
If the medication error did result in an adverse event, the primary event term 
should reflect the adverse event that occurred as a result of the medication 
error and identify it in “other suspected causes of serious adverse 
event/adverse event” data field as a medication error.

Sight-threatening adverse events:  An adverse event is considered to be serious 
and sight threatening and should be reported expeditiously if it meets one or more of 
the following criteria:
It causes a decrease of 30 letters in VA score (compared with the last 
assessment of VA prior to the most recent assessment) lasting more than 
1 hour.
It requires surgical intervention (i.e., conventional surgery, vitreous tap, or 
biopsy with intravitreal injection of anti-infective agents, or laser or retinal 
cryopexy with gas) to prevent permanent loss of sight.
It is associated with severe intraocular inflammation (i.e., endophthalmitis, 
4anterior chamber cell/flare or 4vitritis; see Section 5.3.5 and Appendix 3 for 
intraocular inflammation grading scales).
In the opinion of the investigator, it may require medical intervention to prevent 
permanent loss of sight.
All above listed sight-threatening adverse events should be reported as serious events, 
listing the underlying cause (if known) of the event as the primary event term.


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5.3
METHODS AND TIMING FOR CAPTURING AND ASSESSING 
SAFETY PARAMETERS
The investigator is responsible for ensuring that all adverse events (see Section 5.2.1 for 
definition) are recorded on the Adverse Event eCRF and reported to the Sponsor in 
accordance with instructions provided in this section and in Sections 5.45.6. 
For each adverse event recorded on the Adverse Event eCRF, the investigator will make 
an assessment of seriousness (see Section 5.2.2 for seriousness criteria), severity (see 
Section 5.3.3), and causality (see Section 5.3.4).  
5.3.1
Adverse Event Reporting Period
Investigators will seek information on adverse events at each patient contact.  All 
adverse events, whether reported by the patient or noted by study personnel, will be 
recorded in the patient’s medical record and on the Adverse Event eCRF.
After completion of the Week 96 visit of the parent study and informed consent for the 
extension study has been obtained, any adverse events that are ongoing or started after 
the Week 96 visit of the parent study should be reported on the extension study Adverse 
Event eCRF.
All adverse events will be reported until at least 30 days after the last dose of study drug
or the last study visit, whichever is later.  After this period, the investigator should 
report any serious adverse events that are believed to be related to prior study drug 
treatment (see Section 5.6).
5.3.2
Eliciting Adverse Event Information
A consistent methodology of non-directive questioning should be adopted for eliciting 
adverse event information at all patient evaluation timepoints.  Examples of non-directive 
questions include the following:
“How have you felt since your last clinic visit?”
“Have you had any new or changed health problems since you were last here?”
5.3.3
Assessment of Severity of Adverse Events
The adverse event severity grading scale in Table 2 will be used for assessing adverse 
event severity.  


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Table 2
Adverse Event Severity Grading Scale
Severity
Description
Mild
Discomfort noticed, but no disruption of normal daily activity
Moderate
Discomfort sufficient to reduce or affect normal daily activity
Severe
Incapacitating with inability to work or to perform normal daily activity
Note:  Regardless of severity, some events may also meet seriousness criteria.  Refer to 
definition of a serious adverse event (see Section 5.2.2).
5.3.4
Assessment of Causality of Adverse Events
Investigators should use their knowledge of the patient, the circumstances surrounding 
the event, and an evaluation of any potential alternative causes to determine whether an 
adverse event is considered to be related to the study drug, indicating “yes” or “no” 
accordingly.  The following guidance should be taken into consideration (see also 
Table 3):

Temporal relationship of event onset to the initiation of study drug

Course of the event, considering especially the effects of dose reduction, 
discontinuation of study drug, or reintroduction of study drug (as applicable)

Known association of the event with the study drug or with similar treatments

Known association of the event with the disease under study

Presence of risk factors in the patient or use of concomitant medications known to 
increase the occurrence of the event

Presence of non-treatmentrelated factors that are known to be associated with the 
occurrence of the event
Table 3
Causal Attribution Guidance
Is the adverse event suspected to be caused by the study drug on the basis of facts, evidence, 
science-based rationales, and clinical judgment?
YES
There is a plausible temporal relationship between the onset of the adverse event and 
administration of the study drug, and the adverse event cannot be readily explained by 
the patient's clinical state, intercurrent illness, or concomitant therapies; and/or the 
adverse event follows a known pattern of response to the study drug; and/or the 
adverse event abates or resolves upon discontinuation of the study drug or dose 
reduction and, if applicable, reappears upon re-challenge.
NO
An adverse event will be considered related, unless it fulfills the criteria specified below.  
Evidence exists that the adverse event has an etiology other than the study drug 
(e.g., pre-existing medical condition, underlying disease, intercurrent illness, 
or concomitant medication) and/or the adverse event has no plausible temporal 
relationship to administration of the study drug (e.g., cancer diagnosed 2 days after 
first dose of study drug).


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5.3.5
Procedures for Recording Adverse Events
Investigators should use correct medical terminology/concepts when recording adverse 
events on the Adverse Event eCRF.  Avoid colloquialisms and abbreviations.
Only one adverse event term should be recorded in the event field on the Adverse Event 
eCRF.
For the purposes of reporting events of infection and inflammation, the following terms 
and definitions should be used:

Iritis:  defined as the presence of inflammatory cells in the anterior chamber
The presence of aqueous flare alone will not constitute iritis but should be 
documented as an anterior chamber flare for adverse event reporting 
purposes.

Iridocyclitis:  defined as the presence of inflammatory cells in both the aqueous and 
vitreous

Vitritis:  defined as the presence of active inflammation in the vitreous, 
demonstrated by the presence of inflammatory cells (trace or greater)

Active inflammation in the vitreous should be clinically differentiated from cellular 
debris from prior episodes of inflammation, hemorrhage, or other causes.

Endophthalmitis:  defined as diffuse intraocular inflammation predominantly 
involving the vitreous cavity but also involving the anterior chamber, implying a 
suspected underlying infectious cause.  A culture is required prior to initiating 
antibiotic treatment for presumed endophthalmitis.  Results of bacterial or fungal 
cultures, treatment given, and final ophthalmologic outcome should also be provided 
in the details section of the Adverse Event eCRF.
Note:  Trace, benign, aqueous pigmented cells visible on slit-lamp examination that are 
caused by dilation and are not red blood cells or white blood cells or the result of any 
ocular disorder should not be recorded as an adverse event.
5.3.5.1
Diagnosis versus Signs and Symptoms
A diagnosis (if known) should be recorded on the Adverse Event eCRF rather than 
individual signs and symptoms (e.g., record only liver failure or hepatitis rather than 
jaundice, asterixis, and elevated transaminases).  However, if a constellation of signs 
and/or symptoms cannot be medically characterized as a single diagnosis or syndrome 
at the time of reporting, each individual event should be recorded on the Adverse Event 
eCRF.  If a diagnosis is subsequently established, all previously reported adverse events 
based on signs and symptoms should be nullified and replaced by one adverse event 
report based on the single diagnosis, with a starting date that corresponds to the starting 
date of the first symptom of the eventual diagnosis.


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5.3.5.2
Adverse Events That Are Secondary to Other Events
In general, adverse events that are secondary to other events (e.g., cascade events or 
clinical sequelae) should be identified by their primary cause, with the exception of 
severe or serious secondary events.  A medically significant secondary adverse event 
that is separated in time from the initiating event should be recorded as an independent 
event on the Adverse Event eCRF.  For example:

If vomiting results in mild dehydration with no additional treatment in a healthy adult, 
only vomiting should be reported on the eCRF.

If vomiting results in severe dehydration, both events should be reported separately 
on the eCRF.

If a severe gastrointestinal hemorrhage leads to renal failure, both events should be 
reported separately on the eCRF.

If dizziness leads to a fall and consequent fracture, all three events should be 
reported separately on the eCRF.

If neutropenia is accompanied by an infection, both events should be reported 
separately on the eCRF.
All adverse events should be recorded separately on the Adverse Event eCRF if it is 
unclear as to whether the events are associated.
5.3.5.3
Persistent or Recurrent Adverse Events
A persistent adverse event is one that extends continuously, without resolution, between 
patient evaluation timepoints.  Such events should only be recorded once on the 
Adverse Event eCRF.  The initial severity (intensity) of the event will be recorded at the 
time the event is first reported.  If a persistent adverse event becomes more severe, the 
most extreme severity should also be recorded on the Adverse Event eCRF. If the event 
becomes serious, it should be reported to the Sponsor immediately (i.e., no more than 
24 hours after learning that the event became serious; see Section 5.4.2 for reporting 
instructions).  The Adverse Event eCRF should be updated by changing the event from 
“non-serious” to “serious,” providing the date that the event became serious and 
completing all data fields related to serious adverse events.
A recurrent adverse event is one that resolves between patient evaluation timepoints 
and subsequently recurs.  Each recurrence of an adverse event should be recorded as a 
separate event on the Adverse Event eCRF.
5.3.5.4
Abnormal Laboratory Values
Not every laboratory abnormality qualifies as an adverse event.  A laboratory test result 
must be reported as an adverse event if it meets any of the following criteria:

Is accompanied by clinical symptoms

Results in a change in study treatment (e.g., dosage modification, treatment 
interruption, or treatment discontinuation)


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
Results in a medical intervention (e.g., potassium supplementation for hypokalemia) 
or a change in concomitant therapy

Is clinically significant in the investigator’s judgment 
It is the investigator’s responsibility to review all laboratory findings.  Medical and 
scientific judgment should be exercised in deciding whether an isolated laboratory 
abnormality should be classified as an adverse event.
If a clinically significant laboratory abnormality is a sign of a disease or syndrome 
(e.g., alkaline phosphatase and bilirubin 5the upper limit of normal [ULN] associated 
with cholestasis), only the diagnosis (i.e., cholestasis) should be recorded on the 
Adverse Event eCRF.
If a clinically significant laboratory abnormality is not a sign of a disease or syndrome, 
the abnormality itself should be recorded on the Adverse Event eCRF, along with a 
descriptor indicating whether the test result is above or below the normal range 
(e.g., “elevated potassium,” as opposed to “abnormal potassium”).  If the laboratory 
abnormality can be characterized by a precise clinical term per standard definitions, the 
clinical term should be recorded as the adverse event.  For example, an elevated serum 
potassium level of 7.0 mEq/L should be recorded as “hyperkalemia.”
Observations of the same clinically significant laboratory abnormality from visit to visit 
should only be recorded once on the Adverse Event eCRF (see Section 5.3.5.3 for 
details on recording persistent adverse events).
5.3.5.5
Abnormal Vital Sign Values
Not every vital sign abnormality qualifies as an adverse event.  A vital sign result must 
be reported as an adverse event if it meets any of the following criteria:

Is accompanied by clinical symptoms

Results in a change in study treatment (e.g., dosage modification, treatment 
interruption, or treatment discontinuation)

Results in a medical intervention or a change in concomitant therapy

Is clinically significant in the investigator’s judgment 
It is the investigator’s responsibility to review all vital sign findings.  Medical and scientific 
judgment should be exercised in deciding whether an isolated vital sign abnormality 
should be classified as an adverse event.
If a clinically significant vital sign abnormality is a sign of a disease or syndrome 
(e.g., high blood pressure), only the diagnosis (i.e., hypertension) should be recorded on 
the Adverse Event eCRF.


