Clinical trial NCT01602120
Conditions: Geographic Atrophy
Sponsor: Genentech, Inc.
Start date: 2012-05-29; Completion date: 2018-02-09
Enrollment: 159 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a multicenter, open-label extension study of safety and tolerability of lampalizumab administered by intravitreal (ITV) injection to participants with geographic atrophy (GA) who have completed the 18-month treatment in Study CFD4870g (GX01456) (NCT01229215) or 24-week treatment in Study GX29455 (NCT02288559).

Detailed description:

Arms: arm 1: Participants who were administered sham comparator in Study NCT01229215 (CFD4870g), will receive lampalizumab 10 milligrams (mg), intravitreally (ITV), either once in every 4 weeks (Q4W) or once in every 8 weeks (Q8W) in accordance with their previously assigned treatment frequency assignment in Study CFD4870g followed by Q4W administration for the remainder of the extension study up to approximately 96 months. arm 2: Participants will receive lampalizumab 10 mg, ITV, Q4W or Q8W in accordance with their previously assigned treatment frequency assignment in Study NCT01229215 (CFD4870g) followed by Q4W administration for the remainder of the extension study up to approximately 96 months. arm 3: Participants who were administered sham comparator in Study NCT02288559 (GX29455), will receive lampalizumab 10 mg, ITV, Q4W throughout the extension study up to approximately 54 months. arm 4: Participants who were administered lampalizumab in Study NCT02288559 (GX29455), will receive lampalizumab 10 mg, ITV, Q4W throughout the extension study up to approximately 54 months.
Interventions: intervention 1: Lampalizumab
Intervention descriptions: intervention 1: Lampalizumab 10 mg ITV injections as per the schedule specified in respective arms.

Protocol documents:
Prot_SAP_000.pdf: 
 
Official Title: 
 
A MULTICENTER, OPEN-LABEL EXTENSION STUDY TO 
EVALUATE THE LONG-TERM SAFETY AND TOLERABILITY 
OF LAMPALIZUMAB (FCFD4514S) IN PATIENTS WITH 
GEOGRAPHIC ATROPHY WHO HAVE COMPLETED 
GENENTECH-SPONSORED LAMPALIZUMAB STUDIES  
NCT Number: 
 
 NCT01602120  
 
Document Date: 
Protocol/Version 4: 18-May-2017 
 
 
 
 


FINAL PROTOCOL APPROVAL 
CONFIDENTIAL 
The information contained in this document, especially any unpublished data, is the property of 
Genentech, Inc. (or under its control) and therefore is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable Ethics Committee 
or Institutional Review Board.  It is understood that this information will not be disclosed to others 
without written authorization from Genentech except to the extent necessary to obtain informed 
consent from persons to whom the drug may be administered. 
Lampalizumab—Genentech Inc. 
Protocol GX28198, Version 4 
PROTOCOL 
TITLE: 
A MULTICENTER, OPEN-LABEL EXTENSION 
STUDY TO EVALUATE THE LONG-TERM SAFETY 
AND TOLERABILITY OF LAMPALIZUMAB 
(FCFD4514S) IN PATIENTS WITH GEOGRAPHIC 
ATROPHY WHO HAVE COMPLETED 
GENENTECH-SPONSORED LAMPALIZUMAB 
STUDIES 
PROTOCOL NUMBER: GX28198/ NCT01602120 
VERSION NUMBER: 
4 
EUDRACT NUMBER: 
2012-000578-41 
IND NUMBER: 
104996 
TEST PRODUCT: 
Lampalizumab (FCFD4514S; RO5490249) 
MEDICAL MONITOR: 
, M.D. 
SPONSOR: 
Genentech, Inc. 
1 DNA Way 
South San Francisco, CA  94080-4990  U.S.A. 
DATE FINAL: 
Version 1:  14 February 2012 
DATES AMENDED 
Version 2:  24 September 2013 
Version 3:  25 June 2015 
Version 4:  See electronic date stamp below. 
18-May-2017 16:33:32
Title
Approver's Name
Company Signatory (Clinical)
Date and Time (UTC)


Lampalizumab—Genentech, Inc. 
2/Protocol GX28198, Version 4 
PROTOCOL AMENDMENT, VERSION 4: 
RATIONALE 
Protocol GX28198 has been amended for the following reasons:  
• 
The study duration has been extended an additional 30 months to provide study 
patients with access to treatment until potential commercialization of lampalizumab.  
Total study duration is now 96 months (Sections 3.1.3, 3.5, 4.3.1.2, 4.6, 4.6.4, 4.6.5, 
and 4.12.1 and Appendices1-A through 1-E). 
• 
Table 1 (Dosing Schema) has been updated to clarify that no study treatment will be 
administered at the early termination visit. 
• 
Clarifying language has been added to Section 3.1.3 regarding unscheduled safety 
assessment visits in the event of new ocular symptoms after injection. 
• 
Section 3.1.3 has been updated to clarify procedures if study treatment cannot be 
administered at a scheduled visit. 
• 
Language has been added to clarify the rationale for the crossover to monthly 
treatment in Study CFD4870g (Section 3.3). 
• 
The safety plan has been updated to reflect the current safety information for 
lampalizumab (Section 3.5). 
• 
Section 4.1.1 has been updated to include a notation regarding administration of the 
first ITV injection of lampalizumab. 
• 
Formulation information for lampalizumab and ranibizumab has been removed as it 
is included in the pharmacy binder (Sections 4.3.1.1 and 4.4.1.1). 
• 
Dose-holding or study discontinuation criteria language has been clarified (Table 2). 
• 
Intravenous (IV) corticosteroids have been removed from the list of excluded 
concomitant therapies (Section 4.5.2) as study treatment interruption is expected 
only if patients are on IV corticosteroid therapy. 
• 
The safety section (Section 5) language has been modified to reflect updates to the 
protocol template.  Changes include: 
– 
Sections 5.2.2.2 and 5.5 have been revised regarding reporting in the event 
that the EDC system is unavailable. 
– 
Causal attribution guidance language has been updated in Table 4. 
– 
Section 5.3.5.7 has been modified to prohibit use of the term "sudden death" on 
the Adverse Event electronic Case Report Form (eCRF), unless it is combined 
with the presumed cause of death (e.g., "sudden cardiac death"), as use of the 
term "sudden death" will require the Sponsor to query the site for clarification on 
the cause of death. 


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– 
Section 5.3.5.10 has been modified to clarify the reporting of adverse events 
leading to hospitalization. 
– 
Sections 5.3.6.1and 5.3.6.2 have been revised to indicate that pregnancies will 
no longer be reported using the Pregnancy Report eCRF, but will be reported 
on the paper Clinical Trial Pregnancy Reporting Form 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. 
 
• 
Appendices containing instructions regarding pre-injection preparation, 
administration of drug injection, and post-injection procedures have been removed 
as this information is referenced in the pharmacy binder (Appendices 3, 4, 5, 13, 14, 
and 15).  Subsequent appendices have been renumbered accordingly. 
 
Additional minor changes have been made to improve clarity and consistency.  
Substantive new information appears in italics.  This amendment represents cumulative 
changes to the original protocol. 


Lampalizumab—Genentech, Inc. 
4/Protocol GX28198, Version 4 
PROTOCOL AMENDMENT, VERSION 4: 
SUMMARY OF CHANGES 
GLOBAL CHANGES  
The Medical Monitor has been changed from 
, M.D., to 
, M.D. 
PROTOCOL SYNOPSIS 
The protocol synopsis has been updated to reflect the changes to the protocol, where 
applicable. 
SECTION 3.1.3:  All Extension Study Patients 
At the scheduled monthly visits, patients will have safety evaluations 
performedassessments evaluated by the investigator prior to receiving study drug 
injection.  Patients will be contacted by site personnel 7 (± 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 1-F).  
Patients will be instructed to contact the investigator at any time if they have any 
health-related concern.  Patient self-administered antimicrobials in the pre- and 
post-injection period may be used at the investigator’s discretion. 
The extension study is being extended by an additional 2430 months to a total duration 
of 6696 months to provide study patients with access to treatment until potential 
commercialization of lampalizumab.  The monthly treatment arm patients enrolled from 
Study CFD4870g may receive up to 6696 monthly ITV injections of study drug.  
The number of ITV injections of study drug for patients who enrolled from the 
every-other-month treatment arm will vary due to their later crossover to the monthly 
treatment arm, which was relative to their Day 1 visit date.  The patients who enroll from 
study GX29455 may receive up to 2454 monthly ITV injections of study drug.   
All monthly visits will occur relative to the patient’s Day 1 visit date.  Dosing should not 
occur earlier than 23 days after the previous dosing.  Missed study drug doses will not 
be made up only in the following circumstance: 
• 
If, during scheduled visit, a site encounters an unexpected issue (e.g., the IxRS is 
not able to assign the study kit, or other patient care issues), 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 delayed study treatment:  slit lamp 
examination, indirect ophthalmoscopy, and pre-treatment intraocular pressure 
(IOP) measurements.  These assessments are to be 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-A through Appendix 1-E), the images must be obtained at the 
next scheduled visit that the patient attends. 


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Patients are expected to attend their scheduled visits unless there are extenuating 
circumstances justifying their inability to come to the clinic. 
Patients who are prematurely discontinued from the study treatment in the extension 
study (prior to the Month 6696 visit for patients enrolled from Study CFD4870g or prior to 
the Month 2454 visit for patients enrolled from Study GX29455) will be also discontinued 
from the extension study and will be asked to return for an early termination (ET) visit 
≥30 days following their last study drug treatment for monitoring of adverse events and 
the ET visit assessments (Appendix 1-A through Appendix 1-E). 
The VA examiner role will remain masked to the patients' study eye assignment. 
TABLE 1:  Dosing Schema 
Table 1 has been revised to reflect the extension of the study duration and to indicate 
that no study treatment will be administered at the early termination visit. 
SECTION 3.2:  TREATMENT FOR CHOROIDAL NEOVASCULARIZATION 
WITH RANIBIZUMAB 
At the discretion of the investigator, enrolled patients who are receiving study treatment 
and are diagnosed with CNV in either eye may receive treatment with 0.5 mg 
ranibizumab.  For U.S. sites, the drug will be open-label ranibizumab for investigational 
use only supplied by Genentech (see the pharmacy binder Section 4.4.1.1 for the drug 
formulation) and injected no more frequently than monthly.… 
Please see the pharmacy binder for ranibizumab administration (Appendix 13 
pre-injection procedure, Appendix 14 preparation and administration, and Appendix 15 
post-injection procedure) at U.S. sites. 
SECTION 3.3:  RATIONALE FOR STUDY DESIGN 
Patients from Study CFD4870g (including those in sham arms), initially received 
lampalizumab in the extension study at the same dosing frequency previously assigned 
in Study CFD4870g:  patients in the monthly treatment arms continued receiving monthly 
treatment, and patients in the every-other-month treatment arm continued receiving 
every-other-month treatment.  
After Study CFD4870g results demonstrated that monthly administration of 
lampalizumab had a clinically meaningful and statistically significant effect on 
reducing the GA area growth over the 18-month study treatment period (see 
Investigator Brochure for additional details), the every-other-month treatment arm 
patients were later crossed over to the monthly treatment arm for the remainder of their 
study participation, provided informed consent was obtained.   
SECTION 3.5:  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 this study 


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6/Protocol GX28198, Version 4 
is designed to minimize patient risk and will include specific eligibility criteria and 
monitoring assessments as detailed in Section 5 (Assessment of Safety). Lampalizumab 
is not approved and clinical development is ongoing.  The safety plan for patients in 
this study is based on clinical experience with lampalizumab in completed and ongoing 
studies. The anticipated important safety risks for lampalizumab are outlined below. 
Please refer to the most current lampalizumab Investigator's Brochure for a complete 
summary of safety information. 
Several measures will be taken to ensure the safety of patients participating in this 
study.  Eligibility criteria have been designed to exclude patients at a higher risk for 
toxicities.  Patients will undergo safety monitoring during the study, including 
assessments of the nature, frequency, and severity of adverse events.  Guidelines for 
managing adverse events, including criteria for treatment interruption or 
discontinuation, are provided below. 
Potential ocular safety issues currently thought to be associated with the route of 
administration or pharmacology of lampalizumab include decreased best corrected 
visual acuity (BCVA), conjunctival hemorrhage, ocular inflammation (see Section 5.1.3 
for definition and Appendix 2 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 on electronic Case Report 
Forms (eCRFs) for the duration of this study. 
Please see the lampalizumab Investigator's Brochure for further details. 
The incidence and characteristics of adverse events, serious adverse events, and 
laboratory abnormalities will be assessed.…All adverse events and pregnancies will be 
recorded on eCRFs for the duration of this study. 
Patients who are prematurely discontinued from the study treatment (prior to the 
Month 6696 visit for CFD4870g patients and prior to the Month 2454 visit for GX29455 
patients) will be also discontinued from the extension study and will be asked to return 
for an ET evaluation ≥30 days following their last study drug treatment for monitoring of 
adverse events and the early study termination visit assessments (see Appendix 1-A 
through Appendix 1-E). 
SECTION 4.1.1:  Patient Selection 
Note: All patients enrolled in the extension study will have the first 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 4.3.1.2 
and Table 2).  


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7/Protocol GX28198, Version 4 
SECTION 4.3.1.1:  Formulation 
Lampalizumab will be supplied by the Sponsor as sterile, white to off white, lyophilized 
powder in a 6 cc USP/Ph. Eur.  Type 1 glass vial intended for ITV administration.  For 
information on the formulation and handling of lampalizumab, see the pharmacy manual 
and the lampalizumab Investigator’s BrochureSee the pharmacy binder for details 
regarding formulation. 
SECTION 4.3.1.2:  Dosage, Administration, and Storage 
Dosage 
Patients enrolled from Study CFD4870g:  
The dose of 10 mg lampalizumab was administered monthly or every other month 
starting at the Day 1 visit for up to the 18-month of treatment period.…The study 
treatment period has beenwas again extended by another 24 months and now by 30 
additional months for a total treatment period of 6696 months.  Patients in the monthly 
treatment arm may receive up to 6696 ITV injections of study drug.  The number of ITV 
injections of study drug for patients who were in the every-other-month treatment arm 
prior to their crossover to the monthly treatment arm will vary and will depend on the 
date of their crossover relative to their Day 1 visit date.   
Patients enrolled from Study GX29455:  
All study GX29455 patients enrolled in the extension study will receive 10-mg ITV 
injections of lampalizumab.  Dosing frequency for both treatment arms (Q2W and Q4W) 
of Study GX29455 changed to monthly dosing upon entry to this study.  Given that 30 
months have been added to the original 24 month study duration for the patients from 
Study GX29455, thus these patients may receive up to 24 54 ITV injections of study 
drug.  
All patients in Study GX29198 will have scheduled monthly visits and monthly study drug 
treatment for the duration of the study (see Table 1).  The monthly visit will occur relative 
to the Day 1 visit date.  Dosing should not occur earlier than 23 days after the previous 
dosing.  Missed study drug treatments will not be made up unless an extenuating 
circumstance applies (see Section 3.1.3). 
Administration 
Lampalizumab reconstitution with Sterile Water for Injection (SWFI), USP/Ph. Eur., is 
required for preparation of the dose.  The 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, pre-injection 
preparation, administration of the study drug injection, and post-injection procedures 
for the study eye are provided in the pharmacy binder.  


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8/Protocol GX28198, Version 4 
Please refer to Appendix 3, Appendix 4, and Appendix 5 for detailed instructions on 
pre injection preparation, administration of the study drug injection, and post injection 
procedures for the study eye. 
Storage 
Upon receipt of lampalizumab, vials should be refrigerated at 2ºC 8ºC (36ºF 46ºF) until 
use.  Lampalizumab vials should not be used beyond the expiration date provided by 
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. 
Detailed instruction for lampalizumab storage is provided in the pharmacy binder. 
TABLE 2:  Dose-Holding or Study Treatment and/or Study Discontinuation 
Criteria 
Table 2 has been revised to clarify the criteria for dose-holding and study discontinuation. 
SECTION 4.4.1.1:  Formulation for Sites in the United States 
Note: German sites will use commercially available Lucentis.  
At U.S. sites, ranibizumab will be supplied by the Sponsor. as a sterile solution 
aseptically filled in a sterile 2 mL stoppered glass vial.   For information on the 
formulation and handling of ranibizumab, see the pharmacy binder manual for 
ranibizumab.  
Dosage, Administration, and Storage 
At the discretion of the investigator, enrolled patients who are receiving study treatment 
and are diagnosed with CNV in either eye may receive treatment with 0.5 mg 
ranibizumab.  For U.S. sites, the drug will be open-label ranibizumab for investigational 
use only supplied by Genentech.  The ranibizumab injection in the United States will be 
performed using the techniques as discussed in the pharmacy binder Appendix 13, 
Appendix 14, and Appendix 15. 
Ranibizumab vials must be refrigerated at 2°C to 8°C (36°F to 46°F) upon receipt until 
used.  Each vial will be labeled as required by the relevant regulatory agencies.Detailed 
instruction for ranibizumab storage is provided in the pharmacy binder.  Each vial will 
be labeled as required by the relevant regulatory agencies.  


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9/Protocol GX28198, Version 4 
SECTION 4.5.2:  Excluded Concomitant Therapy 
At the discretion of the investigator, patients may continue to receive all medications and 
standard treatments administered for other conditions.  The following 
medications/treatments are prohibited from use during the patient’s participation in the 
study: 
• 
Intravenous corticosteroids 
• 
Ocular or systemic complement inhibitors, (e.g., eculizumab) except lampalizumab. 
• 
Other experimental therapies (except AMD relatedthose involving vitamin and 
mineral supplements) 
 
SECTION 4.6:  STUDY ASSESSMENTS 
Patients enrolled from Study CFD4870g will have up to 6696 study visits (excluding the 
Day 1 visit).  Patients enrolled from Study GX29455 will have up to 2454 study visits 
(excluding the Day 1 visit).  Any patient who discontinues the study prematurely (prior to 
the Month 6696 visit for patients from Study CFD4870g and prior to the Month 2454 visit 
for patients from Study GX29455) will have an ET visit completed ≥ 30 days after his or 
her last study drug treatment.  Study visits will be scheduled every 30 (± 7) days relative 
to the Day 1 visit. 
SECTION 4.6.3:  Assessments during Treatment 
At all study visits the procedures and assessments should be performed prior to study 
drug administration unless otherwise indicated.  All study visit assessments must be 
performed on the same day.  Note:  see Section 3.1.3 for exception regarding delayed 
study treatment administration. 
SECTION 4.6.4:  Study Completion/Early Termination Visit 
For patients who withdraw early from the study (prior to the Month 6696 visit for patients 
enrolled from CFD4870g and prior to the Month 2454 visit for patients enrolled from 
GX29455) for any reason, these patients should complete the ET visit assessments 
≥ 30 days following the last study treatment. Patients who discontinue from the study will 
not be allowed to re-enter the study.  Please see the Study Flowcharts provided in 
Appendix 1-A through Appendix 1-E for the assessments to be performed at the study 
ET visit. 
SECTION 4.6.5:  Study Treatment Discontinuation /Early Termination Visit 
Patients who prematurely discontinue the study treatment (prior to the Month 6696 visit 
for patients enrolled from CFD4870g or prior to the Month 2454 visit for patients enrolled 
from GX29455) will be also discontinued from the study, and they will be asked to return 
for an ET evaluation ≥30 days following their last study drug treatment for monitoring of 
adverse events and the study ET visit assessments.   


