Clinical trial NCT02288559
Conditions: Geographic Atrophy
Sponsor: Genentech, Inc.
Start date: 2015-03-30; Completion date: 2017-06-02
Enrollment: 96 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This multicenter, randomized, single-masked, sham injection-controlled study will investigate the exposure-response and safety of lampalizumab administered intravitreally every 2 weeks (Q2W) or every 4 weeks (Q4W) for 24 weeks in participants with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). A safety run-in assessment will be conducted prior to initiating enrollment in the randomized study.

Detailed description:

Arms: arm 1: Participants will receive 10 milligrams (mg) lampalizumab intravitreally Q2W during the safety run-in period. arm 2: Participants will receive 10 mg dose of lampalizumab intravitreally Q2W during the 24-week treatment period. arm 3: Participants will receive 10 mg dose of lampalizumab intravitreally Q4W during the 24-week treatment period. arm 4: Participants randomized to control arms will receive sham injections, that mimics intravitreal injection of lampalizumab.
Interventions: intervention 1: Sham intervention 2: Lampalizumab
Intervention descriptions: intervention 1: Sham injection will be administered as a matching intravitreal injection of lampalizumab. intervention 2: 10 mg dose of lampalizumab administered intravitreally

Protocol documents:
Prot_SAP_000.pdf: 
 
Official Title: 
 
A PHASE II, MULTICENTER, RANDOMIZED, SINGLE-MASKED, 
SHAM INJECTION-CONTROLLED EXPOSURE-RESPONSE 
STUDY OF LAMPALIZUMAB INTRAVITREAL INJECTIONS 
ADMINISTERED EVERY TWO WEEKS OR EVERY FOUR WEEKS 
TO PATIENTS WITH GEOGRAPHIC ATROPHY  
NCT Number: 
 
 NCT02288559 
 
Document Date: 
Protocol/Version 3: 24-Dec-2015 
 
 
 
 




Lampalizumab—Genentech, Inc. 
2/Protocol GX29455, Version 3 
PROTOCOL AMENDMENT, VERSION 3: 
RATIONALE 
Protocol GX29455 has been amended as follows: 
•   To expand enrollment sites from 23 sites to 25−30 sites in the United States 
•   To expand the screening window from 21 days to 28 days and also allow the 
screening period to be extended up to 5 days for exceptional circumstances (if 
approved by the Medical Monitor) 
•   The patient age restriction for inclusion in the study was revised from 
“Age 60−89 years” to “Age ≥
 60 years” 
•   To allow re-screening of patients who have failed screening for reasons other than 
complement factor I biomarker 
•   To allow provision to administer the first study treatment within 1 working day after 
the Day 1 visit in the event of unexpected issues that prevent drug administration on 
Day 1 
•   To revise the pregnancy and contraceptive requirements to align with a global 
update to the protocol template and international recommendations  
•   To allow a single intraoperative administration of a corticosteroid during cataract 
surgery within 3 months prior to screening in order to permit limited use of 
corticosteroids in this specific application which will not impact study results and 
may facilitate patient eligibility for the study 
•   To allow inclusion of patients with appropriately treated and resolved retinal tears (if 
approved by the Medical Monitor) 
•   To clarify the definition of diabetic retinopathy and potentially allow patients with mild 
non−proliferative diabetic retinopathy for inclusion in the study (if approved by the 
Medical Monitor) 
•   To clarify that the Medical Monitor must approve participation of patients who have 
participated in other studies with investigational drugs 
•   To clarify inclusion criteria for patients with a history of a previous malignancy 
•   To include restrictions for patients with hypersensitivity to a biologic agent, 
lampalizumab, or any component of the lampalizumab injection 
•   To allow use of intra−articular or intra−muscular corticosteroids if used in a limited 
fashion and if approved by the Medical Monitor 
•   To clarify active local or systemic infections in the dose interruption, treatment, and 
study discontinuation criteria 
•   To modify the adverse event causal attribution guidance 
•   To add treatment measures for patients who develop a reaction to povidone-iodine 
 
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. 
3/Protocol GX29455, Version 3 
PROTOCOL AMENDMENT, VERSION 3: 
SUMMARY OF CHANGES 
 
PROTOCOL SYNOPSIS  
The protocol synopsis has been updated to reflect the changes to the protocol, where 
applicable. 
SECTION 1.3.4:  Rationale for Study GX29455 
… On the basis of the preclinical Study 09-1554 and CFD4870g Phase II results, the 
proposed  Study GX29455 will further investigate the exposure-response and safety of 
lampalizumab in the CFI profile biomarker-positive patient population over multiple 
intravitreal injections and dose exposures. 
SECTION 3:  STUDY DESIGN 
….  A Q2W safety run-in assessment will precede the randomized study.  Approximately 
90 patients will be enrolled at an estimated 23 25−30 study sites in the United States. 
SECTION 3.1.2:  Four-Arm, Randomized Study 
An estimated 23 25−30 study sites in the United States will participate in the randomized 
study.  Approximately 84 CFI profile biomarker-positive patients with GA secondary to 
AMD will be enrolled.  Biomarker status will be determined using the investigational 
cobas® CFI Profile CTA that will be run at a designated study laboratory testing site. The 
study will consist of a screening period of up to 2128 days (Days 
 −
 2128 to 
 −
 1) and a 
treatment period of 24 weeks.   
Patients who failed screening for reasons other than CFI biomarker status (e.g., GA lesion size, 
BCVA, or prohibited concomitant medication) may be eligible for rescreening up to two 
additional times during the enrollment period of the study.  At rescreening, all screening visit 
assessments will be performed except CFI biomarker sample provided that a valid CFI result is 
available. 
The first study treatment will be administered on the same day as randomization (Day 1 visit).  If 
a site has an unexpected issue (e.g., the IxRS is not able to assign the study kit), with the Medical 
Monitor’s permission, the patient’s first study treatment may be administered within 1 working 
day after the Day 1 visit.  The following assessments will be repeated on the day of the study 
treatment:  BCVA, slit−lamp examination, indirect ophthalmoscopy, and pre- and post-treatment 
IOP measurement (recorded on Day 1 electronic Case Report Form (eCRF) and dated 
accordingly).  After the Day 1 visit, if a patient misses a study visit when ocular images are 
scheduled (see Appendix 1), the images must be obtained at the next scheduled visit. 
SECTION 4.1:  PATIENTS 
Patient Selection and Sex Distribution 
Written informed consent will be obtained prior to initiation of any study procedures.  
The screening evaluation will be performed within 2128 days preceding the Day 1 visit 
(the day of the first study treatment).   


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NOTE: Some patients may require an extended screening period as a result of repeat 
acquisition or evaluation of images or other issues.  After consultation with and 
approval by the Medical Monitor, the screening period may be extended for up to 5 days 
for exceptional circumstances. 
SECTION 4.1.1.1:  General Inclusion Criteria 
•  Age ≥
 60 years 
•  Age 60 89 years 
•   For women who are not postmenopausal (≥12 months of nontherapyinduced 
amenorrhea) or surgically sterile (absence of ovaries and/or uterus):childbearing 
potential:  agreement to remain abstinent or (refrain from heterosexual intercourse) 
or use single or combined 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.  Periodic abstinence (e.g., calendar, ovulation, symptothermal, or 
postovulation methods) and withdrawal are not acceptable methods of 
contraception.  Examples of contraceptive methods with a failure rate of < 1% per 
year include tubal ligation, male sterilization, (hormonal implants, established, 
proper use of combined oral or injected hormonal contraceptives), and certain 
intrauterine devices.  Alternatively, two methods (e.g., two barrier methods such as 
a condom and a cervical cap) may be combined to achieve a failure rate of < 1% 
per year.  Barrier methods must always be supplemented with the use of a 
spermicide. 
A woman is considered to be of childbearing potential if she is postmenarchial, has 
not reached postmenopausal state (≥12 months of amenorrhea with no identified 
cause other than menopause), and has not undergone surgical sterilization (absence 
of ovaries and/or uterus). 
Examples of contraceptive methods with a failure rate of <1% per year include 
bilateral tubal ligation, male sterilization, established, proper use of hormonal 
contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and 
copper intrauterine devices. 
The reliability of sexual abstinence should be evaluated in relation to the duration 
of the clinical trial and the preferred and usual lifestyle of the patient.  Periodic 
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) 
and withdrawal are not acceptable methods of contraception. 
•   For men:  agreement to remain abstinent or use a condomcontraceptive 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. and 
agreement to refrain from donating sperm during this same period.  Men with a 
pregnant partner must agree to remain abstinent or use a condom for the 
duration of the pregnancy. 
 


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SECTION 4.1.2.2:  Ocular Exclusion Criteria:  Study Eye 
   Previous intravitreal drug delivery (e.g., intravitreal corticosteroid injection, 
anti-angiogenic drugs, anti-complement agents, biodegradable/non-biodegradable 
implants or formulations, device implant, or encapsulated cell technology).  NOTE:  
A single intraoperative administration of a corticosteroid during cataract surgery 
for cystoid macular edema prophylaxis at least 3 months prior to screening is 
permitted. 
   History of retinal tear.  NOTE: a retinal tear adequately treated with laser 
photocoagulation and determined to be stable by investigator may be permitted 
after consultation with and approval by the Medical Monitor. 
 
SECTION 4.1.2.3:  Ocular Exclusion Criteria:  Either Eye 
  Proliferative diabetic retinopathy. NOTE:  mild non-proliferative diabetic 
retinopathy (occasional hemorrhage or microaneurysm) in either eye may be 
permitted after consultation with and approval by the Medical Monitor; moreover, 
a patient with onset of mild non-proliferative diabetic retinopathy in either eye 
during study participation may be permitted to continue study treatment after 
consultation with the Medical Monitor. 
   Previous participation in other studies of investigational drugs (excluding vitamin 
and mineral supplements; topical ocular agents  3 months preceding Day 1) may 
be permitted after consultation with and approval by the Medical Monitor 
 
SECTION 4.1.2.4:  Systemic Exclusion Criteria:  Concurrent Conditions 
   Treatment for an active localized or systemic infection 
Ongoing prophylactic use of antimicrobial therapy should be discussed with and 
approved by the Medical Monitor. 
   Active malignancy or history of malignancy within the previous 5 years (12 months 
except completelyfor appropriately treated carcinoma in situ of the cervix, resolved 
cutaneous basal cell carcinoma)non-melanoma skin carcinoma, and prostate cancer 
with a Gleason score of 
 6 and a stable prostate-specific antigen (PSA) 
for
 12 months. 
  History of a severe allergic reaction or anaphylactic reaction to a biologic agent or 
known hypersensitivity to any component of the lampalizumab injection 
   Requirement for continuous use of any medications/treatments indicated in the 
“Excluded ConcomitantProhibited Therapy” section of the protocol (see 
Section 4.4.2) 
   Woman who are not post menopausal (
 12 months of non therapy induced 
amenorrhea) or surgically sterilechildbearing potential  must have a negative serum 
pregnancy test result within 2128 days prior to initiation of study treatment 
 
SECTION 4.4.1:  Permitted Therapy 
Patients who use other maintenance therapies should continue their use.   


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All concomitant medications should be reported to the investigator and recorded on the 
appropriate eCRF.  Patients who use oral contraceptives, hormone-replacement therapy, 
or other maintenance therapy should continue their use.  
A patient with onset of mild nonproliferative diabetic retinopathy in either eye 
during study participation (e.g., an occasional hemorrhageIntra-articular or 
microaneurysm)intra-muscular corticosteroids may be permitted to continue on 
study treatmentused in a limited fashion after consultation with and approval by the 
Medical Monitor.  
SECTION 4.4.2:  Prohibited Therapy 
At the discretion of the investigator, patients may continue to receive all medications and 
standard treatments administered for other conditions.  TheHowever, the following 
medications and treatments will exclude patients from study eligibility and are 
prohibited from use during the patient’s participation in the study and patients required to 
use medications described below will not be eligible for enrollment in the study: 
•   Intravitreal, subtenon, or chronic topical (ocular) corticosteroids in either eye; 
short-term use of topical corticosteroids is permitted after cataract surgery 
•   Oral corticosteroids (prednisone or equivalent) at doses
 >
 10 mg/day (prohibited at 
screening for eligibility; for occurrence during study enrollment, see Table 2, 
Dose−Interruption Criteria)   
•  Intraarticular or intramuscular corticosteroids may be used in a limited fashion after 
consultation with the Medical Monitor 
•   Intravenous corticosteroids (prohibited at screening for eligibility; for occurrence 
during study enrollment, see Table 2, Dose-Interruption Criteria) 
 
SECTION 4.5.6.3:  Genotyping: CFI Profile Biomarker 
Whole−blood samples for CFI profile biomarker status determination will be collected 
and forwarded directly from the sites to the Sponsor-selected laboratory for analysis to 
determine CFI profile biomarker status (see the Central Laboratory Manual for details). 
Whole blood sample for determination of CFI profile biomarker status 
Table 2:  Dose Interruption, Treatment, and Study Discontinuation Criteria 
Table 2 was modified to clarify active local or systemic infections in the dose interruption, 
treatment, and study discontinuation criteria. 
Table 4:  Causal Attribution Guidance 
The causal attribution guidance was modified. 
SECTION 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 


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event (per the definition of serious adverse event in Section 5.2.2), except as outlined 
below. 
There are some hospitalization scenarios that do not require reporting as a serious 
adverse event when there is no occurrence of an adverse event. These scenarios 
include a planned hospitalization or prolonged hospitalization to undergo a diagnostic or 
elective surgical procedure for a preexisting medical condition other than ocular that has 
not changed. 
•  Hospitalization for a preexisting condition, provided that 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. 
 
Appendix 1:  Study Flowchart Safety Run-In Assessment:  Screening, Day 1 
through Hiatus
 and Early Termination 
The study flowchart for safety run-in assessments has been revised to reflect the 
changes to the protocol. 
Appendix 2:  Study Flowchart for Randomized Study:  Q2W Arms:  
Screening, Day 1, Week 2 through Week 24, and Early 
Termination 
The study flowchart for the randomized study Q2W assessments has been revised to 
reflect the changes to the protocol. 
Appendix 3:  Study Flowchart for Randomized Study:  Q4W Arms:  
Screening, Day 1, Week 4 through Week 24, and Early 
Termination 
The study flowchart for the randomized study Q4W assessments has been revised to 
reflect the changes to the protocol. 
Appendix 6:  Pre Injection Procedures for All Patients 
•   Disinfect the periocular skin and eyelid of the study eye in preparation for injection.  
Scrub the eyelid, lashes, and periorbital skin with 10% povidone iodine swabs, 
starting with the eyelid and lashes and continuing with the surrounding periocular 
skin.  Ensure that the eyelid margins and lashes are swabbed, and proceed in a 
systematic fashion, from medial to temporal aspects. 
NOTE: For patients who develop adverse reaction to povidone-iodine, the following approaches 
are permitted:  irrigate the eye with sterile saline after the study treatment (lampalizumab or 
sham) with the aim to rinse away any remaining povidone-iodine or use a limited amount of 
povidone-iodine by placing a swab directly on the treatment site after the lid speculum has been 
placed. 


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SAMPLE INFORMED CONSENT FORMS 
The sample Informed Consent Form has been revised to reflect the changes to the 
protocol. 
 


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TABLE OF CONTENTS 
PROTOCOL AMENDMENT ACCEPTANCE FORM ..........................................16 
PROTOCOL SYNOPSIS 
....................................................................................17 
1.  BACKGROUND ..........................................................................................25 
1.1  
Background on Geographic Atrophy......................................25 
1.2   
Background on Lampalizumab ..............................................25 
1.3  
Study Rationale and Benefit-Risk Assessment......................27 
1.3.1   
Study CFD4711g:  Phase Ia 
..................................................27 
1.3.2   
Study CFD4870g:  Phase Ib/II 
...............................................27 
1.3.2.1   
Phase Ib ................................................................................27 
1.3.2.2  
Phase II .................................................................................27 
1.3.3  
Study GX28198:  Open-Label Extension 
...............................30 
1.3.4   
Rationale for Study GX29455................................................30 
2.   OBJECTIVES..............................................................................................31 
2.1  
Primary Objective ..................................................................31 
2.2   
Secondary Objectives............................................................31 
2.3  
Exploratory Objectives...........................................................31 
3.  STUDY DESIGN 
.........................................................................................31 
3.1  
Description of Study ..............................................................31 
3.1.1  
Safety Run-In Assessment....................................................31 
3.1.1.1   
Dose-Limiting Toxicities Criteria for the Safety 
Run-In Assessment ...............................................................32 
3.1.1.2   
Dose-Limiting Toxicities for the Safety 
Run-In Assessment ...............................................................33 
3.1.1.3   
Dose-Limiting Toxicity Assessments Window for 
the Safety Run-In...................................................................33 
3.1.2   
Four-Arm, Randomized Study ...............................................33 
3.2  
End of Study 
..........................................................................35 
3.3   
Rationale for Study Design....................................................36 
3.3.1   
Rationale for Lampalizumab Dose and Schedule..................36 
3.3.2   
Rationale for Patient Population and Analysis 
Groups...................................................................................36 


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3.3.2.1   
Rationale for Evaluating Lampalizumab in 
Patients with Geographic Atrophy .........................................36 
3.3.3   
Rationale for Control Group...................................................37 
3.3.4   
Rationale for Biomarker Assessments...................................37 
3.4   
Outcome Measures ...............................................................38 
3.4.1  
Primary Efficacy Outcome Measures ....................................38 
3.4.2   
Safety Outcome Measures....................................................38 
3.4.3   
Pharmacokinetic Outcome Measures 
....................................38 
3.4.4  
Exploratory Outcome Measures ............................................39 
4.  MATERIALS AND METHODS ....................................................................39 
4.1  
Patients..................................................................................39 
4.1.1  
Inclusion Criteria....................................................................39 
4.1.1.1  
General Inclusion Criteria......................................................39 
4.1.1.2   
Ocular Inclusion Criteria:  Study Eye.....................................40 
4.1.1.3   
Ocular Inclusion Criteria:  Fellow (Non-Study) 
Eye ........................................................................................40 
4.1.2   
Exclusion Criteria...................................................................40 
4.1.2.1   
Ocular Exclusion Criteria: Geographic Atrophy 
Characteristics.......................................................................41 
4.1.2.2   
Ocular Exclusion Criteria:  Study Eye 
....................................41 
4.1.2.3   
Ocular Exclusion Criteria:  Either Eye....................................42 
4.1.2.4   
Systemic Exclusion Criteria:  Concurrent 
Conditions..............................................................................42 
4.2   
Method of Treatment Assignment and Masking ....................43 
4.2.1   
Safety Run-In Assessment Treatment 
Assignment and Masking.......................................................43 
4.2.2   
Randomized Study Treatment Assignment and 
Masking .................................................................................44 
4.3   
Study Treatment 
....................................................................44 
4.3.1  
Formulation, Packaging, and Handling..................................44 
4.3.1.1   
Lampalizumab .......................................................................44 
4.3.1.2  
Sham.....................................................................................45 
4.3.2  
Dosage, Administration, and Compliance..............................45 
4.3.2.1   
Lampalizumab and Sham 
......................................................45 