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Observations of the same clinically significant vital sign abnormality from visit to visit 
should only be recorded once on the Adverse Event eCRF (see Section 5.3.5.3 for 
details on recording persistent adverse events).
5.3.5.6
Abnormal Liver Function Tests
The finding of an elevated ALT or AST (3baseline value) in combination with either 
an elevated total bilirubin (2ULN) or clinical jaundice in the absence of cholestasis or 
other causes of hyperbilirubinemia is considered to be an indicator of severe liver injury 
(as defined by Hy’s law).  Therefore, investigators must report as an adverse event the 
occurrence of either of the following:

Treatment-emergent ALT or AST 3 baseline value in combination with total 
bilirubin 2 ULN (of which 35% is direct bilirubin)

Treatment-emergent ALT or AST 3 baseline value in combination with 
clinical jaundice
The most appropriate diagnosis or (if a diagnosis cannot be established) the abnormal 
laboratory values should be recorded on the Adverse Event eCRF (see Section 5.3.5.1) 
and reported to the Sponsor immediately (i.e., no more than 24 hours after learning of 
the event), either as a serious adverse event or an adverse event of special interest (see 
Section 5.4.2).
5.3.5.7
Deaths
All deaths that occur during the protocol-specified adverse event reporting period (see 
Section 5.3.1), regardless of relationship to study drug, must be recorded on the 
Adverse Event eCRF and immediately reported to the Sponsor (see Section 5.4.2). This 
includes death attributed to progression of GA secondary to AMD.
Death should be considered an outcome and not a distinct event.  The event or condition 
that caused or contributed to the fatal outcome should be recorded as the single medical 
concept on the Adverse Event eCRF.  Generally, only one such event should be 
reported.  If the cause of death is unknown and cannot be ascertained at the time of 
reporting, “unexplained death” should be recorded on the Adverse Event eCRF.  If the 
cause of death later becomes available (e.g., after autopsy), “unexplained death” should 
be replaced by the established cause of death.  The term "sudden death" should not 
be used unless combined with the presumed cause of death (e.g., "sudden cardiac 
death").
If the death is attributed to progression of "GA secondary to AMD progression,"
geographic atrophy secondary to advanced macular degeneration progression should be 
recorded on the Adverse Event eCRF.  
Deaths that occur after the adverse event reporting period should be reported as 
described in Section 5.6.


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5.3.5.8
Preexisting Medical Conditions
A preexisting medical condition is one that is present at the screening visit for this study.  
Such conditions should be recorded on the General Medical History and Baseline 
Conditions eCRF.
A preexisting medical condition should be recorded as an adverse event only if the 
frequency, severity, or character of the condition worsens during the study.  When 
recording such events on the Adverse Event eCRF, it is important to convey the concept 
that the preexisting condition has changed by including applicable descriptors 
(e.g., “more frequent headaches”).
5.3.5.9
Worsening of Geographic Atrophy in Study Eye
Medical occurrences or symptoms of deterioration that are anticipated as part of the 
normal progression of GA of the study eye should be recorded as an adverse event only 
if judged by the investigator to have unexpectedly worsened in severity or frequency or 
changed in nature at any time during the study.  When recording an unanticipated 
worsening of GA in the study eye on the Adverse Event eCRF, it is important to convey 
the concept that the condition has changed by including applicable descriptors (e.g., 
“accelerated Geographic Atrophy”). 
Events that are clearly consistent with the expected pattern of progression of the 
underlying disease in the study eye should not be recorded as adverse events.  The 
expedited reporting requirements for sight-threatening events (listed in the Section 5.2.3) 
still apply to these unexpected changes in the study eye GA.
5.3.5.10
Hospitalization or Prolonged Hospitalization
Any adverse event that results in hospitalization (i.e., in-patient admission to a hospital)
or prolonged hospitalization should be documented and reported as a serious adverse 
event (per the definition of serious adverse event in Section 5.2.2), except as outlined 
below.  
The following hospitalization scenarios are not considered to be adverse events:

Hospitalization for a preexisting condition, provided that all of the following criteria 
are met:
The hospitalization was planned prior to the study or was scheduled during the 
study when diagnostic procedure or elective surgery became necessary 
because of the expected normal progression of the disease.
The patient has not experienced an adverse event.
5.3.5.11
Adverse Events Associated with an Overdose or Error in 
Drug Administration
An overdose is the accidental or intentional use of a drug in an amount higher than the 
dose being studied.  An overdose or incorrect administration of study drug is not itself an 
adverse event, but it may result in an adverse event.  All adverse events associated with 


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an overdose or incorrect administration of study drug should be recorded on the Adverse 
Event eCRF as an adverse event of special interest.  If the associated adverse event 
fulfills seriousness criteria, the event should be reported to the Sponsor immediately (i.e., 
no more than 24 hours after learning of the event; see Section 5.4.2).
No safety data related to overdosing of lampalizumab are available.
5.3.5.12
Patient-Reported Outcome Data 
Adverse event reports will not be derived from PRO data by the Sponsor, and safety 
analyses will not be performed using PRO data.  However, if any PRO responses 
suggestive of a possible adverse event are identified during site review of the PRO data, 
the investigator will determine whether the criteria for an adverse event have been met 
and, if so, will report the event on the Adverse Event eCRF.
5.4
IMMEDIATE REPORTING REQUIREMENTS FROM 
INVESTIGATOR TO SPONSOR
Certain events require immediate reporting to allow the Sponsor to take appropriate 
measures to address potential new risks in a clinical trial.  The investigator must report 
such events to the Sponsor immediately; under no circumstances should reporting take 
place more than 24 hours after the investigator learns of the event.  The following is a list 
of events that the investigator must report to the Sponsor within 24 hours after learning 
of the event, regardless of relationship to study drug:

Serious adverse events (see Section 5.4.2 for further details)

Adverse events of special interest (see Section 5.4.2 for further details)

Pregnancies (see Section 5.4.3 for further details)
The investigator must report new significant follow-up information for these events to the 
Sponsor immediately (i.e., no more than 24 hours after becoming aware of the 
information).  New significant information includes the following:

New signs or symptoms or a change in the diagnosis

Significant new diagnostic test results

Change in causality based on new information

Change in the event’s outcome, including recovery

Additional narrative information on the clinical course of the event
Investigators must also comply with local requirements for reporting serious adverse 
events to the local health authority and IRB/EC.
5.4.1
Emergency Medical Contacts
Medical Monitor Contact Information for Sites in North and South America
Medical Monitor/Roche Medical Responsible:
, M.D. (Primary)
Mobile Telephone No.:


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Medical Monitor/Roche Medical Responsible:
, M.D., Ph.D.
Telephone No.:
Mobile Telephone No.:
Medical Monitor Contact Information for Rest of World
Medical Monitor/Roche Medical Responsible:
, M.D.
Telephone No.:
Mobile Telephone No.:
Medical Monitor/Roche Medical Responsible:
, M.D.
Telephone No.:
Mobile Telephone No.:
To ensure the safety of study patients, an Emergency Medical Call Center Help Desk will 
access the Roche Medical Emergency List, escalate emergency medical calls, provide 
medical translation service (if necessary), connect the investigator with a Roche Medical 
Responsible (listed above and/or on the Roche Medical Emergency List), and track all 
calls.  The Emergency Medical Call Center Help Desk will be available 24 hours per day, 
7 days per week.  Toll-free numbers for the Help Desk, as well as Medical Monitor and 
Medical Responsible contact information, will be distributed to all investigators. 
5.4.2
Reporting Requirements for Serious Adverse Events and 
Adverse Events of Special Interest
Serious adverse events and adverse events of special interest with onset prior to 
completion of the Week 96 visit of the parent study should be reported in the parent 
study.  After completion of the Week 96 visit of the parent study and an informed 
consent for the extension study has been obtained, the serious adverse events and 
adverse events of special interest that are ongoing or started after the Week 96 visit of 
the parent study should be reported on the extension study eCRF.
The Serious Adverse Event/Adverse Event of Special Interest Reporting Form provided 
to investigators should be completed and submitted to the Sponsor or its designee 
immediately (i.e., no more than 24 hours after learning of the event), either by faxing or 
by scanning and emailing the form using the fax number or email address provided to 
investigators.
Serious adverse events and adverse events of special interest will be reported until at 
least 30 days after administration of the last dose of study drug or the last study visit, 
whichever is later.  Investigators should record all case details that can be gathered 
immediately (i.e., within 24 hours after learning of the event) on the Adverse Event eCRF 
and submit the report via the electronic data capture (EDC) system.  A report will be 
generated and sent to Roche Safety Risk Management by the EDC system.


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In the event that the EDC system is unavailable, the Serious Adverse Event/Adverse 
Event of Special Interest Reporting Form provided to investigators should be completed 
and submitted to the Sponsor or its designee immediately (i.e., no more than 24 hours 
after learning of the event), either by faxing or by scanning and emailing the form using 
the fax number or email address provided to investigators.  Once the EDC system is 
available, all information will need to be entered and submitted via the EDC system.  
Instructions for reporting post-study adverse events are provided in Section 5.6.
5.4.3
Reporting Requirements for Pregnancies
5.4.3.1
Pregnancies in Female Patients
Female patients of childbearing potential will be instructed to immediately inform the 
investigator if they become pregnant during the study or until 30 days after the last dose 
of study drug.  A Clinical Trial Pregnancy Reporting Form should be completed and 
submitted to the Sponsor or its designee immediately (i.e., no more than 24 hours after 
learning of the pregnancy), either by faxing or by scanning and emailing the form using 
the fax number or email address provided to investigators.  Pregnancy should not be 
recorded on the Adverse Event eCRF.  The investigator should discontinue study drug 
and counsel the patient, discussing the risks of the pregnancy and the possible effects 
on the fetus.  Monitoring of the patient should continue until conclusion of the pregnancy.  
Any serious adverse events associated with the pregnancy (e.g., an event in the fetus, 
an event in the mother during or after the pregnancy, or a congenital anomaly/birth 
defect in the child) should be reported on the Adverse Event eCRF.  In addition, the 
investigator will submit a Clinical Trial Pregnancy Reporting Form when updated 
information on the course and outcome of the pregnancy becomes available.  
5.4.3.2
Pregnancies in Female Partners of Male Patients
Male patients will be instructed through the ICF to immediately inform the investigator if 
their partner becomes pregnant during the study or until 120 days after the last dose of 
study drug.  A Clinical Trial Pregnancy Reporting Form should be completed and 
submitted to the Sponsor or its designee immediately (i.e., no more than 24 hours after 
learning of the pregnancy), either by faxing or by scanning and emailing the form using 
the fax number or email address provided to investigators.  Attempts should be made to 
collect and report details of the course and outcome of any pregnancy in the partner of a 
male patient exposed to study drug.  The pregnant partner will need to sign an 
Authorization for Use and Disclosure of Pregnancy Health Information to allow for 
follow-up on her pregnancy.  After the authorization has been signed, the investigator 
will submit a Clinical Trial Pregnancy Reporting Form when updated information on the 
course and outcome of the pregnancy becomes available.  An investigator who is 
contacted by the male patient or his pregnant partner may provide information on the 
risks of the pregnancy and the possible effects on the fetus, to support an informed 
decision in cooperation with the treating physician and/or obstetrician.


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5.4.3.3
Abortions
Any abortion should be classified as a serious adverse event (as the Sponsor considers 
abortions to be medically significant), recorded on the Adverse Event eCRF, and 
reported to the Sponsor immediately (i.e., no more than 24 hours after learning of the 
event; see Section 5.4.2).  
5.4.3.4
Congenital Anomalies/Birth Defects
Any congenital anomaly/birth defect in a child born to a female patient exposed to study 
drug or the female partner of a male patient exposed to study drug should be classified 
as a serious adverse event, recorded on the Adverse Event eCRF, and reported to the 
Sponsor immediately (i.e., no more than 24 hours after learning of the event; see 
Section 5.4.2).
5.5
FOLLOW-UP OF PATIENTS AFTER ADVERSE EVENTS
5.5.1
Investigator Follow-Up
The investigator should follow each adverse event until the event has resolved to 
baseline grade or better, the event is assessed as stable by the investigator, the patient 
is lost to follow-up, or the patient withdraws consent.  Every effort should be made to 
follow all serious adverse events considered to be related to study drug or trial-related 
procedures until a final outcome can be reported.
During the study period, resolution of adverse events (with dates) should be documented 
on the Adverse Event eCRF and in the patient’s medical record to facilitate source data 
verification.
All pregnancies reported during the study should be followed until pregnancy outcome.
5.5.2
Sponsor Follow-Up
For serious adverse events, adverse events of special interest, and pregnancies, the 
Sponsor or a designee may follow up by telephone, fax, electronic mail, and/or a 
monitoring visit to obtain additional case details and outcome information (e.g., from 
hospital discharge summaries, consultant reports, autopsy reports) in order to perform 
an independent medical assessment of the reported case.
5.6
ADVERSE EVENTS THAT OCCUR AFTER THE ADVERSE 
EVENT REPORTING PERIOD
The Sponsor should be notified if the investigator becomes aware of any serious 
adverse event that occurs after the end of the adverse event reporting period (defined as 
the last study visit), if the event is believed to be related to prior study drug treatment.  
The investigator should report these events directly to the Sponsor or its designee, either 
by faxing or by scanning and emailing the Serious Adverse Event/Adverse Event of 
Special Interest Reporting Form using the fax number or email address provided to 
investigators.