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10/Protocol GX28198, Version 4 
SECTION 4.12.1:  Safety Analysis 
Safety will be assessed by adverse events, clinical laboratory evaluations, and 
immunogenicity as measured by ATA.  Safety analyses will include all patients who 
enrolled into the extension study and received at least one lampalizumab injection 
across Study CFD4870g or in Study GX29455 and in the extension study.  These 
patients will be grouped by the first treatment regimen received (lampalizumab or sham) 
when they were enrolled in the CFD4870 or GX29455for safety analyses. 
The primary safety analysis is planned to occur at the time when patients enrolled from 
Study CFD4870g have reached approximately 6696 months follow-up and when patients 
enrolled from Study GX29455 have reached approximately 2454 months follow-up.… 
All verbatim adverse event terms will be mapped to Medical Dictionary for Regulatory 
Activities (MedDRA) thesaurus terms, and adverse event severity will be graded 
according to an adverse event severity grading scale (see Table 3). 
SECTION 4.12.3:  Exploratory Analyses 
Mean GA lesion area growth and mean BCVA change from baseline over time will be 
summarized by treatment group.  These patients will be grouped by parent study and 
the first treatment regimen received (lampalizumab or sham) when they were enrolled in 
Study CFD4870g or Study GX29455.   
SECTION 5.1:  SAFETY PARAMETERS AND DEFINITIONS 
Safety assessments will consist of monitoring and recording adverse events, including 
serious adverse events and non serious adverse events of special interest, performing 
protocol-specified safety laboratory assessments, measuring protocol-specified vital 
signs, and conducting other protocol-specified tests that are deemed critical to the safety 
evaluation of the study. 
SECTION 5.1.3:  Protocol Defined Events of Special Interest/Serious/ Non 
Serious Adverse Events Subject to Expedited Reporting 
Adverse Events of Special Interest (Immediately 
Reportable to the Sponsor) 
This section heading has been revised. 
SECTION 5.2:  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 study.…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 
• 
Non serious adverseAdverse events of special interest 
 


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SECTION 5.2.1:  Emergency Medical Contacts 
Medical Monitor Contact Information for sites in the United States and Germany: 
United States 
Medical Monitor: 
, M.D. 
Telephone No.: 
(office) 
 
Germany 
Medical Monitor: 
, M.D. 
Telephone No.: 
 
Mobile Telephone No.: 
 
or 
Medical Monitor: 
 MBChB, MFPM, MRCOphth 
Mobile Telephone No.: 
 
 
 
SECTION 5.2.2.2:  Events that Occur after Study Drug Initiation 
After initiation of study drug, serious adverse events and non serious adverse events of 
special interest will be reported until the last study visit.… 
In the event that the EDC system is unavailable, athe paper Clinical Trial Serious 
Adverse Event/Adverse Event of Special Interest Reporting Form and fax cover sheet 
provided to investigators should be completed and faxedsubmitted 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 numbersnumber or email 
address provided to investigators (“Protocol Administrative and Contact Information and 
List of Investigators”)..  Once the EDC system is available, all information will need to be 
entered and submitted via the EDC system.   
SECTION 5.3.2:  Eliciting Adverse Events 
A consistent methodology of non-directive questioning should be adopted for eliciting 
adverse eventsevent information at all patient evaluation time points should be 
adopted.timepoints.  Examples of non-directive questions include the following: 
SECTION 5.3.3:  Assessment of Severity and Causality of Adverse Events 
Investigators will seek information on adverse events and serious adverse events at 
each patient contact.  All adverse events and serious adverse events, whether reported 
by the patient or noted by authorized study personnel, will be recorded in the patient’s 
medical record and on the Adverse Event eCRF. 


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The adverse event severity grading scale will be used for assessing adverse event 
severity.  Table 3 provides guidance for assessing adverse event severity. 
SECTION 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 or 
not 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 4).  
• 
Course of the event, considering especiallywith special consideration of the effects 
of dose reduction, discontinuation of study drug, or reintroduction of study drug (as 
applicable) 
 
TABLE 4:  Causal Attribution Guidance 
Table 4 has been revised to match current template language. 
SECTION 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. 
There is one eCRF page for recording adverse events or serious adverse events. 
Only one medical conceptadverse event term should be recorded in the event field on 
the Adverse Event eCRF. 
SECTION 5.3.5.7:  Deaths 
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 only be used 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 of 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"). 
Deaths that occur after the adverse event reporting period should be reported as 
described in Section 5.5. 


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SECTION 5.3.5.10:  Hospitalization or Prolonged Hospitalization or Surgery  
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 a serious adverse event in Section 5.1.2), except as outlined 
below. 
The following hospitalizations are not considered to be adverse events: 
Prolonged hospitalization to undergo a diagnostic or elective surgical procedure for a 
preexisting medical condition other than ocular that has not changed. 
An event that leads to hospitalization under the following circumstance should not be 
reported as an adverse event or a serious adverse event: 
• 
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 elective surgery became necessary because of the expected normal 
progression of the disease. 
The patient has not experienced an adverse event. 
 
SECTION 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 treatment is not 
itself an adverse event, but it may result in an adverse event.  All adverse events 
associated with 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 meets the severity criteria, the event should be reported to the 
Sponsor immediately (i.e., no more than 24 hours after learning of the event; see 
Section 5.2.2). 
SECTION 5.3.6.1:  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 the last study visit.  A 
Pregnancy Report eCRF should be completed by the investigatorA paper 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 with use of the fax number or e-mail 
address provided to investigatorsand submitted via the EDC system.  A pregnancy 
report will automatically be generated and sent to Roche Safety Risk Management.… 
In addition, the investigator will submit a paper Clinical Trial Pregnancy Reporting 
Form when updated information on the course and outcome of the pregnancy 
becomes available. 


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14/Protocol GX28198, Version 4 
In the event that the EDC system is unavailable, the Clinical Trial Pregnancy 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 pregnancy), 
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. 
SECTION 5.3.6.1:  Pregnancies in Female Partners of Male Patients 
Male patients will be instructed through the Informed Consent Form to immediately 
inform the investigator if their partner becomes pregnant during the study or until the last 
study visit.  A Pregnancy Report eCRF should be completed by the investigatorA paper 
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 with use of the fax 
number or e-mail address provided to investigatorsand submitted via the EDC system.  
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.  OnceAfter the authorization has 
been signed, the investigator will update thewill submit a paper Clinical Trial 
Pregnancy Report eCRF with additionalReporting 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. 
In the event that the EDC system is unavailable, follow reporting instructions provided in 
Section . 
SECTION 5.5:  POST STUDY ADVERSE EVENTS THAT OCCUR AFTER 
THE ADVERSE EVENT REPORTING PERIOD 
These events should be reported through use of the Adverse Event eCRF.  However, if 
the EDC system is not available, the investigator should report these events directly to 
the Sponsor or its designee, either by faxing or by scanning and emailing the paper 
Clinical Trial Serious Adverse Event/Adverse Event of Special Interest Reporting Form 
using the below fax number andor email address:  provided to investigators. 
For U.S. Sites:  
Email Address: us_drug.safety@gene.com 
Fax No.: 650 225 4682 
Alternate Fax No.: 650 225 5288 


Lampalizumab—Genentech, Inc. 
15/Protocol GX28198, Version 4 
For Germany Sites:  
Email Address: grenzach.drug_safety@roche.com 
Fax No.: 49 7624143183 
SECTION 6.6:  ELECTRONIC CASE REPORT FORMS 
eCRFs are to be completed through use of a sponsor-designated EDC systemusing the 
RAVE EDC system from Medidata Solutions Inc. (New York, NY).  Sites will receive 
training and have access to a manual for appropriate eCRF completion.  eCRFs will be 
submitted electronically to the Sponsor and should be handled in accordance with 
instructions from the Sponsor. 
APPENDIX 1:  Schedule of Assessments  
The schedules of assessments Appendix 1-A through Appendix 1-D have been revised 
to reflect the changes to the protocol.  Appendices 1-E and 1-F have been added. 
APPENDIX 3:  Pre Injection Procedures for All Patients Receiving the Study 
Drug (Lampalizumab) 
Appendix 3 has been removed. 
APPENDIX 4:  Preparation and Administration of Lampalizumab Injection 
Appendix 4 has been removed. 
APPENDIX 5:  Study Drug Post Injection Procedures for All Patients 
Appendix 5 has been removed. 
APPENDIX 13:  Ranibizumab Pre injection Procedure 
Appendix 13 has been removed. 
APPENDIX 14:  Preparation and Administration of Ranibizumab Injection 
Appendix 14 has been removed. 
APPENDIX 15:  Ranibizumab Post Injection Procedures 
Appendix 15 has been removed. 
SAMPLE INFORMED CONSENT FORMS 
The sample Informed Consent Form has been revised to reflect the changes to the 
protocol. 
 


Lampalizumab—Genentech, Inc. 
16/Protocol GX28198, Version 4 
 
TABLE OF CONTENTS 
PROTOCOL AMENDMENT ACCEPTANCE FORM .......................................... 21 
PROTOCOL SYNOPSIS .................................................................................... 22 
1. 
BACKGROUND .......................................................................................... 31 
1.1 
Background on Disease......................................................... 31 
1.1.1 
Epidemiology ......................................................................... 31 
1.1.2 
Pathophysiology .................................................................... 31 
1.1.3 
Management of Geographic Atrophy ..................................... 31 
1.2 
Background on the Molecule ................................................. 32 
1.3 
Rationale for Doing this Study ............................................... 32 
2. 
OBJECTIVES .............................................................................................. 32 
2.1 
Primary Objective .................................................................. 32 
2.2 
Exploratory Objectives ........................................................... 33 
3. 
STUDY DESIGN ......................................................................................... 33 
3.1 
Description of the Study......................................................... 33 
3.1.1 
Patients Enrolled from Study CFD4870g ............................... 33 
3.1.2 
Patients Enrolled from Study GX29455 ................................. 34 
3.1.3 
All Extension Study Patients .................................................. 34 
3.2 
Treatment for Choroidal Neovascularization with 
Ranibizumab .......................................................................... 37 
3.3 
Rationale for Study Design .................................................... 37 
3.4 
Outcome Measures ............................................................... 37 
3.4.1 
Primary Outcome Measure .................................................... 37 
3.4.2 
Pharmacokinetic/Pharmacodynamic Outcome 
Measures ............................................................................... 38 
3.4.3 
Exploratory Outcome Measures ............................................ 38 
3.5 
Safety Plan ............................................................................ 38 
3.6 
Study Patients ....................................................................... 40 
3.7 
Control Groups ...................................................................... 40 
3.8 
Ethical Considerations ........................................................... 40 
3.9 
Administrative Structure......................................................... 41 
3.10 
Compliance with Laws and Regulations ................................ 41 


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17/Protocol GX28198, Version 4 
4. 
MATERIALS AND METHODS .................................................................... 41 
4.1 
Patients .................................................................................. 41 
4.1.1 
Patient Selection .................................................................... 41 
4.1.2 
Inclusion Criteria .................................................................... 42 
4.1.2.1 
General Inclusion Criteria ...................................................... 42 
4.1.2.2 
Ocular Inclusion Criterion ...................................................... 43 
4.1.3 
Exclusion Criteria ................................................................... 43 
4.1.3.1 
Ocular Exclusion Criteria ....................................................... 43 
4.1.3.2 
Concurrent Systemic Conditions ........................................... 44 
4.2 
Method of Treatment Assignment and Masking .................... 44 
4.3 
Study Treatment .................................................................... 45 
4.3.1 
Lampalizumab ....................................................................... 45 
4.3.1.1 
Formulation ............................................................................ 45 
4.3.1.2 
Dosage, Administration, and Storage .................................... 45 
4.4 
Treatment for Choroidal Neovascularization with 
Ranibizumab .......................................................................... 48 
4.4.1 
Ranibizumab .......................................................................... 48 
4.4.1.1 
Formulation for Sites in the United States ............................. 48 
4.5 
Concomitant and Excluded Therapies ................................... 49 
4.5.1 
Permitted Concomitant Therapy ............................................ 49 
4.5.2 
Excluded Concomitant Therapy ............................................. 50 
4.5.3 
Excluded Concomitant Conditions ......................................... 50 
4.6 
Study Assessments ............................................................... 50 
4.6.1 
Definitions of Study Assessments ......................................... 51 
4.6.1.1 
Clinical Evaluations ............................................................... 51 
4.6.1.2 
Ocular Assessments .............................................................. 51 
4.6.1.3 
Ocular Imaging ...................................................................... 52 
4.6.1.4 
Laboratory Assessments ....................................................... 52 
4.6.2 
Screening and Pretreatment Assessments............................ 53 
4.6.3 
Assessments during Treatment ............................................. 53 
4.6.4 
Study Completion/Early Termination Visit.............................. 54 
4.6.5 
Study Treatment Discontinuation/Early 
Termination Visit .................................................................... 54 
4.6.6 
Unscheduled Safety Assessment Visit .................................. 55 


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18/Protocol GX28198, Version 4 
4.7 
Patient Discontinuation .......................................................... 55 
4.8 
Study Treatment Discontinuation ........................................... 55 
4.9 
Study Discontinuation ............................................................ 55 
4.10 
Post-Trial Access to lampalizumab ........................................ 56 
4.11 
Assay Methods ...................................................................... 57 
4.12 
Statistical Methods ................................................................ 57 
4.12.1 
Safety Analysis ...................................................................... 57 
4.12.2 
Pharmacokinetic and Pharmacodynamic 
Analyses ................................................................................ 57 
4.12.3 
Exploratory Analyses ............................................................. 57 
4.12.4 
Handling of Missing Data ....................................................... 57 
4.12.5 
Determination of Sample Size ............................................... 58 
4.12.6 
Interim Analysis ..................................................................... 58 
4.13 
Data Quality Assurance ......................................................... 58 
5. 
ASSESSMENT OF SAFETY ....................................................................... 58 
5.1 
Safety Parameters and Definitions ........................................ 58 
5.1.1 
Adverse Events ..................................................................... 59 
5.1.2 
Serious Adverse Events (Immediately Reportable 
to the Sponsor) ...................................................................... 59 
5.1.3 
Adverse Events of Special Interest (Immediately 
Reportable to the Sponsor) .................................................... 60 
5.2 
Immediate Reporting Requirements from 
Investigator to Sponsor .......................................................... 61 
5.2.1 
Emergency Medical Contacts ................................................ 62 
5.2.2 
Reporting Requirements for All Serious Adverse 
Events and Adverse Events of Special Interest ..................... 62 
5.2.2.1 
Events That Occur prior to Study Drug Initiation .................... 62 
5.2.2.2 
Events that Occur after Study Drug Initiation ......................... 62 
5.3 
Methods and Timing for Capturing and 
Assessing Safety Parameters ................................................ 63 
5.3.1 
Adverse Event Reporting Period ........................................... 63 
5.3.2 
Eliciting Adverse Events ........................................................ 63 
5.3.3 
Assessment of Severity of Adverse Events ........................... 64 
5.3.4 
Assessment of Causality of Adverse Events ......................... 64 


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19/Protocol GX28198, Version 4 
5.3.5 
Procedures for Recording Adverse Events ............................ 65 
5.3.5.1 
Diagnosis versus Signs and Symptoms................................. 66 
5.3.5.2 
Adverse Events that Are Secondary to Other 
Events.................................................................................... 66 
5.3.5.3 
Persistent or Recurrent Adverse Events ................................ 66 
5.3.5.4 
Abnormal Laboratory Values ................................................. 67 
5.3.5.5 
Abnormal Vital Sign Values ................................................... 67 
5.3.5.6 
Abnormal Liver Function Tests .............................................. 68 
5.3.5.7 
Deaths ................................................................................... 68 
5.3.5.8 
Preexisting Medical Conditions .............................................. 69 
5.3.5.9 
Worsening of Geographic Atrophy in Study Eye .................... 69 
5.3.5.10 
Hospitalization or Prolonged Hospitalization .......................... 70 
5.3.5.11 
Adverse Events Associated with an Overdose or 
Error in Drug Administration .................................................. 70 
5.3.6 
Reporting Requirements for Pregnancies .............................. 70 
5.3.6.1 
Pregnancies in Female Patients ............................................ 70 
5.3.6.2 
Pregnancies in Female Partners of Male Patients ................. 71 
5.3.6.3 
Abortions ............................................................................... 71 
5.3.6.4 
Congenital Anomalies/Birth Defects ...................................... 71 
5.4 
Follow-Up of Patients after Adverse Events .......................... 72 
5.4.1 
Investigator Follow-Up ........................................................... 72 
5.4.2 
Sponsor Follow-Up ................................................................ 72 
5.5 
Adverse Events that occur after the Adverse 
Event Reporting Period.......................................................... 72 
5.6 
Expedited Reporting to Health Authorities, 
Investigators, Institutional Review Boards, and 
Ethics Committees ................................................................. 72 
6. 
INVESTIGATOR REQUIREMENTS............................................................ 73 
6.1 
Study Initiation ....................................................................... 73 
6.2 
Study Completion .................................................................. 74 
6.3 
Informed Consent Form ......................................................... 74 
6.4 
Communication with the Institutional Review 
Board or Ethics Committee .................................................... 75 
6.5 
Study Monitoring Requirements ............................................ 76 


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6.6 
Electronic Case Report Forms ............................................... 76 
6.7 
Source Data Documentation .................................................. 76 
6.8 
Use of Computerized Systems .............................................. 77 
6.9 
Study Medication Accountability ............................................ 77 
6.10. 
Genentech-Provided Ranibizumab Accountability ................. 77 
6.11 
Disclosure of Data ................................................................. 78 
6.12 
Retention of Records ............................................................. 78 
6.13 
Protocol Amendments ........................................................... 78 
7. 
REFERENCES ........................................................................................... 80 
 
 
LIST OF TABLES 
Table 1 
Dosing Schema ........................................................................... 35 
Table 2 
Dose-Holding or Study Discontinuation Criteria .......................... 47 
Table 3 
Adverse Event Severity Grading Scale ....................................... 64 
Table 4 
Causal Attribution Guidance ....................................................... 65 
 
 
LIST OF APPENDICES 
Appendix 1 
Schedule of Assessments .......................................................... 81 
Appendix 2 
Grading Scale for Assessment of Anterior 
Chamber Flare or Cells and Vitreous Cells .............................. 106 
Appendix 3 
Best Corrected Visual Acuity Testing ....................................... 108 
Appendix 4 
Color Fundus Photography ....................................................... 109 
Appendix 5 
Fluorescein Angiography .......................................................... 110 
Appendix 6 
Fundus Autofluorescence ......................................................... 111 
Appendix 7 
Spectral Domain-Optical Coherence Tomography ................... 112 
Appendix 8 
Near-Infrared Imaging .............................................................. 113 
Appendix 9 
Biological Sample Collection and Shipping 
Instructions ............................................................................... 114 


 
Lampalizumab—Genentech, Inc. 
21/Protocol GX28198, Version 4 
PROTOCOL AMENDMENT ACCEPTANCE FORM 
TITLE: 
A MULTICENTER, OPEN-LABEL EXTENSION 
STUDY TO EVALUATE THE LONG-TERM SAFETY 
AND TOLERABILITY OF LAMPALIZUMAB 
(FCFD4514S) IN PATIENTS WITH GEOGRAPHIC 
ATROPHY WHO HAVE COMPLETED GENENTECH-
SPONSORED LAMPALIZUMAB STUDIES 
PROTOCOL NUMBER: GX28198 
VERSION NUMBER: 
4 
EUDRACT NUMBER: 
2012-000578-41 
IND NUMBER 
104996 
TEST PRODUCT: 
Lampalizumab (RO5490249; FCFD4514S) 
MEDICAL MONITOR: 
, M.D. 
SPONSOR: 
Genentech, Inc. 
1 DNA Way 
South San Francisco, CA  94080-4990  U.S.A. 
DATE FINAL: 
14 February 2012 
DATE AMENDED: 
See electronic date stamp on protocol title page. 
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 to 
the local study monitor. 
 


 
Lampalizumab—Genentech, Inc. 
22/Protocol GX28198, Version 4 
PROTOCOL SYNOPSIS 
TITLE: 
A MULTICENTER, OPEN-LABEL EXTENSION STUDY TO 
EVALUATE THE LONG-TERM SAFETY AND TOLERABILITY 
OF LAMPALIZUMAB (FCFD4514S) IN PATIENTS WITH 
GEOGRAPHIC ATROPHY WHO HAVE COMPLETED 
GENENTECH-SPONSORED LAMPALIZUMAB STUDIES 
PROTOCOL NUMBER: 
GX28198 
VERSION NUMBER: 
4 
EUDRACT NUMBER: 
2012-000578-41 
STUDY DRUG: 
Lampalizumab (RO5490249; FCFD4514S) 
PHASE: 
Extension 
INDICATION: 
Geographic Atrophy 
IND: 
104996 
SPONSOR: 
Genentech, Inc. 
1 DNA Way 
South San Francisco, CA  94080-4990  U.S.A. 
DATE FINAL: 
14 February 2012 
DATE AMENDED: 
See electronic date stamp on protocol title page. 
 