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4.3.2.2   
Administration........................................................................46 
4.3.2.3   
Compliance............................................................................47 
4.3.3  
Investigational Medicinal Product Accountability ...................47 
4.3.4   
Post-Trial Access to Lampalizumab ......................................47 
4.4   
Concomitant Therapy ............................................................48 
4.4.1  
Permitted Therapy 
.................................................................48 
4.4.2  
Prohibited Therapy ................................................................48 
4.5  
Study Assessments 
...............................................................49 
4.5.1   
Informed Consent Forms and Screening Log 
........................49 
4.5.2   
Medical History and Demographic Data ................................49 
4.5.3   
Physical Examinations...........................................................49 
4.5.4   
Vital Signs..............................................................................50 
4.5.5  
Other Disease-Specific Assessments....................................50 
4.5.6   
Laboratory Assessments, Other Biological 
Assessments, and Genotyping for the CFI Profile 
Biomarker ..............................................................................50 
4.5.6.1   
Laboratory Assessments .......................................................50 
4.5.6.2  
Other Biological Assessments...............................................51 
4.5.6.3   
Genotyping: CFI Profile Biomarker 
........................................51 
4.5.6.4  
Storage 
..................................................................................52 
4.5.7  
Samples for Roche Clinical Repository..................................52 
4.5.7.1   
Overview of the Roche Clinical Repository............................52 
4.5.7.2   
Sample Collection..................................................................53 
4.5.7.3  
Confidentiality 
........................................................................53 
4.5.7.4  
Consent to Participate in the Roche Clinical 
Repository .............................................................................54 
4.5.7.5   
Withdrawal from the Roche Clinical Repository.....................54 
4.5.7.6   
Monitoring and Oversight.......................................................54 
4.6  
Patient, Treatment, Study, and Site 
Discontinuation 
......................................................................55 
4.6.1   
Patient Discontinuation 
..........................................................55 
4.6.2   
Study Treatment Discontinuation...........................................55 
4.6.3   
Study and Site Discontinuation..............................................55 
5.   ASSESSMENT OF SAFETY.......................................................................56 


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5.1   
Safety Plan ............................................................................56 
5.1.1   
Management of Specific Adverse Events ..............................58 
5.1.1.1   
Dose-Interruption, Treatment and Study 
Discontinuation Criteria..........................................................58 
5.2   
Safety Parameters and Definitions ........................................60 
5.2.1   
Adverse Events .....................................................................60 
5.2.2  
Serious Adverse Events (Immediately Reportable 
to the Sponsor) 
......................................................................60 
5.2.3   
Adverse Events of Special Interest (Immediately 
Reportable to the Sponsor)....................................................61 
5.2.3.1   
Safety Run-In Assessment Period:  Targeted 
Dose-Limiting Toxicities Adverse Events...............................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 Event Information 
.......................................63 
5.3.3   
Assessment of Severity of Adverse Events ...........................64 
5.3.4   
Assessment of Causality of Adverse Events .........................64 
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..........................69 
5.3.5.11   Adverse Events Associated with an Overdose or 
Error in Drug Administration ..................................................69 
5.4   
Immediate Reporting Requirements from 
Investigator to Sponsor..........................................................70 
5.4.1   
Emergency Medical Contacts................................................71 


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5.4.2   
Reporting Requirements for Serious Adverse 
Events and Non-Serious Adverse Events of 
Special Interest......................................................................71 
5.4.2.1   
Events That Occur prior to Study Drug Initiation....................71 
5.4.2.2   
Events That Occur after Study Drug Initiation........................71 
5.4.3   
Reporting Requirements for Pregnancies..............................71 
5.4.3.1   
Pregnancies in Female Patients............................................71 
5.4.3.2   
Pregnancies in Female Partners of Male Patients.................72 
5.4.3.3   
Congenital Anomalies/Birth Defects and 
Abortions ...............................................................................72 
5.5   
Follow-Up of Patients after Adverse Events ..........................73 
5.5.1   
Investigator Follow-Up 
...........................................................73 
5.5.2  
Sponsor Follow-Up 
................................................................73 
5.6  
Post-Study Adverse Events 
...................................................73 
5.7  
Expedited Reporting to Health Authorities, 
Investigators, Institutional Review Boards, and 
Ethics Committees.................................................................73 
6.   STATISTICAL CONSIDERATIONS AND ANALYSIS 
METHODS 
..................................................................................................74 
6.1   
Determination of Sample Size...............................................74 
6.2   
Efficacy Analyses ..................................................................77 
6.3  
Safety Analyses.....................................................................77 
6.4  
Pharmacokinetic Analyses.....................................................77 
6.5  
Handling of Missing Data.......................................................78 
7.   DATA COLLECTION AND MANAGEMENT ...............................................78 
7.1   
Data Quality Assurance 
.........................................................78 
7.2   
Electronic Case Report Forms...............................................78 
7.3   
Source Data Documentation..................................................78 
7.4   
Use of Computerized Systems ..............................................79 
7.5   
Retention of Records 
.............................................................79 
8.  ETHICAL CONSIDERATIONS....................................................................80 
8.1   
Compliance with Laws and Regulations ................................80 
8.2   
Informed Consent 
..................................................................80 
8.3   
Institutional Review Board or Ethics Committee 
....................81 


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8.4   
Confidentiality 
........................................................................ 81 
8.5   
Financial Disclosure .............................................................. 82 
9.   STUDY DOCUMENTATION, MONITORING, AND 
ADMINISTRATION ..................................................................................... 82 
9.1   
Study Documentation............................................................ 82 
9.2   
Protocol Deviations................................................................82 
9.3   
Site Inspections.....................................................................82 
9.4   
Administrative Structure......................................................... 83 
9.5   
Publication of Data and Protection of Trade 
Secrets .................................................................................. 83 
9.6   
Protocol Amendments ........................................................... 84 
10.  REFERENCES ........................................................................................... 85 
 
 
LIST OF TABLES 
Table 1   
Definition of Biomarker Status Using the CFI Profile Test........... 30 
Table 2   
Dose-Interruption, Treatment, and Study-Discontinuation 
Criteria........................................................................................59 
Table 3   
Adverse Event Severity Grading Scale 
....................................... 64 
Table 4   
Causal Attribution Guidance ....................................................... 65 
Table 5   
Scenario Analysis:  Observed Mean Change in Geographic 
Atrophy Area and 80% Confidence Intervals for Difference 
between Lampalizumab Q2W and Q4W Groups ........................ 76 
 
 
LIST OF FIGURES 
Figure 1   
Complement System Pathways and Site of Inhibition by 
Lampalizumab in the Alternative Complement Pathway 
............. 26 
Figure 2a   Dosing Schema for Q2W Treatment Arms.................................. 34 
Figure 2b   Dosing Schema for Q4W Treatment Arms.................................. 35 
 
 
LIST OF APPENDICES 
Appendix 1   Study Flowchart Safety Run-In Assessment:  Screening, 
Day 1 through Hiatus and Early Termination .............................. 86 
Appendix 2   Study Flowchart for Randomized Study:  Q2W Arms:  
Screening, Day 1, Week 2 through Week 24, and Early 
Termination 
................................................................................. 90 


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15/Protocol GX29455, Version 3 
Appendix 3   Study Flowchart for Randomized Study:  Q4W Arms:  
Screening, Day 1, Week 4 through Week 24, and Early 
Termination 
.................................................................................94 
Appendix 4   Study Flowchart:  Unscheduled Safety Visit Assessments .........97 
Appendix 5   Grading Scale for Assessment of Anterior Chamber Flare or 
Cells and Vitreous Cells 
..............................................................98 
Appendix 6  Pre-Injection Procedures for All Patients ..................................100 
Appendix 7  Preparation and Administration of Lampalizumab Injection ......102 
Appendix 8  Preparation and Administration of Sham Injection ....................105 
Appendix 9  Post-Injection Procedures for All Patients 
.................................106 
Appendix 10  Best Corrected Visual Acuity Testing........................................107 
Appendix 11  Color Fundus Photography .......................................................108 
Appendix 12  Fluorescein Angiography ..........................................................109 
Appendix 13  Fundus Autofluorescence .........................................................110 
Appendix 14  Near-Infrared Imaging...............................................................111 
Appendix 15  Biological Sample Collection and Shipping Instructions............112 
Appendix 16  The cobas® CFI Profile Clinical Trial Assay (CTA)...................113 


 
Lampalizumab—Genentech, Inc. 
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PROTOCOL AMENDMENT ACCEPTANCE FORM 
TITLE: 
A PHASE II, MULTICENTER, RANDOMIZED, 
SINGLE-MASKED, SHAM 
INJECTION-CONTROLLED EXPOSURE-RESPONSE 
STUDY OF LAMPALIZUMAB INTRAVITREAL 
INJECTIONS ADMINISTERED EVERY TWO WEEKS 
OR EVERY FOUR WEEKS TO PATIENTS WITH 
GEOGRAPHIC ATROPHY 
PROTOCOL NUMBER:  GX29455 
VERSION NUMBER:  
3 
EUDRACT NUMBER:  Not applicable 
IND NUMBER:  
104996 
TEST PRODUCT:  
Lampalizumab 
MEDICAL MONITOR: 
, M.D. 
SPONSOR: 
Genentech, Inc. 
 
I agree to conduct the study in accordance with the current protocol. 
  
   
 
Principal Investigator’s Name  (print) 
  
 
 
  
 
Principal Investigator’s Signature 
   
Date 
Please return the signed copy of this form as instructed by your study monitor or the 
Sponsor. Please retain the original of this document in your study files. 
  


 
Lampalizumab—Genentech, Inc. 
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PROTOCOL SYNOPSIS 
TITLE: 
A PHASE II, MULTICENTER, RANDOMIZED, SINGLE-MASKED, 
SHAM INJECTION-CONTROLLED EXPOSURE-RESPONSE 
STUDY OF LAMPALIZUMAB INTRAVITREAL INJECTIONS 
ADMINISTERED EVERY TWO WEEKS OR EVERY FOUR WEEKS 
TO PATIENTS WITH GEOGRAPHIC ATROPHY 
PROTOCOL NUMBER:  GX29455 
VERSION NUMBER:  
3 
EUDRACT NUMBER:  
Not applicable 
IND NUMBER:  
104996 
TEST PRODUCT:  
Lampalizumab 
PHASE: 
II 
INDICATION:  
Geographic atrophy secondary to age-related macular degeneration 
SPONSOR: 
Genentech, Inc. 
 
Objectives 
Primary Objective 
The primary objective for this study is as follows: 
•   To investigate exposure-response of lampalizumab administered intravitreally every 
2 weeks (Q2W) or 4 weeks (Q4W) compared with sham control in complement factor I (CFI) 
profile biomarker-positive geographic atrophy (GA) patients; treatment response will be 
measured as change in GA area by FAF (fundus autofluorescence) 
Secondary Objectives 
The secondary objectives for this study are as follows: 
•   To characterize the serum pharmacokinetics of lampalizumab following multiple Q2W and 
Q4W intravitreal doses 
•   To characterize systemic immunogenicity of lampalizumab following multiple Q2W and 
Q4W intravitreal doses 
•   To evaluate the ocular and systemic safety of lampalizumab Q2W and Q4W intravitreal 
doses compared with sham control 
Exploratory Objectives  
The exploratory objectives for this study are as follows: 
•   To evaluate the pharmacokinetic-pharmacodynamic (PK−PD) relationship of lampalizumab 
in aqueous humor samples  
•   To evaluate the potential association of genetic variants in CFI, complement-pathway genes, 
and age related macular degeneration (AMD) associated genes with disease characteristics 
and response to administration of lampalizumab 
Study Design 
Description of Study  
The GX29455 Phase II is a multicenter, randomized, single-masked, sham injection- controlled 
study of the exposure-response and safety of lampalizumab administered intravitreally Q2W or 
Q4W for 24 weeks to CFI profile biomarker-positive patients with GA secondary to AMD.  Profile 


 
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biomarker-positive patients will be determined by the investigational cobas® CFI Profile Clinical 
Trial Assay (CTA).  All outcome measures will be evaluated at 24 weeks.  A Q2W safety run-in 
assessment will precede the randomized study.  Approximately 90 patients will be enrolled at an 
estimated 25−30 study sites in the United States. 
Number of Patients 
Approximately 90 patients will be enrolled. 
Target Population 
Inclusion Criteria 
Patients must meet the following criteria for study entry: 
General Inclusion Criteria 
•   Willingness to provide signed Informed Consent and Health Insurance Portability and 
Accountability Act authorization  
•  Age ≥ 60 years 
•   CFI profile biomarker−positive result  
•   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 postmenarchial, has not 
reached postmenopausal state (≥12 months of amenorrhea with no identified cause other 
than menopause), and has not undergone surgical sterilization (absence of ovaries and/or 
uterus). 
Examples of contraceptive methods with a failure rate of <1% per year include bilateral 
tubal ligation, male sterilization, established, proper use of hormonal contraceptives that 
inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. 
The reliability of sexual abstinence should be evaluated in relation to the duration of the 
clinical trial and the preferred and usual lifestyle of the patient.  Periodic abstinence 
(e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are 
not acceptable methods of contraception. 
•  For men:  agreement to remain abstinent 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. 
•   Ability and willingness to undertake all scheduled visits and assessments 
Ocular Inclusion Criteria:  Study Eye 
•   Best Corrected Visual Acuity (BCVA) Early Treatment of Diabetic Retinopathy Study 
(ETDRS) 
For the safety run-in assessment:  BCVA of 20/80 to 20/400 inclusive (Snellen equivalent) 
using ETDRS charts  
For the randomized study:  BCVA of 20/50 to 20/400 inclusive (Snellen equivalent) using 
ETDRS charts 
•   Well demarcated area of GA secondary to AMD 
•   GA must be ≥ 1 disc area (DA) (2.54 mm
2) in the absence of CNV 
•  If GA is multifocal, at least one focal lesion must be ≥ 0.5 DA (1.27 mm2) 
•   The total lesion size must be
 ≤
 to 7 DA (17.78 mm
2) and must reside completely within the 
FAF imaging field 
•   Presence of hyperautofluorescence adjacent to the area of GA (banded or diffuse 
perilesional FAF patterns) 


 
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•   Sufficiently clear ocular media, adequate pupillary dilation, and fixation to permit quality 
fundus imaging 
Ocular Inclusion Criteria:  Fellow (Non-Study) Eye 
•   GA secondary to AMD in the absence of prior or active CNV 
 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from study entry 
Ocular Exclusion Criteria:  Geographic Atrophy Characteristics 
•   GA in the study eye that extends beyond FAF imaging field or fails to meet single or 
multifocal lesion criteria 
•   Absence or minimal hyperfluorescence adjacent to GA in the study eye (e.g., focal or no 
perilesional FAF pattern) 
•   GA in either eye due to causes other than AMD (e.g., Stargardt disease, cone-rod 
dystrophy, chloroquine/hydroxychloroquine toxicity) 
Ocular Exclusion Criteria:  Study Eye 
•   History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD  
•   Previous subfoveal focal laser photocoagulation 
•  Laser photocoagulation (juxtafoveal or extrafoveal)  
•   Prior treatment with Visudyne
®, external-beam radiation therapy, or transpupillary 
thermotherapy  
•  Previous intravitreal drug delivery (e.g., intravitreal corticosteroid injection, anti-angiogenic 
drugs, anti-complement agents, biodegradable/non-biodegradable implants or formulations, 
device implant, or encapsulated cell technology).  NOTE:  A single intraoperative 
administration of a corticosteroid during cataract surgery for cystoid macular edema 
prophylaxis at least 3 months prior to screening is permitted. 
•   Previous cell-based (e.g., regenerative or trophic) intraocular treatment 
•   RPE tear involving the macula 
•   History of retinal tear.  NOTE: a retinal tear adequately treated with laser 
photocoagulation and determined to be stable by investigator may be permitted after 
consultation with and approval by the Medical Monitor. 
•   Any concurrent ocular or intraocular condition (e.g., cataract or epiretinal membrane) that, 
in the opinion of the investigator, could do either of the following: 
•   Require medical or surgical intervention during the study period to prevent or treat vision 
loss that might result from that condition; or 
•  If allowed to progress untreated, could likely contribute to loss of at least 2 Snellen 
equivalent lines of BCVA during the study period 
•   Active vitreous hemorrhage 
•   History of retinal detachment or macular hole (Stage 3 or 4) 
•   Aphakia or absence of the posterior capsule 
•   Previous violation of the posterior capsule is also excluded unless it occurred as a result of 
yttrium aluminum garnet (YAG) laser posterior capsulotomy in association with prior 
posterior chamber intraocular lens implantation 
•   Spherical equivalent of the refractive error demonstrating more than 8 diopters of myopia 
•   For patients who have undergone prior refractive or cataract surgery, the preoperative 
refractive error in the study eye should not have exceeded 8 diopters of myopia 
•  Intraocular surgery (including cataract surgery) within 3 months preceding Day 1 
•   Glaucoma that is uncontrolled (defined as IOP ≥ 30 mmHg despite treatment with 
anti-glaucoma medication) 
•   History of glaucoma-filtering surgery 