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5.7
EXPEDITED REPORTING TO HEALTH AUTHORITIES, 
INVESTIGATORS, INSTITUTIONAL REVIEW BOARDS, AND 
ETHICS COMMITTEES
The Sponsor will promptly evaluate all serious adverse events and adverse events of 
special interest against cumulative product experience to identify and expeditiously 
communicate possible new safety findings to investigators, IRBs, ECs, and applicable 
health authorities based on applicable legislation.
To determine reporting requirements for adverse event cases, the Sponsor will assess 
the expectedness of these events using the following reference document:

Lampalizumab Investigator’s Brochure
The Sponsor will compare the severity of each event and the cumulative event 
frequency reported for the study with the severity and frequency reported in the 
applicable reference document.
Reporting requirements will also be based on the investigator's assessment of causality 
and seriousness, with allowance for upgrading by the Sponsor as needed.
6.
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN
6.1
DETERMINATION OF SAMPLE SIZE
This study is open to all patients who complete study treatment and the Week 96 visit in 
parent Studies GX29176 and GX29185 and who meet the eligibility criteria (see 
Sections 4.1.1 and 4.1.2).
6.2
SUMMARIES OF DEMOGRAPHIC AND BASELINE 
CHARACTERISTICS AND CONDUCT OF THE STUDY
Demographic and disease characteristics (such as GA area, BCVA, and VA under 
low-luminance conditions prior to enrollment) for patients enrolled in the extension study 
will be summarized in all patients and by treatment group in the parent study 
(Study GX29176 or Study GX29185).  Patient disposition and exposure to study drug 
(number of study treatments and duration of treatment) will be summarized in all 
patients and by treatment group in the parent study.
6.3
SAFETY ANALYSES
The safety analyses will include patients enrolled in this study who receive at least 
1 dose of study drug in all patients and according to treatment received in the parent 
study.
Verbatim descriptions of treatment-emergent adverse events will be coded, and their 
incidence will be summarized, as appropriate.  Separate summaries will be generated 
for serious adverse events, deaths, adverse events leading to discontinuation of study 
drug, and adverse events judged to be related to lampalizumab.  In addition, separate 


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summaries will be prepared for systemic (non-ocular) and ocular adverse events.  
Descriptive summaries will be generated for VA and IOP.  All patients will receive 
lampalizumab treatment in this study; therefore, caution must be taken when interpreting 
safety results as there is no inactive/sham treatment group for comparison.
6.4
ANATOMIC AND CLINICAL OUTCOME ANALYSES
The anatomic and clinical outcome analyses will include all patients enrolled in this 
study who have received at least one dose of study drug.  The analyses will be
summarized in all patients and by treatment group in the parent study.
Descriptive summaries will be generated for all anatomic and clinical outcomes, 
including PROs, over time.  Correlation between anatomic and clinical outcomes will be 
summarized.  Additional details of analysis will be included in the Data Analysis Plan.
6.5
PHARMACOKINETIC ANALYSES
The PK analyses will include all enrolled patients who have received at least one dose of 
study drug and have at least one serum sample.  The analyses will be summarized by 
treatment group in the parent study. Serum concentrations of lampalizumab will be 
summarized descriptively.
Concentrations of lampalizumab from the optional collection of aqueous humor may be 
reported and/or summarized as appropriate.  Additional PK/PD and exposureresponse 
analyses may be conducted as appropriate.  Population PK modeling may be performed 
to characterize inter-individual variability, which may be reported separately from the 
Clinical Study Report.
6.6
IMMUNOGENICITY ANALYSES
The immunogenicity analyses will include patients with at least one predose (defined as 
prior to the first dose in the extension study for the prior sham patients, and prior to 
the first dose in the parent study for the prior lampalizumab patients) and one 
postdose ATA assessment.  The analysis will be summarized by treatment group in the 
parent study.
The number and proportion of ATA-positive and ATA-negative patients during this study 
will be summarized by treatment group.  The relationship between ATA status and the 
safety, efficacy, PK, and biomarker endpoints will be analyzed and reported descriptively 
in subgroup analyses.  Patients are considered to be ATA--positive if they are 
ATA-negative at baseline (defined as the last measurement prior to the first dose in the 
extension study for the prior sham patients, and the last measurement prior to the first 
dose in the Parent study for the prior lampalizumab patients) but develop an ATA 
response following study drug administration (i.e., treatment-induced ATA response) or if 
they are ATA-positive at baseline and the titer of one or more post-baseline samples is 
at least 4-fold greater (i.e., 0.60 titer units) than the titer of the baseline sample (i.e., 


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treatment-enhanced ATA response).  Patients are considered to be ATA-negative if they 
are ATA-negative at baseline and all post-baseline samples are negative or if they are 
ATA-positive at baseline but do not have any post-baseline samples with a titer that is at 
least 4-fold greater than the titer of the baseline sample (i.e., treatment unaffected).
The relationship between ATA status and the safety, efficacy, PK, and biomarker 
endpoints will be analyzed and reported descriptively via subgroup analyses.
6.7
HANDLING OF MISSING DATA
All efforts will be made to minimize missing data; no imputation will be performed for 
the missing data for the analyses.
6.8
OPTIONAL INTERIM ANALYSIS
Interim safety analyses will be conducted periodically by independent Data Monitoring 
Committee (iDMC) to monitor safety and study conduct of this extension study. No 
formal interim efficacy/futility analyses are planned.  Exploratory efficacy and/or safety 
analyses may be performed with interim data (e.g., to support regulatory submissions).
7.
DATA COLLECTION AND MANAGEMENT
7.1
DATA QUALITY ASSURANCE
The Sponsor will be responsible for data management of this study, including quality 
checking of the data.  Data entered manually will be collected via the EDC using eCRFs.  
Sites will be responsible for data entry into the EDC system.  In the event of discrepant 
data, the Sponsor will request data clarification from the sites, which the sites will resolve 
electronically in the EDC system.
The Sponsor will produce an EDC Study Specification document that describes the 
quality checking to be performed on the data.  Central laboratory data and Reading 
Center Images data will be sent directly to the Sponsor using the Sponsor’s standard 
procedures to handle and process the electronic transfer of these data.
eCRFs and correction documentation will be maintained in the EDC system’s audit trail.  
System backups for data stored by the Sponsor, and records retention for the study data 
will be consistent with the Sponsor’s standard procedures.
The Sponsor will supply eCRF specifications for this study.
Data from PRO questionnaires will be recorded on worksheets, and the data will be 
entered into the EDC by sites.  
7.2
ELECTRONIC CASE REPORT FORMS 
eCRFs are to be completed through use of a Sponsor-designated EDC system.  Sites 
will receive training and have access to a manual for appropriate eCRF completion.  


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eCRFs will be submitted electronically to the Sponsor and should be handled in 
accordance with instructions from the Sponsor.
All eCRFs should be completed by designated, trained site staff.  eCRFs should be 
reviewed and electronically signed and dated by the investigator or a designee.
At the end of the study, the investigator will receive patient data for his or her site in a 
readable format on a compact disc that must be kept with the study records.  
Acknowledgement of receipt of the compact disc is required.
7.3
SOURCE DATA DOCUMENTATION
Study monitors will perform ongoing source data verification to confirm that critical 
protocol data (i.e., source data) entered into the eCRFs by authorized site personnel are 
accurate, complete, and verifiable from source documents. 
Source documents (paper or electronic) are those in which patient data are recorded 
and documented for the first time.  They include, but are not limited to, hospital records; 
clinical and office charts; laboratory notes; memoranda; PROs; evaluation checklists; 
pharmacy dispensing records; recorded data from automated instruments; copies of 
transcriptions that are certified after verification as being accurate and complete; 
microfiche; photographic negatives; microfilm or magnetic media; X-rays; patient files; 
and records kept at pharmacies, laboratories, and medico-technical departments 
involved in a clinical trial.
Before study initiation, the types of source documents that are to be generated will be 
clearly defined in the Trial Monitoring Plan.  This includes any protocol data to be 
entered directly into the eCRFs (i.e., no prior written or electronic record of the data) and 
considered source data.
Source documents that are required to verify the validity and completeness of data 
entered into the eCRFs must not be obliterated or destroyed and must be retained per 
the policy for retention of records described in Section 7.5.
To facilitate source data verification, the investigators and institutions must provide the 
Sponsor direct access to applicable source documents and reports for trial-related 
monitoring, Sponsor audits, and IRB/EC review.  The study site must also allow 
inspection by applicable health authorities.
7.4
USE OF COMPUTERIZED SYSTEMS
When clinical observations are entered directly into a study site’s computerized medical 
record system (i.e., in lieu of original hardcopy records), the electronic record can serve 
as the source document if the system has been validated in accordance with health 
authority requirements pertaining to computerized systems used in clinical research.  An 
acceptable computerized data collection system allows preservation of the original entry 


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of data.  If original data are modified, the system should maintain a viewable audit trail 
that shows the original data as well as the reason for the change, name of the person 
making the change, and date of the change.
7.5
RETENTION OF RECORDS
Records and documents pertaining to the conduct of this study and the distribution of 
IMP, including eCRFs, PRO data, ICFs, laboratory test results, and medication inventory 
records, must be retained by the Principal Investigator for at least 15 years after 
completion or discontinuation of the study or for the length of time required by relevant 
national or local health authorities, whichever is longer.  After that period of time, the 
documents may be destroyed, subject to local regulations.  
No records may be disposed of without the written approval of the Sponsor.  Written 
notification should be provided to the Sponsor prior to transferring any records to 
another party or moving them to another location.
8.
ETHICAL CONSIDERATIONS
8.1
COMPLIANCE WITH LAWS AND REGULATIONS
This study will be conducted in full conformance with the ICH E6 guideline for GCP and 
the principles of the Declaration of Helsinki or the laws and regulations of the country in 
which the research is conducted, whichever affords the greater protection to the 
individual.  The study will comply with the requirements of the ICH E2A guideline 
(Clinical Safety Data Management:  Definitions and Standards for Expedited Reporting).  
Studies conducted in the United States or under a U.S. Investigational New Drug (IND) 
Application will comply with U.S. FDA regulations and applicable local, state, and federal 
laws.  Studies conducted in the European Union or European Economic Area will comply 
with the E.U. Clinical Trial Directive (2001/20/EC).
8.2
INFORMED CONSENT
The Sponsor’s sample ICF (and ancillary sample ICFs, if applicable) will be provided to 
each site.  If applicable, it will be provided in a certified translation of the local language.  
The Sponsor or its designee must review and approve any proposed deviations from the 
Sponsor's sample ICFs or any alternate consent forms proposed by the site (collectively, 
the "Consent Forms") before IRB/EC submission.  The final IRB/ECapproved Consent 
Forms must be provided to the Sponsor for health authority submission purposes 
according to local requirements.
If applicable, the ICF will contain separate sections for any optional procedures.  The 
investigator or authorized designee will explain to each patient the objectives, methods, 
and potential risks associated with each optional procedure.  Patients will be told that 
they are free to refuse to participate and may withdraw their consent at any time for any 
reason.  A separate, specific signature will be required to document a patient's 