Primary Objective 
The primary objective of this study is to investigate the long-term ocular and systemic safety 
and tolerability of lampalizumab administered intravitreal (ITV) monthly. 
Exploratory Objectives 
The exploratory objectives of this study are the following: 
• 
To assess long-term geographic atrophy (GA) area progression with fundus 
autofluorescence (FAF), color fundus photographs (CFP), and spectral domain-optical 
coherence tomography (SD-OCT) 
• 
To evaluate potential anatomic biomarkers for earlier-stage GA progression and 
pharmacodynamic outcomes (e.g., retinal substructure analysis by SD-OCT)  
• 
To assess the incidence of anti-therapeutic antibodies (ATA) to lampalizumab 
• 
Clinical genotyping to assess relationships between genetic polymorphisms associated with 
age-related macular degeneration (AMD), disease characteristics, and response to 
administration of lampalizumab 
 


 
Lampalizumab—Genentech, Inc. 
23/Protocol GX28198, Version 4 
Study Design 
Study GX28198 is a multicenter, open-label extension study of safety and tolerability of 
lampalizumab administered by ITV injection to patients with GA who have completed the 
18-month treatment in Study CFD4870g or the 24-week treatment in Study GX29455.  As such, 
Study GX28198 is considered the extension for patients enrolled in these studies and is referred 
to as the extension study throughout the remainder of this protocol synopsis.  CFD4870g 
patients who discontinued from study treatment early but remained on study for safety 
evaluation, or discontinued prior to completion of the 18-month treatment period, were not 
eligible for Study GX28198. Patients who participated in Study GX29455 and discontinued from 
study treatment prior to completion of the 24-week treatment period are not eligible for the 
extension study.  Site investigators will be ophthalmologists with subspecialty expertise in 
virtreoretinal diseases.  
The extension study enrolled 2 groups of patients from Study CFD4870g:  patients previously 
exposed to lampalizumab and patients who were lampalizumab-naïve (i.e., received sham 
treatment).  Eligible patients who consented to participate in the extension study were enrolled 
at the conclusion of the Month 18 visit for Study CFD4870g; the Month 18 visit served as the 
final visit for Study CFD4870g and the Day 1 visit for the extension study.  Upon enrollment, all 
patients received 10-mg ITV injections of lampalizumab.  Initially, patients continued on the 
same dosing frequency (monthly or every-other-month) assigned previously during their 
participation in Study CFD4870g.  Patients in the every-other-month treatment arm were later 
crossed over to the monthly treatment arm for the remainder of their study participation period. 
The extension study will enroll 2 groups of patients from Study GX29455:  patients previously 
exposed to lampalizumab and patients who were lampalizumab-naïve (i.e., received sham).  
Eligible patients who consent to participate in the extension study will be enrolled at their 
conclusion of Study GX29455 (i.e., the Week 24 visit); the Week 24 visit will serve as the final 
visit for Study GX29455 and the Day 1 visit for the extension study. 
All patients from Study GX29455 who enroll in the extension study will receive 10-mg ITV 
administrations of lampalizumab.  The dosing frequency for both treatment arms (every 2 weeks 
[Q2W] and every 4 weeks [Q4W]) of Study GX29455 will change to monthly dosing to align with 
dosing in the extension study.  
A patient must satisfy all eligibility criteria at Day 1 visit and will be enrolled using an interactive 
response system (IxRS).  All patients enrolled in the extension study will have the first ITV 
injection of lampalizumab administered by the investigator at the Day 1 visit (unless 
dose-holding is medically justified by the investigator) which is scheduled on the same day and 
immediately following the conclusion of the Month 18 visit for Study CFD4870g or Week 24 visit 
for Study GX29455.  Requisite Study CFD4870g Month 18 and Study GX29455 Week 24 
assessment data will be extracted and incorporated into extension study Day 1 datasets. 
All patients who enroll in Study GX28198 will have scheduled monthly visits with monthly 
study -drug treatment for the duration of their study participation. 
At the scheduled monthly visits, patients will have safety assessments evaluated by the 
investigator prior to receiving study drug injection.  Patients will be contacted by site personnel 
7 (± 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 
concern.  Patient self-administered antimicrobials in the pre- and post-injection period may be 
used at the investigator’s discretion.  
The study eye for the extension study will be the same eye that received lampalizumab or sham 
administrations in Study CFD4870g or in Study GX29455.  Only the study eye will receive 
administration of lampalizumab in the extension.    


 
Lampalizumab—Genentech, Inc. 
24/Protocol GX28198, Version 4 
The extension study is being extended by an additional 30 months to a total duration of 
96 months to provide study patients with access to treatment until potential 
commercialization of lampalizumab.  The monthly treatment arm patients enrolled from 
Study CFD4870g may receive up to 96 monthly ITV injections of study drug.  The number of 
ITV injections of study drug for patients who enrolled from the every-other-month treatment arm 
will vary due to their later crossover to the monthly treatment arm, which was relative to their 
Day 1 visit date.  The patients who enroll from study GX29455 may receive up to 54 monthly 
ITV injections of study drug.   
All monthly visits will occur relative to the patient’s Day 1 visit date.  Dosing should not occur 
earlier than 23 days after the previous dosing. Missed study drug doses will be made up only in 
the following circumstance: 
• 
If, during scheduled visit, a site encounters an unexpected issue (e.g., the IxRS is not able 
to assign the study kit, or other patient care issues), 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 delayed study treatment:  slit lamp examination, indirect 
ophthalmoscopy, and pre-treatment intraocular pressure (IOP) measurements.  These 
assessments are to be 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, 
the images must be obtained at the next scheduled visit that the patient attends. 
Patients are expected to attend their scheduled visits unless there are extenuating 
circumstances justifying their inability to come to the clinic 
Patients who are prematurely discontinued from the study treatment in the extension study 
(prior to the Month 96 visit for patients enrolled from Study CFD4870g or prior to the 
Month 54 visit for patients enrolled from Study GX29455) will be also discontinued from the 
extension study; they will be asked to return for an early termination (ET) visit 30 days following 
their last study drug treatment for monitoring of adverse events and the ET visit assessments. 
Patients will remain masked to their treatment assignment in Study CFD4870g or 
Study GX29455, and investigators are not permitted to provide treatment assignment in 
Study CFD4870g or Study 29455 until permitted by the Sponsor.  The extension study is 
conducted in the United States and Germany. 
The VA examiner role will remain masked to the patients' study eye assignment. 
Outcome Measures 
Primary Outcome Measure 
• 
Nature, incidence and severity of ocular and non-ocular adverse events  
 
Pharmacokinetic/Pharmacodynamic Outcome Measures 
Scheduled pharmacokinetic assessments are not planned in the extension study.  However, as 
necessary to assist in safety evaluations, serum lampalizumab concentration measurements will 
be performed.  
Exploratory Outcome Measures 
• 
Change in GA lesion area from baseline assessed by FAF, CFP, and SD-OCT 
• 
Change from baseline in candidate anatomic biomarkers by SD-OCT 
• 
The incidence of positive serum antibodies to lampalizumab 
• 
Clinical genotyping to assess relationships between genetic polymorphisms associated with 
AMD, disease characteristics, and response to administration of lampalizumab  
 


 
Lampalizumab—Genentech, Inc. 
25/Protocol GX28198, Version 4 
Safety Plan 
Lampalizumab is not approved and clinical development is ongoing.  The safety plan for 
patients in this study is based on clinical experience with lampalizumab in completed and 
ongoing studies. The anticipated important safety risks for lampalizumab are outlined below. 
Please refer to the most current lampalizumab Investigator's Brochure for a complete 
summary of safety information. 
Several measures will be taken to ensure the safety of patients participating in this study.  
Eligibility criteria have been designed to exclude patients at a higher risk for toxicities.  
Patients will undergo safety monitoring during the study, including assessments of the 
nature, frequency, and severity of adverse events.  Guidelines for managing adverse events, 
including criteria for treatment interruption or discontinuation, are provided below. 
Potential ocular safety issues currently thought to be associated with the route of administration 
or pharmacology of lampalizumab include decreased best corrected visual acuity (BCVA), 
conjunctival hemorrhage, ocular inflammation, 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. 
Systemic levels of lampalizumab following multiple ITV injections 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, masked aggregate 
adverse event reports will be reviewed periodically to identify potential systemic safety effects, 
such as cardiovascular events, neoplasms, or alteration in immune function (e.g., reports of 
infections with 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.  At the time of study enrollment, if a patient has an ongoing 
adverse event from Study CFD4870g or Study GX29455, the event will be continuously 
followed in the extension study.  Any new adverse events will be collected from the time of 
Day 1 visit (the first study drug administration) in the extension study until a patient completes 
the study or discontinues prematurely.  Safety will be assessed on an ongoing basis using 
expeditious reporting of serious adverse events and adverse events of special interest.  
All adverse events and pregnancies will be recorded for the duration of the study.  
Periodic review of safety will be performed by an internal Genentech Safety Review Committee, 
composed of the Medical Monitor, Drug Safety Scientist, and Biostatistician.  External experts 
may be consulted.  
Starting with the Day 1 visit, all patients will be contacted by study site personnel 7 (± 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. Patient-administered antimicrobials in the pre- and 
post-injection period may be used at the investigator’s discretion. 
Patients will be instructed to contact the investigator at any time if they have health-related 
concerns.  If warranted, patients will be asked to return to the clinic as soon as possible for an 
unscheduled safety assessment visit. 
A finger-counting test will be conducted for each patient within 15 minutes following study 
treatment by the investigator; hand motion or light perception will be tested when necessary.  
Intraocular pressure will be measured bilaterally prior to study treatment and at 
60 (± 10) minutes after study treatment for the study eye only.  If there are no safety concerns at 
60 (±10) minutes post treatment, the patient will be discharged from the clinic.  If the IOP is 
increased by ≥ 10 mmHg from the pre-injection measurement at 60 (±10) minutes the patient 
will remain in the clinic and will be treated according to the investigator’s clinical judgment prior 
to the patient’s discharge; if applicable, an Adverse Event eCRF page will be completed. 
Detailed ocular examinations, including indirect ophthalmoscopy and slit-lamp examination, will 
be performed throughout the study.  Routine hematology, serum chemistry, coagulation, and 
urinalysis profiles, as well as blood samples for antibodies to lampalizumab, will be obtained 
from all patients.  
The visual acuity (VA) examiner will be masked to the patient’s treated (study) eye and will 
perform only the VA (including refraction).  The VA examiner is not allowed to perform any other 
tasks involving direct patient care. 


 
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26/Protocol GX28198, Version 4 
Patients who are prematurely discontinued from the study treatment (prior to the Month 96 visit 
for CFD4870g patients and prior to the Month 54 visit for GX29455 patients) will be also 
discontinued from the extension study and will be asked to return for an ET evaluation ≥30 days 
following their last study drug treatment for monitoring of adverse events and the early study 
termination visit assessments.   
Serious adverse events will be collected and reported in compliance with Good Clinical Practice 
guidelines. 
Refer to the main body of the protocol for dose-holding and study discontinuation criteria for 
adverse events. 
Study Treatment for Patients Enrolled from Study CFD4870g 
The dose of 10 mg lampalizumab was administered monthly or every other month starting at the 
Day 1 visit for up to the 18-month of treatment period.  Later, the treatment period duration was 
extended by 24 months and patients in the every-other-month treatment arm were crossed over 
to the monthly treatment arm to receive monthly study drug treatment for the remainder of their 
study treatment period, provided that their informed consent has been obtained.  The study 
treatment period was again extended by another 24 months and now by 30 additional months 
for a total treatment period of 96 months.  Patients in the monthly treatment arm may receive up 
to 96 ITV injections of study drug.  The number of ITV injections of study drug for patients who 
were in the every-other-month treatment arm prior to their crossover to the monthly treatment 
arm will vary and will depend on the date of their crossover relative to their Day 1 visit date.   
Study Treatment for Patients Enrolled from Study GX29455 
The extension study will enroll 2 groups of patients from Study GX29455:  patients previously 
exposed to lampalizumab and patients who were lampalizumab-naïve (sham arm).  Eligible 
patients who consented to participate in the extension study will be enrolled at the conclusion of 
the Week 24 visit for Study GX29455; the Week 24 visit will serve as the final visit for Study 
GX29455 and the Day 1 visit for the extension study. 
All study GX29455 patients enrolled in the extension study will receive 10-mg ITV injections of 
lampalizumab.  Dosing frequency for both treatment arms (Q2W and Q4W) of Study GX29455 
changed to the monthly dosing upon entry to this study.  Given that 30 months have been 
added to the original 24 month study duration for the patients from Study GX29455, these 
patients may receive up to 54 ITV injections of study drug.  
All patients in Study GX29198 will have scheduled monthly visits and monthly study-drug 
treatment for the duration of the study. The monthly visit will occur relative to Day 1 visit date.  
Dosing should not occur earlier than 23 days after the previous dosing.  Missed study drug 
treatments will not be made up unless an extenuating circumstance applies. 
Permitted Concomitant Therapy and Clinical Practice 
Permitted concomitant medications are any prescription drugs or over-the-counter preparations 
other than protocol-specified procedural treatments (e.g., dilating drops, fluorescein dyes) and 
pre- and post-injection medications (e.g., proparacaine, investigator-applied antimicrobials [if 
applicable] pre and post injection) used by a patient at the time of study enrollment on the Day 1 
visit and through study completion or the ET visit. 
Patients who use other maintenance therapies should continue their use.  Patients required to 
use medications described in Excluded Concomitant Therapy will not be eligible for enrollment 
or continuation in the study.  All concomitant medications should be reported to the investigator 
and recorded on the appropriate eCRF. 
The onset of glaucoma in the study eye during a patient’s study participation should be treated 
as clinically indicated. 
Of note, the following are some common therapies that are permitted: 
• 
Short-term use of topical corticosteroids after cataract surgery, yttrium aluminum garnet 
capsulotomy, or peripheral iridotomy. 
• 
Oral corticosteroids at doses ≤ 10 mg/day prednisone or equivalent 
• 
Onset of ocular hypertension or glaucoma in the study eye during a patient’s study 
participation should be treated as clinically indicated. 


 
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• 
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 may apply with 
cataract surgery. 
• 
At the discretion of the investigator, enrolled patients who are receiving study treatment and 
are diagnosed with choroidal neovascularization (CNV) may be treated with ranibizumab if 
they are diagnosed in either eye with CNV.  
 
NOTE: If treatment with ranibizumab is to be given (to study and/or non-study eye) at the same 
visit as a study eye treatment with lampalizumab, the treatment with ranibizumab must be 
administered first.  The safety assessments (including IOP check) required to proceed to the 
study eye treatment with lampalizumab must be assessed prior to calling IxRS for the study 
drug kit assignment.  Individual trays and sterile prep must be separately prepared for each 
treatment.  
Excluded Concomitant Therapy 
At the discretion of the investigator, patients may continue to receive all medications and 
standard treatments administered for other conditions.  The following medications/treatments 
are prohibited from use during the patient’s participation in the study: 
• 
Systemic anti-vascular endothelial growth factor (VEGF) agents  
• 
ITV anti-VEGF agents (other than ranibizumab) in either eye 
• 
ITV, subtenon, or chronic topical (ocular) corticosteroids in the study eye 
• 
Systemic or IV immunomodulatory therapy (e.g., azathioprine, methotrexate, 
mycophenolate mofetil, cyclosporine, cyclophosphamide, anti-tumor necrosis 
factor α agents) 
• 
Ocular or systemic complement inhibitors, (e.g., eculizumab) except lampalizumab 
• 
Treatment with Visudyne in either eye 
• 
Other experimental therapies (except those involving vitamin and mineral supplements) 
 
Excluded Concomitant Conditions 
Medical or surgical conditions or clinical laboratory findings giving reasonable suspicion of a 
disease or condition that contraindicates the use of an investigational drug, or that might affect 
interpretation of the study results, or that may render a study patient at high risk for treatment 
complications; when such a condition is identified, consultation with the Medical Monitor will be 
required to determine a patient’s eligibility to continue in the extension study. 
Statistical Methods 
Safety Analysis 
Safety will be assessed by adverse events, clinical laboratory evaluations, and immunogenicity 
as measured by ATA.  Safety analyses will include all patients who enrolled into the extension 
study and received at least 1 lampalizumab injection in the extension study.  These patients will 
be grouped by the treatment received (lampalizumab or sham) when they were enrolled in 
Study CFD4870g or Study GX29455 for safety analyses.   
The primary safety analysis is planned to occur at the time when patients enrolled from 
Study CFD4870g have reached approximately 96 months follow up and when patients enrolled 
from Study GX29455 have reached approximately 54 months follow- up.  The timing of the 
primary analysis may be adjusted according to the start of the open-label extension for Studies 
GX29176 and GX29185, to which patients from the extension study may have the opportunity to 
enroll.  Earlier safety analyses of this study may be performed on an ad hoc basis. 
All verbatim adverse event terms will be mapped to Medical Dictionary for Regulatory 
Activities (MedDRA) thesaurus terms, and adverse event severity will be graded according to 
an adverse event severity grading scale. 
Missing Data   
All efforts will be made to minimize missing data; no imputation will be performed for the 
safety analysis.  


 
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Determination of Sample Size   
This study is open to all patients who complete Study CFD4870g and Study GX29455 and who 
meet eligibility criteria.  Accordingly, the sample size for this study is not based on a formal 
sample size calculation. 
Interim Analysis 
The primary analysis time will occur after all patients enrolled from Study CFD4870g have 
reached approximately 96 months follow up and when patients enrolled from Study GX29455 
have reached approximately 54 months follow-up.  Earlier analyses may be performed on an 
ad hoc basis. 
 


 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
ACP 
alternative complement pathway 
AE 
adverse event 
AMD 
age-related macular degeneration 
AREDS 
Age-Related Eye Disease Study 
ATA 
anti-therapeutic antibody 
BCVA 
best corrected visual acuity 
CFB 
complement factor B 
CFD 
complement factor D 
CFP 
color fundus photographs 
Cmax 
maximum observed serum concentration 
CNV 
choroidal neovascularization 
CRO 
contract research organization 
DA 
disk area 
DAP 
Data Analysis Plan 
DLC 
dose-limiting criteria 
DLT 
dose-limiting toxicity 
eCRF 
electronic Case Report Form 
EDC 
electronic data capture 
ET 
early termination 
ETDRS 
Early Treatment of Diabetic Retinopathy Study 
FA 
fluorescein angiogram 
Fab 
antigen-binding fragment 
FAF 
fundus autofluorescence 
FDA 
Food and Drug Administration 
FP 
fundus photography 
GA 
geographic atrophy 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IOP 
intraocular pressure 
ITV 
intravitreal 
IxRS 
interactive response system 
MTD 
maximum tolerated dose 


 
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Abbreviation 
Definition 
NI 
near infrared 
PK 
pharmacokinetic 
Q2W 
every 2 weeks 
Q4W 
every 4 weeks 
RPE 
retinal pigment epithelial 
SAE 
serious adverse event 
SD-OCT 
spectral domain−optical coherence tomography 
TAE 
targeted adverse event 
VA 
visual acuity 
VEGF 
vascular endothelial growth factor 
YAG 
yttrium aluminum garnet 


 
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1. 
BACKGROUND 
1.1 
BACKGROUND ON DISEASE  
1.1.1 
Epidemiology 
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in 
people 50 years of age or older in the developed world (Friedman et al. 2004).  
The overall prevalence of AMD is projected to increase by more than 50% by the year 
2020.  Advanced AMD is classified into two clinical forms:  geographic atrophy (GA) and 
exudative disease characterized by choroidal neovascularization (CNV) (Age-Related 
Eye Disease Study [AREDS] Research Group 2003).  Progression of GA may be 
associated with a significant decrease in visual function with approximately 40% of a 
subset of GA patients losing at least 3 Snellen equivalent lines of vision over a 2 year 
period (Sunness et al. 2007).   
1.1.2 
Pathophysiology 
The pathogenesis of AMD is not well understood; however, environmental factors and 
the alternative complement pathway (ACP) have been implicated in AMD 
(de Jong 2006).  Increased activation of the ACP has been found in drusen, 
lipoproteinous depositions in the space between the retinal pigment epithelial (RPE) and 
Bruch’s membrane, which are a hallmark of AMD.  Moreover, a role for ACP activation in 
AMD has been supported by human genetics (Yates et al. 2007).  Complement factor D 
(CFD) is a rate-limiting enzyme that plays a pivotal role in the activation and 
amplification of ACP activity.  Evidence for CFD in the pathogenesis of AMD includes 
protection against oxidative-stress-mediated photoreceptor degeneration in a murine 
model with genetic deficiency of CFD (Rohrer et al. 2007), and detection of increased 
systemic activation of complement, including CFD, in the serum of AMD patients versus 
controls, suggesting that AMD may be a systemic disease with local manifestations in 
the aging macula (Scholl et al. 2008).  
1.1.3 
Management of Geographic Atrophy 
Currently, intravitreal (ITV) anti-VEGF (vascular endothelial growth factor) therapy is the 
standard of care for the wet form of advanced AMD; however, there is no treatment that 
definitively halts or reduces the progression of GA and vision function loss.  Although the 
AREDS Research Group has shown that antioxidant vitamin and mineral 
supplementation had a statistically significant but modest effect on reducing the 
progression of AMD, it was the reduction in progression to neovascular AMD rather than 
progression to central GA that was principally responsible for this observation (AREDS 
Research Group 2001).  Currently, there is no approved treatment to prevent or reduce 
progression of GA, creating a significant unmet need for these patients.  By inhibiting 
ACP activity, lampalizumab may offer the potential to impede or arrest the progression of 
GA and visual function loss.  