 
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•   History of corneal transplant 
Ocular Exclusion Criteria:  Either Eye 
•  Proliferative diabetic retinopathy. NOTE:  mild non-proliferative diabetic retinopathy 
(occasional hemorrhage or microaneurysm) in either eye may be permitted after 
consultation with and approval by the Medical Monitor; moreover, a patient with onset of 
mild non-proliferative diabetic retinopathy in either eye during study participation may 
be permitted to continue study treatment after consultation with the Medical Monitor. 
•   Active or history of neovascular (wet) AMD 
•   History of idiopathic or autoimmune-associated uveitis 
•   Active uveitis and/or vitritis (see definitions and grading scales for iritis/anterior uveitis and 
vitritis in the full protocol)  
•   History of ocular or intraocular conditions that contraindicate the use of an investigational 
drug or may affect interpretation of study results or my render the patient at high risk for 
treatment complications 
•   Previous participation in other studies of investigational drugs (excluding vitamin and 
mineral supplements; topical ocular agents ≥ 3 months preceding Day 1 may be permitted 
after consultation with and approval by the Medical Monitor) 
•   Previous systemic treatment with a complement inhibitor 
•   Previous treatment with inhibitors/modulators of the visual cycle (e.g., fenretinide) 
•   Previous expression vector mediated intraocular treatments  
•   Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis  
•   History of infectious or inflammatory ocular disease 
Systemic Exclusion Criteria:  Concurrent Conditions 
•   Uncontrolled blood pressure (defined as systolic
 >
 180 mmHg and/or diastolic > 110 mmHg 
while patient is sitting) 
If a patient’s initial measurement exceeds these values, a second reading may be taken 
30 or more minutes later.  If the patient’s blood pressure must be controlled by 
antihypertensive medication, the patient can become eligible if medication is taken 
continuously for at least 30 days prior to Day 1. 
•   Atrial fibrillation not managed by medication/cardioversion and the patient is under the care 
of a primary care physician or cardiologist 
•   Medical conditions that may be associated with a clinically significant risk for bleeding 
•   Active or history of other disease, metabolic dysfunction, physical examination finding, or 
clinical laboratory finding giving reasonable suspicion of a disease or condition that 
contraindicates the use 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 
•   Treatment for an active localized or systemic infection 
Ongoing prophylactic use of antimicrobial therapy should be discussed with and approved 
by the Medical Monitor. 
•   Predisposition or history of increased risk for infection 
•   Active malignancy within the previous 12 months except for appropriately treated 
carcinoma in situ of the cervix, resolved non-melanoma skin carcinoma, and prostate 
cancer with a Gleason score of ≤ 6 and a stable prostate-specific antigen (PSA) 
for ≥12 months. 
•   History of allergy to fluorescein, not amenable to treatment 
•  History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known 
hypersensitivity to any component of the lampalizumab injection 
•  Inability to obtain FAF or near infrared images, fundus photographs, or fluorescein 
angiograms of sufficient quality to be analyzed and graded by the central reading center  


 
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•  Inability to comply with study or follow-up procedures 
•   Requirement for continuous use of any medications/treatments indicated in the “Prohibited 
Therapy” section of the protocol 
•   Women who are pregnant or lactating or intending to become pregnant during the study 
•   Woman of childbearing potential must have a negative serum pregnancy test result within 
28 days prior to initiation of study treatment 
Length of Study 
The approximate length of study is 24 weeks, not including the screening period. 
End of Study 
The end of the study is defined as the date when the last patient, last visit (LPLV) occurs.  
The LPLV is expected approximately 24 weeks after the last patient is randomized to the study. 
Outcome Measures 
Primary Efficacy Outcome Measures 
The primary efficacy outcome measure for this study is as follows: 
•   Mean change in GA area from baseline to Week 24 as measured by FAF 
Safety Outcome Measures 
The safety outcome measures for this study are as follows: 
•   The incidence of DLTs for Q2W multidose safety run-in assessment  
•  Incidence and severity of ocular and non-ocular (systemic) adverse events 
•   Mean change in BCVA from baseline to Week 24 using the Early Treatment of Diabetic 
Retinopathy Study (ETDRS) visual acuity chart 
•   The incidence of changes and abnormalities in clinical ocular examinations  
•   The incidence of changes and abnormalities in clinical laboratory assessments  
•   The incidence of positive serum antibodies to lampalizumab 
Pharmacokinetic Outcome Measures 
The PK profile from the serum concentration−time data following administration of 
lampalizumab will be determined.  Derived PK parameters may include the following: 
•   Maximum observed serum concentration (C
max) 
•   Time of maximum observed serum concentration (t
max) 
•   Observed steady-state trough concentration 
•   Accumulation ratio based on trough concentration 
Optional anterior chamber (aqueous humor) paracentesis samples will be collected to assess 
PK and PD relationships.  Additional PK analyses may be conducted as appropriate. 
Exploratory Outcome Measures 
The exploratory outcome measures for this study include the following: 
•   PK−PD relationship of lampalizumab in aqueous humor samples  
•   Evaluation of potential associations of genetic variants in CFI, complement-pathway genes, 
and AMD-associated genes with disease characteristics and response to administration of 
lampalizumab  
Investigational Medicinal Products 
Lampalizumab 
Lampalizumab Drug Product is provided as a sterile, white to off-white, lyophilized powder in a 
6-cc USP/European Pharmacopoeia Type 1 glass vial and is intended for intravitreal 
administration.  Each glass vial contains a nominal 40 mg of lampalizumab.  After reconstitution 
with Sterile Water for Injection, the Drug Product is formulated as 100 mg/mL lampalizumab in 
40 mM L-histidine hydrochloride, 28 mM sodium chloride, 160 mM sucrose, 0.04% (w/v) 
polysorbate 20, pH 5.3. 


 
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Lampalizumab Intravitreal Injections 
A 10-mg dose of lampalizumab will be used in this study and will be administered to patients 
randomized to lampalizumab treatment arms intravitreally Q2W or Q4W during the 24-week 
treatment period. 
Comparator 
Sham vials will be identical to vials of lampalizumab, but the sham vials will be empty. 
A sham injection is a procedure that mimics an intravitreal injection of lampalizumab, except 
that the blunt end of an empty syringe is pressed against an anesthetized eye instead of a 
needle attached to a lampalizumab-filled syringe.  Patients randomized to the control arms will 
receive sham injections Q2W or Q4W during the 24-week treatment period and will undergo the 
same assessments as the lampalizumab treatment arms. 
Non-Investigational Medicinal Products 
None. 
Statistical Methods 
Primary Analysis 
Primary efficacy analyses will include all randomized patients with at least one post-baseline GA 
area measurement by FAF.  Patients will be grouped according to the treatment assigned at 
randomization.  Safety analyses will include all randomized patients who receive at least one 
dose of study treatment, with patients grouped according to the treatment actually received.  
Patients in the sham Q2W and sham Q4W groups will be pooled in the analyses. 
The analysis of data for the 24-week treatment period will be performed when all randomized 
patients have either completed the 24-week treatment period or have discontinued from the 
study prior to Week 24, and all data from this period are in the database and have been cleaned 
and verified.   
Determination of Sample Size   
The GX29455 study is designed to evaluate the efficacy of lampalizumab administered 
intravitreally Q2W and Q4W to CFI profile biomarker-positive GA patients.  The focus of the 
efficacy outcome analyses will be on estimation of the magnitude of the treatment effect.   
The primary efficacy endpoint is the mean change in GA area from baseline to Week 24.  
The sample size was selected to provide adequate precision for the estimation of the treatment 
effect with respect to the primary endpoint.  A total of approximately 90 patients will be enrolled 
in the study including the run-in and randomized components. 
Approximately 84 patients will be randomized in a 3:1:2:1 ratio to one of four treatment groups:  
lampalizumab Q2W, sham Q2W, lampalizumab Q4W, or sham Q4W.  With the assumption of a 
15% drop-out rate by Week 24 and a standard deviation of 0.85 mm2  for the change in GA area 
from baseline to Week 24 (estimated from the CFD4870g Phase II study with lampalizumab in 
GA),  the 80% CI for the estimated difference in treatment effect for select hypothetical 
scenarios are presented in the full protocol.  Assuming a GA area measurement error 
of 
 ±
  0.043 mm
2 (from CFD4870g image center technical report), the proposed sample size is 
considered sufficient for differentiating the treatment effect between lampalizumab Q2W and 
lampalizumab Q4W groups if the observed difference is 0.290 mm
2 (20% relative to sham) or 
larger. 
These calculations are based on the following assumptions: 
The standard deviation of the change in GA area from baseline to Week 24 is 0.85 mm2.  
The drop-out rate is 15% by Week 24 (estimated from the CFD4870g Phase II study with 
lampalizumab in GA). 


 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
ACP 
alternative complement pathway 
AE 
adverse event 
ALT 
alanine transaminase 
AMD 
age-related macular degeneration 
AST 
aspartate transaminase 
ATA 
anti-therapeutic antibody 
BCVA 
best corrected visual acuity 
C3 
complement component 
Cmax 
maximum observed serum concentration 
CFB 
complement factor B 
CFD 
complement factor D 
CFH 
complement factor H 
CFI 
complement factor I 
CFP 
color fundus photograph 
CNV 
choroidal neovascularization 
CRO 
contract research organization 
CTA 
Clinical Trial Assay 
DA 
disc area 
DLT 
dose-limiting toxicity 
ETDRS 
Early Treatment of Diabetic Retinopathy Study 
EC 
Ethics Committee 
eCRF 
electronic Case Report Form 
ECG 
electrocardiogram 
FAM 
Fundus Autofluorescence in Age-Related Macular 
Degeneration 
EDC 
electronic data capture 
FA 
fluorescein angiography 
FAF 
fundus autofluorescence 
FDA 
U.S. Food and Drug Administration 
 


 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS (cont.) 
Abbreviation 
Definition 
GA 
geographic atrophy 
HIPAA 
Health Insurance Portability and Accountability Act 
ICH 
International Conference on Harmonisation 
IMP 
investigational medicinal product 
IND 
Investigational New Drug 
IOP 
intraocular pressure 
IRB 
Institutional Review Board 
IxRS 
interactive voice and Web response system 
LPLV 
last patient, last visit 
MTD 
maximum tolerated dose 
NI 
near-infrared 
PCR 
polymerase chain reaction 
PD 
pharmacodynamic 
PK 
pharmacokinetic 
Q2W 
every 2 weeks 
Q4W 
every 4 weeks 
RCR 
Roche Clinical Repository 
RPE 
retinal pigment epithelium 
SAE 
serious adverse event 
SNP 
single−nucleotide polymorphisms 
Tmax 
time to maximum concentration 
ULN 
upper limit of normal 
USP 
United States Pharmacopeia 
VA 
visual acuity 
VEGF 
vascular endothelial growth factor 
YAG 
yttrium aluminum garnet 


 
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1.   
BACKGROUND 
1.1   
BACKGROUND ON GEOGRAPHIC ATROPHY  
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in 
industrial countries (Lim et al. 2012).  Advanced AMD has been classified into two 
clinical forms:  geographic atrophy (GA) characterized by loss of the choriocapillaris, 
retinal pigment epithelium (RPE) and photoreceptors, and exudative AMD characterized 
by choroidal neovascularization (CNV) (Holz et al. 2014a).  The majority of severe vision 
loss in advanced disease has been associated with neovascular AMD; however, with 
available treatments for this form of AMD, visual impairment related to GA is increasing 
relative to neovascular AMD.  GA represents a significant unmet medical need; there are 
no approved or efficacious treatments to prevent the onset or progression of this form of 
advanced AMD and associated visual loss.  
1.2   
BACKGROUND ON LAMPALIZUMAB 
The pathogenesis of AMD is complex and remains to be established; however, genetics, 
hyperactivity of the alternative complement pathway (ACP), and environmental factors 
have been implicated in AMD pathophysiology (de Jong 2006; Loyet et al. 2012; 
Holz et al. 2014b).  Increased activation of the ACP has been found in drusen, a 
hallmark clinical observation associated with AMD.  Moreover, a role for ACP in AMD 
has been supported by human genetics (Yates et al. 2007; Scholl et al. 2008).  At 
present, the largest study evaluating AMD genetics is a meta-analysis with 17,000 AMD 
cases and >60,000 controls that identified multiple genetic risk loci, including four genes 
(complement factor H [CFH], complement factor B [CFB], complement factor I [CFI], and 
complement component [C3]) in the ACP (Fritsche et al. 2013). 
Complement factor D (CFD) is a highly specific chymotrypsin-like serine protease that 
plays a pivotal and rate-limiting role in the activation and amplification of the ACP 
(see Figure 1).  The substrate for CFD is another alternative pathway serine protease, 
factor B.  Following cleavage by CFD, CFB converts into the proteolytically active factor 
Bb and initiates the ACP. 


 
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Figure 1  Complement System Pathways and Site of Inhibition by 
Lampalizumab in the Alternative Complement Pathway 
 
CFD =
  complement factor D; MAC
 =
 membrane attack complex; MBL =
 mannose-binding lectin. 
 
Lampalizumab is an antigen-binding fragment of a humanized monoclonal antibody 
directed against CFD.  Lampalizumab inhibits CFD-mediated cleavage of CFB, 
preventing activation of the ACP.  Lampalizumab is specific for the ACP and shows no 
inhibitory effect on classic complement pathway activation.  By inhibiting ACP activity, 
lampalizumab may impede the progression of GA and vision 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 factor D 
(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). 


 
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See the Lampalizumab Investigator
's Brochure for additional details on nonclinical and 
clinical studies. 
1.3   
STUDY RATIONALE AND BENEFIT-RISK ASSESSMENT 
The Phase Ia (Study CFD4711g) and Phase Ib/II (Study CFD4870g) studies provided 
preliminary evidence of a positive benefit-risk profile for the use of lampalizumab in 
patients with GA secondary to AMD and support further evaluation of lampalizumab in 
this study. 
1.3.1   
Study CFD4711g:  Phase Ia 
Study CFD4711g was a Phase Ia, first-in-human study of lampalizumab; it was an 
open-label, multicenter, single-dose, dose-escalation study designed to investigate the 
safety, tolerability, pharmacokinetics, and immunogenicity of six dose levels (0.1, 0.5, 1, 
2, 5, and 10 mg) of lampalizumab administered as a single intravitreal injection to 
patients with GA (Do et al. 2014).  Determination of the maximum tolerated dose (MTD) 
of lampalizumab was also an objective of this study.  Study CFD4711g enrolled 
18 patients in the United States.  Lampalizumab was found to have an acceptable safety 
and tolerability profile at all six doses tested following a single intravitreal administration.  
The MTD for the study was considered to be 10 mg, the highest dose tested.  All 
enrolled patients completed the study. 
1.3.2   
Study CFD4870g:  Phase Ib/II 
1.3.2.1   
Phase Ib 
The Phase Ib portion of Study CFD4870g served as the initial assessment of the safety 
and tolerability of multiple, monthly, intravitreal administrations with the 10-mg dose of 
lampalizumab.  This safety run-in portion of Study CFD4870 was designed to obtain 
10 evaluable GA patients exposed to a minimum of 3 monthly doses of lampalizumab at 
10 mg to evaluate the safety and tolerability of lampalizumab administered by intravitreal 
injection prior to initiating the Phase II randomized component of this study.  At the 
safety hiatus assessment for the run-in portion of the Phase Ib component of 
Study CFD4870g, the 10-mg dose was found to be well tolerated following multiple, 
monthly, intravitreal injections, and these results enabled enrollment into the Phase II 
component of Study CFD4870g. 
1.3.2.2   
Phase II 
The Phase II component of Study CFD4870g was a multicenter, randomized, 
single-masked, sham injection−controlled study of the safety, tolerability, and efficacy 
of lampalizumab (10-mg dose) intravitreal injections administered monthly or every other 
month to patients with GA.  This study enrolled 129 patients at 26 sites in the 
United States and 6 sites in Germany. 
Preliminary clinical evidence of lampalizumab’s efficacy was demonstrated in the 
Phase II component of Study CFD4870g.  The Phase II met its primary endpoint of 
mean change from baseline in GA area at 18 months as measured by fundus 


 
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autofluorescence (FAF) and met its secondary endpoint of mean change from baseline 
in GA area at 18 months as assessed by color fundus photographs (CFPs) in the 
lampalizumab monthly group.  A positive treatment effect in slowing the progression of 
GA area growth was observed in the monthly group beginning at 6 months and 
extending through the study duration of 18 months.  The mean difference in GA area 
between the monthly lampalizumab group compared with the pooled sham group at 
Month 18 was 0.595 mm2 (80% CI: 0.109, 1.081; p
 =
 0.1170, less than the prespecified 
type I error rate of 0.2).  This difference corresponds to a reduction in GA area of 20.4% 
(80% CI: 4%, 37%) with monthly lampalizumab treatment; the reduction in GA area was 
calculated as 100%
 ×
 [(mean GA area change in pooled sham − mean GA area change 
in lampalizumab)/mean GA area change in pooled sham]. 
The Phase II results demonstrated a clinically meaningful and statistically significant 
effect of lampalizumab administered monthly on reducing GA area growth over the 
18-month study treatment period.  There was no apparent treatment benefit observed in 
the lampalizumab every-other-month all-comer treatment group. 
Results from Study CFD4870g demonstrated an acceptable safety and tolerability profile 
with lampalizumab administered as 10-mg intravitreal injections monthly or every other 
month over 18 months. 
Exploratory Genetic Analysis Using Four Single- Nucleotide 
Polymorphisms in the Alternative Complement Pathway 
Although AMD risk may involve multiple factors, it is well accepted that there is a strong 
genetic contribution.  The largest study evaluating AMD genetics to date, a 
meta-analysis, identified AMD-associated single−nucleotide polymorphisms (SNPs) at 
multiple genetic loci, including five genes (CFH, CFB, CFI, C2, and C3) in the 
complement pathway (Fritsche et al. 2013).  With the exception of C2, all of these 
proteins are associated with the ACP.  The strong correlation of genetic variants in the 
ACP with the risk of AMD led to the hypothesis that patients with GA and with 
risk-associated variants at the ACP loci may have higher basal ACP complement 
activation and may derive greater potential treatment benefit from inhibition of the ACP 
with lampalizumab. 
Four SNPs representing CFH, C2/CFB, C3, and CFI were selected and individually 
tested for an association with the observed efficacy of lampalizumab and for an 
association with the rate of GA progression in patients in the sham treatment group.  
The most statistically significant AMD risk SNPs in these ACP genes were chosen on 
the basis of a previously reported genomewide meta-analysis (Fritsche et al. 2013).  C2 
and CFB are tightly linked genetically and are represented by a single risk SNP.  
Patients who were heterozygous or homozygous for the risk alleles were grouped 
together for this analysis and were referred to as risk allele carriers.  In patients who had 
genetic testing performed in the Phase II component of Study CFD4870g, approximately 


 
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96%, 98%, 47%, and 57% were carriers of CFH, C2/CFB, C3, and CFI risk alleles, 
respectively. 
Phase II Exploratory Analyses with CFH, C2/CFB, C3, and CFI 
Single−Nucleotide Polymorphisms 
Because very few patients in Study CFD4870g were non-carriers of the risk alleles for 
CFH and C2/CFB, these two SNPs could not be evaluated for an association with 
treatment response or for the rate of GA progression in patients receiving sham 
treatment. 
Exploratory analysis of the C3 SNP did not show a significant association with treatment 
response or with the GA area progression in patients receiving sham treatment. 
Exploratory analysis of the CFI SNPs indicated that there was greater efficacy in the 
subgroup of patients who were carriers of the CFI risk allele compared with patients who 
were non-carriers of the CFI risk allele.  In CFI risk allele carriers, the mean difference in 
GA growth between the monthly group and the sham group at Month 18 was 1.839 mm2, 
corresponding to a reduction in GA area of 44% (approximately 80% CI: 25%, 63%; 
p
 =
 0.0037).  In CFI risk allele carriers, the mean difference in GA growth between the 
every-other-month group and the sham group at Month 18 was 0.734 mm2, 
corresponding to a reduction in GA area of 18% (approximately 80% CI: − 1%, 36%; 
p
 =
 0.2266).  In non-carriers of the CFI risk allele, there was no apparent lampalizumab 
treatment response in either the monthly or every-other-month group. 
The prognostic effects of the CFI risk allele were also examined.  In patients in the 
sham group, the change in GA area at Month 18 was 4.169 mm2 (80% CI: 3.582, 4.756) 
in CFI risk allele carriers and 2.792 mm
2 (80% CI: 2.293, 3.292) in non-carriers of the 
CFI risk allele; the difference in the GA progression between CFI risk allele carriers and 
non-carriers at Month 18 was approximately 49%. 
The results from the exploratory analysis suggest that the CFI risk allele may be both 
prognostic for more rapid progression of GA and predictive for treatment response to 
lampalizumab. 
Definition of Complement Factor I Profile Biomarker 
CFI profile biomarker-positive is defined as risk allele carriers of CFI that are also risk 
allele carriers at CFH and/or C2/CFB, and CFI profile biomarker-negative is defined as 
non-carriers of the CFI risk allele or carriers of the CFI risk allele who are non-carriers of 
the risk alleles at both CFH and C2/CFB (see Table 1).  The CFI profile biomarker was 
defined using these three risk alleles on the basis of the association of the CFI risk allele 
with lampalizumab response, the high frequency of risk alleles at CFH and C2/CFB in 
Study CFD4870g, and the fact that the CFH and C2/CFB SNPs are highly significant in 
genomewide studies of AMD genetic risk (p
 =
 1
 ×
 10434 and p
 =
 4
 ×
 1089, respectively 
[Fritsche et al. 2013]).  The inclusion of CFH and C2/CFB genotypes in the definition of 


 
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CFI profile biomarker-positive is intended to increase the likelihood of identifying patients 
with complement-driven GA disease.  Of note, all CFI risk allele carriers in 
Study CFD4870g were also risk allele carriers at CFH and/or C2/CFB. 
Table 1   Definition of Biomarker Status Using the CFI Profile Test  
 
CFI 
CFH 
C2/CFB 
CFI profile 
biomarker-positive 
+ 
+ 
+ 
 
+ 
+ 
− 
 
+ 
− 
+ 
CFI profile 
biomarker-negative 
+ 
− 
− 
 
− 
+ 
+ 
 
− 
+ 
− 
 
− 
− 
+ 
 
− 
− 
− 
Note:   “+” indicates that the patient is a risk allele carrier (i.e., heterozygous or 
homozygous for the risk allele) and “−” indicates that the patient is a non-carrier of 
the risk allele. 
 