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agreement to participate in optional procedures.  Patients who decline to participate will 
not provide a separate signature.
The Consent Forms must be signed and dated by the patient before his or her 
participation in the study.  The case history or clinical records for each patient shall 
document the informed consent process and that written informed consent was obtained 
prior to participation in the study.
The Consent Forms should be revised whenever there are changes to study procedures 
or when new information becomes available that may affect the willingness of the patient 
to participate.  The final revised IRB/EC-approved Consent Forms must be provided to 
the Sponsor for health authority submission purposes.
Patients must be re-consented to the most current version of the Consent Forms (or to a 
significant new information/findings addendum in accordance with applicable laws and 
IRB/EC policy) during their participation in the study.  For any updated or revised 
Consent Forms, the case history or clinical records for each patient shall document the 
informed consent process and that written informed consent was obtained using the 
updated/revised Consent Forms for continued participation in the study.
A copy of each signed ICF must be provided to the patient.  All signed and dated 
Consent Forms must remain in each patient’s study file or in the site file and must be 
available for verification by study monitors at any time.
For sites in the United States, each ICF may also include patient authorization to allow 
use and disclosure of personal health information in compliance with the U.S. HIPAA of 
1996.  If the site utilizes a separate Authorization Form for patient authorization for use 
and disclosure of personal health information under the HIPAA regulations, the review, 
approval, and other processes outlined above apply except that IRB review and approval 
may not be required per study site policies.
8.3
INSTITUTIONAL REVIEW BOARD OR ETHICS COMMITTEE
This protocol, the Consent Forms, any information to be given to the patient, and 
relevant supporting information must be submitted to the IRB/EC by the Principal 
Investigator and reviewed and approved by the IRB/EC before the study is initiated.  
In addition, any patient recruitment materials must be approved by the IRB/EC. 
The Principal Investigator is responsible for providing written summaries of the status of 
the study to the IRB/EC annually or more frequently in accordance with the requirements, 
policies, and procedures established by the IRB/EC.  Investigators are also responsible 
for promptly informing the IRB/EC of any protocol amendments (see Section 9.6).
In addition to the requirements for reporting all adverse events to the Sponsor, 
investigators must comply with requirements for reporting serious adverse events to the 


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local health authority and IRB/EC.  Investigators may receive written IND safety reports 
or other safety-related communications from the Sponsor.  Investigators are responsible 
for ensuring that such reports are reviewed and processed in accordance with health 
authority requirements and the policies and procedures established by their IRB/EC, and 
archived in the site’s study file. 
8.4
CONFIDENTIALITY
The Sponsor maintains confidentiality standards by coding each patient enrolled in the 
study through assignment of a unique patient identification number.  This means that 
patient names are not included in datasets that are transmitted to any Sponsor location.
Patient medical information obtained by this study is confidential and may be disclosed 
to third parties only as permitted by the ICF (or separate authorization for use and 
disclosure of personal health information) signed by the patient, unless permitted or 
required by law.
Medical information may be given to a patient’s personal physician or other appropriate 
medical personnel responsible for the patient’s welfare, for treatment purposes.
Data generated by this study must be available for inspection upon request by 
representatives of national and local health authorities; Sponsor monitors, 
representatives, and collaborators; and the IRB/EC for each study site, as appropriate.
8.5
FINANCIAL DISCLOSURE
Investigators will provide the Sponsor with sufficient, accurate financial information in 
accordance with local regulations to allow the Sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate health authorities.  
Investigators are responsible for providing information on financial interests during the 
study and for 1 year after completion of the study (i.e., LPLV).
9.
STUDY DOCUMENTATION, MONITORING, AND 
ADMINISTRATION
9.1
STUDY DOCUMENTATION
The investigator must maintain adequate and accurate records to enable the conduct of 
the study to be fully documented, including, but not limited to, the protocol, protocol 
amendments, Consent Forms, and documentation of IRB/EC and governmental 
approval.  In addition, at the end of the study, the investigator will receive the patient 
data, including an audit trail containing a complete record of all changes to the data.
9.2
PROTOCOL DEVIATIONS
The investigator should document and explain any protocol deviations.  The investigator 
should promptly report any deviations that might have an impact on patient safety and 


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data integrity to the Sponsor and to the IRB/EC in accordance with established IRB/EC 
policies and procedures.
9.3
SITE INSPECTIONS
Site visits will be conducted by the Sponsor or an authorized representative for 
inspection of study data, patients’ medical records, and eCRFs.  The investigator will 
permit national and local health authorities; Sponsor monitors, representatives, and 
collaborators; and the IRBs/ECs to inspect facilities and records relevant to this study.
9.4
ADMINISTRATIVE STRUCTURE
This research study is being sponsored globally by F. Hoffmann-La Roche Ltd of Basel, 
Switzerland and may be implemented in individual countries by Roche’s local affiliates.  
The Sponsor will perform project management, study management, monitoring, vendor 
management, and statistical programming.  An IxRS will be used for patient 
randomization and for management of study drug requests and shipments.  
A central laboratory will be used for most laboratory assessments and for storage of 
other laboratory samples (i.e., anti-lampalizumab antibody serum samples) prior to being 
shipped to Sponsor or its designee for analysis.  Data will be recorded by an EDC 
system using eCRFs (see Section 7.1) or forwarded to Sponsor electronically.  A central 
reading center will be used for ocular imaging analyses (i.e., FAF, NI, CFP, FA, and 
SD-OCT) and microperimetry data, which will be forwarded to the Sponsor electronically.
9.5
PUBLICATION OF DATA AND PROTECTION OF 
TRADE SECRETS
Regardless of the outcome of a trial, the Sponsor is dedicated to openly providing 
information on the trial to healthcare professionals and to the public, both at scientific 
congresses and in peer-reviewed journals. The Sponsor will comply with all 
requirements for publication of study results.  For more information, refer to the Roche 
Global Policy on Sharing of Clinical Trials Data at the following Web site:
http://www.rochetrials.com/pdf/RocheGlobalDataSharingPolicy.pdf
The results of this study may be published or presented at scientific congresses.  For all 
clinical trials in patients involving an IMP for which a marketing authorization application 
has been filed or approved in any country, the Sponsor aims to submit a journal 
manuscript reporting primary clinical trial results within 6 months after the availability of 
the respective clinical study report.  In addition, for all clinical trials in patients involving 
an IMP for which a marketing authorization application has been filed or approved in any 
country, the Sponsor aims to publish results from analyses of additional endpoints and 
exploratory data that are clinically meaningful and statistically sound.
The investigator must agree to submit all manuscripts or abstracts to the Sponsor prior 
to submission for publication or presentation.  This allows the Sponsor to protect 


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proprietary information and to provide comments based on information from other 
studies that may not yet be available to the investigator.
In accordance with standard editorial and ethical practice, the Sponsor will generally 
support publication of multicenter trials only in their entirety and not as individual center 
data.  In this case, a coordinating investigator will be designated by mutual agreement.
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors’ authorship requirements.  Any formal publication 
of the study in which contribution of Sponsor personnel exceeded that of conventional 
monitoring will be considered as a joint publication by the investigator and the 
appropriate Sponsor personnel.
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of data from this study will become and remain the exclusive and unburdened 
property of the Sponsor, except where agreed otherwise.
9.6
PROTOCOL AMENDMENTS
Any protocol amendments will be prepared by the Sponsor.  Protocol amendments will 
be submitted to the IRB/EC and to regulatory authorities in accordance with local 
regulatory requirements.
Approval must be obtained from the IRB/EC and regulatory authorities (as locally 
required) before implementation of any changes, except for changes necessary to 
eliminate an immediate hazard to patients or changes that involve logistical or 
administrative aspects only (e.g., change in Medical Monitor or contact information).


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10.
REFERENCES
de Jong PT. Age-related macular degeneration. N Engl J Med 2006;355:147485.
Friedman DS, O’Colmain BJ, Muñoz B, et al. Prevalence of age-related macular 
degeneration in the United States. Arch Ophthalmol 2004;122:56472.
Fritsche L, Chen W, Schu M, et al. Seven new loci associated with age-related macular 
degeneration. Nat Genet 2013;45:4339.
Lindblad AS, Clemons TE. Responsiveness of the National Eye Institute Visual Function 
Questionnaire to progression to advanced age-related macular degeneration, 
vision loss, and lens opacity: AREDS report number 14. Arch Ophthalmol 
2005;123:120714.
Lindblad AS, Lloyd PC, Clemons TE, et al. Change in area of geographic atrophy in the 
Age-Related Eye Disease Study: AREDS report number 26. Arch Ophthalmol 
2009;127:116874.
Rohrer B, Guo Y, Kunchithapautham K, et al. Eliminating complement factor D reduces 
photoreceptor susceptibility to light-induced damage. Invest Ophthalmol Vis Sci 
2007;48:52829.
Rudnicka AR, Jarrar Z, Wormald R, et al. Age and gender variations in age-related 
macular degeneration prevalence in populations of European ancestry: a 
meta-analysis. Ophthalmology 2012;119:57180.
Scholl HPN, Charbel Issa P, Walier M, et al. Systemic complement activation in
age-related macular degeneration. PLoS One 2008;3:e2593.
Sunness JS, Schuchard R, Shen N, et al. Landmark-driven fundus perimetry using the 
scanning laser ophthalmoscope. Invest Ophthalmol Vis Sci 1995;36:186374.
Sunness JS, Applegate CA, Haselwood D, et al. Fixation patterns and reading rates in 
eye with central scotomas from advanced atrophic age-related macular 
degeneration and Stargardt disease. Ophthalmology 1996;103:145866.
Sunness JS, Bressler NM, Tian Y, et al. Measuring geographic atrophy in advanced 
age-related macular degeneration. Invest Ophthalmol Vis Sci 1999a;40:17619.
Sunness JS, Gonzalez-Baron J, Applegate CA, et al. Enlargement of atrophy and visual 
acuity loss in the geographic atrophy form of age-related macular degeneration. 
Ophthalmology 1999b;106:176879.
Yates JRW, Sepp T, Matharu BK, et al. Complement C3 variant and the risk of 
age-related macular degeneration. N Engl J Med 2007;357:55361.


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Appendix 1
Schedule of Assessments
Table 1
Study Flowchart for Q4W Arm:  Day 1, Week 4 through Week 52, and Early Termination
Assessment Window (Days)
Day 1 a
Week
ET b
Data Extracted 
from Parent 
Study
Data 
Obtained at 
Day 1 Visit
4
8
12
16
20
24
28
32
36
40
44
48
52
30
5
5
5
5
5
5
5
5
5
5
5
5
5
Written informed consent
x c
Review of inclusion and exclusion 
criteria 
x
Demographic information (age, sex, 
and self-reported race/ethnicity)d
x
NEI VFQ-25e (as applicable)
x
x
x
x
FRI Indexe (as applicable)
x
x
x
x
Vital signsf
x
Central laboratory samples 
(hematology, coagulation, chemistry 
panel, and urinalysis) g
x
Biomarker plasma sample g
x
Urine pregnancy testg, h
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Serum ATA sampleg
x
x
x


Appendix 1
Schedule of Assessments (cont.)
Lampalizumab—F. Hoffmann-La Roche Ltd
77/Protocol GX30191, Version 2
Table 1
Study Flowchart for Q4W Arm:  Day 1, Week 4 through Week 52, and Early Termination (cont.)
Assessment Window(Days)
Day 1 a
Week
ET b
Data 
Extracted 
from Parent 
Study
Data 
Obtained 
at Day 1 
Visit
4
8
12
16
20
24
28
32
36
40
44
48
52
30
5
5
5
5
5
5
5
5
5
5
5
5
5
Serum PK sample for 
lampalizumab concentration g
x
x
x
Optional aqueous sampleg, i
x
BCVA testing (starting at 4 m)j
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
LL BCVA testing (starting at 4 m) j
x
x
x
x
x
MNRead or Radner Reading 
Chartsj, k (as applicable)
x
x
x
Pretreatment IOP measurementj
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Mesopic microperimetry at 
selected sites (study eye only)l
x
x
x
Slit lamp examination
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Dilated binocular indirect 
ophthalmoscopy
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
FAFm
x
x
x
x
x
SD-OCT m
x
x
x
x
Near-infrared imagingm
x
x
x
x
x


Appendix 1
Schedule of Assessments (cont.)
Lampalizumab—F. Hoffmann-La Roche Ltd
78/Protocol GX30191, Version 2
Table 1
Study Flowchart for Q4W Arm:  Day 1, Week 4 through Week 52, and Early Termination (cont.)
Assessment Window(Days)
Day 1 a
Week
ET b
Data 
Extracted 
from Parent 
Study
Data 
Obtained 
at Day 1 
Visit
4
8
12
16
20
24
28
32
36
40
44
48
52
30
5
5
5
5
5
5
5
5
5
5
5
5
5
Color fundus photographym
x
x
x
Fluorescein angiographym
x
x
Administration of lampalizumab 
injection to study eye
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Post-treatment finger-counting 
and IOP measurementn
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Concomitant medicationso
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Adverse eventsp
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Concurrent ocular proceduresq
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Follow-up call r
x
x
x
x
x
x
x
x
x
x
x
x
x
x
ATAanti-therapeutic antibody; BCVAbest corrected visual acuity; eCRF electronic Case Report Form; ETearly termination; FAFfundus 
autofluorescence; FRIFunctional Reading Independence; ICF informed consent form; IOPintraocular pressure; LL BCVA low-luminance 
BCVA; MNReadMinnesota Low-Vision Reading Test; NEI VFQ-25National Eye Institute Visual Functioning Questionnaire 25-Item Version; 
OLEopen-label extension; PKpharmacokinetic; Q4W every 4 weeks; SD-OCTspectral domainoptical coherence tomography; VA visual 
acuity.
Note:  All ocular assessments are to be performed for both eyes unless noted otherwise.  All assessments are to be performed on the same day 
except for study laboratory sample collections, which can be collected up to 7 days before or after scheduled visit. The study drug injection may 
be delayed for reasons specified in the Section 3.1.1.  All study visits will be scheduled relative to date of Day 1 visit.