 
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1.2 
BACKGROUND ON THE MOLECULE  
Lampalizumab is an antigen-binding fragment (Fab) of a humanized monoclonal 
antibody directed against the complement component factor D (CFD).  Lampalizumab 
binds human factor D with a dissociation equilibrium constant of approximately 20 pM.  
Factor D is a highly specific serine protease that is a rate-limiting enzyme of the ACP.  
The substrate for factor D is another alternative pathway serine protease, complement 
factor B (CFB).  Following cleavage by CFD, CFB converts into the proteolytically active 
complement factor Bb and initiates the ACP.  Lampalizumab inhibits ACP activity by 
preventing CFD−mediated cleavage of CFB.  Lampalizumab activity is specific for the 
ACP and shows no inhibitory effect on the classical or mannose-binding lectin 
complement pathways.  
Through inhibition of ACP activity, lampalizumab may offer the potential to impede or 
arrest the progression of GA and visual function loss.  Evidence for CFD in the 
pathogenesis of AMD includes protection against oxidative stress-mediated 
photoreceptor degeneration in a murine model with genetic deficiency of CFD (Rohrer et 
al. 2007) and detection of increased systemic activation of complement components, 
including CFD, in the serum of patients with AMD versus controls, which suggests 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 
RATIONALE FOR DOING THIS STUDY 
The open-label extension study will provide data to investigate the long-term safety and 
tolerability of lampalizumab in patients with GA.  At present, there is no approved 
treatment to prevent the progression of GA and vision loss; lampalizumab is being 
studied as a potential treatment for this indication.  For patients who complete 
the18-month treatment assignment in Study CFD4870g or 24-week treatment 
assignment in Study GX29455, Study GX28198 will permit the evaluation of long-term 
safety and tolerability of lampalizumab in participants continuing from the active 
treatment arms.  In addition, Study GX28198 will provide the opportunity for eligible 
patients from the sham treatment arms in Study CFD4870g or Study GX29455 to 
receive lampalizumab. 
2. 
OBJECTIVES  
2.1 
PRIMARY OBJECTIVE 
The primary objective of this study is as follows: 
• 
To investigate the long-term ocular and systemic safety and tolerability of 
lampalizumab administered ITV monthly  


 
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2.2 
EXPLORATORY OBJECTIVES 
The exploratory objectives of this study are as follows: 
• 
To assess long-term GA area progression with fundus autofluorescence (FAF), 
color fundus photographs (CFP), and spectral domain-optical coherence 
tomography (SD-OCT) 
• 
To evaluate potential anatomic biomarkers for earlier-stage GA progression and 
pharmacodynamic outcomes (e.g., retinal substructure analysis by SD-OCT)  
• 
To assess the incidence of anti-therapeutic antibodies (ATA) to lampalizumab 
• 
Clinical genotyping to assess relationships between genetic polymorphisms 
associated with AMD, disease characteristics, and response to administration of 
lampalizumab 
 
3. 
STUDY DESIGN 
3.1 
DESCRIPTION OF THE STUDY 
Study GX28198 is a multicenter, open-label extension study of safety and tolerability of 
lampalizumab administered by ITV injection to patients with GA who have completed the 
18-month treatment in Study CFD4870g or 24-week treatment in Study GX29455.  
As such, Study GX28198 is considered the extension for patients enrolled in these 
studies and is referred to as the extension study throughout the remainder of this 
protocol. CFD4870g patients who discontinued from study treatment early but remained 
in the study for safety evaluation, or discontinued prior to completion of the 18-month 
treatment period, were not eligible for Study GX28198.  Patients who participated in 
Study GX29455 and discontinued from study treatment prior to completion of the 
24-week treatment period are not eligible for the extension study.  Site investigators will 
be ophthalmologists with subspecialty expertise in vitreoretinal diseases.   
3.1.1 
Patients Enrolled from Study CFD4870g 
The extension study enrolled 2 groups of patients from Study CFD4870g:  patients 
previously exposed to lampalizumab and patients who were lampalizumab-naïve 
(i.e., received sham treatment).  Eligible patients who consented to participate in the 
extension study were enrolled at the conclusion of the Month 18 visit for Study 
CFD4870g; the Month 18 visit served as the final visit for Study CFD4870g and the 
Day 1 visit for the extension study.  Upon enrollment, all patients received 10-mg ITV 
injections of lampalizumab.  Initially, patients continued on the same dosing frequency 
(monthly or every-other month) assigned previously during their participation in 
Study CFD4870g.  Patients in the every-other-month treatment arm were later crossed 
over to the monthly treatment arm for the remainder of their study participation period 
(see Section 3.3). 


 
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3.1.2 
Patients Enrolled from Study GX29455 
The extension study will enroll 2 groups of patients from Study GX29455:  patients 
previously exposed to lampalizumab and patients who were lampalizumab-naïve (i.e., 
received sham).  Eligible patients who consent to participate in the extension study will 
be enrolled at their conclusion of Study GX29455 (i.e., the Week 24 visit); the Week 24 
visit will serve as the final visit for Study GX29455 and the Day 1 visit for the extension 
study. 
All patients from Study GX29455 who enroll in the extension study will receive 10-mg 
ITV administrations of lampalizumab.  The dosing frequency for both treatment arms 
(every 2 weeks [Q2W] and every 4 weeks [Q4W]) of Study GX29455 will change to 
monthly dosing to align with dosing in the extension study.  
3.1.3 
All Extension Study Patients 
A patient must satisfy all eligibility criteria at Day 1 visit and will be enrolled using an 
interactive response system (IxRS).  All patients enrolled in the extension study will have 
the first ITV injection of lampalizumab administered by the investigator at the Day 1 visit 
(unless dose holding is medically justified by the investigator) which is scheduled on the 
same day and immediately following the conclusion of the Month 18 visit for Study 
CFD4870g or Week 24 visit for Study GX29455.  Requisite Study CFD4870g Month 18 
and Study GX29455 Week 24 assessment data will be extracted and incorporated into 
extension study Day 1 datasets. 
All patients who enroll in Study GX28198 will have scheduled monthly visits with monthly 
study-drug treatment for the duration of their study participation (see Table 1). 


 
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Table 1 
Dosing Schema 
 
Treatment  
Day 1a 
Monthly Lampalizumab Dosing 
Visit Month 1 through Visit Month 95b 
or Visit Month 1 through 
Visit Month 53c  
 ETe or 
Final visit 
Month 96d or 
Month 54d 
Lampalizumab 10-mg ITV 
injections 
x 
x 
 
ET =  early termination; ITV = intravitreal.  
a Day 1 visit will occur at the conclusion of the Month 18 visit for Study CFD4870g or Week 24 
visit for Study GX29455; the first study drug administration for the extension study is at the 
Day 1 visit. 
b Patients enrolled from Study CFD4870g in the monthly treatment arm continue to receive 
monthly lampalizumab treatment (Months 1−95) without change; patients in the every-other-
month treatment arm were crossed over to the monthly treatment arm and are receiving 
monthly lampalizumab treatment for the remainder of their 95-month study treatment period.  
c  Patients enrolled from Study GX29455 will receive monthly treatment (visit Months 1−53) with 
lampalizumab irrespective of the treatment arm (Q2W or Q4W) they were randomized to in 
Study GX29455.  
d Month 96 visit is a final study visit for patients enrolled from Study CFD4870g and Month 54 
visit is the final study visit for patients enrolled from Study GX29455; no study treatment will be 
administered at the final visit. 
e Patients may undergo an ET visit as per protocol section 4.7 through 4.9; no study 
treatment will be administered at this visit. 
 
At the scheduled monthly visits, patients will have safety assessments evaluated by the 
investigator prior to receiving study drug injection.  Patients will be contacted by site 
personnel 7 (± 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 1-F).  Patients will be instructed to contact the 
investigator at any time if they have any health-related concern.  Patient 
self-administered antimicrobials in the pre- and post-injection period may be used at the 
investigator’s discretion. 
The study eye for the extension study will be the same eye that received lampalizumab 
or sham administrations in Study CFD4870g or in Study GX29455.  Only the study eye 
will receive administration of lampalizumab in the extension.    
The extension study is being extended by an additional 30 months to a total duration of 
96 months to provide study patients with access to treatment until potential 
commercialization of lampalizumab.  The monthly treatment arm patients enrolled from 
Study CFD4870g may receive up to 96 monthly ITV injections of study drug.  
The number of ITV injections of study drug for patients who enrolled from the 
every-other-month treatment arm will vary due to their later crossover to the monthly 


 
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treatment arm, which was relative to their Day 1 visit date.  The patients who enroll from 
study GX29455 may receive up to 54 monthly ITV injections of study drug.   
All monthly visits will occur relative to the patient’s Day 1 visit date.  Dosing should not 
occur earlier than 23 days after the previous dosing.  Missed study drug doses will be 
made up only in the following circumstance: 
• 
If, during scheduled visit, a site encounters an unexpected issue (e.g., the IxRS is 
not able to assign the study kit, or other patient care issues), 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 delayed study treatment:  slit lamp 
examination, indirect ophthalmoscopy, and pre-treatment intraocular pressure 
(IOP) measurements.  These assessments are to be 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-A through Appendix 1-E), the images must be obtained at the 
next scheduled visit that the patient attends. 
Patients are expected to attend their scheduled visits unless there are extenuating 
circumstances justifying their inability to come to the clinic. 
Patients who are prematurely discontinued from the study treatment in the extension 
study (prior to the Month 96 visit for patients enrolled from Study CFD4870g or prior to 
the Month 54 visit for patients enrolled from Study GX29455) will be also discontinued 
from the extension study and will be asked to return for an early termination (ET) visit 
≥30 days following their last study drug treatment for monitoring of adverse events and 
the ET visit assessments (Appendix 1-A through Appendix 1-E). 
Patients will remain masked to their treatment assignment in Study CFD4870g or 
Study GX29455, and investigators are not permitted to provide treatment assignment in 
Study CFD4870g or Study GX29455 until permitted by the Sponsor.  The extension 
study is being conducted in the United States and Germany. 
The VA examiner role will remain masked to the patients' study eye assignment. 


 
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3.2 
TREATMENT FOR CHOROIDAL NEOVASCULARIZATION WITH 
RANIBIZUMAB 
At the discretion of the investigator, enrolled patients who are receiving study treatment 
and are diagnosed with CNV in either eye may receive treatment with 0.5 mg 
ranibizumab.  For U.S. sites, the drug will be open-label ranibizumab for investigational 
use only supplied by Genentech (see the pharmacy binder for the drug formulation) and 
injected no more frequently than monthly.  Sites in Germany will use commercially 
available ranibizumab (Lucentis) in Germany and consult with the region-specific 
Lucentis Prescribing Information for the recommended dose, frequency, and 
administration of treatment.  
Please see the pharmacy binder for ranibizumab administration (pre-injection procedure, 
preparation and administration, and post-injection procedure) at U.S. sites. 
3.3 
RATIONALE FOR STUDY DESIGN 
The primary objective of the extension study is to assess the long-term ocular and 
systemic safety and tolerability of lampalizumab in GA patients.   
Patients from Study CFD4870g (including those in sham arms), initially received 
lampalizumab in the extension study at the same dosing frequency previously assigned 
in Study CFD4870g:  patients in the monthly treatment arms continued receiving monthly 
treatment, and patients in the every-other-month treatment arm continued receiving 
every-other-month treatment.  
After Study CFD4870g results demonstrated that monthly administration of 
lampalizumab had a clinically meaningful and statistically significant effect on 
reducing the GA area growth over the 18-month study treatment period (see 
Investigator Brochure for additional details), the every-other-month treatment arm 
patients were crossed over to the monthly treatment arm for the remainder of their study 
participation, provided informed consent was obtained.   
All patients, regardless of treatment arm in the 6-month GX29455 exposure-response 
study (including those in sham arms) who are subsequently enrolled in the extension 
study will be assigned to the 10-mg lampalizumab monthly dosing frequency. 
The extension study design will permit an assessment of several exploratory outcomes 
(see Section 3.4.3) that may offer a better understanding of disease progression and 
treatment effects.  
3.4 
OUTCOME MEASURES  
3.4.1 
Primary Outcome Measure 
• 
Nature, incidence, and severity of ocular and non-ocular adverse events  


 
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3.4.2 
Pharmacokinetic/Pharmacodynamic Outcome Measures  
Scheduled pharmacokinetic assessments are not planned in the extension study.  
However, as necessary to assist in safety evaluations, serum lampalizumab 
concentration measurements will be performed.  
3.4.3 
Exploratory Outcome Measures 
• 
Change in GA lesion area from baseline assessed by FAF, CFP, and SD-OCT 
• 
Change from baseline in candidate anatomic biomarkers by SD-OCT 
• 
The incidence of positive serum antibodies to lampalizumab 
• 
Clinical genotyping to assess relationships between genetic polymorphisms 
associated with AMD, disease characteristics, and response to administration of 
lampalizumab  
3.5 
SAFETY PLAN  
Lampalizumab is not approved and clinical development is ongoing.  The safety plan for 
patients in this study is based on clinical experience with lampalizumab in completed 
and ongoing studies. The anticipated important safety risks for lampalizumab are 
outlined below. Please refer to the most current lampalizumab Investigator's Brochure 
for a complete summary of safety information. 
Several measures will be taken to ensure the safety of patients participating in this 
study.  Eligibility criteria have been designed to exclude patients at a higher risk for 
toxicities.  Patients will undergo safety monitoring during the study, including 
assessments of the nature, frequency, and severity of adverse events.  Guidelines for 
managing adverse events, including criteria for treatment interruption or 
discontinuation, are provided below. 
Potential ocular safety issues currently thought to be associated with the route of 
administration or pharmacology of lampalizumab include decreased best corrected 
visual acuity (BCVA), conjunctival hemorrhage, ocular inflammation (see Section 5.1.3 
for definition and Appendix 2 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. 
Systemic levels of lampalizumab following multiple ITV injections 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, 
masked aggregate adverse event reports will be reviewed periodically to identify 
potential systemic safety effects, such as cardiovascular events, neoplasms, or 
alteration in immune function (e.g., reports of infections with encapsulated bacteria such 
as Neisseria meningitidis, Streptococcus pneumonia, and Haemophilus influenza). 


 
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The incidence and characteristics of adverse events, serious adverse events, and 
laboratory abnormalities will be assessed.  At the time of study enrollment, if a patient 
has an ongoing adverse event from Study CFD4870g or Study GX29455, the event will 
be continuously followed in the extension study.  Any new adverse events will be 
collected from the time of Day 1 visit (the first study drug administration) in the extension 
study until a patient completes the study or discontinues prematurely.  Safety will be 
assessed on an ongoing basis using expeditious reporting of serious adverse events 
and adverse events of special interest.  All adverse events and pregnancies will be 
recorded for the duration of this study. 
Periodic review of safety will be performed by an internal Genentech Safety Review 
Committee, composed of the Medical Monitor, Drug Safety Scientist, and Biostatistician.  
External experts may be consulted.  
Starting with the Day 1 visit, all patients will be contacted by study site personnel 
7 (± 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. 
Patient-administered antimicrobials in the pre- and post-injection period may be used at 
the investigator’s discretion. 
Patients will be instructed to contact the investigator at any time if they have 
health-related concerns.  If warranted, patients will be asked to return to the clinic as 
soon as possible for an unscheduled safety assessment visit (Appendix 1-F). 
A finger-counting test will be conducted for each patient within 15 minutes following 
study treatment by the investigator; hand motion or light perception will be tested when 
necessary.  IOP will be measured bilaterally prior to study treatment and at 
60 (± 10) minutes after study treatment for the study eye only.  If there are no safety 
concerns at 60 (± 10) minutes post treatment, the patient will be discharged from the 
clinic.  If the IOP is increased by ≥ 10 mmHg from the pre-injection measurement at 
60 (± 10) minutes the patient will remain in the clinic and will be treated according to the 
investigator’s clinical judgment prior to the patient’s discharge; if applicable, an Adverse 
Event eCRF page will be completed (see Section 5.3.5). 
Detailed ocular examinations, including indirect ophthalmoscopy and slit-lamp 
examination, will be performed throughout the study.  Routine hematology, serum 
chemistry, coagulation, and urinalysis profiles, as well as blood samples for 
antibodies to lampalizumab, will be obtained from all patients (see Appendix 1-A through 
Appendix  1-E).  
The VA examiner will be masked to the patient’s treated (study) eye and will perform 
only the VA (including refraction).  The VA examiner is not allowed to perform any other 
tasks involving direct patient care. 


 
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Patients who are prematurely discontinued from the study treatment (prior to the 
Month 96 visit for CFD4870g patients and prior to the Month 54 visit for GX29455 
patients) will be also discontinued from the extension study and will be asked to return 
for an ET evaluation ≥30 days following their last study drug treatment for monitoring of 
adverse events and the early study termination visit assessments (see Appendix 1-A 
through Appendix 1-E).   
Serious adverse events will be collected and reported in compliance with Good Clinical 
Practice guidelines. 
See Section 4.8 for dose-holding and study discontinuation criteria for adverse events.  
If a patient’s eye is injected with ranibizumab, the same post-dose safety assessments 
(finger counting, IOP measurement, and follow-up call) should be followed as for the 
study treatment.  Treatment (dose) holding and/or treatment discontinuation for adverse 
events will be determined using the criteria in Table 2 in Section 4.3.1.2.  Associated 
adverse events should be recorded on the Adverse Event eCRF. 
3.6 
STUDY PATIENTS  
All patients who complete Study CFD4870g or Study GX29455 and who satisfy eligibility 
criteria are offered the opportunity to participate in the extension study.   
3.7 
CONTROL GROUPS 
This is an open-label extension study.  There is no control group for this study.   
3.8 
ETHICAL CONSIDERATIONS  
The patient population to be enrolled in this study must meet eligibility criteria and agree 
to participate in the extension study following an informed consent process.  This study 
will comply with laws and guidelines as discussed in Compliance with Laws and 
Regulations (see Section 3.10), Informed Consent (see Section 6.3), Disclosure of Data 
(see Section 6.11), and Institutional Review Board Approval (see Section 6.4).   


 
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3.9 
ADMINISTRATIVE STRUCTURE  
This study will be sponsored by Genentech, which is the U.S.-based global affiliate of 
F. Hoffmann-La Roche; F. Hoffmann-La Roche will serve as the legal sponsor in 
Germany.  Genentech will perform study management, oversight of data management, 
and statistical programming.  A contract research organization (CRO) will be responsible 
for project management, monitoring, vendor management, and data management 
(including quality checking of the data).  An IxRS will be used for patient enrollment 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 Genentech for 
analysis).  Data will be recorded by an electronic data capture (EDC) system using 
eCRFs (see Section 6.6).  A central reading center will be used for ocular imaging 
analyses (FAF, near infrared [NI], CFP, FA and SD-OCT).  
3.10 
COMPLIANCE WITH LAWS AND REGULATIONS 
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, and applicable local, state, and federal laws, as well as other 
applicable country laws. 
4. 
MATERIALS AND METHODS  
4.1 
PATIENTS 
4.1.1 
Patient Selection 
Patients who have completed study treatment and the Month 18 visit of 
Study CFD4870g or Week 24 visit of Study GX29455 will be eligible to participate in the 
extension study. 
Patients who discontinued from study treatment early but remained on study for safety 
evaluation, or discontinued from Study CFD4870g prior to completion of the 18 month 
treatment period, will not be eligible for the extension study.  
Patients who discontinued from study treatment prior to completion of the 24-week 
treatment period in Study GX29455 will not be eligible for the extension study. 
Written informed consent will be obtained prior to enrollment and the initiation of any 
study procedures.  On the same day, patients will be enrolled in the extension study at 
the conclusion of the Month 18 completion visit for Study CFD4870g or of the Week 24 
completion visit for Study GX29455 provided inclusion/exclusion criteria are met; the 
Month 18 CFD4870g visit data or Week 24 GX29455 visit data will serve as the Day 1 
visit data for the extension study.  In the case where a patient misses the final 


 
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Month 18 visit for Study CFD4870g or final Week 24 visit for Study GX29455, eligibility 
for the extension study will be determined by the Sponsor. 
Note: All patients enrolled in the extension study will have the first 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 4.3.1.2 
and Table 2). 
4.1.2 
Inclusion Criteria 
Patients must meet all of the following criteria to be eligible for study entry: 
4.1.2.1 
General Inclusion Criteria 
• 
Willingness and ability to provide signed Informed Consent; in addition, at U.S. sites, 
Health Insurance Portability and Accountability Act (HIPPA) authorization, in other 
countries as applicable according to national laws 
• 
Ability and willingness to undertake all scheduled visits and assessments 
• 
For CFD4870g patients:  Previous enrollment and completion (Month 18 visit) of 
Study CFD4870g without early treatment discontinuation (lampalizumab or sham)  
• 
For GX29455 patients:  Previous enrollment and completion (Week 24 visit) of 
Study GX29455 without early treatment discontinuation (lampalizumab or sham)  
• 
For women of childbearing potential:  agreement to remain abstinent (refrain from 
heterosexual intercourse) or use contraceptive methods that result in a failure rate 
of  < 1% per year during the treatment period and for at least 30 days after the last 
dose of study drug.   
A woman is considered to be of childbearing potential if she is post-menarcheal, has 
not reached a post-menopausal state (≥ 12 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. 


 
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• 
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 30 days plus 90 days (a 
spermatogenesis cycle) after the last dose of study drug.  Men must refrain from 
donating sperm during this same period. 
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. 
 