1.3.3   
Study GX28198:  Open-Label Extension 
Study GX28198 is an ongoing, multicenter, open-label extension study of the safety and 
tolerability of lampalizumab administered by intravitreal injection to eligible patients with 
GA who have completed the 18-month treatment in Study CFD4870g.   
For additional details on nonclinical and clinical studies, see the current Lampalizumab 
Investigator’s Brochure. 
1.3.4   
Rationale for Study GX29455 
Study CFD4870g Phase II results provided evidence that ACP inhibition with 
lampalizumab may reduce the progression of GA; moreover, lampalizumab administered 
as 10-mg intravitreal injections monthly over 18 months demonstrated an acceptable 
safety and tolerability profile in patients with GA secondary to AMD.   
Exploratory genetic analyses from the Phase II Study CFD4870g suggest that in a 
biomarker-defined population (CFI profile biomarker-positive), GA lesions may progress 
more rapidly and potentially derive greater treatment benefit from lampalizumab than in 
patients negative for the biomarker (CFI profile biomarker-negative).  On the basis of the 
preclinical Study 09-1554 and CFD4870g Phase II results, Study GX29455 will further 
investigate the exposure-response and safety of lampalizumab in the CFI profile 
biomarker-positive patient population over multiple intravitreal injections and dose 
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2.   
OBJECTIVES 
2.1   
PRIMARY OBJECTIVE 
The primary efficacy objective for this study is as follows: 
•   To investigate exposure-response of lampalizumab administered intravitreally every 
2 weeks (Q2W) or 4 weeks (Q4W) compared with sham control in CFI profile 
biomarker-positive GA patients; treatment response will be measured as change in 
GA area by FAF 
 
2.2   
SECONDARY OBJECTIVES 
The secondary objectives for this study are as follows: 
•   To characterize the serum pharmacokinetics of lampalizumab following multiple 
Q2W and Q4W intravitreal doses 
•   To characterize systemic immunogenicity of lampalizumab following multiple Q2W 
and Q4W intravitreal doses 
•   To evaluate the ocular and systemic safety of lampalizumab Q2W and Q4W 
intravitreal doses compared with sham control 
 
2.3   
EXPLORATORY OBJECTIVES 
•   To evaluate the pharmacokinetic-pharmacodynamic (PK−PD) relationship of 
lampalizumab in aqueous humor samples  
•   To evaluate the potential association of genetic variants in CFI, 
complement-pathway genes, and AMD−associated genes with disease 
characteristics and response to administration of lampalizumab 
 
3.   
STUDY DESIGN 
The GX29455 Phase II is a multicenter, randomized, single-masked, sham 
injection-controlled study of the exposure-response and safety of lampalizumab 
administered intravitreally Q2W or Q4W for 24 weeks to CFI profile biomarker-positive 
patients with GA secondary to AMD.  Profile biomarker-positive patients will be 
determined by the investigational cobas® CFI Profile Clinical Trial Assay (CTA).  
All outcome measures will be evaluated at 24 weeks.  A Q2W safety run-in assessment 
will precede the randomized study.  Approximately 90 patients will be enrolled at an 
estimated 25−30 study sites in the United States. 
3.1   
DESCRIPTION OF STUDY 
3.1.1   
Safety Run-In Assessment 
A safety run-in assessment with multiple 10-mg intravitreal administrations of 
lampalizumab at the Q2W frequency will be conducted at approximately 10 sites prior to 
initiating enrollment in the randomized study.  This assessment is being performed to 
obtain an initial evaluation of the safety and tolerability of Q2W dosing.  All patients in 
the safety run-in assessment will receive lampalizumab Q2W to obtain safety data from 


 
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3 evaluable patients (defined as a patient who has received ≥
 3 study drug injections).  
The safety run-in screening period is up to 21 days (Days−21 to−1), and the screening 
assessments may be completed over several separate days provided these days fall 
within the specified screening interval. Patient eligibility and enrollment for the safety 
run-in assessment will follow the same process and criteria described in Section 3.1.2 
for the randomized study, with the exception of best corrected visual acuity (BCVA) 
inclusion criteria, the option of manual enrollment without interactive voice and Web 
response system (IxRS), and the option of receiving patient biomarker qualifying status 
directly from the laboratory versus contacting IxRS. 
The safety run-in assessment will be open label; all patients will receive study drug.  
Each patient will receive study drug injection on Day 1 and will be contacted by study 
site personnel on Day 2 and Day 8 (±
 2 days) after each injection to elicit reports of any 
decrease in vision, eye pain, unusual redness, or any other new ocular signs or 
symptoms in the study eye (see Appendix 1).  If warranted, patients will be asked to 
return to the clinic for an unscheduled safety assessment visit (see Appendix 4).  
All safety run-in patients will also return for safety assessment visits every 2 weeks 
(±
 2 days).  After the third evaluable patient completes the Week 6 (±
 2 days) visit 
following the previous third study drug administration, a hiatus in treatment of 
approximately 3 days will ensue.  During the hiatus, the Genentech Safety Review 
Committee (which consists of the Medical Monitor, Drug Safety Scientist, and 
Biostatistician) will review the safety results for the run-in assessment.  If the results 
show acceptable safety in accordance with the dose-limiting toxicity (DLT) criteria (see 
Section 3.1.1.1), subsequently, the randomized study will be initiated. 
Following the hiatus assessment and an initial acceptable safety profile for the Q2W 
dosing frequency, patients who participate in the safety run-in assessment will continue 
on the Q2W open-label study drug administration for the remainder of the 24-week 
treatment course, and study visit frequency and assessments will follow the same 
regimen as that of the Q2W arm of the randomized study (see Appendix 2).  These 
patients will receive a maximum of 12 study drug treatments during the study. 
Missed doses will not be replaced. 
A schedule of assessments is provided in Appendix 1 and Appendix 2. 
  
3.1.1.1   
Dose-Limiting Toxicities Criteria for the Safety Run-In 
Assessment 
If
 ≥
 2 patients experience the same DLT during the safety run-in assessment, all patients 
in that cohort will be discontinued from the study and follow the early termination process, 
and the study will be terminated.  If a single DLT occurs during the safety run-in, the 
cohort will be expanded to obtain 3 additional patients. If ≥
 1 of the patients in the 
expanded cohort experiences a DLT, all patients will be discontinued from the study and 
follow the early termination process, and the study will be terminated.  Successful 


 
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completion of the safety run-in will be required to subsequently initiate the randomized 
study. 
3.1.1.2   
Dose-Limiting Toxicities for the Safety Run-In Assessment 
DLTs are any of the following adverse events that occur during the safety run-in 
assessment period and are believed by the investigator or the Sponsor to be study drug 
related: 
•   Intraocular inflammation (e.g., iritis, uveitis, or vitritis) defined as a change of two 
units on standard grading scales (see Appendix 5) after the study drug injection.  
In accordance with this definition, study exclusion criteria establish a baseline grade 
of 0, and an increase to 2
 + or greater would constitute a DLT.  Intraocular 
inflammation of Grade 4
 ± would be considered a major toxicity requiring interruption 
of enrollment and further evaluation by the internal Safety Review Committee to 
determine whether further enrollment/treatment is appropriate. 
•   Endophthalmitis secondary to an encapsulated bacteria (i.e., Streptococcus 
pneumonia, Haemophilus influenza,or Neisseria meningitidis) 
•   Sustained elevation of intraocular pressure (IOP), defined as a measurement of 
≥
 30 mmHg on three consecutive study treatment visits 
•   Sustained loss of BCVA ≥
 15 letters after the study drug injection that is not 
attributable to the injection procedure, progression of GA, or change in the ocular 
media (i.e., cornea, aqueous humor, lens, vitreous humor) as measured on the 
three consecutive study treatment visits 
3.1.1.3   
Dose-Limiting Toxicity Assessments Window for the Safety 
Run-In 
The safety run-in patients will be assessed for DLTs every 2 weeks (± 2 days) after each 
study drug injection or during unscheduled visits, if prompted by the Day 2 or Day 8 
follow-up calls.  This regimen will continue for all safety run-in patients until the third 
evaluable patient receives the third study drug injection and completes the Week 6 
(± 2 days) visit. 
3.1.2   
Four-Arm, Randomized Study 
An estimated 25−30 study sites in the United States will participate in the randomized 
study.  Approximately 84 CFI profile biomarker-positive patients with GA secondary to 
AMD will be enrolled.  Biomarker status will be determined using the investigational 
cobas® CFI Profile CTA that will be run at a designated study laboratory testing site. The 
study will consist of a screening period of up to 28 days (Days 
 −
 28 to 
 −
 1) and a 
treatment period of 24 weeks.   
A patient must satisfy all eligibility criteria at both the screening and the Day 1 visits, 
including receipt of all screening visit images by the central reading center.  Study sites 
will have to verify biomarker eligibility of a patient prior to the Day 1 visit by contacting 
IxRS.  


 
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Patients who failed screening for reasons other than CFI biomarker status (e.g., GA lesion size, 
BCVA, or prohibited concomitant medication) may be eligible for rescreening up to two 
additional times during the enrollment period of the study.  At rescreening, all screening visit 
assessments will be performed except CFI biomarker sample provided that a valid CFI result is 
available. 
Eligible patients will be enrolled on Day 1, the same day treatment is to be initiated, and 
randomized through an IxRS in a ratio of 3:1:2:1 so that approximately: 
•   36 patients will receive study drug injections Q2W and 12 patients will receive sham 
injections Q2W for 24 weeks of treatment (12 total treatments)  
•   24 patients will receive study drug injections Q4W and 12 patients will receive sham 
injections Q4W for 24 weeks (6 total treatments) 
For additional details on dosing schema for Q2W and Q4QW treatment arms, see  
Figure 2a and Figure 2b, respectively. 
Randomized patients will be stratified on the basis of baseline GA lesion size (<
 10 mm2 
versus ≥
 10 mm2) and baseline BCVA (better than/equal to 20/100 versus worse than 
20/100).  Sham arms will be pooled for analyses.  To obtain a similar distribution of 
patients in the randomized study with baseline BCVA better than/equal to 20/100 and 
worse than 20/100, a maximum of approximately 45 patients will be allotted to either of 
the baseline BCVA groups (i.e., better than/equal to 20/100 group or worse than 
20/100 group).  If the study enrolls the maximum allotted number of patients to either 
baseline BCVA group, additional screened patients who would have been enrolled in the 
baseline BCVA group that has been maximized will be screen-failed. 
Figure 2a Dosing Schema for Q2W Treatment Arms 
Day Visit  
Week Visit  
 
Treatment Arms 
1   
2  4  6  8  10  12  14  16  18  20  22  24 a 
n 
Lampalizumab b 
x 
x  x  x  x  x   x   x   x   x   x   x 
  −
     48
Sham c 
x 
x  x  x  x  x   x   x   x   x   x   x 
 −
    12 
Q2W =
 every 2 weeks. 
a  Study treatment is not administered at Week 24 visit (final visit). 
b  Q2W intravitreal injections of 10 mg lampalizumab.  
c  Q2W sham injections. 
 


 
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Figure 2b Dosing Schema for Q4W Treatment Arms 
Day Visit 
Week Visit  
 
Treatment Arms 
1   
4   8   12   16   20   24 a 
n 
Lampalizumab b  
x   
x   x   x   x   x 
 −
    24 
Sham c 
x   
x   x   x   x   x 
 −
    12 
Q4W =
 every 4 weeks. 
a  Study treatment is not administered at Week 24 visit (final visit). 
b Q4W intravitreal injections of 10 mg lampalizumab. 
c Q4W sham injections. 
 
Only one eye will be chosen as the study eye.  If both eyes are eligible, the eye with the 
worse visual function (as determined by the investigator and the patient) will be the study 
eye; if both eyes have the same visual function, the eye with the larger GA area will be 
selected as the study eye.  Investigators and other site staff members will not be masked 
to patient treatment assignment (drug vs. sham).  The BCVA examiner will be masked to 
the study eye and treatment assigned (drug vs. sham) and will perform only the BCVA 
assessment.  The BCVA examiner is not allowed to perform any other tasks involving 
direct patient care.  Patients will be masked to their treatment assignment (study drug vs. 
sham).  Randomized patients will receive the first study drug or sham treatment 
administered by the investigator on Day 1.  All patients will have scheduled safety and 
ocular assessment at the Q2W or Q4W treatment visits during the 24-week study 
(see Figure 2a and Figure 2b).  Safety assessments will be evaluated by the investigator 
prior to study drug or sham administration.  Missed doses will not be replaced.  Patients 
who are discontinued from study treatment prematurely will be discontinued from the 
study as well.  Patients withdrawn from the study prior to completion will be asked to 
return for an early termination visit 30 (+
 7) days following their last study treatment.  
The first study treatment will be administered on the same day as randomization (Day 1 visit).  If 
a site has an unexpected issue (e.g., the IxRS is not able to assign the study kit), with the Medical 
Monitor’s permission, the patient’s first study treatment may be administered within 1 working 
day after the Day 1 visit.  The following assessments will be repeated on the day of the study 
treatment:  BCVA, slit−lamp examination, indirect ophthalmoscopy, and pre- and post-treatment 
IOP measurement (recorded on Day 1 electronic Case Report Form (eCRF) and dated 
accordingly).  After the Day 1 visit, if a patient misses a study visit when ocular images are 
scheduled (see Appendix 1 ), the images must be obtained at the next scheduled visit.  
3.2   
END OF STUDY 
The end of the study is defined as the date when the last patient, last visit (LPLV) occurs.  
The LPLV is expected approximately 24 weeks after the last patient is randomized to the 
study. 


 
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3.3   
RATIONALE FOR STUDY DESIGN 
3.3.1   
Rationale for Lampalizumab Dose and Schedule 
To provide a more extensive characterization of lampalizumab in patients with GA 
secondary to AMD, Study GX29455 will further investigate the exposure-response 
relationship with a 10-mg dose of study drug administered intravitreally at Q2W and 
Q4W intervals.  The 10-mg monthly dosing regimen was found to be the most 
efficacious in the Phase II component of Study CFD4870g; moreover, the 10-mg dose 
was observed to have an acceptable safety profile in Study CFD4870g. Data to support 
the Q2W dosing frequency are provided by the preclinical cynomolgus monkey 
Study 09-1554.  For additional details on nonclinical and clinical studies, see the current 
Lampalizumab Investigator’s Brochure.   
3.3.2   
Rationale for Patient Population and Analysis Groups 
3.3.2.1   
Rationale for Evaluating Lampalizumab in Patients with 
Geographic Atrophy  
Currently, there are no approved treatments to prevent the progression of GA secondary 
to AMD and the associated decrease in visual function.  Consequently, a significant 
unmet medical need exists for treatment of this serious vision-impairing disease.  
Study GX29455 will enroll patients with the diagnosis of GA secondary to AMD.  On the 
basis of the results from Study CFD4870g, patients in Study GX29455 will be stratified 
by baseline GA lesion size and baseline BCVA.  Moreover, consistent with Study 
CFD4870g results, select clinical and genetic eligibility criteria have been chosen to 
enrich the Study GX29455 study population for patients at increased risk for rapid 
expansion of GA area to maximize the opportunity of detecting disease progression and 
treatment response over the planned 24-week study duration.  The select clinical 
eligibility criteria and rationale for these criteria are presented below. 
Presence of Hyperautofluorescence (i.e., Banded or Diffuse Junctional 
Fundus Autofluorescence Patterns) Adjacent to the Geographic Atrophy 
Lesion in the Study Eye 
Holz et al. (2007) previously described four major perilesional FAF patterns (none, focal, 
banded, and diffuse) that were correlated with the rate of GA lesion growth in the 
longitudinal natural history investigation of patients with GA secondary to AMD in the 
multicenter Fundus Autofluorescence in Age-Related Macular Degeneration 
(FAM)-study.  This study reported that GA lesions with banded or diffuse junctional 
patterns showed a significantly increased rate of GA lesion progression versus lesions 
with focal or no hyperautofluorescence patterns.  Moreover, approximately 70% of the 
FAM study patients exhibited banded or diffuse junctional perilesional FAF patterns. 
Geographic Atrophy in Both Study Eye and Non-Study (Fellow) Eye 
In patients with GA, bilateral disease represents the majority of the population 
(approximately 60%−67%) with this form of advanced AMD as reported in two 
natural history studies (Holz et al. 2007; Sunness et al. 2007); moreover, bilateral 