Appendix 1
Schedule of Assessments (cont.)
Lampalizumab—F. Hoffmann-La Roche Ltd
79/Protocol GX30191, Version 2
Table 1
Study Flowchart for Q4W Arm:  Day 1, Week 4 through Week 52, and Early Termination (cont.)
a The Day 1 visit will be performed on the same day as the Week 96 visit in the parent study.  If a site is not able to collect images at the Week 96 
visit of the parent study, the Day 1 visit study treatment will be interrupted and the images will be collected as soon as possible and prior to 
study treatment administration at the next study treatment visit (e.g., Week 4 or Week 6).  The reason for study treatment interruption at 
Day 1 visit will be recorded on the study treatment interruption eCRF.
b For patients who discontinue from the study, early termination assessments will be performed after a minimum of 30 days has elapsed following 
the last study drug treatment.
c At the sites where investigator intends to ask his patients to self-administer antimicrobials pre and post injection, the ICF needs to be signed at 
an earlier date (e.g., Week 90 or 92 visit in parent study) in order to allow the ICF to be in place prior to the patient receiving pre-injection 
antimicrobials.  In addition, during the Week 96 visit, if the ICF is signed prior to completion of the Week 96 assessments of the parent study, 
then the Week 96 parent study blood draws and the Day 1 OLE blood draw can be performed at the same time.
d The sites will transcribe demographics data from the parent study to OLE RAVE eCRF.
e To be administered by the site staff (except for the VA examiner) prior to any other visit assessments being performed on that day.  
f
Vital signs include measurements of temperature, respiratory rate, pulse rate, and systolic and diastolic blood pressure while the patient is in a 
seated position after resting for 5 minutes.
g If laboratory sample is being obtained on study visit day, it must obtained prior to fluorescein angiography (if applicable) and prior to study drug 
treatment.
h Starting on Day 1, collect and perform the urine pregnancy test for women of childbearing potential, including those who have had tubal ligation, 
at each study drug treatment visit.  If positive, collect the serum pregnancy sample and forward to central laboratory for testing, do not administer 
study drug, and if positive, withdraw the patient from the study.  
i Optional aqueous sample will be collected from the patients who consented to it.
j
Perform prior to dilating the eyes.
k Either MNRead charts or Radner Reading Charts will be performed during the study visit prior to dilating the eyes (see the tables in Appendix 14
and Appendix 15, respectively, for which chart to use according to country of the site).  The test will be administered first monocularly (right/left 
eye) and then binocularly (both eyes).
l
To be performed post-dilation on the study eye only; the data will be forwarded to the central reading center.
m Performed for both eyes; results will be forwarded to the central reading center.  See the center reading center manual.  If a patient misses a 
study visit when ocular images are scheduled to be obtained, the images should be obtained at the next scheduled visit.  


Appendix 1
Schedule of Assessments (cont.)
Lampalizumab—F. Hoffmann-La Roche Ltd
80/Protocol GX30191, Version 2
Table 1
Study Flowchart for Q4W Arm:  Day 1, Week 4 through Week 52, and Early Termination (cont.)
n Finger-counting test followed by hand-motion and light-perception tests (when necessary) will be performed by the physician within 15 minutes 
after study drug treatment.  At study drug treatment visits, post-treatment IOP measurement in the study eye only between 30 and 50 minutes 
post-treatment with study drug will be performed by the qualified site staff (except for the VA examiner).  If the IOP is increased by 10 mmHg 
from pre-treatment, the IOP will be measured again 6080 minutes post-treatment.  If there are no safety concerns, the patient will be permitted 
to leave the clinic.  If the IOP value is of concern to the investigator, the patient will remain in the clinic and will be managed in accordance with 
the investigator’s clinical judgment.  Both the last post-treatment IOP measured prior to any intervention for increased IOP (if applicable) and the 
last post-intervention IOP (if applicable) will be recorded on the Post-Treatment IOP eCRF.  If the study eye is treated with a Lucentisinjection 
during the same visit as study drug treatment, the treatment with Lucentis must be performed first.  Measure and record the post-Lucentis 
treatment IOP value on the eCRF.
o Record on the concomitant medications log any concomitant medications (i.e., any prescription medications or over-the-counter preparations 
other than protocol-specified procedural medications, such as proparacaine) that patients continue taking (no stop date) after the Week 96 visit 
of the parent study is completed or concomitant medications that patients started during the extension study.  Record concomitant 
medications through the patient’s early termination visit.
p Any adverse events ongoing after the Week 96 visit from the parent study is complete should be transcribed to OLE Adverse Events eCRF log. 
After the Week 96 visit completion for the parent study, new adverse events will be recorded in the extension study through a minimum of
30 days after the last dose of study drug or the last study visit, whichever is later.  Adverse events assessed by the investigator as related to 
the study drug should be followed until the event resolves or until the event is assessed as irreversible, chronic, or stable, even if patient’s 
participation in the study has ended.  
q Record all concurrent ocular procedures performed during the extension study on the study eye or non-study eye.
r
Patients will be contacted by study site personnel 4 (2) days after each study drug treatment to elicit reports of any decrease in vision, eye pain, 
unusual redness, or any other new ocular symptoms in the study eye.  At sites where the investigator’s decision is for the patients to take pre-
and post-treatment antimicrobials, patients will also be asked whether they have taken the prescribed, self-administered, post-treatment 
antimicrobials.  Patients will be instructed to contact the investigator at any time if they have any health-related concerns.  If warranted, patients 
will be asked to return to the clinic as soon as possible for a safety assessment visit.


Appendix 1
Schedule of Assessments (cont.)
Lampalizumab—F. Hoffmann-La Roche Ltd
81/Protocol GX30191, Version 2
Table 2
Study Flowchart for Q4W Arm:  Week 56 through Week 96 and Early Termination
Assessment Window (Days)
Week
ET a
56
60
64
68
72
76
80
84
88
92
96 b
30
5
5
5
5
5
5
5
5
5
5
5
NEI VFQ-25c (as applicable)
x
x
FRI Indexc (as applicable)
x
x
Vital signs
x
Central laboratory samples (hematology, coagulation, chemistry 
panel, and urinalysis) d
x
Urine pregnancy testd, e
x
x
x
x
x
x
x
x
x
x
x
Serum ATA sampled
x
x
Serum PK sample for lampalizumab concentrationd
x
x
Optional aqueous sampled, f
x
BCVA testing (starting at 4 m)g
x
x
x
x
x
x
x
x
x
x
x
x
LL BCVA (starting at 4 m)g
x
x
MNRead or Radner Reading Chartsg, h (as applicable)
x
x
Pretreatment IOP measurementg
x
x
x
x
x
x
x
x
x
x
x
x
Mesopic microperimetry at selected sites (study eye only)i
x
x
Slit lamp examination
x
x
x
x
x
x
x
x
x
x
x
x
Dilated binocular indirect ophthalmoscopy
x
x
x
x
x
x
x
x
x
x
x
x
FAFj
x
x
x
SD-OCTj
x
x
x


Appendix 1
Schedule of Assessments (cont.)
Lampalizumab—F. Hoffmann-La Roche Ltd
82/Protocol GX30191, Version 2
Table 2
Study Flowchart for Q4W Arm:  Week 56 through Week 96 and Early Termination (cont.)
Assessment Window (Days)
Week
ET a
56
60
64
68
72
76
80
84
88
92
96 b
30
5
5
5
5
5
5
5
5
5
5
5
Near-infrared imagingj
x
x
x
Color fundus photographyj
x
x
Fluorescein angiographyj
x
Administration of lampalizumab injection to study eye 
x
x
x
x
x
x
x
x
x
x
x
Post-treatment finger counting and IOP measurementk
x
x
x
x
x
x
x
x
x
x
x
Concomitant medicationsl
x
x
x
x
x
x
x
x
x
x
x
x
Adverse eventsm
x
x
x
x
x
x
x
x
x
x
x
x
Concurrent ocular proceduresn
x
x
x
x
x
x
x
x
x
x
x
x
Follow-up callo
x
x
x
x
x
x
x
x
x
x
x
ATAanti-therapeutic antibody; BCVAbest corrected visual acuity; eCRF electronic Case Report Form; ETearly termination; FAFfundus 
autofluorescence; FRIFunctional Reading Independence; IOPintraocular pressure; LL BCVA low-luminance BCVA; MNReadMinnesota 
Low-Vision Reading Test; NEI VFQ-25National Eye Institute Visual Functioning Questionnaire 25-Item Version; OLEopen-label extension; 
PKpharmacokinetic; Q4W every 4 weeks; SD-OCTspectral domainoptical coherence tomography; VA visual acuity.
The study drug injection may be delayed for reasons specified in Section 3.1.1.  All study visits will be scheduled relative to the Day 1 visit date.
a For patients who discontinue from the study, early termination assessments will be performed after a minimum of 30 days has elapsed following 
the last study drug treatment.


Appendix 1
Schedule of Assessments (cont.)
Lampalizumab—F. Hoffmann-La Roche Ltd
83/Protocol GX30191, Version 2
Table 2
Study Flowchart for Q4W Arm:  Week 56 through Week 96 and Early Termination (cont.)
b This study may potentially extend beyond Week 96.  The sites will be informed in timely manner. 
c To be administered by the site staff (except for the VA examiner) prior to any other visit assessments being performed on that day.  
d If laboratory sample is being obtained on study visit day, it must be obtain prior to fluorescein angiography (if applicable) and prior to study drug 
treatment.
e Starting on Day 1, collect and perform the urine pregnancy test for women of childbearing potential, including those who have had tubal ligation, 
at each study drug treatment visit.  If positive, collect the serum pregnancy sample and forward to central laboratory for testing, do not administer 
study drug, and if positive withdraw the patient from the study.  
f
Optional aqueous sample will be collected from the patients who consented to it.
g Perform prior to dilating the eyes.
h Either MNRead charts or Radner Reading Charts will be performed during the study visit prior to dilating the eyes (see the tables in Appendix 14
and Appendix 15, respectively, for which chart to use according to country of the site).  The test will be administered first monocularly (right/left 
eye) and then binocularly (both eyes).
i
To be performed post-dilation on the study eye only; the data will be forwarded to the central reading center.
j
Performed for both eyes; and results will be forwarded to the central reading center.  See the center reading center manual.  If a patient misses a 
study visit when ocular images are scheduled to be obtained, the images should be obtained at the next scheduled visit.  
k Finger-counting test followed by hand-motion and light-perception tests (when necessary) will be performed by the physician within 15 minutes 
after study drug treatment.  At study drug treatment visits, post-treatment IOP measurement in the study eye only between 30 and 50 minutes 
post-treatment with study drug will be performed by the qualified site staff (except for the VA examiner).  If the IOP is increased by 10 mmHg 
from pretreatment, the IOP will be measured again 6080 minutes post-treatment.  If there are no safety concerns, the patient will be permitted 
to leave the clinic.  If the IOP value is of concern to the investigator, the patient will remain in the clinic and will be managed in accordance with 
the investigator’s clinical judgment.  Both the last post-treatment IOP measured prior to any intervention for increased IOP (if applicable) and the 
last post-intervention IOP (if applicable) will be recorded on the Post-Treatment IOP eCRF.  If the study eye is treated with a Lucentisinjection 
during the same visit as study drug treatment, the treatment with Lucentis must be performed first.  Measure and record the post-Lucentis 
treatment IOP value on the eCRF.