4.1.2.2 
Ocular Inclusion Criterion 
• 
Sufficiently clear ocular media, adequate pupillary dilation, and fixation to permit 
quality fundus imaging 
 
4.1.3 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from study entry: 
4.1.3.1 
Ocular Exclusion Criteria 
• 
Vitrectomy surgery, submacular surgery, or other surgical intervention for AMD in 
the study eye 
• 
Subfoveal focal laser photocoagulation in the study eye 
• 
Treatment with Visudyne, external-beam radiation therapy, or transpupillary 
thermotherapy in the study eye 
• 
ITV drug delivery (e.g., ITV corticosteroid injection, anti-angiogenic drugs, anti-
complement drugs, or device implantation) in the study eye.  Lampalizumab in study 
eye and ranibizumab in either eye are permitted.  
• 
Any concurrent ocular or intraocular condition in the study eye that contraindicates 
the use of an investigational drug or may affect interpretation of the study results or 
may render the patient at high risk for treatment complications 
• 
Idiopathic or autoimmune-associated uveitis/vitritis in either eye 
• 
RPE tear involving the macula in the study eye  
• 
Retinal detachment or macular hole (Stage 3 or 4) in the study eye 
• 
Aphakia or absence of the posterior capsule in the study eye 
• 
Violation of the posterior capsule in the study eye is also excluded unless it occurred 
as a result of yttrium aluminum garnet (YAG) laser posterior capsulotomy in 
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• 
Uncontrolled glaucoma in the study eye (defined as IOP ≥30 mmHg despite 
treatment with anti-glaucoma medication) 
• 
Planned or anticipated glaucoma-filtering surgery in the study eye 
• 
Planned or anticipated corneal transplant in the study eye 
• 
Diabetic retinopathy in either eye 
• 
Scleritis, keratitis, or endophthalmitis in either eye 
 
4.1.3.2 
Concurrent Systemic Conditions 
• 
Uncontrolled blood pressure (defined as systolic greater than 180 mmHg and/or 
diastolic greater than 110 mmHg while the patient is sitting)  
• 
Medical conditions that may be associated with a clinically significant risk 
for bleeding 
• 
Metabolic dysfunction, physical examination finding, or clinical laboratory finding 
giving reasonable suspicion of a disease or condition that contraindicates the use of 
an investigational drug or that might affect interpretation of the results of the study or 
that renders the patient at high risk for treatment complications 
• 
Predisposition to increased risk for infection 
• 
Active malignancy within the past 12 months except for appropriately treated 
carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer 
with a Gleason score of < 6 and a stable prostate-specific antigen for > 12 months.  
• 
Allergy to fluorescein, not amenable to treatment 
• 
Inability to obtain study images of sufficient quality to be analyzed and graded by the 
central reading center 
• 
Inability to comply with study or follow-up procedures 
• 
Requirement for continuous use of any medications/treatments indicated in the 
“Excluded Concomitant Therapy” Section 4.5.2 
 
4.2 
METHOD OF TREATMENT ASSIGNMENT AND MASKING  
This is an open-label extension study.  All patients enrolled in the extension study will 
receive 10-mg ITV administrations of lampalizumab.   
Dosing frequency in the extension study was either monthly or every other month in 
accordance with the Study CFD4870g treatment frequency assignment.  Patients in the 
every-other-month treatment arm were later crossed over to the monthly treatment arm 
for the remainder of their study participation, provided that their informed consents have 
been obtained.  The patients who joined the extension study from Study GX29455 will 
receive 10-mg ITV administration of lampalizumab monthly.  


 
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The patients will remain masked to their previous lampalizumab or sham treatment 
assignments in Study CFD4870g or Study GX29455 until the Sponsor permits 
investigators to release this information.  The VA examiner will remain masked to 
patients’ study eye assignment and will perform only the VA (including refraction).  The 
VA examiner is not allowed to perform any other tasks involving direct patient care. 
4.3 
STUDY TREATMENT 
4.3.1 
Lampalizumab 
4.3.1.1 
Formulation  
See the pharmacy binder for details regarding formulation. 
4.3.1.2 
Dosage, Administration, and Storage 
Dosage 
Patients enrolled from Study CFD4870g:  
The dose of 10 mg lampalizumab was administered monthly or every other month 
starting at the Day 1 visit for up to the 18-month of treatment period.  Later, the 
treatment period duration was extended by 24 months and patients in the 
every-other-month treatment arm were crossed over to the monthly treatment arm to 
receive monthly study drug treatment for the remainder of their study treatment period, 
provided that their informed consent has been obtained.  The study treatment period was 
again extended by another 24 months and now by 30 additional months for a total 
treatment period of 96 months.  Patients in the monthly treatment arm may receive up to 
96 ITV injections of study drug.  The number of ITV injections of study drug for patients 
who were in the every-other-month treatment arm prior to their crossover to the monthly 
treatment arm will vary and will depend on the date of their crossover relative to their 
Day 1 visit date.   
Patients enrolled from Study GX29455:  
The extension study will enroll 2 groups of patients from Study GX29455:  patients 
previously exposed to lampalizumab and patients who are lampalizumab-naïve (sham 
arm).  Eligible patients who consent to participate in the extension study will be enrolled 
at the conclusion of the Week 24 visit for Study GX29455; the Week 24 visit will serve as 
the final visit for Study GX29455 and the Day 1 visit for the extension study. 
All study GX29455 patients enrolled in the extension study will receive 10-mg ITV 
injections of lampalizumab.  Dosing frequency for both treatment arms (Q2W and Q4W) 
of Study GX29455 changed to monthly dosing upon entry to this study.  Given that 
30 months have been added to the original 24 month study duration for the patients 
from Study GX29455, these patients may receive up to 54 ITV injections of study drug.  


 
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All patients in Study GX29198 will have scheduled monthly visits and monthly study drug 
treatment for the duration of the study (see Table 1).  The monthly visit will occur relative 
to the Day 1 visit date.  Dosing should not occur earlier than 23 days after the previous 
dosing.  Missed study drug treatments will not be made up unless an extenuating 
circumstance applies (see Section 3.1.3). 
Administration 
Detailed instructions for reconstitution of lampalizumab, pre-injection preparation, 
administration of the study drug injection, and post-injection procedures for the study 
eye are provided in the pharmacy binder.  
Storage 
Detailed instruction for lampalizumab storage is provided in the pharmacy binder. 
Lampalizumab Dose-Holding and Study Discontinuation Criteria 
Study treatment interruption and/or patient discontinuation from the study (if applicable) 
due to adverse events will be determined using the criteria listed in Table 2.  If any of 
these criteria are met, treatment will be held and will not be resumed earlier than the 
next scheduled study visit; with select adverse events, patients may be discontinued 
from the study.  The reason for holding treatment should be recorded on the Dose 
Holding eCRF and, if applicable, on the Adverse Event eCRF. 


 
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Table 2 
Dose-Holding or Study Discontinuation Criteria  
Event 
Dose-Holding or Study Discontinuation Criteria 
Intraocular inflammation 
Hold dose if intraocular inflammation (iritis, iridocyclitis or vitritis) is ≥  1+ in 
the study eye (see definitions of intraocular inflammation in Section 5.1.3 
and inflammation grading scales in Appendix 2); study drug treatment may 
be permitted subsequently as determined by the investigator.  Patients 
with ≥ 3+ intraocular inflammation will be discontinued from the study 
treatment.   
VA decrease 
Hold dose if there is a treatment-related decrease in BCVA of ≥ 30 letters 
in the study eye compared with the last assessment of VA prior to the most 
recent treatment; study drug treatment may be permitted subsequently as 
determined by the investigator.   
IOP 
Hold dose if IOP in the study eye is ≥ 30 mmHg.  Study drug may be 
permitted when IOP has been controlled either spontaneously or by 
treatment as determined by the investigator. 
Vitreous hemorrhage 
Hold dose in the event of a vitreous hemorrhage in the study eye; study drug
treatment may be permitted subsequently as determined by the investigator. 
Rhegmatogenous retinal 
break  
Hold dose 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 
Patients with a rhegmatogenous retinal detachment or Stage 3 or Stage 4 
macular holes will be discontinued from the study. 
Active infection 
Hold dose 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 be discontinued 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 investigator and Sponsor. 
Oral corticosteroids 
(prednisone >10 mg/day 
or equivalent) 
Hold dose.  Study treatment may be resumed when oral corticosteroids 
dosing is prednisone ≤10 mg/day or equivalent. 
 
IV corticosteroids 
Hold dose.  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. 
 
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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4.4 
TREATMENT FOR CHOROIDAL NEOVASCULARIZATION WITH 
RANIBIZUMAB  
4.4.1 
Ranibizumab 
4.4.1.1 
Formulation for Sites in the United States 
Note: German sites will use commercially available Lucentis.  
At U.S. sites, ranibizumab will be supplied by the Sponsor.  For information on the 
formulation and handling of ranibizumab, see the pharmacy binder for ranibizumab.  
Dosage, Administration, and Storage 
At the discretion of the investigator, enrolled patients who are receiving study treatment 
and are diagnosed with CNV in either eye may receive treatment with 0.5 mg 
ranibizumab.  For U.S. sites, the drug will be open-label ranibizumab for investigational 
use only supplied by Genentech.  The ranibizumab injection in the United States will be 
performed using the techniques as discussed in the pharmacy binder.  Sites in Germany 
will use commercially available ranibizumab (Lucentis) and consult with the 
region-specific Lucentis Prescribing Information for the recommended dose, frequency, 
and administration of treatment.  
NOTE:  If treatment with ranibizumab is to be given (to study and/or non-study eye) at 
the same visit as a study eye treatment with lampalizumab, the treatment with 
ranibizumab must be administered first.  The safety assessments (including IOP check) 
to proceed to the study eye treatment with lampalizumab must be assessed prior to 
calling the IxRS for the study treatment kit assignment.  Individual trays and sterile prep 
must be separately prepared for each treatment.    
Note:  Sites will contact the IxRS to report the treatment with the Genentech-supplied 
ranibizumab and record this information on the specific eCRF page.  For German sites, 
ranibizumab will be recorded on the concomitant medications eCRF. 
Detailed instruction for ranibizumab storage is provided in the pharmacy binder.  Each 
vial will be labeled as required by the relevant regulatory agencies.  


 
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4.5 
CONCOMITANT AND EXCLUDED THERAPIES  
4.5.1 
Permitted Concomitant Therapy  
Permitted concomitant medications are any prescription drugs or over-the-counter 
preparations other than protocol-specified procedural treatments (e.g., dilating drops, 
fluorescein dyes, etc.) and pre- and post-injection medications (e.g., proparacaine, 
investigator-applied antimicrobials (if applicable) pre and post injection, etc.) used by a 
patient at the time of study enrollment on the Day 1 visit and through study completion 
or the ET visit. 
Patients who use other maintenance therapies should continue their use.  Patients 
required to use medications described in Excluded Concomitant Therapy (see 
Section 4.5.2 will not be eligible for enrollment or continuation in the study.  
All concomitant medications should be reported to the investigator and recorded on the 
appropriate eCRF. 
The onset of glaucoma in the study eye during a patient’s study participation should be 
treated as clinically indicated.  
Of note, the following are some common therapies that are permitted: 
• 
Short-term use of topical corticosteroids after cataract surgery, YAG capsulotomy, 
or peripheral iridotomy. 
• 
Oral corticosteroids at doses ≤ 10 mg/day prednisone or equivalent 
• 
Onset of ocular hypertension or glaucoma in the study 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 Table 2) may apply with cataract surgery. 
• 
At the discretion of the investigator, enrolled patients who are receiving study 
treatment and are diagnosed with CNV may be treated with ranibizumab if they are 
diagnosed in either eye with CNV.  
NOTE: If treatment with ranibizumab is to be given (to study and/or non-study eye) 
at the same visit as a study eye treatment with lampalizumab, the treatment with 
ranibizumab must be administered first.  The safety assessments (including 
IOP check) required to proceed to the study eye treatment with lampalizumab must 
be assessed prior to calling IxRS for the study drug kit assignment.  Individual trays 
and sterile prep must be separately prepared for each treatment. 
 


 
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4.5.2 
Excluded Concomitant Therapy 
At the discretion of the investigator, patients may continue to receive all medications and 
standard treatments administered for other conditions.  The following 
medications/treatments are prohibited from use during the patient’s participation in the 
study: 
• 
Systemic anti-VEGF agents  
• 
ITV anti-VEGF agents (other than ranibizumab) in either eye  
• 
ITV, subtenon, or chronic topical (ocular) corticosteroids in the study eye 
• 
Systemic or IV immunomodulatory therapy (e.g., azathioprine, methotrexate, 
mycophenolate mofetil, cyclosporine, cyclophosphamide, anti-tumor necrosis 
factor α agents)  
• 
Ocular or systemic complement inhibitors, (e.g., eculizumab) except lampalizumab 
• 
Treatment with Visudyne in either eye 
• 
Other experimental therapies (except those involving vitamin and 
mineral supplements) 
 
4.5.3 
Excluded Concomitant Conditions 
• 
Medical or surgical conditions or clinical laboratory findings giving reasonable 
suspicion of a disease or condition that contraindicates the use of an investigational 
drug, or that might affect interpretation of the study results, or that may render a 
study patient at high risk for treatment complications; when such a condition is 
identified, consultation with the Medical Monitor will be required to determine a 
patient’s eligibility to continue on the extension study 
 
4.6 
STUDY ASSESSMENTS  
Please refer to the detailed schedules of assessments provided in Appendix 1-A through 
Appendix 1-F.  
Patients enrolled from Study CFD4870g will have up to 96 study visits (excluding the 
Day 1 visit).  Patients enrolled from Study GX29455 will have up to 54 study visits 
(excluding the Day 1 visit).  Any patient who discontinues the study prematurely (prior to 
the Month 96 visit for patients from Study CFD4870g and prior to the Month 54 visit for 
patients from Study GX29455) will have an ET visit completed ≥ 30 days after his or her 
last study drug treatment.  Study visits will be scheduled every 30 (± 7) days relative to 
the Day 1 visit. 


 
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4.6.1 
Definitions of Study Assessments 
4.6.1.1 
Clinical Evaluations 
• 
Demographic Data:  date of birth and sex will be collected; the patient’s 
race/ethnicity data will also be entered.  At a minimum, year of birth and sex will be 
retrieved. 
• 
Vital Signs:  will include measurements of pulse, temperature, respiration rate, and 
systolic and diastolic blood pressure while the patient is in a seated position.  Vital 
signs should be obtained before injection of lampalizumab. 
• 
Physical Examination: should include an evaluation of the head, eyes, ears, nose, 
throat, and cranial nerves.  If any abnormalities are noted during the study, the 
patient may be referred to another physician with specialty expertise.  
The investigator should use his or her clinical judgment for appropriate treatment 
and/or medical referral.  New or worsened clinically significant abnormalities should 
be recorded as adverse events on the Adverse Event eCRF.  Height and weight will 
be collected for patients enrolling from CFD4870g study.  
• 
Medical History (including surgeries, procedures and ocular therapy history): 
the patient’s data will be retrieved from the CFD4870g and GX29455 databases. 
 
4.6.1.2 
Ocular Assessments 
• 
BCVA on ETDRS chart at a starting distance of 4 meters (perform prior to dilating 
eyes; see Appendix 3) 
• 
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 (see definition of ocular inflammation see Section 5.1.3; for 
inflammation grading scales, see Appendix 2) 
• 
Dilated binocular indirect ophthalmoscopy 
• 
Finger-counting test, or hand motion, or light perception tests performed by the 
investigator within 15 minutes post-injection for the study eye only  
• 
IOP measurement at 60 (±10) minutes post-injection for the study eye only; if IOP 
increased  ≥10 mmHg from pre-injection, the patient will remain in the clinic and will 
be treated according to the investigator’s clinical judgment prior to the patient’s 
discharge; if applicable, an Adverse Event eCRF page will be completed (see 
Section 5.2.2).  The method of IOP measurement used for a patient must remain 
consistent throughout the study 
Note:  if the study eye is treated with a ranibizumab injection during the same visit 
as the study treatment with lampalizumab, the treatment with ranibizumab has to be 
performed first.  Please measure and record the post-ranibizumab treatment IOP 
value on the appropriate eCRF. 
 


 
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4.6.1.3 
Ocular Imaging 
An independent review of digital color fundus photographs, fluorescein angiograms, 
FAF, NI, and SD-OCT images (including exploratory anatomic biomarker studies) 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. 
The central reading center will provide sites with a study manual and training material for 
specified study ocular images.  Before any study images are obtained, site personnel, 
test images, systems and software (where applicable) will be certified/validated by the 
reading center as specified in the study manual.  “Grandfathering” certifications for 
personnel and equipment from CFD4870g or GX29455 will be allowed as per reading 
center guidelines.  All ocular images will be obtained by trained site personnel at the 
study sites and forwarded to the central reading center for independent analysis and/or 
storage.    
Ocular images obtained include the following: 
• 
Stereoscopic, digital color fundus photographs of both eyes (see Appendix 4)  
• 
Fluorescein angiograms of both eyes (perform after laboratory samples 
are obtained; see Appendix 5) 
• 
FAF, SD-OCT, and NI images of both eyes;(see Appendix 6, Appendix 7, and 
Appendix 8, respectively) 
Note: after enrollment, if a patient misses a study visit during which ocular images 
were scheduled to be taken (see Appendix 1-A through Appendix 1-E), the images 
should be obtained at the next scheduled visit.  
 
Additional details on obtaining these images are included in the central reading 
center manual. 
4.6.1.4 
Laboratory Assessments 
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.  
All specimens will be forwarded to the central laboratory for processing.  The central 
laboratory will either perform the analysis or forward to Genentech for analysis.  
Instructions for obtaining, processing, storing, and shipping of all specimens are 
provided in the Laboratory Manual.  Laboratory supply kits will be provided to the sites 
by the central laboratory.  See Appendix 1-A through Appendix 1-E for the collection 
timepoints of samples. 


 
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The following assessments will be performed: 
• 
Hematology:  hemoglobin, hematocrit, quantitative platelet count, RBC, WBC, and 
differentials including neutrophils, bands, lymphocytes, basophils, eosinophils, and 
monocytes (absolute and percent) 
• 
Coagulation: aPTT and PT 
• 
Serum chemistry:  sodium, potassium, chloride, bicarbonate, glucose, blood urea 
nitrogen (BUN), creatinine, calcium, phosphorus, total and direct bilirubin, total 
protein, albumin, AST, ALT, LDH, alkaline phosphatase, and uric acid 
• 
Urinalysis:  specific gravity, pH, blood, protein, ketones, glucose, bilirubin, 
urobilinogen, microscopic examination (if any of the preceding urinalysis tests, other 
than glucose and ketones, are abnormal) 
• 
Serum sample to measure anti-lampalizumab antibodies (ATA) and drug 
concentration at ATA sample timepoint collections 
Optional Clinical Genotyping Samples: 
• 
An optional, single, whole-blood sample will be collected for genotyping analysis at 
any time during the study from German study site patients; of note, blood samples 
for genotyping analysis from the U.S. study site patients were collected previously in 
Study CFD4870g and Study GX29455.  The genotyping samples will be used to 
evaluate relationships between genetic polymorphisms associated with AMD, 
baseline disease characteristics, and response to administration of lampalizumab. 
4.6.2 
Screening and Pretreatment Assessments 
After a patient has signed the extension study informed consent form and has completed 
all Month 18 visit assessments for Study CFD4870g or completed all Week 24 
assessments for Study GX29455, he or she will be offered the opportunity to enroll in 
this extension study on the same day (Day 1) if they satisfy all eligibility criteria.  The 
patient’s study CFD4870g Month 18 visit assessments or Study GX29455 Week 24 visit 
assessment will be utilized for a patient’s eligibility to enter this study.  If applicable as 
per investigator discretion, the patient will confirm administration of antimicrobials prior to 
the Day 1 visit.   
Please see the Study Flowchart provided in Appendix 1-A (for patients from 
Study CFD4870g) and Appendix 1-D (for patients from Study GX29455) for the schedule 
of screening and pretreatment assessments on the Day 1 visit. 
4.6.3 
Assessments during Treatment 
After a patient has signed the informed consent form, the site will contact the IxRS to 
obtain a patient enrollment ID number assignment and to report the study drug 
distribution on the Day 1 visit (at conclusion of Month 18 visit in study CFD4870g or 
Week 24 visit in study GX29455).  Patient self-administered antimicrobials in the pre- 
and post-injection period may be used at the investigator’s discretion. 


 
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At all study visits the procedures and assessments should be performed prior to study 
drug administration unless otherwise indicated.  All study visit assessments must be 
performed on the same day.  Note:  see Section 3.1.3 for exception regarding delayed 
study treatment administration. 
The study scheduled visits should occur every 30 (±7) days relative to the Day 1 visit 
date.  Dosing should not occur earlier than 23 days after the previous dosing. 
Please see the Study Flowcharts provided in Appendix 1-A through Appendix 1-E for the 
schedule of treatment period assessments. 
4.6.4 
Study Completion/Early Termination Visit 
For patients who withdraw early from the study (prior to the Month 96 visit for patients 
enrolled from CFD4870g and prior to the Month 54 visit for patients enrolled from 
GX29455) for any reason, these patients should complete the ET visit assessments 
≥ 30 days following the last study treatment. Patients who discontinue from the study will 
not be allowed to re-enter the study.  Please see the Study Flowcharts provided in 
Appendix 1-A through Appendix 1-E for the assessments to be performed at the study 
ET visit. 
4.6.5 
Study Treatment Discontinuation/Early Termination Visit  
Patients who prematurely discontinue the study treatment (prior to the Month 96 visit for 
patients enrolled from CFD4870g or prior to the Month 54 visit for patients enrolled from 
GX29455) will be also discontinued from the study, and they will be asked to return for 
an ET evaluation ≥30 days following their last study drug treatment for monitoring of 
adverse events and the study ET visit assessments.   
Please see the Study Flowcharts provided in Appendix 1-A through Appendix 1-E for the 
assessments to be performed at the ET visit. 