 
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GA has been associated with an increased rate of lesion progression compared 
with unilateral GA lesions (Sunness et al. 2007). 
Complement Factor I Profile Biomarker-Positive Selection 
Exploratory analyses of the Phase II CFD4870g study suggest that the CFI profile 
biomarker-positive population may progress more rapidly and have a significantly 
greater treatment benefit with lampalizumab than the CFI profile biomarker-negative 
population; therefore, the objectives of Study GX29455 will be investigated in CFI profile 
biomarker-positive patients.  Furthermore, based on the exploratory lampalizumab 
treatment results at 6 months in Study CFD4870g with the CFI biomarker-positive 
patient population, the objectives of Study GX29455 are expected to be completed in the 
proposed 24-week study.   
The cobas® CFI Profile Clinical Trial Assay 
A valid CFI biomarker result will be determined at a designated study laboratory testing 
site using the cobas CFI Profile CTA, which is a real-time polymerase chain reaction 
(PCR) test developed by Roche Molecular Systems to identify genotypes of three SNPs 
associated with CFH, CFI, and C2/CFB in DNA extracted from whole-blood samples 
from patients with GA secondary to AMD.  The cobas CFI Profile CTA is intended to be 
used as an Investigational Use Only assay to characterize the complement factor profile 
of study participants.  The cobas CFI Profile CTA biomarker status results will then be 
used to determine eligibility for enrollment. 
The cobas CFI Profile CTA consists of two kits and will use the cobas 4800 platform.  
The cobas DNA Sample Preparation Kit (DNA isolation kit) provides the necessary 
components to manually extract genomic DNA from whole blood samples.  The cobas 
CFI Profile CTA contains the necessary PCR master mix, oligonucleotides, cofactor, and 
controls to detect three SNPs associated with CFI, CFH, and C2/CFB. 
3.3.3   
Rationale for Control Group 
A sham control group will be used as a comparator for the exposure-response and 
safety of lampalizumab administered Q2W or Q4W.  Patients randomized to the sham 
control group will undergo the same assessments as patients randomized to the 
lampalizumab intravitreal injection groups. 
Sham injections, rather than placebo intravitreal injections, were selected to minimize 
the known risk of intravitreal injection-related adverse events (e.g., endophthalmitis), and 
no potential patient value would be derived from an intravitreal injection of placebo. 
3.3.4   
Rationale for Biomarker Assessments  
On the basis of the results of the Phase II Study CFD4870g, lampalizumab is 
hypothesized to be most effective in CFI Profile biomarker-positive patients.  To further 
assess the exposure-response of lampalizumab, Study GX29455 will enroll only CFI 
Profile−positive patients.  The response to lampalizumab treatment will be evaluated in a 


 
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prespecified population defined by the genetic biomarker test (cobas® CFI Profile CTA) 
on the basis of the common genetic variants of CFI, CFH, and C2/CFB.  The whole 
blood sample CFI profile results will be determined by utilizing an investigational cobas 
CFI Profile CTA (see Appendix 16).  Although the CFI profile test is based on the 
common genetic variants of CFI, CFH, and C2/CFB test, recent studies have identified 
rare variants in CFI that have been associated with increased AMD risk (van de Ven 
et al. 2013).  Given the potential for rare variants in CFI and other complement pathway 
genes to affect disease characteristics including progression and the response to 
lampalizumab treatment, additional exploratory genetic analysis may be conducted using 
the biomarker clinical genotyping sample including sequencing of CFI, other 
complement-pathway genes, and AMD associated genes.  
3.4   
OUTCOME MEASURES  
3.4.1   
Primary Efficacy Outcome Measures 
The primary efficacy outcome measure for this study is as follows: 
•   Mean change in GA area from baseline to Week 24 as measured by FAF 
3.4.2   
Safety Outcome Measures 
The safety outcome measures for this study are as follows: 
•   The incidence of DLTs for Q2W multidose safety run-in assessment  
•   Incidence and severity of ocular and non-ocular (systemic) adverse events 
•   Mean change in BCVA from baseline to Week 24 using the Early Treatment of 
Diabetic Retinopathy Study (ETDRS) visual acuity chart 
•   The incidence of changes and abnormalities in clinical ocular examinations  
•   The incidence of changes and abnormalities in clinical laboratory assessments  
•   The incidence of positive serum antibodies to lampalizumab 
 
3.4.3   
Pharmacokinetic Outcome Measures  
The PK profile from the serum concentration−time data following administration of 
lampalizumab will be determined.  Derived PK parameters may include the following: 
•   Maximum observed serum concentration (C
max) 
•   Time of maximum observed serum concentration (t
max) 
•   Observed steady-state trough concentration 
•   Accumulation ratio based on trough concentration 
 
Optional anterior chamber (aqueous humor) paracentesis samples will be collected to 
assess PK and PD relationships.  Additional PK analyses may be conducted as 
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3.4.4   
Exploratory Outcome Measures 
Exploratory outcome measures for this study include the following: 
•   PK-PD relationship of lampalizumab in aqueous humor samples  
•   Evaluation of potential associations of genetic variants in CFI, complement-pathway 
genes, and AMD-associated genes with disease characteristics and response to 
administration of lampalizumab  
 
4.   
MATERIALS AND METHODS  
4.1   
PATIENTS  
Patient Selection and Sex Distribution 
Written informed consent will be obtained prior to initiation of any study procedures.  
The screening evaluation will be performed within 28 days preceding the Day 1 visit 
(the day of the first study treatment).  
NOTE: Some patients may require an extended screening period as a result of 
repeat acquisition or evaluation of images or other issues.  After consultation with 
and approval by the Medical Monitor, the screening period may be extended for up 
to 5 days for exceptional circumstances.  
Only one eye will be chosen as the study eye.  If both eyes are eligible, the eye with the 
worse visual function (as determined by the investigator and patient) will be the study 
eye.  If both eyes have the same visual function, the eye with the larger area of GA will 
be selected as the study eye. 
The protocol allows enrollment of both men and women, provided the entry criteria are 
met.  However, women who are pregnant or breastfeeding will be excluded from the 
study.  The remaining inclusion/exclusion criteria apply to both male and female patients 
and pertain to issues of patient health performance and safety. 
4.1.1   
Inclusion Criteria 
Patients must meet the following criteria for study entry. 
4.1.1.1   
General Inclusion Criteria 
•   Willingness to provide signed Informed Consent and Health Insurance Portability 
and Accountability Act authorization  
•  Age ≥
 60 years 
•   CFI profile biomarker−positive result  
•   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 postmenarchial, has 
not reached postmenopausal state (≥12 months of amenorrhea with no identified 


 
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cause other than menopause), and has not undergone surgical sterilization (absence 
of ovaries and/or uterus). 
Examples of contraceptive methods with a failure rate of <1% per year include 
bilateral tubal ligation, male sterilization, established, proper use of hormonal 
contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and 
copper intrauterine devices. 
The reliability of sexual abstinence should be evaluated in relation to the duration 
of the clinical trial and the preferred and usual lifestyle of the patient.  Periodic 
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) 
and withdrawal are not acceptable methods of contraception. 
•   For men:  agreement to remain abstinent 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. 
•   Ability and willingness to undertake all scheduled visits and assessments 
 
4.1.1.2   
Ocular Inclusion Criteria:  Study Eye 
•   BCVA ETDRS 
For the safety run-in assessment:  BCVA of 20/80 to 20/400 inclusive (Snellen 
equivalent) using ETDRS charts  
For the randomized study:  BCVA of 20/50 to 20/400 inclusive (Snellen 
equivalent) using ETDRS charts 
•   Well−demarcated area of GA secondary to AMD 
•   GA must be ≥ 1 disc area (DA) (2.54 mm
2) in the absence of CNV 
•   If GA is multifocal, at least one focal lesion must be ≥
 0.5 DA (1.27 mm2) 
•   The total lesion size must be 
 ≤
  to 7 DA (17.78 mm
2) and must reside completely 
within the FAF imaging field 
•   Presence of hyperautofluorescence adjacent to the area of GA (banded or diffuse 
perilesional FAF patterns) 
•   Sufficiently clear ocular media, adequate pupillary dilation, and fixation to permit 
quality fundus imaging 
4.1.1.3   
Ocular Inclusion Criteria:  Fellow (Non-Study) Eye  
•   GA secondary to AMD in the absence of prior or active CNV 
4.1.2   
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from study entry. 


 
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4.1.2.1   
Ocular Exclusion Criteria:  Geographic Atrophy Characteristics 
•   GA in the study eye that extends beyond FAF imaging field or fails to meet single or 
multifocal lesion criteria 
•   Absence or minimal hyperfluorescence adjacent to GA in the study eye (e.g., focal 
or no perilesional FAF pattern) 
•   GA in either eye due to causes other than AMD (e.g., Stargardt disease, cone-rod 
dystrophy, chloroquine/hydroxychloroquine toxicity) 
 
4.1.2.2   
Ocular Exclusion Criteria:  Study Eye 
•   History of vitrectomy surgery, submacular surgery, or other surgical intervention for 
AMD  
•   Previous subfoveal focal laser photocoagulation 
•   Laser photocoagulation (juxtafoveal or extrafoveal)  
•   Prior treatment with Visudyne
®, external-beam radiation therapy, or transpupillary 
thermotherapy  
•   Previous intravitreal drug delivery (e.g., intravitreal corticosteroid injection, 
anti-angiogenic drugs, anti-complement agents, biodegradable/non-biodegradable 
implants or formulations, device implant, or encapsulated cell technology).  NOTE:  
A single intraoperative administration of a corticosteroid during cataract surgery 
for cystoid macular edema prophylaxis at least 3 months prior to screening is 
permitted. 
•   Previous cell-based (e.g., regenerative or trophic) intraocular treatment 
•   RPE tear involving the macula 
•   History of retinal tear.  NOTE: a retinal tear adequately treated with laser 
photocoagulation and determined to be stable by investigator may be permitted 
after consultation with and approval by the Medical Monitor. 
•   Any concurrent ocular or intraocular condition (e.g., cataract or epiretinal membrane) 
that, in the opinion of the investigator, could do either of the following: 
Require medical or surgical intervention during the study period to prevent or 
treat vision loss that might result from that condition; or 
If allowed to progress untreated, could likely contribute to loss of at least 
2 Snellen equivalent lines of BCVA during the study period 
•   Active vitreous hemorrhage 
•   History of retinal detachment or macular hole (Stage 3 or 4) 
•   Aphakia or absence of the posterior capsule 
Previous violation of the posterior capsule is also excluded unless it occurred as a 
result of yttrium aluminum garnet (YAG) laser posterior capsulotomy in association 
with prior posterior chamber intraocular lens implantation 
•   Spherical equivalent of the refractive error demonstrating more than 8 diopters of 
myopia 


 
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•   For patients who have undergone prior refractive or cataract surgery, the 
preoperative refractive error in the study eye should not have exceeded 8 diopters 
of myopia 
•   Intraocular surgery (including cataract surgery) within 3   months preceding Day 1 
•   Glaucoma that is uncontrolled (defined as IOP ≥ 30 mmHg despite treatment with 
anti-glaucoma medication) 
•   History of glaucoma-filtering surgery 
•   History of corneal transplant 
 
4.1.2.3   
Ocular Exclusion Criteria:  Either Eye 
•  Proliferative diabetic retinopathy. NOTE:  mild non-proliferative diabetic 
retinopathy (occasional hemorrhage or microaneurysm) in either eye may be 
permitted after consultation with and approval by the Medical Monitor; moreover, 
a patient with onset of mild non-proliferative diabetic retinopathy in either eye 
during study participation may be permitted to continue study treatment after 
consultation with the Medical Monitor. 
•   Active or history of neovascular (wet) AMD 
•   History of idiopathic or autoimmune-associated uveitis 
•   Active uveitis and/or vitritis (see definitions and grading scales for iritis/anterior 
uveitis and vitritis in Appendix 5)  
•   History of ocular or intraocular conditions that contraindicate the use of an 
investigational drug or may affect interpretation of study results or my render the 
patient at high risk for treatment complications 
•   Previous participation in other studies of investigational drugs (excluding vitamin 
and mineral supplements; topical ocular agents ≥ 3 months preceding Day 1) may 
be permitted after consultation with and approval by the Medical Monitor 
•   Previous systemic treatment with a complement inhibitor 
•   Previous treatment with inhibitors/modulators of the visual cycle (e.g., fenretinide) 
•   Previous expression vector mediated intraocular treatments  
•   Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis  
•   History of infectious or inflammatory ocular disease 
 
4.1.2.4   
Systemic Exclusion Criteria:  Concurrent Conditions 
•   Uncontrolled blood pressure (defined as systolic
 >
 180 mmHg and/or diastolic 
>
 110 mmHg while patient is sitting) 
If a patient’s initial measurement exceeds these values, a second reading may be 
taken 30 or more minutes later.  If the patient’s blood pressure must be controlled by 
antihypertensive medication, the patient can become eligible if medication is taken 
continuously for at least 30 days prior to Day 1. 
•   Atrial fibrillation not managed by medication/cardioversion and the patient is  under 
the care of a primary care physician or cardiologist 


 
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•   Medical conditions that may be associated with a clinically significant risk for 
bleeding 
•   Active or history of other disease, metabolic dysfunction, physical examination 
finding, or clinical laboratory finding giving reasonable suspicion of a disease 
or condition that contraindicates the use 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 
•   Treatment for an active localized or systemic infection 
Ongoing prophylactic use of antimicrobial therapy should be discussed with and 
approved by the Medical Monitor. 
•   Predisposition or history of increased risk for infection 
•   Active malignancy within the previous 12 months except for appropriately treated 
carcinoma in situ of the cervix, resolved non-melanoma skin carcinoma, and 
prostate cancer with a Gleason score of
 ≤
 6 and a stable prostate-specific antigen 
(PSA) for
 ≥12 months. 
•   History of allergy to fluorescein, not amenable to treatment 
•  History of a severe allergic reaction or anaphylactic reaction to a biologic agent or 
known hypersensitivity to any component of the lampalizumab injection 
•   Inability to obtain FAF or near infrared images, fundus photographs, or fluorescein 
angiograms 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 
“Prohibited Therapy” section of the protocol (see Section 4.4.2) 
•   Women who are pregnant or lactating or intending to become pregnant during the 
study 
•   Woman of childbearing potential  must have a negative serum pregnancy test 
result within 28 days prior to initiation of study treatment 
 
4.2   
METHOD OF TREATMENT ASSIGNMENT AND MASKING  
4.2.1   
Safety Run-In Assessment Treatment Assignment and Masking 
The safety run-in assessment is open label; all patients will receive study drug.  After 
written informed consent has been obtained, all patients will receive a screening number 
assigned through the IxRS.  A patient must satisfy all eligibility criteria (see 
Sections 4.1.1 and 4.1.2) at both the screening and the Day 1 visit (first study treatment) 
prior to enrollment.  As part of the screening process, the central reading center will 
evaluate FAF images, CFP, and fluorescein angiography (FA) to provide an objective, 
assessment of patient eligibility.  After all patient eligibility requirements are confirmed, 
site personnel will contact the IxRS on the Day 1 visit for assignment of a patient 
identification number (a separate number from the screening number). The study 
treatment kit will be also assigned by IxRS at that time.  All patients enrolled in the safety 


 
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run-in assessment will receive a 10-mg dose of lampalizumab Q2W for the duration of 
their study participation.  
The site study staff, vendors, and Sponsor study personnel will not be masked to the 
patients’ treatment arm assignment (study drug vs. sham).  The BCVA examiner will be 
masked to the study eye and treatment assigned (study drug vs. sham) and will perform 
only the refraction and BCVA assessment.  The BCVA examiner will be also masked to 
the BCVA scores of a patient’s previous visits and may only know patient’s refraction 
data from previous visits.  The BCVA examiner is not allowed to perform any other tasks 
involving direct patient care.  Patients will be masked to their treatment assignment. 
4.2.2   
Randomized Study Treatment Assignment and Masking 
The randomized study is single masked. After written informed consent has been 
obtained, all patients will receive a screening number assigned through the IxRS.  
A patient must satisfy all eligibility criteria (see Sections 4.1.1 and 4.1.2) at both the 
screening and the Day 1 visit (first study treatment) prior to randomization.  As part of 
the screening process, the central reading center (masked to patient treatment 
assignment) will evaluate FAF images, CFP, and FA to provide an objective, masked 
assessment of patient eligibility.  Patient biomarker eligibility criteria will be verified by 
contacting IxRS prior to the Day 1 visit.  After all patient eligibility requirements are 
confirmed and Day 1 visit assessments performed, site personnel will contact the IxRS 
on the Day 1 visit for assignment of a patient identification number (a separate number 
from the screening number).  The study treatment kit number will be also assigned by 
IxRS at that time.  Patients will be randomized in a 3:1:2:1 ratio to one of four treatment 
groups:  lampalizumab Q2W, sham Q2W, lampalizumab Q4W, or sham Q4W.  Patients 
will be randomized on the same day the study treatment is to be initiated (Day 1 visit).   
The site study staff, vendors, and Sponsor study personnel will not be masked to the 
patients’ treatment arm assignment (study drug vs sham).  The BCVA examiner will be 
masked to the study eye and treatment assigned (study drug versus sham) and will only 
perform the refraction and BCVA assessment.  The BCVA examiner will be also masked 
to the BCVA scores of a patient’s previous visits and may only know patient’s refraction 
data from previous visits.  The BCVA examiner is not allowed to perform any other tasks 
involving direct patient care.  Patients will be masked to their treatment assignment. 
4.3   
STUDY TREATMENT  
4.3.1   
Formulation, Packaging, and Handling 
4.3.1.1   
Lampalizumab  
Lampalizumab vials will be supplied by the Sponsor.   
Formulation 
Lampalizumab Drug Product is provided as a sterile, white to off-white, lyophilized 
powder in a 6-cc USP/European Pharmacopoeia Type 1 glass vial and is intended for 
intravitreal administration.  Each glass vial contains a nominal 40 mg of lampalizumab.  