Appendix 1
Schedule of Assessments (cont.)
Lampalizumab—F. Hoffmann-La Roche Ltd
84/Protocol GX30191, Version 2
Table 2
Study Flowchart for Q4W Arm:  Week 56 through Week 96 and Early Termination (cont.)
l
Record on the concomitant medications log any concomitant medications (i.e., any prescription medications or over-the-counter preparations 
other than protocol-specified procedural medications, such as proparacaine) that patients continue taking (no stop date) after the Week 96 visit 
of the parent study is completed or concomitant medications that patients started during the extension study. Record concomitant 
medications through the patient’s early termination visit.
m Any adverse events ongoing from the parent study after Week 96 completion should be transcribed to OLE Adverse Events eCRF log. After 
the Week 96 visit completion for the parent study, new adverse events will be recorded in the extension study through minimum of 30 days 
after the last dose of study drug or the last study visit, whichever is later.
n Record all concurrent ocular procedures performed during the extension study on the study eye or non-study eye.
o Patients will be contacted by study site personnel 4 (2) days after each study drug treatment to elicit reports of any decrease in vision, eye pain, 
unusual redness, or any other new ocular symptoms in the study eye.  At sites where the investigator’s decision is for the patients to take pre-
and post-treatment antimicrobials, patients will also be asked whether they have taken the prescribed, self-administered, post-treatment 
antimicrobials.  Patients will be instructed to contact the investigator at any time if they have any health-related concerns.  If warranted, patients 
will be asked to return to the clinic as soon as possible for a safety assessment visit.


Appendix 1
Schedule of Assessments (cont.)
Lampalizumab—F. Hoffmann-La Roche Ltd
85/Protocol GX30191, Version 2
Table 3
Study Flowchart for Q6W Arm:  Day 1, Week 6 through Week 96, and Early Termination
Assessment Windows (Days)
Day 1 a
Week
ET b
Data 
Extracted 
from 
Parent 
Study
Data
Obtained 
at Day 1 
Visit
6
12
18
24
30
36
42
48
54
60
66
72
78
84
90
96 c
30
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
Written informed consent
x d
Review of inclusion and 
exclusion criteria
x
Demographic information (age, 
sex, self-reported 
race/ethnicity)e
x
NEI VFQ-25 f (as applicable)
x
x
x
x
x
FRI Indexf (as applicable)
x
x
x
x
x
Vital signsg
x
Central laboratory samples 
(hematology, coagulation, 
chemistry, panel, and 
urinalysis)h
x
Biomarker plasma sampleh
x
Urine pregnancy testh, i
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x


Appendix 1
Schedule of Assessments (cont.)
Lampalizumab—F. Hoffmann-La Roche Ltd
86/Protocol GX30191, Version 2
Table 3
Study Flowchart for Q6W Arm:  Day 1, Week 6 through Week 96, and Early Termination (cont.)
Assessment Windows (Days)
Day 1 a
Week
ET b
Data 
Extracted 
from 
Parent 
Study
Data 
Obtained 
at Day 1 
Visit
6
12
18
24
30
36
42
48
54
60
66
72
78
84
90
96 c
30
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
Serum ATA sampleh
x
x
x
x
Serum PK sample for 
lampalizumab concentrationh
x
x
x
x
Optional aqueous sampleh, j
x
x
BCVA testing (starting at 4 m)k
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
LL BCVA testing (starting at 
4 m)k
x
x
x
x
x
x
MNRead or Radner Reading 
Chartsk, l (as applicable)
x
x
x
x
Pretreatment IOP 
measurementk
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Mesopic microperimetry at 
selected sites (study eye 
only) m
x
x
x
x
Slit lamp examination
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Dilated binocular indirect 
ophthalmoscopy
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
FAFn
x
x
x
x
x
x
x


Appendix 1
Schedule of Assessments (cont.)
Lampalizumab—F. Hoffmann-La Roche Ltd
87/Protocol GX30191, Version 2
Table 3
Study Flowchart for Q6W Arm:  Day 1, Week 6 through Week 96, and Early Termination (cont.)
Assessment Windows (Days)
Day 1 a
Week
ET
b
Data 
Extracted 
from 
Parent 
Study
Data 
Obtained 
at Day 1 
Visit
6
12
18
24
30
36
42
48
54
60
66
72
78
84
90
96 c
30
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
SD-OCT n
x
x
x
x
x
x
Near-infrared imagingn
x
x
x
x
x
x
x
Color fundus photographyn
x
x
x
x
Fluorescein angiographyn
x
x
Administration of 
lampalizumab injection to 
study eye
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Post-treatment finger counting 
and IOP measuremento
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Concomitant medicationsp
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Adverse eventsq
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Concurrent ocular proceduresr
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Follow-up call s
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
ATAanti-therapeutic antibody; BCVAbest corrected visual acuity; eCRF electronic Case Report Form; ET early termination; FAFfundus 
autofluorescence; FRI Index Functional Reading Independence Index; ICFinformed consent form; IOPintraocular pressure; 
LL BCVA low-luminance BCVA; MNReadMinnesota Low-Vision Reading Test; NEI VFQ-25National Eye Institute Visual Functioning 
Questionnaire 25-Item Version; OLEopen-label extension; PKpharmacokinetic; Q6W every 6 weeks; SD-OCTspectral domainoptical 
coherence tomography; VA visual acuity.


Appendix 1
Schedule of Assessments (cont.)
Lampalizumab—F. Hoffmann-La Roche Ltd
88/Protocol GX30191, Version 2
Table 3
Study Flowchart for Q6W Arm:  Day 1, Week 6 through Week 96, and Early Termination (cont.)
Note:  All ocular assessments are to be performed for both eyes unless noted otherwise.  All assessments are to be performed on the same day 
except for study laboratory sample collection, which can be collected up to 7 days before or after scheduled visit. The study drug injection may be 
delayed for reasons specified in Section 3.1.1. All study visits will be scheduled relative to the Day 1 visit date.
a Day 1 visit will be performed on the same day as Week 96 visit in parent study. If a site is not able to collect images at parent study Week 96 
visit then Day 1 visit study treatment will be interrupted and the images will be collected as soon as possible and prior to study treatment 
administration at the next study treatment visit (e.g. Week 4 or Week 6).  The reason for study treatment interruption at Day 1 visit will be 
recorded on the study treatment interruption eCRF.
b For patients who discontinue early from the study, early termination assessments will be performed after a minimum of 30 days has elapsed 
following the last study drug treatment.
c This study may potentially extend beyond the Week 96 visit.  The sites will be informed in timely manner.
d At the sites where investigator intends to ask his patients to self-administer antimicrobials pre and post injection, the ICF needs to be signed at 
an earlier date (e.g., Week 90 or 92 visit in parent study) in order to allow the ICF to be in place prior to the patient receiving pre-injection 
antimicrobials.  In addition, during the Week 96 visit, if the ICF is signed prior to completion of the Week 96 assessments of the parent study, 
then the Week 96 parent study blood draws and the Day 1 OLE blood draw can be performed at the same time.
e The sites will transcribe demographics data from the parent study to OLE RAVE eCRF.
f
To be administered by the site staff (except for the VA examiner) prior to any other visit assessments being performed on that day.
g Vital signs include measurements of temperature, respiratory rate, pulse rate, and systolic and diastolic blood pressure while the patient is in a 
seated position after resting for 5 minutes.
h If laboratory sample is being obtained on study visit day, it must be obtain prior to fluorescein angiography (if applicable) and prior to study drug 
treatment.
i
Starting on Day 1, collect and perform the urine pregnancy test for women of childbearing potential, including those who have had tubal ligation, 
at each study drug treatment visit.  If positive, collect the serum pregnancy sample and forward to central laboratory for testing, do not administer 
study drug, and if positive, withdraw the patient from the study.
j
Optional aqueous sample will be collected from the patients who consented to it
k Perform prior to dilating the eyes.
l
Either MNRead charts or Radner Reading Charts will be performed during the study visit prior to dilating the eyes (see the tables in Appendix 14
and Appendix 15, respectively, for which chart to use according to country of the site).  The test will be administered first monocularly (right/left 
eye) and then binocularly (both eyes).


Appendix 1
Schedule of Assessments (cont.)
Lampalizumab—F. Hoffmann-La Roche Ltd
89/Protocol GX30191, Version 2
Table 3
Study Flowchart for Q6W Arm:  Day 1, Week 6 through Week 96, and Early Termination (cont.)
m To be performed post-dilation on the study eye only; the data will be forwarded to the central reading center.
n Performed for both eyes; results will be forwarded to the central reading center.  See the center reading center manual.  If a patient misses a 
study visit when ocular images are scheduled to be obtained, the images should be obtained at the next scheduled visit.  
o Finger-counting test followed by hand-motion and light-perception tests (when necessary) will be performed by the physician within 15 minutes 
after study drug treatment.  At study drug treatment visits, post-treatment IOP measurement in the study eye only between 30 and 50 minutes 
post-treatment with study drug will be performed by the qualified site staff (except for the VA examiner).  If the IOP is increased by 10 mmHg 
from pretreatment, the IOP will be measured again 6080 minutes post-treatment.  If there are no safety concerns, the patient will be permitted 
to leave the clinic.  If the IOP value is of concern to the investigator, the patient will remain in the clinic and will be managed in accordance with 
the investigator’s clinical judgment.  Both the last post-treatment IOP measured prior to any intervention for increased IOP (if applicable) and the 
last post-intervention IOP (if applicable) will be recorded on the Post-Treatment IOP eCRF.  If the study eye is treated with a Lucentisinjection 
during the same visit as study drug treatment, the treatment with Lucentis must be performed first.  Measure and record the post-Lucentis 
treatment IOP value on the eCRF.
p Record on the concomitant medications log any concomitant medications (i.e., any prescription medications or over-the-counter preparations 
other than protocol-specified procedural medications, such as proparacaine) that patients continue taking (no stop date) after the Week 96 visit 
of the parent study is completed or concomitant medications that patients started during the extension study  Record concomitant 
medications through the patient’s early termination visit.  
q Any adverse events ongoing from the parent study after Week 96 completion should be transcribed to OLE Adverse Events eCRF log.  After 
the Week 96 visit completion for the parent study, new adverse events will be recorded in the extension study through minimum of 30 days 
after the last dose of study drug or the last study visit, whichever is later.  Adverse events assessed by the investigator as related to the study 
drug should be followed until the event resolves or until the event is assessed as irreversible, chronic, or stable, even if patient’s participation in 
the study has ended.  
r
Record all concurrent ocular procedures performed during the study on the study eye or non-study eye.
s Patients will be contacted by study site personnel 4 (2) days after each study drug treatment to elicit reports of any decrease in vision, eye pain, 
unusual redness, or any other new ocular symptoms in the study eye.  At sites where the investigator’s decision is for the patients to take pre-
and post-treatment antimicrobials, patients will also be asked whether they have taken the prescribed, self-administered, post-treatment 
antimicrobials.  Patients will be instructed to contact the investigator at any time if they have any health-related concerns.  If warranted, patients 
will be asked to return to the clinic as soon as possible for a safety assessment visit.