 
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4.6.6 
Unscheduled Safety Assessment Visit 
If a patient experiences eye pain, a decrease in vision, unusual redness, or any other new 
ocular symptoms in the study eye, the investigator will determine whether the patient should 
return to the clinic for a safety assessment as soon as possible.  If a visit is required, the 
assessments listed in Appendix 1-F will be performed. 
4.7 
PATIENT DISCONTINUATION 
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 e.g., missed doses, visits 
 
Every effort should be made to obtain information on patients who withdraw from the 
study.  The primary reason for withdrawal from the study should be documented on the 
appropriate eCRF.  However, patients will not be followed for any reason after consent 
has been withdrawn.  Patients who withdraw from the study will not be replaced. 
4.8 
STUDY TREATMENT DISCONTINUATION 
The investigator has the right to discontinue a patient from the study treatment for any 
medical condition that the investigator determines may jeopardize the patient’s safety if 
he or she continues in the study treatment, for reasons of non-compliance (e.g., missed 
doses, visits), if the patient becomes pregnant, or if the investigator determines it is in 
the best interest of the patient.  The reason for the treatment discontinuation should be 
recorded on the appropriate eCRF. 
Treatment discontinued patients will be also discontinued from the study and will not be 
replaced or allowed to re-enter the study. 
4.9 
STUDY 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 
 


 
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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 International Council for Harmonisation (ICH) guideline for 
Good Clinical Practice 
• 
No study activity (i.e., all patients have completed the study and all obligations have 
been fulfilled)  
 
4.10 
POST-TRIAL ACCESS TO LAMPALIZUMAB 
The Sponsor will offer post-study access to the study drug lampalizumab free of charge 
to eligible patients in accordance with the Roche Global Policy on Continued Access to 
IMPs as outlined below. 
A patient will be eligible to receive study drug after the end of the study if all of the 
following conditions are met: 
• 
The patient has a sight-threatening or severe medical condition and requires 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 the end of 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 IMPs is available at the following Web 
site:  
http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf. 


 
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4.11 
ASSAY METHODS  
Drug concentration will be determined in serum using a validated ELISA method.  ATA 
will be detected in serum using a validated ELISA.  
4.12 
STATISTICAL METHODS 
4.12.1 
Safety Analysis 
Safety will be assessed by adverse events, clinical laboratory evaluations, and 
immunogenicity as measured by ATA.  Safety analyses will include all patients who 
enrolled into the extension study and received at least one lampalizumab injection in 
the extension study.  These patients will be grouped by the treatment received 
(lampalizumab or sham) when they were enrolled in the CFD4870 or GX29455 for 
safety analyses. 
The primary safety analysis is planned to occur at the time when patients enrolled from 
Study CFD4870g have reached approximately 96 months follow-up and when patients 
enrolled from Study GX29455 have reached approximately 54 months follow-up.  
The timing of the primary analysis may be adjusted according to the start of the 
open-label extension for Studies GX29176 and GX29185, to which patients from the 
extension study may have the opportunity to enroll.  Earlier safety analyses of this study 
may be performed on an ad hoc basis. 
All verbatim adverse event terms will be mapped to Medical Dictionary for Regulatory 
Activities (MedDRA) thesaurus terms, and adverse event severity will be graded 
according to an adverse event severity grading scale (see Table 3). 
4.12.2 
Pharmacokinetic and Pharmacodynamic Analyses 
Scheduled pharmacokinetic and pharmacodynamic assessments are not planned in the 
extension study.  However, to assist in safety evaluations, serum lampalizumab 
concentration measurements may be performed. 
4.12.3 
Exploratory Analyses  
Mean GA lesion area growth and mean BCVA change from baseline over time will be 
summarized by treatment group.  These patients will be grouped by parent study and 
the treatment received (lampalizumab or sham) when they were enrolled in 
Study CFD4870g or Study GX29455.   
4.12.4 
Handling of Missing Data 
All efforts will be made to minimize missing data; no imputation will be performed for 
the safety analysis.  


 
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4.12.5 
Determination of Sample Size 
This study is open to all patients who complete Study CFD4870g or Study GX29455 and 
who meet eligibility criteria.  Accordingly, the sample size for this study is not based on a 
formal sample size calculation. 
4.12.6 
Interim Analysis 
The primary analysis time will occur as specified in Section 4.12.1.  Earlier analyses may 
be performed on an ad hoc basis. 
4.13 
DATA QUALITY ASSURANCE 
The data will be collected via Electronic Data Capture (EDC) using eCRFs.  The site will 
be responsible for data entry into the EDC system.  In the event of discrepant data, the 
CRO will request data clarification from the sites, which the sites will resolve 
electronically in the EDC system.  The CRO will be responsible for the data 
management of this trial, including quality checking of the data.   
Genentech will perform oversight of the data management of this trial.  Genentech will 
produce an EDC Study Specification document that describes the quality checking to be 
performed on the data.  Central Laboratory data and Central Reading Center data will be 
sent directly to Genentech, using Genentech’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 at 
Genentech and records retention for the study data will be consistent with Genentech’s 
standard procedures. 
5. 
ASSESSMENT OF SAFETY  
5.1 
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, measuring protocol-specified vital 
signs, and conducting other protocol-specified tests that are deemed critical to the safety 
evaluation of the study. 
Certain types of adverse events require immediate reporting to the Sponsor, as outlined 
in Section 5.2. 


 
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5.1.1 
Adverse Events  
According to the ICH guideline for Good Clinical Practice, an adverse event is any 
untoward medical occurrence in a clinical investigation subject administered a 
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 
• 
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., ECG, 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 assignment of study treatment (e.g., screening invasive 
procedures such as biopsies) 
 
5.1.2 
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) 
 


 
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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 5.2.2 for 
reporting instructions). 
5.1.3 
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 5.2.2 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 indicating an infection in a 
patient exposed to a medicinal product. This term only applies 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. 


 
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• 
Sight-threatening adverse events 
An adverse event is considered to be 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-infectives, 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 5.1.3 for definition and 
Appendix 2 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 primary event term. 
5.2 
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 study.  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 
• 
Adverse events of special interest 
• 
Pregnancies 
 
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. 


 
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5.2.1 
Emergency Medical Contacts 
Medical Monitor Contact Information for sites in the United States and Germany: 
United States 
Medical Monitor: 
, M.D. 
Telephone No.: 
(office) 
 
Germany 
Medical Monitor: 
, M.D. 
Telephone No.: 
 
Mobile Telephone No.: 
 
or 
Medical Monitor: 
, MBChB, MFPM, MRCOphth 
Mobile Telephone No.: 
 
 
 
To ensure the safety of study patients, an Emergency Medical Call Center Help Desk will 
access the Sponsor Medical Emergency List, escalate emergency medical calls, provide 
medical translation service (if necessary), connect the investigator with a Sponsor 
Medical Monitor, 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 
and Medical Monitor contact information will be distributed to all investigators 
(see "Protocol Administrative and Contact Information & List of Investigators").  
5.2.2 
Reporting Requirements for All Serious Adverse Events and 
Adverse Events of Special Interest 
5.2.2.1 
Events That Occur prior to Study Drug Initiation 
After informed consent has been obtained but prior to the Day 1 visit in the extension 
study, all adverse events will be reported to either Study CFD4870g or Study GX29455 
databases.  If the events are ongoing at the Day 1 visit in the extension study they will 
also be transcribed to this study database.   
5.2.2.2 
Events that Occur after Study Drug Initiation 
After initiation of study drug, serious adverse events and adverse events of special 
interest will be reported until the last study visit.  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 paper Clinical Trial 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 5.5. 
5.3 
METHODS AND TIMING FOR CAPTURING AND ASSESSING 
SAFETY PARAMETERS 
The investigator is responsible for ensuring that all adverse events (see Section 5.1.1 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 5.1.2 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. 
At the time of enrollment, any adverse events or serious adverse events that are 
ongoing from Study CFD4870g or study GX29455 should be recorded on the 
GX29198 eCRF. 
After initiation of study drug, all adverse events will be reported until the last study visit.  
After this period, the investigator should report any serious adverse events that are 
believed to be related to study drug treatment (see Section 5.6). 
5.3.2 
Eliciting Adverse Events 
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?”  
 


 
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5.3.3 
Assessment of Severity of Adverse Events 
The adverse event severity grading scale will be used for assessing adverse event 
severity.  Table 3 provides guidance for assessing adverse event severity. 
Table 3 
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 5.1.2). 
 
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 4).  
• 
Temporal relationship of event onset to the initiation of study drug 
• 
Course of the event, with special consideration of 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 
 


 
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Table 4 
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., preexisting 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). 
 
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:  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:  the presence of inflammatory cells in both the aqueous and vitreous 
• 
Vitritis:  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:  diffuse intraocular inflammation predominantly involving the 
vitreous cavity but also involving the anterior chamber, implying a suspected 
underlying infectious cause 
 
Note:  Trace benign, aqueous pigmented cells visible on slit-lamp examination that are 
caused by dilation and are not RBCs or WBCs or the result of any ocular disorder should 
not be recorded as an adverse event. 


 
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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. 
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 intensity 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 5.2.2 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.   


 
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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) 
• 
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 × 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 if 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 


 
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• 
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. 
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 elevated ALT or AST (>3×ULN) in combination with either 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×ULN in combination with total bilirubin>2×ULN 
• 
Treatment-emergent ALT or AST>3×ULN 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 an serious adverse event or as a non-serious adverse event of 
special interest (see Section 5.2.2). 
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 5.2.2).   
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 


 
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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"). 
Deaths that occur after the adverse event reporting period should be reported as 
described in Section 5.5. 
5.3.5.8 
Preexisting Medical Conditions 
A preexisting medical condition is one that is present at the screening visit for 
Study CFD4870g or Study GX29455.  Such conditions should be recorded on the 
General Medical History and Baseline Conditions eCRF of these 2 studies databases.  
In a case where the site identifies a preexisting condition after Study CFD4870g or 
Study GX29455 closes the condition should be entered to the extension study medical 
history eCRF page. 
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., 
worsening, exacerbation, or 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 in 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 study eye GA on the Adverse Event eCRF, it is important to convey the 
concept that the condition has changed by including applicable descriptors 
(e.g., “accelerated GA”).  The expedited reporting requirements for sight-threatening 
events (listed in Section 5.2) apply to these unexpected changes in the study eye GA. 
Events that are clearly consistent with the expected pattern of progression of the 
underlying disease should not be recorded as adverse events. 


 
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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 a serious adverse event in Section 5.1.2), except as outlined 
below. 
An event that leads to hospitalization under the following circumstance should not be 
reported as an adverse event or a serious adverse event: 
• 
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 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 treatment is not 
itself an adverse event, but it may result in an adverse event.  All adverse events 
associated with an overdose or incorrect administration of study drug should be 
recorded on the Adverse Event eCRF.  If the associated adverse event meets the severity 
criteria, the event should be reported to the Sponsor immediately (i.e., no more than 
24 hours after learning of the event; see Section 5.2.2). 
No safety data related to overdosing of lampalizumab are available. 
5.3.6 
Reporting Requirements for Pregnancies 
5.3.6.1 
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 the last study visit.  A 
paper 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 with use of the fax 
number or e-mail 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 


 
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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 paper Clinical Trial Pregnancy Reporting Form 
when updated information on the course and outcome of the pregnancy becomes 
available. 
5.3.6.2 
Pregnancies in Female Partners of Male Patients  
Male patients will be instructed through the Informed Consent Form to immediately 
inform the investigator if their partner becomes pregnant during the study or until the last 
study visit.  A paper 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 with 
use of the fax number or e-mail 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 paper 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. 
5.3.6.3 
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 5.2.2).   
5.3.6.4 
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 5.2.2). 


 
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5.4 
FOLLOW-UP OF PATIENTS AFTER ADVERSE EVENTS 
5.4.1 
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.   
5.4.2 
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. 
5.5 
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.   
These events should be reported through use of the Adverse Event eCRF.  However, if 
the EDC system is not available, the investigator should report these events directly to 
the Sponsor or its designee, either by faxing or by scanning and emailing the paper 
Clinical Trial Serious Adverse Event/Adverse Event of Special Interest Reporting Form 
using the fax number or email address provided to investigators. 
5.6 
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. 


 
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To determine reporting requirements for single 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. 
INVESTIGATOR REQUIREMENTS 
6.1 
STUDY INITIATION 
Before the start of this study and any study-related procedures at a specific site, the 
following documents must be on file with Genentech or a Genentech representative: 
• 
U.S. FDA Form 1572 for each site (for all studies conducted under 
U.S. Investigational New Drug [IND] regulations), signed by the Principal 
Investigator 
• 
The names of any sub-investigators must appear on this form.  Investigators must 
also complete all regulatory documentation as required by local and national 
regulations 
• 
Current curricula vitae and evidence of licensure of the Principal Investigator and all 
sub-investigators 
• 
Complete financial disclosure forms for the Principal Investigator and all 
sub-investigators listed on the U.S. FDA Form 1572  
• 
Federal-wide Assurance number or IRB statement of compliance 
• 
Written documentation of IRB/EC approval of the protocol (identified by protocol 
number or title and date of approval) and Informed Consent Form (identified by 
protocol number or title and date of approval) 
• 
A copy of the IRB/EC-approved Informed Consent Form 
Genentech or its designee must review any proposed deviations from the sample 
Informed Consent Form 
• 
Current laboratory certification of the laboratory performing the analysis (if other 
than a Genentech-approved central laboratory), as well as current references 
ranges for all laboratory tests 
• 
A Clinical Research Agreement signed and dated by the study site 
• 
Investigator Brochure Receipt signed and dated by the Principal Investigator 


 
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• 
Certified translations of an approved Informed Consent Form, and any other written 
information to be given to the patient (when applicable), IRB/EC approval letters, 
and pertinent correspondence 
• 
A Protocol Acceptance Form signed and dated by the Principal Investigator 
• 
For global studies, list documents as appropriate for additional countries 
 
6.2 
STUDY COMPLETION 
The following data and materials are required by Genentech before a study can be 
considered complete or terminated: 
• 
Laboratory findings, clinical data, and all special test results from screening through 
the end of the study follow-up period 
• 
All laboratory certifications for laboratories performing the analysis (is other than 
Genentech-approved central laboratory), as well as current normal laboratory 
ranges for all laboratory tests 
• 
eCRFs (including queries) properly completed by appropriate study personnel and 
electronically signed and dated by the investigator 
• 
Completed Drug Accountability Records (Retrieval Record, Drug Inventory Log, and 
Inventory of Returned Clinical Material forms) 
• 
Copies of protocol amendments and IRB/EC approval/notification, if appropriate 
• 
A summary of the study prepared by the Principal Investigator (IRB summary close 
letter is acceptable) 
• 
All essential documents (e.g., curriculum vitae for each Principal Investigator and 
sub-investigator, U.S. FDA Form 1572 for each site) 
• 
A signed and dated Protocol Amendment Acceptance Form(s)[if applicable] 
• 
Updated financial disclosure forms for the Principal Investigator and all 
sub-investigators listed on the U.S. FDA Form 1572 (applicable for 1 year after the 
last patient has completed the study) 
 
6.3 
INFORMED CONSENT FORM 
The Sponsor’s sample Informed Consent Form (and ancillary sample Informed Consent 
Forms such as a Child’s Informed Assent Form or Home Nursing Informed Consent 
Form, 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 Informed Consent Forms 
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. 


 
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If applicable, the Informed Consent Form 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 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 Consent Form 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 Consent Form may also include patient authorization 
to allow use and disclosure of personal health information in compliance with the U.S. 
Health Insurance Portability and Accountability Act of 1996 (HIPAA).  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. 
6.4 
COMMUNICATION WITH THE INSTITUTIONAL REVIEW BOARD 
OR ETHICS COMMITTEE 
This protocol, the Informed 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 for review and approval before the study is initiated.  In addition, any patient 
recruitment materials must be approved by the IRB/EC.  


 
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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 regulatory 
requirements and policies and procedures established by the IRB/EC.  Investigators are 
also responsible for promptly informing the IRB/EC of any protocol amendments (see 
Section 6.13). 
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 
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 regulatory 
requirements and with the policies and procedures established by their IRB/EC and 
archived in the site’s study file.  
6.5 
STUDY MONITORING REQUIREMENTS 
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. 
6.6 
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.  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. 
6.7 
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, patient-reported outcomes, 
evaluation checklists, pharmacy dispensing records, recorded data from automated 
instruments, copies of transcriptions that are certified after verification as being accurate 


 
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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. 
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 6.12. 
To facilitate source data verification, the investigator(s) and institution(s) 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. 
6.8 
USE OF COMPUTERIZED SYSTEMS 
When clinical observations are entered directly into an investigational 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 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. 
6.9 
STUDY MEDICATION ACCOUNTABILITY 
All IMPs required for completion of this study (lampalizumab) will be provided by the 
Sponsor where required by local health authority regulations.  The study site will 
acknowledge receipt of IMP by returning the appropriate documentation to confirm 
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 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. 
Accurate records of all study drug received at, dispensed from, returned to and disposed 
of by the study site should be recorded by using the Drug Inventory Log. 
6.10. Genentech-Provided Ranibizumab Accountability 
Ranibizumab for U.S. sites will be provided by Genentech.  The recipient will 
acknowledge receipt of the drug by returning the appropriate documentation form 
indicating shipment content and condition.  Damaged supplies will be replaced. 


 
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Accurate records of all ranibizumab vials received at, dispensed from, returned to and 
disposed of by the study site should be recorded by using the Ranibizumab Inventory 
Log. 
Ranibizumab is supplied in single-use vials.  Partially used vials of ranibizumab will 
either be disposed of at the study site according to the study site’s institutional standard 
operating procedure or returned to Genentech with the appropriate documentation, as 
determined by the study site.  If the study site chooses to destroy ranibizumab, the 
method of destruction must be documented. 
Genentech must evaluate and approve the study site’s ranibizumab destruction standard 
operating procedure prior to the initiation of drug destruction by the study site. 
6.11 
DISCLOSURE OF DATA 
Patient medical information obtained by this study is confidential and may only be 
disclosed to third parties as permitted by the Informed Consent Form (or separate 
authorization to use and disclose personal health information) signed by the patient or 
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 the U.S. FDA and other regulatory agencies, national and local health 
authorities, Genentech monitors/representatives and collaborators, and the IRB/EC for 
each study site, if appropriate. 
6.12 
RETENTION OF RECORDS 
Records and documents pertaining to the conduct of this study and the distribution of 
IMP, including eCRFs, Informed Consent Forms, 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.  
6.13 
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. 


 
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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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7. 
REFERENCES 
Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, 
clinical trial of high-dose supplementation with vitamins C and E, beta carotene, 
and zinc for age-related macular degeneration and vision loss: AREDS Report 8. 
Arch Ophthalmol 2001;119:1417−36. 
Age-Related Eye Disease Study Research Group. Potential public health impact of Age-
Related Eye Disease Study results: AREDS Report 11. Arch Ophthalmol 
2003;121:1621−24. 
de Jong PTVM. Age-related macular degeneration. New Engl J Med 2006;355:1474−85. 
Friedman DS, O’Colmain BJ, Munoz B, et al. Eye Diseases Prevalence Research Group. 
Prevalence of age-related macular degeneration in the United States. Arch 
Ophthalmol 2004;122:564−72. 
Rohrer B, Guo Y, Kunchithapautham K, et al. Eliminating complement factor D reduces 
photoreceptor susceptibility to light-induced damage. Invest Ophthalmol Vis Sci 
2007;48:5282−89. 
Scholl HPN, Issa PC, Walier M, et al. Systemic complement activation in age-related 
macular degeneration. PLoS ONE 2008;3:e2593. 
Sunness JS, Applegate CA, Bressler NM, et al. Designing clinical trials for age-related 
geographic atrophy of the macula: enrollment data from the geographic atrophy 
natural history study. Retina 2007;7:204−10. 
Yates JRW, Sepp T, Matharu BK, et al. Complement C3 variant and the risk of age-
related macular degeneration New Engl J Med 2007;357:553−61. 
 