 
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After reconstitution with Sterile Water for Injection, the drug product is formulated as 
100 mg/mL lampalizumab in 40 mM L-histidine hydrochloride, 28 mM sodium chloride, 
160 mM sucrose, 0.04% (w/v) polysorbate 20, pH 5.3. 
4.3.1.2   
Sham 
Sham vials will be supplied by the Sponsor. 
Sham vials will be identical to vials of lampalizumab, but the sham vials will be empty. 
Storage 
Upon receipt of lampalizumab and sham, vials should be refrigerated at 2°C−8°C 
(36°F−46°F) until use.  Lampalizumab vials should not be used beyond the expiration 
date provided by the manufacturer.  No preservative is used in lampalizumab drug 
product; therefore, the vial is intended for single use only.  Vial contents should not be 
frozen or shaken and should be protected from direct sunlight.  Within 2 hours following 
dose preparation (reconstitution), lampalizumab should be administered; the prepared 
dose may be maintained at room temperature prior to administration. 
For further details, see the Lampalizumab Investigator’s Brochure and/or Pharmacy 
Binder. 
4.3.2   
Dosage, Administration, and Compliance 
4.3.2.1   
Lampalizumab and Sham  
Dosage 
Guidelines for treatment interruption or discontinuation are provided in Section 5.1.1.1.  
Adverse events associated with an overdose or incorrect administration of study drug 
should be recorded on the Adverse Event eCRF. 
Safety Run-In Assessment:  A safety run-in assessment with multiple 10-mg 
intravitreal administrations of lampalizumab at the Q2W frequency will be conducted 
prior to initiating enrollment in the randomized study.  A schedule of assessments is 
provided in Appendix 1.  Patients in the safety run-in assessment will receive 
lampalizumab injections Q2W to obtain safety data from 3 evaluable patients (defined as 
a patient who has received ≥
 3 study drug injections).  Each patient will receive study 
drug on Day 1 and will be contacted by study site personnel on Day 2 and Day 8 
(± 2 days) after each injection to elicit reports of any decrease in vision, eye pain, 
unusual redness, or any other new ocular signs or symptoms in the study eye; if 
warranted, patients will be asked to return to the clinic for an unscheduled safety 
assessment visit (see Appendix 4).  All safety run-in patients will also return for safety 
assessment visits every 2 weeks (± 2 days).  After the third evaluable patient completes 
the Week 6 (± 2 days) visit following the third study drug administration, a hiatus in 
treatment of approximately 3 days will ensue.  During the hiatus, the Genentech Safety 
Review Committee consisting of the Medical Monitor, Drug Safety Scientist, and 
Biostatistician will review the safety results for the run-in assessment.  If the results show 


 
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acceptable safety in accordance with the DLT criteria (see Section 3.1.1.1), 
subsequently, the randomized study will be initiated. 
Following the hiatus assessment and an initial acceptable safety profile for the Q2W 
dosing frequency, patients who participate in the safety run-in assessment will continue 
on the Q2W study drug administration for the remainder of the 24-week treatment 
course.  The study treatment visit frequency and assessments (see Appendix 2) will 
follow the same regimen as the Q2W arm of the randomized study.  These patients will 
receive a maximum of 12 study drug treatments during the study.  
Missed doses will not be made up. 
Randomized Study 
Lampalizumab Intravitreal Injections:  A 10-mg dose of lampalizumab will be used in 
this study and will be administered intravitreally during the 24-week treatment period 
starting at the Day 1 visit for a total of 12 injections to patients randomized to the Q2W 
treatment arm and a total of 6 injections to patients randomized to the Q4W treatment 
arm. 
Missed doses will not be made up. 
A schedule of assessments is provided in Appendix 2 and Appendix 3. 
Sham Injections:  Patients randomized to the control arms will receive sham injections. 
A total of 12 sham injections will be administered in the Q2W arm, and 6 sham injections 
will be administered in the Q4W arm during the 24-week treatment period.  Sham arms 
will undergo the same assessments as the lampalizumab treatment arms 
(see Appendix 2 and Appendix 3). 
A sham injection is a procedure that mimics an intravitreal injection of lampalizumab, 
except that the blunt end of an empty syringe is pressed against an anesthetized eye 
instead of a needle attached to a lampalizumab-filled syringe. 
Missed doses will not be made up. 
A schedule of assessments is provided in Appendix 2 and Appendix 3. 
4.3.2.2   
Administration 
See Appendix 6 for the pre-injection procedures of lampalizumab and sham treatments 
for all patients, Appendix 7 for the injection procedures of the study drug, Appendix 8 for 
the injection procedures of the sham treatment, and Appendix 9 for the post-injection 
procedures for all treated patients. 


 
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4.3.2.3   
Compliance 
This study will be conducted in accordance with the U.S. Food and Drug Administration 
(FDA) regulations; the International Conference on Harmonisation (ICH) E6 Guideline for 
Good Clinical Practice; and applicable local, state, and federal laws, as well as other 
applicable country laws.  
4.3.3   
Investigational Medicinal Product Accountability 
All investigational medicinal products (IMPs) required for completion of this study 
(lampalizumab and sham) will be provided by the Sponsor.  The study site will 
acknowledge receipt of IMPs and confirm the shipment condition and content.  Any 
damaged shipments will be replaced.  
IMPs will either be disposed of at the study site according to the study site’s institutional 
standard operating procedure or 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 IMPs received at, dispensed from, returned to, and disposed of 
by the study site should be recorded on the Drug Inventory Log. 
4.3.4   
Post-Trial Access to Lampalizumab 
The Sponsor (Genentech) is a member of the Roche group and is subject to Roche’s 
global policies.  The Sponsor will offer post-trial access to the study drug (lampalizumab) 
free of charge to eligible patients in accordance with the Roche Global Policy on 
Continued Access to Investigational Medicinal Product, as outlined below.   
A patient will be eligible to receive study drug after 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 
continued study drug treatment for his or her well-being.  
•   There are no appropriate alternative treatments available to the patient. 
•   The patient and his or her doctor comply with and satisfy any legal or regulatory 
requirements that apply to them. 
 
A patient will not be eligible to receive study drug after 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 wouldn
't 
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. 


 
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•   The Sponsor has reasonable safety concerns regarding the study drug as treatment 
for GA. 
•   Provision of study drug is not permitted under the laws and regulations of the 
patient
's country. 
 
The Roche Global Policy on Continued Access to Investigational Medicinal Product is 
available at the following Web site: 
http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf  
4.4   
CONCOMITANT THERAPY 
Concomitant medications are any prescription drugs or over-the-counter preparations 
other than protocol-specified procedural medications (e.g., dilating drops; fluorescein 
dyes; etc.) and pre- and post-injection medications (e.g., proparacaine, etc.) used by a 
patient within 7 days preceding Day 1 and through the conclusion of the patient’s study 
participation or early termination visit.  
4.4.1   
Permitted Therapy  
Patients who use other maintenance therapies should continue their use.   
All concomitant medications should be reported to the investigator and recorded on the 
appropriate eCRF.  Patients who use oral contraceptives, hormone-replacement therapy, 
or other maintenance therapy should continue their use.  
Intra-articular or intra-muscular corticosteroids may be used in a limited fashion after 
consultation with and approval by the Medical Monitor. The onset of glaucoma in the 
study eye during a patient’s study participation should be treated as clinically indicated  
4.4.2   
Prohibited Therapy 
At the discretion of the investigator, patients may continue to receive all medications and 
standard treatments administered for other conditions.  However, the following 
medications and treatments will exclude patients from study eligibility and are 
prohibited from use during the patient’s participation in the study: 
•   Systemic anti-vascular endothelial growth factor (VEGF) agents  
•   Intravitreal anti-VEGF agents in either eye 
•   Intravitreal, subtenon, or chronic topical (ocular) corticosteroids in either eye; 
short-term use of topical corticosteroids is permitted after cataract surgery 
•   Oral corticosteroids (prednisone or equivalent) at doses
 >
 10 mg/day (prohibited at 
screening for eligibility; for occurrence during study enrollment, see Table 2 , 
Dose−Interruption Criteria)   
•   Intravenous corticosteroids (prohibited at screening for eligibility; for occurrence 
during study enrollment, see Table 2, Dose-Interruption Criteria) 


 
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•   Systemic or intravenous immunomodulatory therapy (e.g., azathioprine, 
methotrexate, mycophenolate mofetil, cyclosporine, cyclophosphamide, tocilizumab, 
eculizumab, or an anti-tumor necrosis factor agent) 
•   Treatment with Visudyne in either eye 
•   Other experimental therapies (except vitamins and minerals) 
 
4.5   
STUDY ASSESSMENTS  
4.5.1   
Informed Consent Forms and Screening Log 
Written informed consent for participation in the study must be obtained before 
performing any study-specific screening tests or evaluations.  Informed Consent Forms 
for enrolled patients and for patients who are not subsequently enrolled will be 
maintained at the study site. 
All screening and Day 1 visits evaluations must be completed and reviewed to confirm 
that patients meet all eligibility criteria before enrollment (safety run-in patients and 
randomized patients).  The investigator will maintain a screening log to record details of 
all patients screened and to confirm eligibility or record reasons for screening failure, as 
applicable. 
4.5.2   
Medical History and Demographic Data 
Medical history includes clinically significant diseases, including chronic and ongoing 
conditions (e.g., trauma, cancer, cardiovascular, and ophthalmic history); tobacco use; 
surgeries; cancer history; reproductive status; and all medications (e.g., prescription 
drugs, over-the-counter drugs, herbal or homeopathic remedies, nutritional supplements) 
used by the patient within 7 days prior to Day 1 visit. 
Demographic data will include age, sex, and self-reported race/ethnicity. 
4.5.3   
Physical Examinations 
A targeted physical examination should include an evaluation of the head, eyes, ears, 
nose, throat, and cranial nerves.  Height and weight will be collected.  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.  Should any clinically 
significant abnormalities be found at screening or Day 1 prior to study treatment, the 
condition should be noted in the patient’s medical history, and the investigator must 
perform (or refer the patient for) a directed physical examination prior to patient 
enrollment.  Changes from baseline abnormalities should be recorded in patient notes.  
New or worsened clinically significant abnormalities should be recorded as adverse 
events on the Adverse Event eCRF. 


 
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4.5.4   
Vital Signs  
Vital signs will include measurements of systolic and diastolic blood pressure, pulse, 
respiration rate, and temperature while the patient is in a seated position after resting for 
at least 5 minutes.  Vital signs should be taken before the study treatment as indicated 
(see Appendix 1, Appendix 2, and Appendix 3). 
4.5.5   
Other Disease-Specific Assessments 
Ocular Assessments 
•   BCVA at a starting distance of 4 meters (perform prior to dilating eyes; see 
Appendix 10) 
•   IOP measurement (perform prior to dilating eyes; the method used for a patient 
must remain consistent throughout the study) 
•   Slit-lamp examination (for grading scales for cells, see Appendix 5)  
•   Dilated binocular indirect high-magnification ophthalmoscopy 
•   Finger counting test, or hand motion or light perception tests (when necessary) 
performed within 15 minutes post-treatment for the study eye only by physician 
•   IOP measurement 60 (±10) minutes post-treatment for the study eye only; the 
method used for a patient must remain consistent throughout the study 
Ocular Imaging 
•   FAF and NI images of both eyes (see Appendix 13 and Appendix 14) 
•   Stereoscopic, digital CFPs of both eyes (see Appendix 11) 
•   FAs of both eyes (perform after laboratory samples are obtained) (see Appendix 12) 
Except as noted, all ocular assessments should be performed for both eyes. 
4.5.6   
Laboratory Assessments, Other Biological Assessments, and 
Genotyping for the CFI Profile Biomarker 
4.5.6.1   
Laboratory Assessments 
Specimens in this section will be forwarded to the central laboratory where the following 
tests will be performed: 
•   Hematology:  hemoglobin, hematocrit, quantitative platelet count, RBCs, WBCs, and 
differentials including neutrophils, bands, lymphocytes, basophils, eosinophils, and 
monocytes (absolute and percent) 
•   Serum chemistry:  sodium, potassium, chloride, bicarbonate, glucose, blood urea 
nitrogen (BUN), creatinine, calcium, phosphorus, total and direct bilirubin, total 
protein, albumin, SGOT (AST), SGPT (ALT), lactic dehydrogenase (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 
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•   Coagulation:  aPTT and PT 
•   Screening visit serum pregnancy test (β-human chorionic gonadotropin):  for women 
of childbearing potential, including those who have had tubal ligation.  If positive, 
study drug will not be administered. 
 
Instructions for obtaining, processing, storing, and shipping all specimens for central 
laboratory evaluations are provided in the Laboratory Manual. 
4.5.6.2   
Other Biological Assessments 
Samples in this section will be forwarded from the central laboratory to designated 
laboratories for analysis. 
•   Serum samples will be obtained to measure lampalizumab concentration; drug 
concentration will be determined in serum using an ELISA method. 
•   Serum samples will be obtained for measurement of anti-lampalizumab antibodies; 
anti-therapeutic antibodies will be detected in serum using a bridging ELISA.  
•   Optional anterior chamber (aqueous humor) paracentesis samples will be obtained 
to assess lampalizumab and CFD levels, and PK-PD relationships. 
•   Systemic alternative complement pathway activity assay (AH50)  
•   Whole blood sample to evaluate the potential association of genetic variants in CFI, 
complement-pathway genes, and AMD-associated genes with disease 
characteristics and response to administration of lampalizumab 
 
4.5.6.3   
Genotyping: CFI Profile Biomarker  
Whole−blood samples will be collected and forwarded directly from the sites to the 
Sponsor-selected laboratory for analysis to determine CFI profile biomarker status (see 
the Central Laboratory Manual for details). 
The cobas® CFI Profile Clinical Trial Assay 
A valid CFI biomarker result will be determined at a designated study laboratory testing 
site using the cobas CFI Profile CTA, which is a real-time PCR test developed by Roche 
Molecular Systems to identify genotypes of three SNPs associated with CFH, CFI, and 
C2/CFB in DNA extracted from whole blood samples from patients with GA secondary to 
AMD.  The cobas CFI Profile CTA is intended to be used as an Investigational Use Only 
assay to characterize the complement factor profile of study participants.  The cobas CFI 
Profile CTA biomarker status results will be used in Study GX29455 to determine the 
eligibility of patients for enrollment. 
The cobas CFI Profile CTA consists of two kits and will use the cobas 4800 platform.  
The cobas DNA Sample Preparation Kit (DNA isolation kit) provides the necessary 
components to manually extract genomic DNA from whole blood samples.  The cobas 
CFI Profile CTA contains the necessary PCR master mix, oligonucleotides, cofactor, and 
controls to detect three SNPs associated with CFI, CFH, and C2/CFB. 


 
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4.5.6.4   
Storage 
The samples (except for hematology, serum chemistry, urinalysis, coagulation, and 
serum and urine pregnancy tests that will be destroyed after their analysis during the 
study) will be stored for up to 5 years after the date of final closure of the associated 
clinical database. 
In addition, residuals of serum pharmacokinetics, serum anti-therapeutic antibodies 
(ATAs), biomarker whole blood clinical genotyping samples, and aqueous humor 
samples will be stored for up to 15 years after the date of the final closure of the 
associated clinical database provided the patient has given specific Roche Clinical 
Repository (RCR) consent for residual samples to be stored for the optional research. 
See Appendix 16 and the Central Lab Manual for detailed instructions. 
4.5.7   
Samples for Roche Clinical Repository 
Genentech is a member of the Roche group and participates in the collection and/or 
submission of biological samples to the RCR.  Collection and submission of biological 
samples to the RCR is contingent upon the review and approval of the RCR portion of 
the Informed Consent Form by each site
's Institutional Review Board or Ethics 
Committee (IRB/EC) and, if applicable, an appropriate regulatory body.  If a site is not 
granted the necessary approval for RCR sampling, this section of the protocol will not be 
applicable at that site. 
4.5.7.1   
Overview of the Roche Clinical Repository 
The RCR is a centrally administered group of facilities used for the long-term storage of 
human biologic specimens, including body fluids, solid tissues, and derivatives thereof 
(e.g., DNA, RNA, proteins, peptides).  The collection and analysis of RCR specimens will 
facilitate the rational design of new pharmaceutical agents and the development of 
diagnostic tests, which may allow for individualized drug therapy for patients in the future. 
Specimens for the RCR will be collected from patients who give specific consent to 
participate in this optional research.  RCR specimens will be used to achieve the 
following objectives: 
•   To study the association of biomarkers with efficacy, adverse events, or disease 
progression 
•   To increase knowledge and understanding of disease biology 
•   To study drug response, including drug effects and the processes of drug absorption 
and disposition 
•   To develop biomarker or diagnostic assays and establish the performance 
characteristics of these assays 
 


 
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4.5.7.2   
Sample Collection 
The following samples will be collected for research purposes, including but not limited 
to research on dynamic (non-inherited) biomarkers related AMD and related diseases, 
lampalizumab, and signaling pathways related to AMD and the complement pathway: 
•   Residual aqueous humor sample 
•   Residual serum PK sample 
•   Residual serum ATA sample 
•   Residual biomarker whole blood clinical genotyping sample 
 
For all samples, dates of consent should be recorded on the associated RCR page of 
the eCRF.  For sampling procedures, storage conditions, and shipment instructions, see 
the laboratory manual. 
RCR specimens will be destroyed no later than 15 years after the date of final closure of 
the associated clinical database. The RCR storage period will be in accordance with the 
IRB/EC-approved Informed Consent Form and applicable laws (e.g., health authority 
requirements). 
The dynamic biomarker specimens will be subject to the confidentiality standards 
described in Section 8.4.  The genetic biomarker specimens will undergo additional 
processes to ensure confidentiality, as described below. 
4.5.7.3   
Confidentiality 
Given the sensitive nature of genetic data, Roche has implemented additional processes 
to ensure patient confidentiality for RCR specimens and associated data.  Upon receipt 
by the RCR, each specimen is "double-coded" by replacing the patient identification 
number with a new independent number.  Data generated from the use of these 
specimens and all clinical data transferred from the clinical database and considered 
relevant are also labeled with this same independent number.  A "linking key" between 
the patient identification number and this new independent number is stored in a secure 
database system.  Access to the linking key is restricted to authorized individuals and is 
monitored by audit trail.  Legitimate operational reasons for accessing the linking key are 
documented in a standard operating procedure.  Access to the linking key for any other 
reason requires written approval from the Pharma Repository Governance Committee 
and Roche
's Legal Department, as applicable. 
Data generated from RCR specimens must be available for inspection upon request by 
representatives of national and local health authorities, and Roche monitors, 
representatives, and collaborators, as appropriate. 
Patient medical information associated with RCR specimens is confidential and may be 
disclosed to third parties only as permitted by the Informed Consent Form (or separate 


 
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authorization for use and disclosure of personal health information) signed by the patient, 
unless permitted or required by law. 
Data derived from RCR specimen analysis on individual patients will generally not be 
provided to study investigators unless a request for research use is granted.  The 
aggregate results of any research conducted using RCR specimens will be available in 
accordance with the effective Roche policy on study data publication. 
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of the RCR data will become and remain the exclusive and unburdened property 
of Roche, except where agreed otherwise. 
4.5.7.4   
Consent to Participate in the Roche Clinical Repository 
The Informed Consent Form will contain a separate section that addresses participation 
in the RCR.  The investigator or authorized designee will explain to each patient the 
objectives, methods, and potential hazards of participation in the RCR.  Patients will be 
told that they are free to refuse to participate and may withdraw their specimens at any 
time and for any reason during the storage period.  A separate, specific signature will be 
required to document a patient
's agreement to provide optional RCR specimens.  
Patients who decline to participate will not provide a separate signature. 
The investigator should document whether or not the patient has given consent to 
participate by completing the RCR Research Sample Informed Consent eCRF. 
In the event of an RCR participant
's death or loss of competence, the participant
's 
specimens and data will continue to be used as part of the RCR research. 
4.5.7.5   
Withdrawal from the Roche Clinical Repository 
Patients who give consent to provide RCR specimens have the right to withdraw their 
specimens from the RCR at any time for any reason.  If a patient wishes to withdraw 
consent to the testing of his or her specimens, the investigator must inform the Medical 
Monitor in writing of the patient
's wishes through use of the RCR Subject Withdrawal 
Form and, if the trial is ongoing, must enter the date of withdrawal on the RCR Research 
Sample Withdrawal of Informed Consent eCRF.  The patient will be provided with 
instructions on how to withdraw consent after the trial is closed.  A patient
's withdrawal 
from Study GX29455 does not, by itself, constitute withdrawal of specimens from the 
RCR.  Likewise, a patient
's withdrawal from the RCR does not constitute withdrawal from 
Study GX29455. 
4.5.7.6   
Monitoring and Oversight 
RCR specimens will be tracked in a manner consistent with Good Clinical Practice by a 
quality-controlled, auditable, and appropriately validated laboratory information 
management system, to ensure compliance with data confidentiality as well as 
adherence to authorized use of specimens as specified in this protocol and in the 


 
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Informed Consent Form.  Roche monitors and auditors will have direct access to 
appropriate parts of records relating to patient participation in the RCR for the purposes 
of verifying the data provided to Roche.  The site will permit monitoring, audits, IRB/EC 
review, and health authority inspections by providing direct access to source data and 
documents related to the RCR samples. 
4.6   
PATIENT, TREATMENT, STUDY, AND SITE DISCONTINUATION 
Patients withdrawn from the study prior to completion will be asked to return for an early 
termination evaluation 30 (+7) days following their last study treatment for monitoring of 
adverse events and assessments listed for the early termination visit (see Appendix 1, 
Appendix 2, and Appendix 3).  The reason for the study discontinuation should be 
recorded on the appropriate eCRF.  Discontinued patients will not be replaced or 
allowed to re-enter the study. 
4.6.1   
Patient Discontinuation 
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  
 
Every effort should be made to obtain information on patients who are discontinued 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. 
4.6.2   
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 primary reason for study treatment discontinuation 
should be documented on the appropriate eCRF.  Patients who discontinue study 
treatment prematurely will not be replaced or allowed to re-start the study treatment.  
4.6.3   
Study and Site Discontinuation 
The Sponsor has the right to terminate this study at any time.  Reasons for terminating 
the study may include, but are not limited to, the following: 
•   The incidence or severity of adverse events in this or other studies indicates a 
potential health hazard to patients. 