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Appendix 2
Study Flowchart:  Unscheduled Safety Assessment Visit
Assessmentsa
Vital signs (blood pressure, respiration rate, pulse, and temperature)
Best corrected visual acuity (4-m starting distance)b
Slit-lamp examination
Dilated binocular indirect high-magnification ophthalmoscopy
IOPc
Adverse eventsd
Concurrent ocular procedures
Concomitant medications
IOPintraocular pressure.
a If determined to be necessary by the investigator, perform the listed assessments.  All ocular 
assessments should be performed on both eyes.
b Perform finger-counting test followed by hand-motion and light-perception tests when 
necessary.
c The method used for the IOP measurement for a patient must remain consistent throughout 
the study.
d Adverse event causality to be evaluated by the qualified ophthalmologist.


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Appendix 3
Grading Scale for Assessment of Anterior Chamber Flare or 
Cells and Vitreous Cells
Table 1
Grading Scale for Anterior Chamber Flare or Cells
Grade
Description
Flare
0
No protein is visible in the anterior chamber when viewed by an experienced observer 
using slit lamp biomicroscopy; a small, bright, focal slit beam of white light; and high 
magnification.
Trace
Trace amount of protein is detectable in the anterior chamber.  This protein is visible 
only with careful scrutiny by an experienced observer using slit lamp biomicroscopy; a 
small, bright, focal slit beam of white light; and high magnification.
1
Slight amount of protein is detectable in the anterior chamber.  The presence of protein 
in the anterior chamber is immediately apparent to an experienced observer using slit 
lamp biomicroscopy and high magnification, but such protein is detected only with 
careful observation with the naked eye and a small, bright, focal slit-beam of white light.
2 to 3
Moderate amount of protein is detectable in the anterior chamber.  These grades are 
similar to 1, but the opacity would be readily visible to the naked eye of an observer 
using any source of a focused beam of white light.  This is a continuum of moderate 
opacification, with 2being less apparent than 3.
4
A large amount of protein is detectable in the anterior chamber.  This grade is similar to 
3, but the density of the protein approaches that of the lens.  Additionally, frank fibrin 
deposition is frequently seen in acute circumstances.  It should be noted that, because 
fibrin may persist for a period of time after partial or complete restoration of the 
bloodaqueous barrier, it is possible to have resorbing fibrin present with lower numeric 
assignations for flare (e.g., 1flare with fibrin).
Cells
0
No cells are seen in any optical section when a large slit lamp beam is swept across the 
anterior chamber.
Trace
Few (13) cells are observed when the slit lamp beam is swept across the anterior 
chamber.  When the instrument is held stationary, not every optical section contains 
circulating cells.
1
310 cells per optical section are seen when the slit lamp beam is swept across the 
anterior chamber.  When the instrument is held stationary, every optical section contains 
circulating cells.
2
1025 cells are seen when the slit lamp beam is swept across the anterior chamber.  
When the instrument is held stationary, every optical section contains circulating cells.
3
2550 cells are seen when the slit lamp beam is swept across the anterior chamber.  
When the instrument is held stationary, every optical section contains circulating cells.  
Keratic precipitates or cellular deposits on the anterior lens capsule may be present.
4
More than 50 cells are seen when the slit lamp beam is swept across the anterior 
chamber.  When the instrument is held stationary, every optical section contains cells or 
hypopyon is noted.  With regard to fibrin deposition, hypopyon may persist for some 
period of time after the active exudation of cells into the anterior chamber has diminished 
or ceased entirely, making it possible to have 1circulating cells in the anterior chamber 
with a resolving hypopyon.
Modified from:  Hogan et al. (1959).


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Appendix 3
Grading Scale for Assessment of Anterior Chamber Flare or 
Cells and Vitreous Cells (cont.)
Table 2
Grading Scale for Vitreous Cells
Cells in Retro-Illuminated Field
Description
Grade
0
Clear
0
120
Few opacities
Trace
2150
Scattered opacities
1
51100
Moderate opacities
2
101250
Many opacities
3
251
Dense opacities
4
Modified from:  Nussenblatt et al. (1996).
REFERENCES
Hogan MH, Kimura SJ, Thygeson P. Signs and symptoms of uveitis. I. Anterior uveitis. 
Am J Ophthalmol 1959;47(5, Part 2):15570.
Nussenblatt RB, Whitcup SM, Palestine AG. Uveitis: fundamentals and clinical practice. 
2nd revised ed. St Louis: Mosby, 1996;64.


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Appendix 4
Best Corrected Visual Acuity Testing
SCOPE
Best corrected visual acuity will be measured by trained and certified personnel at the 
study sites.  The visual acuity (VA) examiner will be masked to patients’ study eye 
assignment.  VA will be measured at the intervals specified in the protocol (see 
Section 4.5.4 and Appendix 1). 
EQUIPMENT
The following are needed to conduct the examination:

Examination lane of adequate dimensions to allow testing at required distances

Standard chair with a firm back

Set of three Precision Visionor Lighthouse distance acuity charts (modified Early 
Treatment Diabetic Retinopathy Study Charts R, 1, and 2 in the United States and 
Charts 1, 2, and 3 in the European Union)

Retro-illuminated box

Study frame

Study lens set
TRAINING AND CERTIFICATION
A VA specifications document, procedure manual, and training materials will be provided 
to the investigational sites, and examiner certification will be obtained.  The VA 
examination room also must be certified before any VA examinations are performed.


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Appendix 5
Low-Luminance Best Corrected Visual Acuity Testing
There are the same requirements as the best corrected visual acuity described in
Appendix 4; however, low-luminance visual acuity will be measured by placing a 
2.0-logunit neutral density filter (Kodak Wratten 2.0 Neutral Density Filter) over the best 
correction for that eye and having the participant read the normally illuminated Early 
Treatment Diabetic Retinopathy Study Chart. 


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Appendix 6
Color Fundus Photography
SCOPE
Stereo color fundus photographs will be obtained by trained personnel at the study sites.  
Fundus photography will be performed at the intervals specified in the protocol 
(see Appendix 1).  Analysis (if applicable) of fundus photographs will be performed by 
the Central Reading Center.
EQUIPMENT
See the Central Reading Center manual.
PROCEDURE
The Central Reading Center will provide a study manual and training materials.  The 
fundus photographer and photography equipment will be certified by the reading center 
before any study images are taken.  See the Central Reading Center manual for further 
details.


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Appendix 7
Fluorescein Angiography
SCOPE
Fluorescein angiography (FA) will be performed at study sites by trained personnel who 
are certified by the Central Reading Center.  The FA assessments will be extracted from 
the Week 96 visit of the parent study and will be obtained at the early termination visit 
(see Appendix 1).  Analysis (if applicable) of FAs will be performed by the Central 
Reading Center.
EQUIPMENT
Digital angiograms must be used while conducting an angiographic evaluation for the 
study.
Film-based angiography is not acceptable.
DIGITAL IMAGING SYSTEMS AND CERTIFICATION
Digital imaging systems are required.  The system and software at the site will be 
certified by the central reading center prior to obtaining any study angiograms.  This 
certification and validation process will ensure that the central reading center will be able 
to correctly calculate the required measurements.
PROCEDURES
The Central Reading Center will provide a study manual and training materials.  
Photographers, systems, and software will be certified prior to obtaining angiograms of 
patients.


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Appendix 8
Fundus Autofluorescence
SCOPE
Fundus autofluorescence (FAF) will be performed at the study sites by trained personnel 
who are certified by the Central Reading Center.  FAF imaging will be performed for 
each patient at the intervals specified in the protocol (see Appendix 1) and will be
forwarded to the Central Reading Center.  Analysis (if applicable) of FAF images will be 
performed by the Central Reading Center.
EQUIPMENT
Equipment utilized during this study is described in the Central Reading Center Manual.  
The ability to transfer images to electronically exportable digital files is required (i.e., no 
printed FAF images will be sent to the Central Reading Center).
PROCEDURES AND CERTIFICATION
The Central Reading Center will provide the study manual and training materials.  
FAF operators, systems, and software will be certified prior to any evaluation of patients.


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Appendix 9
Spectral Domain-Optical Coherence Tomography
SCOPE
Spectral domain optical coherence tomography (SD-OCT) will be performed at the study 
sites by trained personnel who are certified by the Central Reading Center.  SD-OCT 
imaging will be performed for each patient at the intervals specified in the protocol 
(see Appendix 1).
The SD-OCT images of both eyes will be obtained at protocol-specified visits and will be 
forwarded to the Central Reading Center.
EQUIPMENT
Equipment utilized during this study is described in the Central Reading Center Manual.  
The ability to transfer images to electronically exportable digital files is required (i.e., no 
printed SD-OCT images will be sent to the Central Reading Center).
PROCEDURES AND CERTIFICATION
The Central Reading Center will provide the study manual and training materials.  
SD-OCT operators, systems, and software will be certified prior to any evaluation of 
patients.


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Appendix 10
Near-Infrared Imaging
Near-infrared (NI) images will be obtained to complement the Central Reading Center’s 
evaluation of fundus autofluorescence images.
SCOPE
NI imaging will be performed at the study sites by trained personnel who are certified by 
the Central Reading Center.  NI imaging will be performed for each patient at the 
intervals specified in the protocol (see Appendix 1).
The NI images of both eyes will be obtained at protocol-specified visits and will be 
forwarded to the Central Reading Center.
EQUIPMENT
Equipment utilized during this study is described in the Central Reading Center Manual.  
The ability to transfer images to electronically exportable digital files is required (i.e., no 
printed NI images will be sent to the central reading center).
PROCEDURES AND CERTIFICATION
The central reading center will provide the study manual and training materials.  
NI operators, systems, and software will be certified prior to any evaluation of patients.


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Appendix 11
Optional Mesopic Microperimetry (Selected Sites Only)
SCOPE
Mesopic microperimetry of the study eye only will be performed at selected study sites 
for the patients who signed the optional microperimetry consent section of the Informed 
Consent Form by trained personnel who are certified by the central reading center.  The 
microperimetry will be performed on patients who meet eligibility criteria as defined in the 
Central Reading Center Manual and in this protocol.
The microperimetry results of the study eye will be obtained at protocol-specified visits 
(see Appendix 1) and will be forwarded to the central reading center.
EQUIPMENT
Equipment utilized during this study is described in the Central Reading Center Manual.  
The ability to transfer images to electronically exportable digital files is required (i.e., no 
printed microperimetry results will be sent to the central reading center).
PROCEDURES AND CERTIFICATION
The central reading center will provide the study manual and training materials.  
Microperimetry operators, systems, and software will be certified prior to any evaluation 
of patients.


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Appendix 12
National Eye Institute Visual Functioning Questionnaire 
25-Item Version
The study center and investigator will include the following credit or attribution statement 
for the National Eye Institute Visual Functioning Questionnaire 25-Item Version (NEI 
VFQ-25) questionnaire in any public presentation, publication, or other dissemination of 
or reference to the NEI VFQ-25 as used in this study.
The following form, based upon NEI VFQ-25, was developed at RAND under the 
sponsorship of the NEI and was adapted by the Sponsor for use in this study.  
Six questions from the appendix of optional additional questions for the NEI VFQ 
pertaining to the near activities and distance activities were added to the form.  Minor 
changes (not affecting the items of the questionnaire) were made to the form, and a 
header was added with the study number, Sponsor’s name, visit, and patient identifiers.
INSTRUCTIONS TO THE PATIENT
“I am going to read you some statements about problems, which involve your vision or 
feelings that you have about the condition of your vision.  After each question, I will read 
you a list of possible answers.  Please choose the response that best describes your 
situation.
Please answer all the questions as if you were wearing your glasses or contact lenses 
(if any).
Please take as much time as you need to answer each question.  All your answers are 
confidential.  In order for this study survey to improve our knowledge about vision 
problems and how they affect your quality of life, your answers must be as accurate as 
possible.  Remember, if you wear glasses or contact lenses for a particular activity;
please answer all of the following questions as though you were wearing them.”