 


 
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Appendix 1  
Schedule of Assessments 
Appendix 1-A: 
Schedule of Assessments for Patients Enrolled from Study CFD4870g:  Day 1, Months 1−30, and 
Early Termination 
 
 
CFD4870g 
Month 17   
Day 
Visit Month 
 
Day 1a 
1−5 
6 
7−11 
12 
13−17 
18 
19−23 
24 
25−29 
30 
ETb 
Assessment windows 
(days) between 
monthly visits 
 
Extracted 
from 
CFD4870g 
Month 18 
 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
b 
Written informed 
consent signed 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review of inclusion 
and exclusion criteria 
 
 
x 
 
 
 
 
 
 
 
 
 
 
 
Demographic 
informationc 
 
 
x 
 
 
 
 
 
 
 
 
 
 
 
Site to contact IxRS 
(as applicable)d 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Physical examination 
 
x 
 
 
 
 
 
 
 
 
 
 
 
x 
Vital signse 
 
x 
 
 
 
 
 
 
 
 
 
 
 
x 
Central laboratory 
samples (hematology, 
coagulation, serum 
chemistry, urinalysis)f 
 
x 
 
 
 
 
 
 
 
 
 
 
 
x 
Urine sample for 
pregnancy testing 
(if applicable)f 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 


Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-A: 
Schedule of Assessments for Patients Enrolled from Study CFD4870g:  Day 1, Months 1−30, and 
Early Termination (cont.) 
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CFD4870g 
Month 17   
Day 
Visit Month 
 
Day 1a 
1−5 
6 
7−11 
12 
13−17 
18 
19−23 
24 
25−29 
30 
ETb 
Assessment windows 
(days) between 
monthly visits 
 
Extracted 
from 
CFD4870g 
Month 18 
 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
b 
Serum sample for 
anti-lampalizumab 
antibody and 
corresponding drug 
concentrationf 
 
x 
 
 
x 
 
x 
 
 
 
x 
 
 
x 
Optional single, 
whole-blood sample 
for genotypingf 
 
 
 
Collect 1 sample at any timepoint from study patients at German sites 
Patient-reported 
weight and height 
 
 
 
Collect patient-reported weight and height once during the study 
BCVA testing 
(starting at 4 pm)g 
 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
IOPh 
 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
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 


Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-A: 
Schedule of Assessments for Patients Enrolled from Study CFD4870g:  Day 1, Months 1−30, and 
Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
83/Protocol GX28198, Version 4 
 
CFD4870g 
Month 17   
Day 
Visit Month 
 
Day 1a 
1−5 
6 
7−11 
12 
13−17 
18 
19−23 
24 
25−29 
30 
ETb 
Assessment windows 
(days) between 
monthly visits 
 
Extracted 
from 
CFD4870g 
Month 18 
 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
b 
SD-OCTi 
 
 
x 
Perform every 3 months starting at Month 3 visit (6, 9, 12, 15, 18, 21, 24, 27, 30) 
x 
FAF and NIi 
 
x 
 
 
x 
 
 
 
x 
 
 
 
x 
x 
Fundus photographyi 
 
x 
 
 
x 
 
 
 
x 
 
 
 
x 
x 
Fluorescein 
angiographyi 
 
x 
 
 
x 
 
 
 
x 
 
 
 
x 
x 
Patient-administered 
pre- and post-study 
drug injection 
antimicrobials 
(if applicable)j 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Administration of 
study drug injections 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Post-injection 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 


Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-A: 
Schedule of Assessments for Patients Enrolled from Study CFD4870g:  Day 1, Months 1−30, and 
Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
84/Protocol GX28198, Version 4 
 
CFD4870g 
Month 17   
Day 
Visit Month 
 
Day 1a 
1−5 
6 
7−11 
12 
13−17 
18 
19−23 
24 
25−29 
30 
ETb 
Assessment windows 
(days) between 
monthly visits 
 
Extracted 
from 
CFD4870g 
Month 18 
 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
b 
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 call 
(if applicable)o 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
BCVA = best corrected visual acuity; ET = early termination; FAF = fundus autofluorescence; IOP = intraocular pressure; IxRS = interactive response 
system; NA = not applicable; NI = near infrared; SD OCT = spectral domain optical coherence tomography.  
Notes:  All ocular assessments are to be performed for both eyes unless noted otherwise.  All assessments are to be performed on the same day. 
a Day 1 visit will occur at the study CFD4870g Month 18 visit conclusion.  The Study CFD4870g Month 18 visit assessments will be extracted from 
that study’s database and will be used for the extension study Day 1 visit.  All study patients will receive their first study drug injection in the 
extension study at the Day 1 visit (unless dose holding is medically justified by the investigator).  Study drug treatment related data will be 
entered into the extension study database.  Written informed consent will be obtained prior to enrollment and the initiation of any study 
procedures and treatment. 
b 
 For patients who withdraw early from the study, ET assessments will be performed ≥ 30 days after the last study treatment injection. 
c Demographics data will be re-entered into the extension study database on a Demographics eCRF.   
d At each visit starting at Day 1 contact IxRS to obtain study drug kit assignment (if applicable).  At the ET visit, contact the IxRS to request 
patient’s status be changed to “early termination.”  At the final study visit, contact IxRS to request to change patient status to “completed.” 
e Vital signs consist of blood pressure, respiration, pulse, and temperature.  


Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-A: 
Schedule of Assessments for Patients Enrolled from Study CFD4870g:  Day 1, Months 1−30, and 
Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
85/Protocol GX28198, Version 4 
f Obtain prior to study drug treatments and prior to fluorescein angiography (if applicable).  ATA samples may be also used to measure 
lampalizumab concentration to assist in safety evaluation.  For patients at German sites, the optional, single, whole-blood sample for genotyping 
analysis may be collected at any study visit. For women of childbearing potential perform urine pregnancy test prior to every study treatment. If 
positive, collect the serum sample for pregnancy test to be performed by the central lab and do not administer the study treatment.  For detailed 
description of the laboratory assessments to be performed, see separate Laboratory Manual. 
g The VA examiner will be masked to patients’ treated (study) eye and will perform only the VA (including refraction).  The VA examiner is not 
allowed to perform any other tasks involving direct patient care. 
h At Day 1, pre study drug administration IOP (performed prior to dilating eyes) data will be extracted from CFD4870g study (as applicable)  while 
post study drug administration IOP will be obtained after the study drug treatment in the extension study and entered into the study database.   
i SD-OCT, FAF, and NI images, fluorescein angiograms, and fundus photographs (as applicable) will be forwarded to the central reading center. 
Note: after enrollment, if a patient misses a study visit during which ocular images were scheduled to be taken, the images should be obtained at 
the next scheduled visit.   
j Patient self-administered antimicrobials may be used at the investigator’s discretion. If applicable inform the patient to self-administer them prior 
to the Month 18 (CFD 4870g) visit. 
k Finger-counting test followed by hand-motion and light-perception tests (when necessary) will be performed by the investigator within 15 minutes 
post-study drug treatment injection.  At study treatment injection visits, IOP measurement will be obtained bilaterally prior to study treatment and 
then at 60 (±10) minutes post-injection in the study eye only.  If there are no safety concerns at 60 (±10) minutes, the patient will be discharged 
from the clinic.  If at 60 (±10) minutes the post-injection IOP remains elevated by ≥10 mmHg from the pre-injection measurement, the patient will 
remain in the clinic and will be treated according to the investigator’s clinical judgment prior to the patient’s discharge; if applicable, an Adverse 
Event eCRF page will be completed (see Section 5.3.1). Note: if the study eye is treated with a ranibizumab injection during the same visit as the 
study treatment with lampalizumab, the treatment with ranibizumab has to be performed first. Please measure and record the post- ranibizumab 
treatment IOP value on the eCRF irrespective of the study treatment administration later.   
l At enrollment, any concomitant medications that are ongoing from Study CFD4870g should be entered into the eCRF for the extension study.  
Record any concomitant medications currently used by the patient and through the conclusion of the patient’s study participation or ET visit 
(i.e., any prescription medications or over-the-counter preparations other than protocol-specified procedural medications, and pre-injection and 
post-injection medications, such as proparacaine, investigator applied pre- and post-injection antimicrobials (if applicable)).   


Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-A: 
Schedule of Assessments for Patients Enrolled from Study CFD4870g:  Day 1, Months 1−30, and 
Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
86/Protocol GX28198, Version 4 
m Adverse events will be recorded starting on Day 1 after the study treatment injection through the last study visit.  At the time of study enrollment, 
if the patient has any ongoing adverse events from Study CFD4870g, these events will also be entered into the extension study eCRF.  Adverse 
events assessed by the physician as related to study drug should be followed until the event resolves or the event is assessed as irreversible, 
chronic, or stable, even if the patient’s participation in the study has been terminated. 
n Record all concurrent ocular procedures performed on the study or non-study eye. 
o Subsequent to the initial study treatment visit, patients treated with study drug will receive a telephone call 7 (±2) days after each treatment visit 
to   solicit adverse events. 


 
Lampalizumab—Genentech, Inc. 
87/Protocol GX28198, Version 4 
Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-B: 
Schedule of Assessments for Patients Enrolled from Study CFD4870g:  Months 31−66 and 
Early Termination 
 
 
Visit Montha  
 
31−35 
36 
37−41 
42 
43−47 
48 
49−53 
54 
55−59 
60 
61−65 
66 
ETb 
Assessment 
windows (days) 
between monthly 
visits 
±7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
≥30 
Site to contact IxRS 
(as applicable)b 
x 
x 
x 
x 
x 
X 
x 
x 
x 
x 
x 
x 
x 
Physical 
examination 
 
 
 
 
 
 
 
 
 
 
 
 
x 
Vital signsc 
 
 
 
 
 
 
 
 
 
 
 
 
x 
Central laboratory 
samples 
(hematology, 
coagulation, serum 
chemistry, 
urinalysis)d 
 
 
 
 
 
 
 
 
 
 
 
 
x 
Urine pregnancy 
test (if applicable)d 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Serum sample for 
anti-lampalizumab 
antibody and 
corresponding drug 
concentrationd 
 
x 
 
x 
 
 
 
x 
 
 
 
x 
x 


Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-B: 
Schedule of Assessments for Patients Enrolled from Study CFD4870g:  Months 31−66 and 
Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
88/Protocol GX28198, Version 4 
 
Visit Montha  
 
31−35 
36 
37−41 
42 
43−47 
48 
49−53 
54 
55−59 
60 
61−65 
66 
ETb 
Assessment 
windows (days) 
between monthly 
visits 
±7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
≥30 
Optional single 
whole-blood sample 
for genotypingd 
Collect 1 sample at any timepoint from study patients at German site 
Patient-reported 
weight and height 
Collect patient-reported weight and height once during the study 
BCVA testing 
(starting at 4 pm)e 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
IOPf 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Slit-lamp 
examination 
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 
SD-OCTg 
Perform at Months 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63 and 66 
 
FAF and NIg 
 
 
 
x 
 
 
 
x 
 
 
 
x 
x 
Fundus 
photographyg 
 
 
 
x 
 
 
 
x 
 
 
 
x 
x 


Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-B: 
Schedule of Assessments for Patients Enrolled from Study CFD4870g:  Months 31−66 and 
Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
89/Protocol GX28198, Version 4 
 
Visit Montha  
 
31−35 
36 
37−41 
42 
43−47 
48 
49−53 
54 
55−59 
60 
61−65 
66 
ETb 
Assessment 
windows (days) 
between monthly 
visits 
±7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
≥30 
Fluorescein 
angiographyg 
 
 
 
x 
 
 
 
x 
 
 
 
x 
x 
Patient-administered 
pre- and post-study 
drug injection 
antimicrobials 
(if applicable)h 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Administration of 
study drug injections 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Post-injection finger 
counting and IOP 
measurementi 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Concomitant 
medicationsj 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Adverse eventsk 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Concurrent ocular 
proceduresl 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 


Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-B: 
Schedule of Assessments for Patients Enrolled from Study CFD4870g:  Months 31−66 and 
Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
90/Protocol GX28198, Version 4 
 
Visit Montha  
 
31−35 
36 
37−41 
42 
43−47 
48 
49−53 
54 
55−59 
60 
61−65 
66 
ETb 
Assessment 
windows (days) 
between monthly 
visits 
±7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
≥30 
Follow-up call  
(if applicable)m 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
BCVA = best corrected visual acuity; ET = early termination; FAF = fundus autofluorescence; IOP = intraocular pressure; IxRS = interactive response 
system; NA = not applicable; NI = near infrared; SD OCT = spectral domain optical coherence tomography.  
Notes:  All ocular assessments are to be performed for both eyes unless noted otherwise.  All assessments are to be performed on the same day. 
a At each visit starting at Day 1, contact IxRS to obtain study drug kit assignment (if applicable).  At the ET visit, contact the IxRS to request 
patient’s status be changed to “early termination.”  At the final study visit, contact IxRS to request to change patient status to “completed.” 
b For patients who withdraw early from the study, ET assessments will be performed ≥ 30 days after the last study treatment injection. 
c Vital signs consist of blood pressure, respiration, pulse, and temperature. 
d Obtain prior to study drug treatments and prior to fluorescein angiography (if applicable).  ATA samples may be also used to measure 
lampalizumab concentration to assist in safety evaluation.  For patients at German sites, the optional, single, whole-blood sample for genotyping 
analysis may be collected at any study visit. For women of childbearing potential perform urine pregnancy test prior to every study treatment. If 
positive, collect the serum sample for pregnancy test to be performed by the central lab and do not administer the study treatment. For detailed 
description of the laboratory assessments to be performed, see separate Laboratory Manual. 
e The VA examiner will be masked to patients’ treated (study) eye and will perform only the VA (including refraction).  The VA examiner is not 
allowed to perform any other tasks involving direct patient care. 
f At Day 1, pre study drug administration IOP (performed prior to dilating eyes) data will be extracted from CFD4870g study  (as applicable)  while 
post study drug administration IOP will be entered into the extension study database.   


Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-B: 
Schedule of Assessments for Patients Enrolled from Study CFD4870g:  Months 31−66 and 
Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
91/Protocol GX28198, Version 4 
g SD-OCT, FAF, and NI images, fluorescein angiograms, and fundus photographs (as applicable) will be forwarded to the central reading center. 
Note: after enrollment, if a patient misses a study visit during which ocular images were scheduled to be taken, the images should be obtained at 
the next scheduled visit. 
 
h Patient self-administered antimicrobials may be used at the investigator’s discretion. If applicable inform the patient to self-administer them prior 
to the Month 18 (CFD 4870g) visit. 
i Finger-counting test followed by hand-motion and light-perception tests (when necessary) will be performed by the investigator within 15 minutes 
post-study drug treatment injection.  At study treatment injection visits, IOP measurement will be obtained bilaterally prior to study treatment and 
then at 60 (±10) minutes post-injection in the study eye only.  If there are no safety concerns at 60 (±10) minutes, the patient will be discharged 
from the clinic.  If at 60 (±10) minutes the post-injection IOP remains elevated by ≥10 mmHg from the pre-injection measurement, the patient will 
remain in the clinic and will be treated according to the investigator’s clinical judgment prior to the patient’s discharge; if applicable, an Adverse 
Event eCRF page will be completed (see Section 5.2.2). Note: if the study eye is treated with a ranibizumab injection during the same visit as the 
study treatment with lampalizumab, the treatment with ranibizumab has to be performed first. Please measure and record the post- ranibizumab 
treatment IOP value on the eCRF irrespective of the study treatment administration later.   
j At enrollment, any concomitant medications that are ongoing from Study CFD4870g should be entered into the eCRF for the extension study.  
Record any concomitant medications currently used by the patient and through the conclusion of the patient’s study participation or ET visit 
(i.e., any prescription medications or over-the-counter preparations other than protocol-specified procedural medications, and pre-injection and 
post-injection medications, such as proparacaine, investigator applied pre- and post-injection antimicrobials (if applicable)).   
k Adverse events will be recorded starting on Day 1 after the study treatment injection through the last study visit.  At the time of study enrollment, 
if the patient has any ongoing adverse events from Study CFD4870g, these events will also be entered into the extension study eCRF.  Adverse 
events assessed by the physician as related to study drug should be followed until the event resolves or the event is assessed as irreversible, 
chronic, or stable, even if the patient’s participation in the study has been terminated. 
l Record all concurrent ocular procedures performed on the study or non-study eye. 
m Subsequent to the initial treatment visit, patients treated with study drug will receive a telephone call 7 (±2) days after each treatment visit to   
solicit adverse events. 


 
Lampalizumab—Genentech, Inc. 
92/Protocol GX28198, Version 4 
Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-C: 
Schedule of Assessments for Patients Enrolled from Study CFD4870g:  Months 67−96 
and Early Termination 
 
 
Visit Montha 
ET,b 
67−71 
72 
73−77 
78 
79−83 
84 
85−89 
90 
91−95 
96 
Assessment windows (days) 
between monthly visits 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
≥30 
Site to contact IxRS 
(as applicable)b 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Physical examination 
 
 
 
 
 
 
 
 
 
 
x 
Vital signsc 
 
 
 
 
 
 
 
 
 
 
x 
Central laboratory samples 
(hematology, coagulation, 
serum chemistry, 
urinalysis)d 
 
 
 
 
 
 
 
 
 
 
x 
Urine pregnancy test 
(if applicable)d 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Serum sample for 
anti-lampalizumab antibody 
and corresponding drug 
concentrationd 
 
 
 
 
 
 
 
 
 
x 
x 
Optional single whole-blood 
sample for genotypingd 
Collect 1 sample at any timepoint from study patients at German site 
Patient-reported weight and 
height 
Collect patient-reported weight and height once during the study 
BCVA testing (starting at 
4 pm)e 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 


Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-C: 
Schedule of Assessments for Patients Enrolled from Study CFD4870g:  Months 67−96 
and Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
93/Protocol GX28198, Version 4 
 
Visit Montha 
ET,b 
67−71 
72 
73−77 
78 
79−83 
84 
85−89 
90 
91−95 
96 
Assessment windows (days) 
between monthly visits 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
≥30 
IOPf 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Slit-lamp examination 
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 
SD-OCTg 
Perform at Months  69, 72, 75, 78, 81, 84, 87, 90, 93 and 96 
x 
FAF and NIg 
 
 
 
x 
 
 
 
x 
 
x 
x 
Fundus photographyg 
 
 
 
x 
 
 
 
x 
 
x 
x 
Fluorescein angiographyg 
 
 
 
x 
 
 
 
x 
 
x 
x 
Patient-administered 
pre- and post-study drug 
injection antimicrobials 
(if applicable)h 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
Administration of study 
drug injections 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
Post-injection finger 
counting and IOP 
measurementi 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
Concomitant medicationsj 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 


Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-C: 
Schedule of Assessments for Patients Enrolled from Study CFD4870g:  Months 67−96 
and Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
94/Protocol GX28198, Version 4 
 
Visit Montha 
ET,b 
67−71 
72 
73−77 
78 
79−83 
84 
85−89 
90 
91−95 
96 
Assessment windows (days) 
between monthly visits 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
≥30 
Adverse eventsk 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Concurrent ocular 
proceduresl 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Follow-up call 
(if applicable)m 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
BCVA = best corrected visual acuity; ET = early termination; FAF = fundus autofluorescence; IOP = intraocular pressure; IxRS = interactive 
response system; NA = not applicable; NI = near infrared; SD OCT = spectral domain optical coherence tomography.  
Notes:  All ocular assessments are to be performed for both eyes unless noted otherwise.  All assessments are to be performed on the same day. 
a At each visit starting at Day 1, contact IxRS to obtain study drug kit assignment (if applicable).  At the ET visit, contact the IxRS to request 
patient’s status be changed to “early termination.”  At the final study visit, contact IxRS to request to change patient status to “completed.” 
b For patients who withdraw early from the study, ET assessments will be performed ≥ 30 days after the last study treatment injection. 
c Vital signs consist of blood pressure, respiration, pulse, and temperature. 
d Obtain prior to study drug treatments and prior to fluorescein angiography (if applicable).  ATA samples may be also used to measure 
lampalizumab concentration to assist in safety evaluation.  For patients at German sites, the optional, single, whole-blood sample for 
genotyping analysis may be collected at any study visit. For women of childbearing potential perform urine pregnancy test prior to every 
study treatment. If positive, collect the serum sample for pregnancy test to be performed by the central lab and do not administer the study 
treatment. For detailed description of the laboratory assessments to be performed, see separate Laboratory Manual. 
e The VA examiner will be masked to patients’ treated (study) eye and will perform only the VA (including refraction).  The VA examiner is 
not allowed to perform any other tasks involving direct patient care. 
f At Day 1, pre study drug administration IOP (performed prior to dilating eyes) data will be extracted from Study CFD4870g (as applicable)  
while post study drug administration IOP will be entered into the extension study database.   


Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-C: 
Schedule of Assessments for Patients Enrolled from Study CFD4870g:  Months 67−96 
and Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
95/Protocol GX28198, Version 4 
g SD-OCT, FAF, and NI images, fluorescein angiograms, and fundus photographs (as applicable) will be forwarded to the central reading 
center. Note: after enrollment, if a patient misses a study visit during which ocular images were scheduled to be taken, the images should be 
obtained at the next scheduled visit. 
 
h Patient self-administered antimicrobials may be used at the investigator’s discretion. If applicable inform the patient to self-administer them 
prior to the Month 18 (CFD4870g) visit. 
i Finger-counting test followed by hand-motion and light-perception tests (when necessary) will be performed by the investigator within 
15 minutes post-study drug treatment injection.  At study treatment injection visits, IOP measurement will be obtained bilaterally prior to 
study treatment and then at 60 (±10) minutes post-injection in the study eye only.  If there are no safety concerns at 60 (±10) minutes, the 
patient will be discharged from the clinic.  If at 60 (±10) minutes the post-injection IOP remains elevated by ≥10 mmHg from the pre-
injection measurement, the patient will remain in the clinic and will be treated according to the investigator’s clinical judgment prior to the 
patient’s discharge; if applicable, an Adverse Event eCRF page will be completed (see Section 5.2.2). Note: if the study eye is treated with a 
ranibizumab injection during the same visit as the study treatment with lampalizumab, the treatment with ranibizumab has to be performed 
first. Please measure and record the post- ranibizumab treatment IOP value on the eCRF irrespective of the study treatment administration 
later.   
j At enrollment, any concomitant medications that are ongoing from Study CFD4870g should be entered into the eCRF for the extension study.  
Record any concomitant medications currently used by the patient and through the conclusion of the patient’s study participation or ET visit 
(i.e., any prescription medications or over-the-counter preparations other than protocol-specified procedural medications, and pre-injection 
and post-injection medications, such as proparacaine, investigator applied pre- and post-injection antimicrobials (if applicable)).   
k Adverse events will be recorded starting on Day 1 after the study treatment injection through the last study visit.  At the time of study 
enrollment, if the patient has any ongoing adverse events from Study CFD4870g, these events will also be entered into the extension study 
eCRF.  Adverse events assessed by the physician as related to study drug should be followed until the event resolves or the event is assessed 
as irreversible, chronic, or stable, even if the patient’s participation in the study has been terminated. 
l Record all concurrent ocular procedures performed on the study or non-study eye. 
m Subsequent to the initial treatment visit, patients treated with study drug will receive a telephone call 7 (±2) days after each treatment visit 
to   solicit adverse events. 