 
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•   Patient enrollment is unsatisfactory. 
•   Data recording is inaccurate or incomplete 
 
The Sponsor will notify the investigator if the Sponsor decides to discontinue the study.   
The Sponsor has the right to close a site at any time.  Reasons for closing a site may 
include, but are not limited to, the following: 
•   Excessively slow recruitment 
•   Poor protocol adherence 
•   Inaccurate or incomplete data recording 
•   Non-compliance with the ICH guideline for Good Clinical Practice 
•   No study activity (i.e., all patients have completed and all obligations have been 
fulfilled) 
5.   
ASSESSMENT OF SAFETY  
5.1   
SAFETY PLAN 
At present, lampalizumab is in clinical development and is not an approved drug.  
Consequently, an extensive safety profile for lampalizumab remains to be established. 
The safety plan for this study is designed to help minimize patient risk and will include 
specific eligibility criteria and monitoring assessments as detailed below. 
Safety considerations associated with the intravitreal route of administration or 
pharmacology of lampalizumab include endophthalmitis, traumatic complications 
(i.e., conjunctival hemorrhage, conjunctival edema, eye irritation, eye pain or ocular 
foreign body sensation), and post-injection transient increase in IOP. 
There is a potential risk for retinal edema/inflammation or sterile inflammatory reactions, 
traumatic cataracts or retinal detachments related to the administration of lampalizumab.  
As lampalizumab is a biologic agent, there is also a risk of developing ATAs; however, 
there have been no reported adverse events associated with the development of ATAs 
in patients receiving lampalizumab in the completed Studies CFD4711g and CFD4870g.  
Multiple lampalizumab administrations in Study CFD4870g showed no apparent adverse 
systemic effects associated with inhibition of the alternative complement pathway; 
nevertheless, monitoring for potential systemic adverse events, such as lowered 
infection threshold to encapsulated bacteria (i.e., Streptococcus pneumonia, 
Haemophilus influenza or Neisseria meningitides), will be performed (AH50 assay).  
The incidence and characteristics of adverse events, serious adverse events, 
and laboratory abnormalities will be assessed.  Ongoing review of safety will be 
performed by an internal Genentech Safety Review Committee consisting of the Medical 
Monitor, Drug Safety Scientist, and Biostatistician.  External experts may be consulted.  
All adverse events will be recorded on eCRFs for the duration of the study. 


 
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For the patients in the safety run-in assessment, safety monitoring and review of safety 
data after each study drug treatment will be performed to determine whether the DLT 
criteria are met.  All DLTs occurring within the pre-specified window of study drug 
administration should be reported to Genentech within 24 hours of becoming aware of 
the event.  DLTs will be reviewed expeditiously by the Genentech Safety Review 
Committee.   
After each study drug injection, all safety run-in patients will be contacted by study site 
personnel on post-injection Day 2 and Day 8 (±
 2 days) to elicit reports of any decrease 
in vision, eye pain, unusual redness, or any other new ocular sign or symptom in the 
study eye; if warranted, patients will be asked to return to the clinic for an unscheduled 
safety assessment visit (see Appendix 4).  All safety run-in patients will also return for 
safety assessment visits every 2 weeks (± 2 days) (see Appendix 1).  Subsequently, 
safety run-in patients will follow the same visits schedule as the Q2W arms of the 
randomized study (see Appendix 2) until study completion at the Week 24 visit.  
The randomized study patients will have safety assessments performed at each 
scheduled study visit according to their treatment arm assignment (Q2W or Q4W) 
(see Appendix 2 and Appendix 3). The study patients will be contacted by study site 
personnel 3 (± 1) days after each study treatment to elicit reports of any decrease in 
vision, eye pain, unusual redness, or any other new ocular signs or symptoms in the 
study eye. If warranted, patients will be asked to return to the clinic for an unscheduled 
safety assessment visit (Appendix 4) and will receive instructions to contact the 
investigator at any time should they have any health-related concerns. 
Following the study treatment, patients will remain in the clinic for 60 (±
 10) minutes.  
A finger counting will be tested for each patient within 15 minutes following study 
treatment by the physician; hand motion or light perception will be tested when 
necessary.  IOP will be measured bilaterally prior to dosing; IOP will be measured again 
60 (±
 10) minutes after study treatment for the study eye only.  All IOP measurements 
will be performed by qualified site personnel.  If there are no safety concerns at 
60 (±
 10) minutes, the patient may be discharged from the clinic.  If the IOP is increased 
by ≥
 10 mmHg from the pre-treatment measurement at 60 (±
 10) minutes and is of 
concern to the investigator, the patient will remain in the clinic to be treated in 
accordance with the investigator’s clinical judgment prior to discharge.  If applicable, the 
Adverse Event CRF page will be completed. 
Detailed ocular examinations, including slit-lamp and indirect ophthalmoscopy, will be 
performed throughout the study.  Laboratory testing will include hematology, serum 
chemistry, coagulation, AH50, and urinalysis; blood samples for serum study drug 
concentrations, antibodies to lampalizumab; biomarker whole blood samples will also be 
obtained from all patients (see Appendix 1, Appendix 2, and Appendix 3).  Optional 
aqueous humor samples will be obtained from patients who consent to this procedure 
and sample collection. 


 
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Treatment interruption and/or treatment discontinuation for adverse events will be 
determined using the criteria in Table 2.  
Patients withdrawn from the study prior to completion will be asked to return for early 
termination visit assessments 30 (+
 7) days following the last study treatment visit 
(see Appendix 1, Appendix 2, and Appendix 3).  The visit will include assessment of all 
adverse events (serious and non-serious; ocular and non-ocular).  
Serious adverse events will be collected and reported in compliance with Good Clinical 
Practice guidelines.  
5.1.1   
Management of Specific Adverse Events 
5.1.1.1   
Dose-Interruption, Treatment and Study Discontinuation 
Criteria 
Treatment interruption and patient discontinuation from the study treatment and 
the study for adverse events will be determined using the criteria listed in Table 2.  If the 
criteria are met, treatment will either be interrupted or discontinued. The reason for 
treatment interruption should be recorded on the Dose Interruption eCRF; study 
discontinuation should be reported on Study Discontinuation eCRF.  If applicable, report 
an adverse events on the Adverse Event eCRF. 


 
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Table 2   Dose-Interruption, Treatment, and Study-Discontinuation Criteria 
Event 
Dose-Interruption Criteria 
Intraocular inflammation 
Interrupt study treatment if intraocular inflammation (iritis, 
iridocyclitis or vitritis) is
 ≥
 1+
 in the study eye.  Patients with ≥  2+ 
intraocular inflammation will be discontinued from the study. 
VA loss 
Interrupt study treatment 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 
Sponsor and investigator. 
IOP 
Interrupt study treatment if IOP in the study eye is ≥
 30 mmHg.  
Treatment may be permitted when IOP has been lowered to 
<
 30 mmHg, either spontaneously or by treatment, as determined by 
the Sponsor and investigator. 
Vitreous hemorrhage 
Interrupt study treatment in the event of a vitreous hemorrhage in 
the study eye; study drug treatment may be permitted subsequently 
as determined by the Sponsor and investigator. 
Rhegmatogenous retinal 
break  
Interrupt study treatment if a retinal break is present in the study 
eye.  Following successful repair, study drug treatment may be 
permitted subsequently as determined by the Sponsor and 
investigator. 
Rhegmatogenous retinal 
detachment or macular 
hole 
Patients with a rhegmatogenous retinal detachment or Stage 3 or 4 
macular holes will be discontinued from treatment and the study. 
Active local or 
systemic infection 
Interrupt study treatment if any of the following are present:  
infectious conjunctivitis, infectious keratitis, infectious scleritis, or 
endophthalmitis in either eye, or if the patient is currently receiving 
treatment for an active local or systemic infection.  Patients with 
endophthalmitis in either eye will be discontinued from the study.  
For other conditions, study drug treatment may be permitted 
subsequently as determined by the Sponsor and investigator. 
Cataract surgery and YAG 
laser treatment  
If cataract surgery or YAG laser is required, consultation with the 
Sponsor is required.  Cataract surgery and YAG laser for posterior 
capsular opacification may be permitted in either eye; however, 
dose interruption may be required for the study eye and will be 
determined by the Sponsor and investigator; uncomplicated 
cataract surgery or YAG laser therapy will be required to resume 
study treatment. 
Laser photocoagulation for 
CNV 
A single treatment of CNV with laser photocoagulation may be 
permitted in either eye; if permitted, dose interruption may be 
required for the study eye and will be determined by the Sponsor 
and investigator. 
Oral corticosteroids 
(prednisone or equivalent) 
>10−mg/day 
Interrupt study treatment.  Study treatment may be resumed when 
oral corticosteroid dosing (prednisone or equivalent) is ≤
 10 mg/day. 
IV corticosteroids 
Interrupt study treatment.  Study treatment may be resumed when 
the patient has completed IV corticosteroid treatment and oral 
corticosteroid dosing (prednisone or equivalent) is ≤10 mg/day. 
BCVA =
 best corrected visual acuity; CNV
 =
 choroidal neovascularization; IOP
 =
 intraocular 
pressure; IV
 =
 intravenous; VA
 =
 visual acuity; YAG
 =
 yttrium aluminum garnet. 


 
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5.2   
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, and other 
protocol-specified tests that are deemed critical to the safety evaluation of the study. 
Certain types of events require immediate reporting to the Sponsor, as outlined in 
Section 5.4. 
5.2.1   
Adverse Events 
According to the ICH guideline for 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) 
 
5.2.2   
Serious Adverse Events (Immediately Reportable to the 
Sponsor) 
A serious adverse event is any adverse event that meets any of the following criteria: 
•   Is fatal (i.e., the adverse event actually causes or leads to death) 
•   Is life threatening (i.e., the adverse event, in the view of the investigator, places the 
patient at immediate risk of death) 
This does not include any adverse event that had it occurred in a more severe 
form or was allowed to continue might have caused death. 
•   Requires or prolongs inpatient hospitalization (see Section 5.3.5.10) 
•   Results in persistent or significant disability/incapacity (i.e., the adverse event 
results in substantial disruption of the patient’s ability to conduct normal life 
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•   Is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to 
study drug 
•   Is a significant medical event in the investigator
's judgment (e.g., may jeopardize the 
patient or may require medical/surgical intervention to prevent one of the outcomes 
listed above) 
 
The terms "severe" and "serious" are not synonymous.  Severity refers to the intensity of 
an adverse event (e.g., rated as mild, moderate, or severe; see Section 5.3.3); the event 
itself may be of relatively minor medical significance (such as severe headache without 
any further findings). 
Severity and seriousness need to be independently assessed for each adverse event 
recorded on the eCRF. 
Serious adverse events are required to be reported by the investigator to the Sponsor 
immediately (i.e., no more than 24 hours after learning of the event; see Section 5.4.2 for 
reporting instructions). 
5.2.3   
Adverse Events of Special Interest (Immediately Reportable to 
the Sponsor) 
Non-serious or serious adverse events of special interest are required to be reported by 
the investigator to the Sponsor immediately (i.e., no more than 24 hours after learning of 
the event; see Section 5.4.2 for reporting instructions).  Adverse events of special 
interest for this study include the following: 
•  Cases of potential drug-induced liver injury that include an elevated alanine 
transaminase (ALT) or aspartate transaminase (AST) in combination with either an 
elevated bilirubin or clinical jaundice, as defined by Hy’s law (see Section 5.3.5.6) 
•   Suspected transmission of an infectious agent by the study drug, as defined below 
Any organism, virus, or infectious particle (e.g., prion protein transmitting 
transmissible spongiform encephalopathy), pathogenic or non-pathogenic, is 
considered an infectious agent.  A transmission of an infectious agent may be 
suspected from clinical symptoms or laboratory findings that indicate an 
infection in a patient exposed to a medicinal product.  This term applies only 
when a contamination of the study drug is suspected. 
•   Adverse events resulting from medication error 
Examples of medication errors include, but are not limited to, overdose, 
incorrect dose, incorrect route, incorrect drug, incorrect administration, or 
incorrect kit. 
If the medication error did result in an adverse event, the primary event term 
should reflect the adverse event that occurred as a result of the medication 
error and identify it in “other suspected causes of SAE/AE” 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 visual acuity (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 Appendix 5 for intraocular 
inflammation grading scales). 
•   In the opinion of the investigator, it may require medical intervention to prevent 
permanent loss of sight. 
 
All of the above-listed, sight-threatening adverse events should be reported as serious 
events. 
5.2.3.1   
Safety Run-in Assessment Period:  Targeted Dose-Limiting 
Toxicities Adverse Events  
DLTs are any of the following adverse events that occur during the safety run-in 
assessment period (prior to hiatus) and are believed by the investigator or the sponsor to 
be study drug related: 
•   Intraocular inflammation (e.g., iritis, uveitis, or vitritis) defined as a change of two 
units on standard grading scales (see Appendix 5) after the study drug injection.  
In accordance with this definition, study exclusion criteria establish a baseline grade 
of 0, and an increase to 2+ or greater would constitute a DLT.  Intraocular 
inflammation of Grade 4+ would be considered a major toxicity requiring interruption 
of enrollment and further evaluation by the internal Safety Review Committee to 
determine if further enrollment/treatment is appropriate. 
•   Endophthalmitis secondary to an encapsulated bacteria (i.e., Streptococcus 
pneumonia, Haemophilus influenza or Neisseria meningitidis) 
•   Sustained elevation of IOP defined as a measurement of  ≥
 30 mmHg on 
three consecutive  study treatment visits 
•   Sustained loss of BCVA ≥
 15 letters after the study drug injection that is not 
attributable to the injection procedure, progression of GA, or change in the ocular 
media (i.e., cornea, aqueous humor, lens, vitreous humor) as measured on the 
three consecutive study treatment visits 
 


 
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5.3   
METHODS AND TIMING FOR CAPTURING AND ASSESSING 
SAFETY PARAMETERS 
The investigator is responsible for ensuring that all adverse events (see Section 5.2.1 for 
definition) are recorded on the Adverse Event eCRF and reported to the Sponsor in 
accordance with instructions provided in this section and in Sections 5.4, 5.5, and 5.6.  
For each adverse event recorded on the Adverse Event eCRF, the investigator will make 
an assessment of seriousness (see Section 5.2.2 for seriousness criteria), severity (see 
Section 5.3.3), and causality (see Section 5.3.4). 
5.3.1   
Adverse Event Reporting Period 
Investigators will seek information on adverse events at each patient contact.  All 
adverse events, whether reported by the patient or noted by study personnel, will be 
recorded in the patient’s medical record and on the Adverse Event eCRF. 
After informed consent has been obtained but prior to initiation of study drug, only 
serious adverse events caused by a protocol-mandated intervention (e.g., invasive 
procedures such as biopsies, discontinuation of medications) should be reported 
(see Section 5.4.2 for instructions for reporting serious adverse events). 
After initiation of study drug, all adverse events will be reported until 30 (+7) days 
after the last dose of study drug.  After this period, the investigator should report any 
serious adverse events that are believed to be related to prior study drug treatment 
(see Section 5.6). 
5.3.2   
Eliciting Adverse Event Information 
A consistent methodology of non-directive questioning should be adopted for eliciting 
adverse event information at all patient evaluation timepoints.  Examples of non-directive 
questions include the following: 
"How have you felt since your last clinic visit?" 
"Have you had any new or changed health problems since you were last here?"  
 


 
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5.3.3   
Assessment of Severity of Adverse Events 
The adverse event severity grading scale in Table 3 will be used 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 
Notes:  Regardless of severity, some events may also meet seriousness criteria.  
Refer to definition of a serious adverse event (see Section 5.2.2). 
 
5.3.4   
Assessment of Causality of Adverse Events 
Investigators should use their knowledge of the patient, the circumstances surrounding 
the event, and an evaluation of any potential alternative causes to determine whether 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): 
•   Temporal relationship of event onset to the initiation of study drug 
•   Course of the event, considering especially the effects of dose reduction, 
discontinuation of study drug, or reintroduction of study drug (as applicable) 
•   Known association of the event with the study drug or with similar treatments 
•   Known association of the event with the disease under study 
•   Presence of risk factors in the patient or use of concomitant medications known to 
increase the occurrence of the event 
•   Presence of non-treatment-related factors that are known to be associated with the 
occurrence of the event 
 


 
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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 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). 
AE =
 adverse event; SAE
 =
 serious
 adverse event. 
 