Appendix 12
National Eye Institute Visual Functioning Questionnaire 
25-Item Version (cont.)
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Appendix 12
National Eye Institute Visual Functioning Questionnaire 
25-Item Version (cont.)
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Appendix 12
National Eye Institute Visual Functioning Questionnaire 
25-Item Version (cont.)
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Appendix 12
National Eye Institute Visual Functioning Questionnaire 
25-Item Version (cont.)
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Appendix 12
National Eye Institute Visual Functioning Questionnaire 
25-Item Version (cont.)
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Appendix 12
National Eye Institute Visual Functioning Questionnaire 
25-Item Version (cont.)
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Appendix 12
National Eye Institute Visual Functioning Questionnaire 
25-Item Version (cont.)
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Appendix 12
National Eye Institute Visual Functioning Questionnaire 
25-Item Version (cont.)
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Appendix 12
National Eye Institute Visual Functioning Questionnaire 
25-Item Version (cont.)
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Appendix 12
National Eye Institute Visual Functioning Questionnaire 
25-Item Version (cont.)
Lampalizumab—F. Hoffmann-La Roche Ltd
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Appendix 12
National Eye Institute Visual Functioning Questionnaire 
25-Item Version (cont.)
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Appendix 12
National Eye Institute Visual Functioning Questionnaire 
25-Item Version (cont.)
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Appendix 13
Functional Reading Independence Index
Please read the following instructions to the patient.
INSTRUCTIONS TO PATIENT
“We are interested in learning more about how your vision affects your everyday reading.  
I’m going to ask you about seven activities that involve reading.  If you wear eyeglasses 
or contact lenses, please answer all the questions as if you were wearing them during 
the activity.
Please take as much time as you need to answer each question.  Remember, there are 
no right or wrong answers.  All of your answers are confidential.  Do you have any 
questions before we begin?
Please think about your vision over the past 7 DAYS when answering each question.”
















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Appendix 14
Minnesota Low-Vision Reading Test
READING SPEED ASSESSMENT
THE MNREAD READING SPEED ASSESSMENT
The Minnesota Low-Vision Reading Test (MNRead) acuity cards are continuous-text 
reading-acuity cards suitable for measuring the reading acuity and reading speed of 
normal and low-vision patients.  These cards were developed at the Minnesota 
Laboratory for Low-Vision Research, University of Minnesota, Minneapolis, Minnesota, 
in research funded by the National Institutes of Health (please refer to Table 1 for 
MNRead selected countries list).
MEASURING READING SPEED
The MNRead acuity cards consist of single, simple sentences with equal numbers of
characters.  The print is a proportionally spaced font, similar to that found in many 
newspapers and books.  The cards contain sentences with 19 different print sizes.  The 
text is printed with high contrast (approximately 85%).  Each sentence contains 
60 characters (including space between each word and at the end of each line) printed 
as three lines with even left and right margins.  The vocabulary used in the sentences is 
selected from words appearing with high frequency in second- to third-grade reading 
materials.
EQUIPMENT
MNRead acuity cards are used to measure reading speed at different print sizes to 
determine the print that supports the patient’s maximum reading speed.  A stopwatch is 
required to record time to a tenth of a second.  An easel or adjustable stand may be 
needed for some patients.
TESTING
Card Illumination
The cards should be evenly lit so that no shadows or glare will interfere with reading.  
The luminance of the white background on the cards should be should be between 
80 and 120 cd/m2.
Viewing Distance
The print sizes and markings on the cards are designed for a testing distance of 40 cm 
but may be tested at a distance of 32 cm.  It is recommended to use a headrest set to 
the appropriate viewing distance in front of the cards, to prevent the patient from 
creeping forward throughout the test.  For patients with central field loss, it is easier to 
allow the patient to position the MNRead card so that the sentence to be read will fall 
into their preferred location for reading.


Appendix 14
Minnesota Low-Vision Reading Test (cont.)
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Testing Procedure
The MNRead assessment is to be conducted first in each eye separately and then with 
both eyes open.  A different card must be used for each test to prevent memorization of 
the printed material.  Rotate cards from one examination to another to vary the text for 
each eye.  Conduct the reading tests in the following order.  Start by testing the right eye 
with the left eye occluded.  Next, conduct the reading speed test in the left eye with the 
right eye occluded and lastly with both eyes open.
The card should be read from a distance of exactly 32 cm.  To keep the testing distance 
constant, use a piece of transparent fishing line, premeasured at 32 cm from the card.  
Measure the 32 cm to the patient’s eye by holding the fishing line parallel to the floor.  A 
ruler or 32-cm measuring device may also be used to set and monitor the distance.  
Instruct the patient that the card may be moved up and down or side to side but not 
closer to or farther from the eyes.  The card must remain upright and must not tilt away 
from or toward the patient.  Either the patient or the examiner may hold the card, 
depending on the physical ability of the patient.  Alternatively, the card may be placed on 
an easel or adjustable stand.
Check to ensure that the reading card number on the scoring sheet corresponds to the 
reading card number that you are using.  The MNRead scoring sheet contains the test 
sentences corresponding to the card beginning on the left-hand column in descending 
order of acuity.  Indicate which eye is being tested.  Start with the largest sentence and 
move onto the subsequent sentences.  Keep on going until the patient cannot read any 
words in a sentence.  Use a blank card to cover each sentence as you work your way 
down the card; uncover the sentence to be read when you say “start.”  Present the test 
sentence; simultaneously, tell the patient to start reading, and activate the stopwatch to 
start the timer.  As the patient reads the text, strike out words not read, not attempted, or 
read incorrectly.  Use a stopwatch to record the time taken to read each sentence (to the 
nearest 0.1 second).
INSTRUCTIONS TO THE PATIENT
“When I say ‘start,’ read the sentence aloud as quickly as you can without making errors, 
but, if you do make an error or realize that you have missed a word, read to the end of 
the sentence and then go back and correct yourself.”
SCORING
Two pieces of information are required to be recorded on the score sheet for each test 
sentence:  the time and the number of errors.  Use a stopwatch to record the time taken 
to read each sentence (to the nearest 0.1 second).  For each sentence on the score 
sheet, mark the total number of words missed, read incorrectly, or not able to be read, 
and the time taken to read the sentence (i.e., the time between when you say “start” and 


Appendix 14
Minnesota Low-Vision Reading Test (cont.)
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when the patient finishes uttering the last word in the sentence).  Sentences that could 
not be read or were not attempted due to vision should be recorded as 0 for time and 
10 for errors.
MEASURING READING FUNCTION
Patients’ average reading speed, critical print size, and reading acuity will be calculated 
using the data transcribed from the scoring sheet onto the electronic Case Report Form 
and will not be calculated by the interviewers.  
Table 1
Detailed Table for Administration of MNRead
Selected Countries
Primary Language
MNRead
Argentina
Spanish
X
Australia
English
X
Mexico
Spanish
X
Peru
Spanish
X
U.S.
English or Spanish
X
UK
English
X


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Appendix 15
Radner Reading Cards
The Radner reading cards consist of “sentence optotypes,” which are optimized reading 
test items, standardized by construction and statistical selection.  The Radner reading 
cards are suitable for measuring reading speed, reading visual acuity (VA), and critical 
print size (please refer to Table 1 for Radner Reading Cards selected countries list).
MEASURING READING SPEED
The test consists of 24 short sentences that are highly comparable in terms of number of 
words, word length, position of words, lexical difficulty, and syntactical complexity.  
These cards were developed by ophthalmologist Wolfgang Radner, M.D., in Vienna, 
Austria in interdisciplinary cooperation with psychologists, linguists, physicists, and 
statisticians.
EQUIPMENT
The Radner reading cards are in the form of a letter-sized booklet with the reading cards 
and includes clear instructions and evaluation sheets.  Eight sentences are printed per 
page.  Each sentence of 14 words is printed on three lines, and print sizes vary from 
6.3 M to 0.25 M (20/400 to 20/16 at 32 cm).
A stopwatch is required to record time to a tenth of a second.  An easel or adjustable 
stand may be needed for some patients.
TESTING
The Radner reading card assessment is to be conducted in each eye separately and 
then with both eyes open.  Different cards must be used for each test to prevent 
memorization of the printed material.  Rotate cards from one examination to another to 
vary the text for each eye.  Conduct the reading tests in the following order.  Start by 
testing the right eye with the left eye occluded.  Next, conduct the reading speed test in 
the left eye with the right eye occluded and lastly with both eyes open.
CARD ILLUMINATION
The cards should be evenly lit so that no shadows or glare will interfere with reading.  
The luminance of the white background on the cards should be between 80 and 
120 cd/m2.
VIEWING DISTANCE
The test should be conducted at a viewing distance of 32 cm.  To keep the testing 
distance constant, use a piece of transparent fishing line, premeasured at 32 cm from 
the card.  Measure the 32 cm to the patient’s eye by holding the fishing line parallel to 
the floor.  A ruler or 32-cm measuring device may also be used to set and monitor the 
distance.  Instruct the patient that the card may be moved up and down or side to side, 


Appendix 15
Radner Reading Cards (cont.)
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but not closer to or farther from the eyes.  The card must remain upright and must not tilt 
away from or toward the patient.  Either the patient or the examiner may hold the card, 
depending on the physical ability of the patient.  Alternatively, the card may be placed on 
an easel or adjustable stand.
TESTING PROCEDURE
Check to ensure that the reading card number on the scoring sheet corresponds to the 
reading card number that you are using.  Sentences should be covered with a piece of 
paper, and the patient should be asked to uncover sentence by sentence and to read 
only one sentence per measurement.  Start the measurement with the stopwatch when 
the patient starts reading and measure the reading time until the end of the sentence.  
Write the reading time on the scoring sheet (to the nearest 0.1 second), and record any 
reading errors on the sheet.  The reading test should be stopped when the reading time 
is longer than 20 seconds or when the patient is making severe errors.
INSTRUCTIONS TO THE PATIENT
“Please read the sentences aloud as quickly and accurately as possible.  Read each 
sentence to the end, and do not correct reading errors.
Please uncover the first sentence and start reading.”
MEASURING READING FUNCTION
Patient’s average reading speed, critical print size, and VA will be calculated using the 
data transcribed from the scoring sheet to the electronic Case Report Form and will not 
be calculated by the interviewers.


Appendix 15
Radner Reading Cards (cont.)
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Table 1
Detailed Table for Administration of Radner Reading Card
Selected Countries
Primary Language
Radner
Austria
German
x
Brazil
Portuguese
x
Canada
English or French
x
Denmark
Danish
x
France
French
x
Germany
German
x
Italy
Italian
x
Netherlands
Dutch
x
Spain
Spanish
x
Switzerland
German, Italian, or French
x
Belgium
French, German, or Dutch
x
Hungary
Hungarian
x
Turkey
Turkish
x
Portugal
Portuguese
x
Sweden
Swedish
x
Turkey
Turkish
x


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Appendix 16
Biological Sample Collection and Shipping Instructions
BIOLOGICAL SAMPLES
Biological samples for the assessment of lampalizumab concentrations 
(pharmacokinetics), anti-lampalizumab antibodies, biomarker plasma, and laboratory 
assessment (hematology, chemistry panel, coagulation, and urinalysis) samples will be 
collected at the timepoints specified in Appendix 1.
Refer to the Central Laboratory Manual for detailed sample collection, storage, and 
shipping instructions.  All necessary transfer tubes, Vacutainers, labels, shipping 
boxes, and forms will be provided by the central laboratory.
OPTIONAL ANTERIOR CHAMBER (AQUEOUS HUMOR) SAMPLE 
COLLECTION
The optional aqueous humor paracentesis samples will be collected by qualified 
physician from patients who consent to the procedure and sample acquisition.  An 
aqueous humor sample will be collected before the patient’s study eye treatment at the 
visits as indicated in Appendix 1.  The aqueous humor sample collection consists of an 
anterior chamber paracentesis (removing approximately 0.1 mL of fluid from the anterior 
chamber of the eye).
The anterior chamber paracentesis will be performed by a qualified physician by placing 
a drop of topical anesthetic on the cornea, passing a 30-gauge needle through the 
limbus into the anterior chamber, and removing 0.1 mL of aqueous fluid.  
Samples will be collected with the kit provided by central laboratory and shipped on dry 
ice to the central laboratory as soon as possible after the draw.