 
Lampalizumab—Genentech, Inc. 
96/Protocol GX28198, Version 4 
Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-D: 
Schedule of Assessments for Patients Enrolled from Study GX29455:  Day 1, Months 1−24 and 
Early Termination 
 
Assessment window (days) 
between monthly visits 
GX29455 
Week 23 or 
Week 24 Visit 
Day 
Visit Month 
ET b 
Day 1 a 
1−5 
6 
7−11 
12 
13−17 
18 
19−23 
24 
Extracted from 
GX29455 
Week 24 Visit 
 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
≥30 
Written informed consent signed 
x 
 
 
 
 
 
 
 
 
 
 
 
Review of inclusion and 
exclusion criteria 
 
 
x 
 
 
 
 
 
 
 
 
 
Demographic information c 
 
 
x 
 
 
 
 
 
 
 
 
 
Site to contact IxRS 
(as applicable) d 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Physical examination 
 
x 
 
 
 
 
 
 
 
 
 
x 
Vital signs e 
 
x 
 
 
 
 
 
 
 
 
 
x 
Central laboratory samples 
(hematology, coagulation, serum 
chemistry, and urinalysis) f 
 
x 
 
 
 
 
 
 
 
 
 
x 
Urine sample for pregnancy 
testing (if applicable) f 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Serum sample for 
anti-lampalizumab antibody and 
corresponding drug 
concentration f 
 
x 
 
 
x 
 
x 
 
 
 
x 
x 
BCVA testing (starting at 4 m) g 
 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 


Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-D: 
Schedule of Assessments for Patients Enrolled from Study GX29455:  Day 1, Months 1−24 
and Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
97/Protocol GX28198, Version 4 
Assessment window (days) 
between monthly visits 
GX29455 
Week 23 or 
Week 24 Visit 
Day 
Visit Month 
ET b 
Day 1 a 
1−5 
6 
7−11 
12 
13−17 
18 
19−23 
24 
Extracted from 
GX29455 
Week 24 Visit 
 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
≥30 
IOP h 
 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Slit-lamp examination 
 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Dilated binocular indirect 
ophthalmoscopy 
 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
SD-OCT i 
 
 
x 
Perform at visits Month 3, 6, 9, 12, 15, 18, 21 and 24 
x 
FAF and NI i 
 
x 
 
 
x 
 
 
 
x 
 
x 
x 
Fundus photography i 
 
x 
 
 
x 
 
 
 
x 
 
x 
x 
Fluorescein angiography i 
 
x 
 
 
x 
 
 
 
x 
 
x 
x 
Patient self-administered 
pre- and post-study drug 
injection antimicrobials 
(if applicable) j 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Administration of study drug 
injections 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Post-injection finger counting 
and IOP measurement k 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Concomitant medications l 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 


Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-D: 
Schedule of Assessments for Patients Enrolled from Study GX29455:  Day 1, Months 1−24 
and Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
98/Protocol GX28198, Version 4 
Assessment window (days) 
between monthly visits 
GX29455 
Week 23 or 
Week 24 Visit 
Day 
Visit Month 
ET b 
Day 1 a 
1−5 
6 
7−11 
12 
13−17 
18 
19−23 
24 
Extracted from 
GX29455 
Week 24 Visit 
 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
≥30 
Adverse events m 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Follow-up call (if applicable) o 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
BCVA = best corrected visual acuity; ET = early termination; FAF = fundus autofluorescence; IOP = intraocular pressure; IxRS = interactive response 
system; NA = not applicable; NI = near infrared; SD-OCT = spectral domain optical coherence tomography.  
Notes:  All ocular assessments are to be performed for both eyes unless noted otherwise.  All assessments are to be performed on the same day. 
a Day 1 visit will occur at the study GX29455 Week 24 visit conclusion.  The Study GX29455 Week 24 visit assessments will be extracted from 
that study’s database and will be used for Study GX28198 Day 1 visit.  All study patients will receive their first study drug injection in Study 
GX28198 at the Day 1 visit (unless dose holding is medically justified by the investigator).  Study drug treatment related data will be entered into 
the Study GX28198 database.  Written informed consent will be obtained prior to enrollment and the initiation of any study procedures and 
treatment. 
b For patients who withdraw early from the study, ET assessments will be performed ≥ 30 days after the last study treatment injection. 
c Demographics data will be re-entered into the Study GX28198 database on a Demographics eCRF.   
d At each visit starting at Day 1 contact IxRS to obtain study drug kit assignment (if applicable).  At the ET visit, contact the IxRS to request 
patient’s status be changed to “early termination.”  At the final study visit, contact IxRS to request to change patient status to “completed.” 
e Vital signs consist of blood pressure, respiration, pulse, and temperature.  
f Obtain prior to study drug treatments and prior to fluorescein angiography (if applicable).  ATA samples may be also used to measure 
lampalizumab concentration to assist in safety evaluation.     For women of childbearing potential perform urine pregnancy test prior to every 
study treatment. If positive, collect the serum sample for pregnancy test to be performed by the central lab and do not administer the study 
treatment.  For detailed description of the laboratory assessments to be performed, see separate Laboratory Manual. 


Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-D: 
Schedule of Assessments for Patients Enrolled from Study GX29455:  Day 1, Months 1−24 
and Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
99/Protocol GX28198, Version 4 
g The VA examiner will be masked to patients’ treated (study) eye and will perform only the VA (including refraction).  The VA examiner is not 
allowed to perform any other tasks involving direct patient care. 
h At Day 1, pre study drug administration IOP (performed prior to dilating eyes) data will be extracted from GX29455 study (as applicable)  while 
post study drug administration IOP will be obtained after the study drug treatment in study GX28198 and entered into the Study GX28198 
database.   
i SD-OCT, FAF, and NI images, fluorescein angiograms, and fundus photographs (as applicable) will be forwarded to the central reading center. 
Note: after enrollment, if a patient misses a study visit during which ocular images were scheduled to be taken, the images should be obtained at 
the next scheduled visit.   
j Patient self-administered antimicrobials may be used at the investigator’s discretion. If applicable inform the patient to self-administer them prior 
to the Week 24 (GX29455) visit. 
k Finger-counting test followed by hand-motion and light-perception tests (when necessary) will be performed by the investigator within 15 minutes 
post-study drug treatment injection.  At study treatment injection visits, IOP measurement will be obtained bilaterally prior to study treatment and 
then at 60 (±10) minutes post-injection in the study eye only.  If there are no safety concerns at 60 (±10) minutes, the patient will be discharged 
from the clinic.  If at 60 (±10) minutes the post-injection IOP remains elevated by ≥10 mmHg from the pre-injection measurement, the patient will 
remain in the clinic and will be treated according to the investigator’s clinical judgment prior to the patient’s discharge; if applicable, an Adverse 
Event eCRF page will be completed (see Section 5.2.2). Note: if the study eye is treated with a ranibizumab injection during the same visit as the 
study treatment with lampalizumab, the treatment with ranibizumab has to be performed first. Please measure and record the post-ranibizumab 
treatment IOP value on the eCRF irrespective of the study treatment administration later.   
l At enrollment, any concomitant medications that are ongoing from Study GX29455 should be entered into the eCRF for Study GX28198.  Record 
any concomitant medications currently used by the patient and through the conclusion of the patient’s study participation or ET visit (i.e., any 
prescription medications or over-the-counter preparations other than protocol-specified procedural medications, and pre-injection and post-
injection medications, such as proparacaine, investigator applied pre- and post-injection antimicrobials if applicable).   
m Adverse events will be recorded starting on Day 1 after the study treatment injection through the last study visit.  At the time of study enrollment, 
if the patient has any ongoing adverse events from Study GX29455, these events will also be entered into the Study GX28198 eCRF.  Adverse 
events assessed by the physician as related to study drug should be followed until the event resolves or the event is assessed as irreversible, 
chronic, or stable, even if the patient’s participation in the study has been terminated. 
 


Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-D: 
Schedule of Assessments for Patients Enrolled from Study GX29455:  Day 1, Months 1−24 
and Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
100/Protocol GX28198, Version 4 
n Record all concurrent ocular procedures performed on the study or non-study eye. 
o Subsequent to the initial treatment visit, patients treated with study drug will receive a telephone call 7 (±2) days after each treatment visit to 
solicit adverse events.


 
Lampalizumab—Genentech, Inc. 
101/Protocol GX28198, Version 4 
Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-E: 
Schedule of Assessments for Patients Enrolled from Study GX29455:  Months 25−54 and 
Early Termination 
 
 
Visit Montha 
ET,b 
25−29 
30 
31−35 
36 
37−41 
42 
43−47 
48 
49−53 
54 
Assessment windows 
(days) between monthly 
visits 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
≥30 
Site to contact IxRS 
(as applicable)b 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Physical examination 
 
 
 
 
 
 
 
 
 
 
x 
Vital signsc 
 
 
 
 
 
 
 
 
 
 
x 
Central laboratory samples 
(hematology, coagulation, 
serum chemistry, 
urinalysis)d 
 
 
 
 
 
 
 
 
 
 
x 
Urine pregnancy test 
(if applicable)d 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Serum sample for 
anti-lampalizumab 
antibody and 
corresponding drug 
concentrationd 
 
 
 
 
 
 
 
 
 
x 
x 
BCVA testing (starting at 
4 pm)e 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
IOPf 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Slit-lamp examination 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 


Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-E: 
Schedule of Assessments for Patients Enrolled from Study GX29455:  Months 25−54 
and Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
102/Protocol GX28198, Version 4 
 
Visit Montha 
ET,b 
25−29 
30 
31−35 
36 
37−41 
42 
43−47 
48 
49−53 
54 
Assessment windows 
(days) between monthly 
visits 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
≥30 
Dilated binocular indirect 
ophthalmoscopy 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
SD-OCTg 
Perform at Months 27, 30, 33, 36, 39, 42, 45, 48, 51 and 54 
x 
FAF and NIg 
 
 
 
x 
 
 
 
x 
 
x 
x 
Fundus photographyg 
 
 
 
x 
 
 
 
x 
 
x 
x 
Fluorescein angiographyg 
 
 
 
x 
 
 
 
x 
 
x 
x 
Patient-administered 
pre- and post-study drug 
injection antimicrobials 
(if applicable)h 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
Administration of study 
drug injections 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
Post-injection finger 
counting and IOP 
measurementi 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
Concomitant medicationsj 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Adverse eventsk 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 


Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-E: 
Schedule of Assessments for Patients Enrolled from Study GX29455:  Months 25−54 
and Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
103/Protocol GX28198, Version 4 
 
Visit Montha 
ET,b 
25−29 
30 
31−35 
36 
37−41 
42 
43−47 
48 
49−53 
54 
Assessment windows 
(days) between monthly 
visits 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
≥30 
Concurrent ocular 
proceduresl 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Follow-up call 
(if applicable)m 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
BCVA = best corrected visual acuity; ET = early termination; FAF = fundus autofluorescence; IOP = intraocular pressure; IxRS = interactive 
response system; NA = not applicable; NI = near infrared; SD OCT = spectral domain optical coherence tomography.  
Notes:  All ocular assessments are to be performed for both eyes unless noted otherwise.  All assessments are to be performed on the same day. 
a At each visit starting at Day 1, contact IxRS to obtain study drug kit assignment (if applicable).  At the ET visit, contact the IxRS to request 
patient’s status be changed to “early termination.”  At the final study visit, contact IxRS to request to change patient status to “completed.” 
b For patients who withdraw early from the study, ET assessments will be performed ≥ 30 days after the last study treatment injection. 
c Vital signs consist of blood pressure, respiration, pulse, and temperature. 
d Obtain prior to study drug treatments and prior to fluorescein angiography (if applicable).  ATA samples may be also used to measure 
lampalizumab concentration to assist in safety evaluation.  For patients at German sites, the optional, single, whole-blood sample for 
genotyping analysis may be collected at any study visit. For women of childbearing potential perform urine pregnancy test prior to every 
study treatment. If positive, collect the serum sample for pregnancy test to be performed by the central lab and do not administer the study 
treatment. For detailed description of the laboratory assessments to be performed, see separate Laboratory Manual. 
e The VA examiner will be masked to patients’ treated (study) eye and will perform only the VA (including refraction).  The VA examiner is 
not allowed to perform any other tasks involving direct patient care. 
f At Day 1, pre study drug administration IOP (performed prior to dilating eyes) data will be extracted from GX29455 study  (as applicable)  
while post study drug administration IOP will be entered into the extension study database.   


Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-E: 
Schedule of Assessments for Patients Enrolled from Study GX29455:  Months 25−54 
and Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
104/Protocol GX28198, Version 4 
g SD-OCT, FAF, and NI images, fluorescein angiograms, and fundus photographs (as applicable) will be forwarded to the central reading 
center. Note: after enrollment, if a patient misses a study visit during which ocular images were scheduled to be taken, the images should be 
obtained at the next scheduled visit. 
 
h Patient self-administered antimicrobials may be used at the investigator’s discretion. If applicable inform the patient to self-administer them 
prior to the Month 18 (GX29455) visit. 
i Finger-counting test followed by hand-motion and light-perception tests (when necessary) will be performed by the investigator within 
15 minutes post-study drug treatment injection.  At study treatment injection visits, IOP measurement will be obtained bilaterally prior to 
study treatment and then at 60 (±10) minutes post-injection in the study eye only.  If there are no safety concerns at 60 (±10) minutes, the 
patient will be discharged from the clinic.  If at 60 (±10) minutes the post-injection IOP remains elevated by ≥10 mmHg from the 
pre-injection measurement, the patient will remain in the clinic and will be treated according to the investigator’s clinical judgment prior to 
the patient’s discharge; if applicable, an Adverse Event eCRF page will be completed (see Section 5.2.2.  Note: if the study eye is treated with 
a ranibizumab injection during the same visit as the study treatment with lampalizumab, the treatment with ranibizumab has to be performed 
first. Please measure and record the post- ranibizumab treatment IOP value on the eCRF irrespective of the study treatment administration 
later.   
j At enrollment, any concomitant medications that are ongoing from Study GX29455 should be entered into the eCRF for the extension study.  
Record any concomitant medications currently used by the patient and through the conclusion of the patient’s study participation or ET visit 
(i.e., any prescription medications or over-the-counter preparations other than protocol-specified procedural medications, and pre-injection 
and post-injection medications, such as proparacaine, investigator applied pre- and post-injection antimicrobials (if applicable)).   
k Adverse events will be recorded starting on Day 1 after the study treatment injection through the last study visit.  At the time of study 
enrollment, if the patient has any ongoing adverse events from Study GX29455g, these events will also be entered into the extension study 
eCRF.  Adverse events assessed by the physician as related to study drug should be followed until the event resolves or the event is assessed 
as irreversible, chronic, or stable, even if the patient’s participation in the study has been terminated. 
l Record all concurrent ocular procedures performed on the study or non-study eye. 
m Subsequent to the initial treatment visit, patients treated with study drug will receive a telephone call 7 (±2) days after each treatment visit 
to   solicit adverse events. 


 
Lampalizumab—Genentech, Inc. 
105/Protocol GX28198, Version 4 
Appendix 1  
Schedule of Assessments (cont.) 
Appendix 1-F: 
Unscheduled Safety Visit Assessments for All Study Patients  
 
Assessments a 
 
Vital signs (blood pressure, respiration rate, temperature, pulse) 
x 
Physical examination 
x 
Best corrected visual acuity (4-m starting distance) b 
x 
Slit-lamp examination 
x 
Dilated binocular indirect high-magnification ophthalmoscopy 
x 
Intraocular pressure c  
x 
Adverse events d 
x 
Concurrent ocular procedures 
x 
Concomitant medications 
x 
a If determined to be necessary by physician, perform 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 events causality to be evaluated by the qualified ophthalmologist. 
 


 
Lampalizumab—Genentech, Inc. 
106/Protocol GX28198, Version 4 
Appendix 2  
Grading Scale for Assessment of Anterior Chamber Flare or 
Cells and Vitreous Cells 
Grading Scale for Anterior Chamber Flare or Cells 
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. 
2−3 +  
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/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.  As for 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 MH, Kimura SJ, Thygeson P. Signs and symptoms of uveitis. I. Anterior uveitis. 
Am J Ophthalmol 1959;47(5, Part 2):155–70. 
 


Appendix 2  
Grading Scale for Assessment of Anterior Chamber Flare or 
Cells and Vitreous Cells (cont.) 
Lampalizumab—Genentech, Inc. 
107/Protocol GX28198, Version 4 
Grading Scale for Vitreous Cells 
Cells in  
Retroilluminated 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 
Note:  The grading will be performed using a Hruby lens.  
Modified from:  Nussenblatt RB, Whitcup SM, Palestine AG. Uveitis. Fundamentals and clinical 
practice. 2nd rev. ed. New York: Mosby, 1996, p. 64. 
 


 
Lampalizumab—Genentech, Inc. 
108/Protocol GX28198, Version 4 
Appendix 3  
Best Corrected Visual Acuity Testing 
Scope 
Best corrected visual acuity (BCVA) will be measured by trained and certified personnel 
at the study sites.  The VA examiner must be masked to the treated (study) eye.  
The VA examiner is not allowed to perform any other tasks involving direct patient care 
which may unmask him/her to patient’s study eye.  VA will be measured at the intervals 
specified in the protocol (see Section 4.5 and Appendix 1-A through Appendix 1-F). 
Equipment 
The following is 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 1, 2, and R) 
• 
Retro-illuminated box 
• 
Trial frame 
• 
Trial 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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109/Protocol GX28198, Version 4 
Appendix 4  
Color Fundus Photography 
Scope 
Stereo color fundus photographs will be taken by trained personnel at the study sites.  
Fundus photography will be performed at the intervals specified in the protocol. 
Analysis 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 material.  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. 


 
Lampalizumab—Genentech, Inc. 
110/Protocol GX28198, Version 4 
Appendix 5  
Fluorescein Angiography 
Scope 
Fluorescein angiography (FA) will be performed at the study sites by trained personnel who 
are certified by the central reading center.  The fluorescein angiograms will be obtained at 
the intervals specified in the protocol (see Section 4.5 and Appendix 1-A through 
Appendix 1-E). 
Equipment 
• 
Digitally based 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 material.  
Photographers, systems, and software will be certified prior to obtaining angiograms 
of patients. 


 
Lampalizumab—Genentech, Inc. 
111/Protocol GX28198, Version 4 
Appendix 6  
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 Section 4.5 and Appendix 1-A through 
Appendix 1-E). 
The FAF images of both eyes will be obtained at protocol-specified visits will be forwarded to 
the central reading center.    
Equipment 
Equipment utilized during this trial is described in the Central Reading Center Manual.  The 
ability to transfer images to electronically export 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. 


 
Lampalizumab—Genentech, Inc. 
112/Protocol GX28198, Version 4 
Appendix 7  
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 Section 4.5 
and Appendix 1-A through Appendix 1-E). 
The SD-OCT images of both eyes will be obtained at protocol specified visits will be 
forwarded to the central reading center.    
Equipment 
Equipment utilized during this trial is described in the Central Reading Center Manual.  The 
ability to transfer images to electronically export 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. 


 
Lampalizumab—Genentech, Inc. 
113/Protocol GX28198, Version 4 
Appendix 8  
Near-Infrared Imaging 
Note:  near infrared images are taken to complement the central reading center evaluation 
of FAF images. 
Scope 
Near Infrared (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 Section 4.5 and Appendix 1-A through Appendix 1-E). 
The NI images of both eyes will be obtained at protocol specified visits will be forwarded to 
the central reading center.    
Equipment 
Equipment utilized during this trial is described in the Central Reading Center Manual.  The 
ability to transfer images to electronically export 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. 


 
Lampalizumab—Genentech, Inc. 
114/Protocol GX28198, Version 4 
Appendix 9  
Biological Sample Collection and Shipping Instructions 
Biological Samples 
Patient samples for assessment of anti-lampalizumab antibodies, laboratory assessment 
samples (hematology, serum chemistry, coagulation, and urinalysis), and the optional, 
single, whole-blood sample for genotyping analysis (German sites only), will be collected 
at the timepoints specified in Section 4.5 of the protocol, Appendix 1-A through 
Appendix 1-E, and in the Laboratory Manual. 
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