 
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.  A culture is required prior to initiating antibiotic 
treatment for presumed endophthalmitis.  Results of bacterial or fungal cultures, 
treatment given, and final ophthalmologic outcome must be provided in the details 
section of the Adverse Event eCRF. 
 
Please note:  Trace benign, aqueous pigmented cells visible on slit-lamp examination 
that are caused by the dilation process and are not red blood cells or white blood cells or 
the result of any ocular disorder should not be recorded as an adverse event. 


 
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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 severity should also be recorded on the Adverse Event eCRF with us of 
the “AE Most Extreme Intensity” eCRF field.  Details regarding any increases in severity 
will be captured on the Adverse Event Intensity Changes eCRF.  If the event becomes 
serious, it should be reported to the Sponsor immediately (i.e., no more than 24 hours 
after learning that the event became serious; see Section 5.4.2 for reporting instructions).  
The Adverse Event eCRF should be updated by changing the event from "non-serious" 


 
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to "serious," providing the date that the event became serious, and completing all data 
fields related to serious adverse events. 
A recurrent adverse event is one that resolves between patient evaluation timepoints 
and subsequently recurs.  Each recurrence of an adverse event should be recorded as a 
separate event on the Adverse Event eCRF. 
5.3.5.4   
Abnormal Laboratory Values 
Not every laboratory abnormality qualifies as an adverse event.  A laboratory test result 
must be reported as an adverse event if it meets any of the following criteria: 
•   Is accompanied by clinical symptoms 
•   Results in a change in study treatment (e.g., dosage modification, treatment 
interruption, or treatment discontinuation) 
•   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 assessments (hematology, 
coagulation, serum chemistry, urinalysis, and pregnancy tests).  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 an elevated ALT or AST (>
 3
 ×
 upper limit of normal [ULN]) in combination 
with either an elevated total bilirubin (>
 2
 ×
 ULN) or clinical jaundice in the absence of 
cholestasis or other causes of hyperbilirubinemia is considered to be an indicator of 
severe liver injury.  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 5.3.5.4) 
and reported to the Sponsor immediately (i.e., no more than 24 hours after learning of 
the event), either as a serious adverse event or a serious or non-serious adverse event 
of special interest (see Section 5.4.2). 
5.3.5.7   
Deaths 
All deaths that occur during the protocol-specified adverse event reporting period 
(see Section 5.3.1), regardless of relationship to study drug, must be recorded on the 
Adverse Event eCRF and immediately reported to the Sponsor (see Section 5.4.2).  
Death should be considered an outcome and not a distinct event.  The event or condition 
that caused or contributed to the fatal outcome should be recorded as the single medical 
concept on the Adverse Event eCRF.  Generally, only one such event should be 
reported.  The term "sudden death" should be used only for the occurrence of an 
abrupt and unexpected death due to presumed cardiac causes in a patient with or 
without preexisting heart disease, within 1 hour after the onset of acute symptoms or, in 


 
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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. 
5.3.5.8   
Preexisting Medical Conditions 
A preexisting medical condition is one that is present at the screening visit for this study.  
Such conditions should be recorded on the General Medical History and Baseline 
Conditions eCRF. 
A preexisting medical condition should be recorded as an adverse event only if the 
frequency, severity, or character of the condition worsens during the study.  When 
recording such events on the Adverse Event eCRF, it is important to convey the concept 
that the preexisting condition has changed by including applicable descriptors 
(e.g., "more frequent headaches"). 
5.3.5.9   
Worsening of Geographic Atrophy in Study Eye 
Medical occurrences or symptoms of deterioration that are anticipated as part of the 
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 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”).  
5.3.5.10   Hospitalization or Prolonged Hospitalization 
Any adverse event that results in hospitalization (i.e., in-patient admission to a hospital) 
or prolonged hospitalization should be documented and reported as a serious adverse 
event (per the definition of serious adverse event in Section 5.2.2), except as outlined 
below. 
•  Hospitalization for a preexisting condition, provided that 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 fulfills 


 
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seriousness criteria, the event should be reported to the Sponsor immediately (i.e., no 
more than 24 hours after learning of the event; see Section 5.4.2). 
No safety data related to overdosing of lampalizumab are available. 
5.4   
IMMEDIATE REPORTING REQUIREMENTS FROM 
INVESTIGATOR TO SPONSOR 
Certain events require immediate reporting to allow the Sponsor to take appropriate 
measures to address potential new risks in a clinical trial.  The investigator must report 
such events to the Sponsor immediately; under no circumstances should reporting take 
place more than 24 hours after the investigator learns of the event.  The following is a list 
of events that the investigator must report to the Sponsor within 24 hours after learning 
of the event, regardless of relationship to study drug: 
•   Serious adverse events 
•   Non-serious 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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5.4.1   
Emergency Medical Contacts 
Medical Monitor Contact Information  
Genentech Medical Monitor contact information: 
Medical Monitor: 
, M.D.  
Telephone Nos.: 
 (office) (U.S.A.) 
 
 (mobile) (U.S.A.) 
 
5.4.2   
Reporting Requirements for Serious Adverse Events and 
Non-Serious Adverse Events of Special Interest 
5.4.2.1   
Events That Occur prior to Study Drug Initiation 
After informed consent has been obtained but prior to initiation of study drug, only 
serious adverse events caused by a protocol-mandated intervention should be reported.  
The Serious Adverse Event/Adverse Event of Special Interest Reporting Form provided 
to investigators should be completed and submitted to Roche 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. 
5.4.2.2   
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 30 (+7) days after the last dose of study drug.  
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 
Safety Risk Management by the EDC system. 
In the event that the EDC system is unavailable, the Serious Adverse Event/Adverse 
Event of Special Interest Reporting Form provided to investigators should be completed 
and submitted to Roche or its designee immediately (i.e., no more than 24 hours after 
learning of the event), either by faxing or by scanning and emailing the form using the 
fax number or email address provided to investigators.  Once the EDC system is 
available, all information will need to be entered and submitted via the EDC system.   
Instructions for reporting post-study adverse events are provided in Section 5.6. 
5.4.3   
Reporting Requirements for Pregnancies 
5.4.3.1   
Pregnancies in Female Patients 
Female patients of childbearing potential will be instructed to immediately inform the 
investigator if they become pregnant during the study or within 30 (+
 7) days after the last 
dose of study drug.  A Pregnancy Report eCRF should be completed by the investigator 
immediately (i.e., no more than 24 hours after learning of the pregnancy) and submitted 
via the EDC system.  A pregnancy report will automatically be generated and sent to 
Safety Risk Management.  Pregnancy should not be recorded on the Adverse Event 


 
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eCRF.  The investigator should discontinue study drug and counsel the patient, 
discussing the risks of the pregnancy and the possible effects on the fetus.  Monitoring 
of the patient should continue until conclusion of the pregnancy.  Any serious adverse 
events associated with the pregnancy (e.g., an event in the fetus, an event in the mother 
during or after the pregnancy, or a congenital anomaly/birth defect in the child) should be 
reported on the Adverse Event eCRF. 
In the event that the EDC system is unavailable, the Clinical Trial Pregnancy Reporting 
Form provided to investigators should be completed and submitted to Roche 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. 
5.4.3.2   
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 within 
30 (+
 7) days after the last dose of study drug.  A Pregnancy Report eCRF should be 
completed by the investigator immediately (i.e., no more than 24 hours after learning of 
the pregnancy) and 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.  Once the authorization has been signed, the investigator will update the 
Pregnancy Report eCRF with additional information on the course and outcome of the 
pregnancy.  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 5.4.3.1. 
5.4.3.3   
Congenital Anomalies/Birth Defects and Abortions 
Any congenital anomaly/birth defect in a child born to a female patient exposed to study 
drug or the female partner of a male patient exposed to study drug should be classified 
as a serious adverse event, recorded on the Adverse Event eCRF, and reported to the 
Sponsor immediately (i.e., no more than 24 hours after learning of the event; see 
Section 5.4.2).  Any abortion should be reported in the same fashion (because the 
Sponsor considers abortions to be medically significant). 


 
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5.5   
FOLLOW-UP OF PATIENTS AFTER ADVERSE EVENTS 
5.5.1   
Investigator Follow-Up 
The investigator should follow each adverse event until the event has resolved to baseline 
grade or better, the event is assessed as stable by the investigator, the patient is lost to 
follow-up, or the patient withdraws consent.  Every effort should be made to follow all 
serious adverse events considered to be related to study drug or trial-related procedures 
until a final outcome can be reported. 
During the study period, resolution of adverse events (with dates) should be documented 
on the Adverse Event eCRF and in the patient’s medical record to facilitate source data 
verification. 
All pregnancies reported during the study should be followed until pregnancy outcome.  
If the EDC system is not available at the time of pregnancy outcome, follow reporting 
instructions provided in Section 5.4.3.1. 
5.5.2   
Sponsor Follow-Up 
For serious adverse events, non-serious adverse events of special interest, and 
pregnancies, the Sponsor or a designee may follow up by telephone, fax, electronic mail, 
and/or a monitoring visit to obtain additional case details and outcome information 
(e.g., from hospital discharge summaries, consultant reports, autopsy reports) in order to 
perform an independent medical assessment of the reported case. 
5.6   
POST-STUDY ADVERSE EVENTS 
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 
30 (+
 7) days after the last dose of study drug, if the event is believed to be related to 
prior study drug treatment.  
The investigator should report these events directly to Roche or its designee, either by 
faxing or by scanning and emailing the Serious Adverse Event/Adverse Event of Special 
Interest Reporting Form using the fax number or email address provided to investigators. 
5.7   
EXPEDITED REPORTING TO HEALTH AUTHORITIES, 
INVESTIGATORS, INSTITUTIONAL REVIEW BOARDS, AND 
ETHICS COMMITTEES 
The Sponsor will promptly evaluate all serious adverse events and non-serious 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.   
STATISTICAL CONSIDERATIONS AND ANALYSIS METHODS 
Primary efficacy analyses will include all randomized patients with at least one 
post-baseline GA area measurement by FAF.  Patients will be grouped according to the 
treatment assigned at randomization.  Safety analyses will include all randomized 
patients who receive at least one dose of study treatment, with patients grouped 
according to the treatment actually received.  Patients in the sham Q2W and sham 
Q4W groups will be pooled in the analyses. 
The analysis of data for the 24-week treatment period will be performed when all 
randomized patients have either completed the 24-week treatment period or have 
discontinued from the study prior to Week 24, and all data from this period are in the 
database and have been cleaned and verified. 
6.1   
DETERMINATION OF SAMPLE SIZE 
The GX29455 study is designed to evaluate the efficacy of lampalizumab administered 
intravitreally Q2W and Q4W to CFI profile biomarker-positive GA patients.  The focus of 
the efficacy outcome analyses will be on estimation of the magnitude of the treatment 
effect.   
The primary efficacy endpoint is the mean change in GA area from baseline to Week 24.  
The sample size was selected to provide adequate precision for the estimation of the 
treatment effect with respect to the primary endpoint.  A total of approximately 
90 patients will be enrolled in the study including the run-in and randomized components. 
Approximately 84 patients will be randomized in a 3:1:2:1 ratio to one of four 
treatment groups:  lampalizumab Q2W, sham Q2W, lampalizumab Q4W, or sham Q4W.  
With the assumption of a 15% drop-out rate by Week 24 and a standard deviation of 
0.85 mm2  for the change in GA area from baseline to Week 24 (estimated from the 
Phase II Study CFD4870g with lampalizumab in GA),  the 80% CI for the estimated 
difference in treatment effect for select hypothetical scenarios are presented in Table 5 .  
Assuming a GA area measurement error of +/- 0.043 mm2 (from CFD4870g image 
center technical report), the proposed sample size is considered sufficient for 


 
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differentiating the treatment effect between lampalizumab Q2W and lampalizumab 
Q4W groups if the observed difference is 0.290 mm2 (20% relative to sham) or larger 
(see Table 5) 


 
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Table 5   Scenario Analysis:  Observed Mean Change in Geographic Atrophy Area and 80% Confidence Intervals 
for Difference between Lampalizumab Q2W and Q4W Groups 
Scenario 
Observed Relative 
Reduction a in ΔGA at 
24 Weeks 
(Q4W, Q2W) 
ΔGA (mm2) at 
24 Weeks in Sham 
(n
 =
 24) 
ΔGA (mm2) at 
24 Weeks in Q4W 
(n
 =
 24) 
ΔGA (mm2) at 
24 Weeks in Q2W 
(n
 =
 36) 
Q4W−Q2W 
80% CI 
1 
40%, 60% 
1.448 
0.869 
0.579 
0.290 
(−0.024, 0.604) 
(−2% a, 42% a) 
2 
40%, 58% 
1.448 
0.869 
0.608 
0.261 
(−0.053, 0.575) 
(−4% a, 40% a) 
3 
40%, 55% 
1.448 
0.869 
0.652 
0.217 
(−0.097, 0.531) 
(−7% a, 37% a) 
Δ =
 change; GA
 =
 geographic atrophy; Q2W
 =
 every 2 weeks; Q4W
 =
 every 4 weeks. 
a  The reduction is relative to GA area (ΔGA area at 6M) in sham and calculated as 100% × [(mean GA area change in pooled sham − mean GA 
area change in lampalizumab)/mean GA area change in pooled sham]. 
 


 
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These calculations are based on the following assumptions: 
The SD of the change in GA area from baseline to Week 24 is 0.85 mm2.  The drop-
out rate is 15% by Week 24 (estimated from the Phase II Study CFD4870g with 
lampalizumab in GA). 
6.2   
EFFICACY ANALYSES 
The primary efficacy endpoint is mean change in GA area from baseline to Week 24.  
If not otherwise specified, analyses of efficacy outcome measures will be stratified by 
baseline GA lesion size (<
 10 mm2 versus 
 ≥
 10 mm2) and baseline BCVA (better than or 
equal to 20/100 versus worse than 20/100).  A data
 −
 as-observed approach with the 
mixed-effect model will be used to handle missing data in the primary analysis.  
Sensitivity analyses based on imputed data may be performed to evaluate the impact of 
missing data on the results.  Two-sided 80% CI will be provided for the estimated 
treatment effects.  Hypothesis testing will be conducted at the two-sided significance 
level of 0.2; no multiple testing adjustment is planned. Additional exploratory analyses 
may be conducted if deemed appropriate. 
6.3   
SAFETY ANALYSES 
Safety will be assessed by adverse events, ocular assessments (e.g., inflammation, IOP, 
BCVA), clinical laboratory evaluation, immunogenicity as measured by ATAs directed 
against lampalizumab.  Patients will be analyzed according to actual treatment received.  
Adverse events will be collected from the time of the first study treatment administration 
until a patient has completed the study or discontinued prematurely.  Adverse events 
reported during the safety run-in and the randomized study may be summarized 
separately.  
Verbatim descriptions of adverse events will be summarized by mapped term, 
appropriate thesaurus level, and toxicity grade (if applicable).  
A treatment-emergent adverse event is defined as any new adverse event reported or 
any worsening of an existing condition on or after the first dose of study treatment.  
Treatment-emergent adverse events will be summarized by treatment group.  
Clinical laboratory data and vital signs will be summarized by descriptive statistics by 
treatment group.  The number and percentage of patients with confirmed positive ATA 
levels will be reported for each treatment group. 
6.4   
PHARMACOKINETIC ANALYSES 
Individual and mean serum lampalizumab concentration−time data will be tabulated and 
plotted by dose level.  The serum pharmacokinetics of lampalizumab may be 
summarized by parameters estimates of maximum observed serum concentration (C
max), 
time of maximum observed serum concentration (t
max), and time to steady-state and 


 
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accumulation ratio.  Estimates for these parameters will be tabulated and summarized 
by descriptive statistics.  Additional PK analyses maybe conducted as appropriate. 
6.5   
HANDLING OF MISSING DATA 
All efforts will be made to avoid missing data.  In the primary analysis, missing data will 
not be imputed.  Sensitivity analyses based on imputed data may be performed to 
evaluate the impact of missing data on the results. 
7.   
DATA COLLECTION AND MANAGEMENT 
7.1   
DATA QUALITY ASSURANCE 
A contract research organization (CRO) will be responsible for the data management of 
this study, including quality checking of the data.  Data entered manually will be 
collected via EDC through use of eCRFs.  Sites 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 Sponsor will perform oversight of the data management of this study.  The Sponsor 
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 the Sponsor using the Sponsor’s standard procedures to handle and 
process the electronic transfer of these data. 
eCRFs and correction documentation will be maintained in the EDC system’s audit trail.  
System backups for data stored by the Sponsor and records retention for the study data 
will be consistent with the Sponsor’s standard procedures.  
7.2   
ELECTRONIC CASE REPORT FORMS  
eCRFs are to be completed through use of a Sponsor-designated EDC system.  Sites 
will receive training and have access to a manual for appropriate eCRF completion.  
eCRFs will be submitted electronically to the Sponsor and should be handled in 
accordance with instructions from the Sponsor. 
All eCRFs should be completed by designated, trained site staff.  eCRFs should be 
reviewed and electronically signed and dated by the investigator or a designee. 
At the end of the study, the investigator will receive patient data for his or her site in a 
readable format on a compact disc that must be kept with the study records.  
Acknowledgement of receipt of the compact disc is required.  
7.3   
SOURCE DATA DOCUMENTATION 
Study monitors will perform ongoing source data verification to confirm that critical 
protocol data (i.e., source data) entered into the eCRFs by authorized site personnel are 
accurate, complete, and verifiable from source documents.  


 
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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 
and complete, microfiche, photographic negatives, microfilm or magnetic media, X-rays, 
patient files, and records kept at pharmacies, laboratories, and medico-technical 
departments involved in a clinical trial. 
Before study initiation, the types of source documents that are to be generated will be 
clearly defined in the Trial Monitoring Plan.  This includes any protocol data to be 
entered directly into the eCRFs (i.e., no prior written or electronic record of the data) and 
considered source data. 
Source documents that are required to verify the validity and completeness of data 
entered into the eCRFs must not be obliterated or destroyed and must be retained per 
the policy for retention of records described in Section 7.5. 
To facilitate source data verification, the investigators and institutions must provide the 
Sponsor direct access to applicable source documents and reports for trial-related 
monitoring, Sponsor audits, and IRB/EC review.  The study site must also allow 
inspection by applicable health authorities. 
7.4   
USE OF COMPUTERIZED SYSTEMS 
When clinical observations are entered directly into a study site’s computerized medical 
record system (i.e., in lieu of original hardcopy records), the electronic record can serve 
as the source document if the system has been validated in accordance with health 
authority requirements pertaining to computerized systems used in clinical research.  
An acceptable computerized data collection system allows preservation of the original 
entry of data.  If original data are modified, the system should maintain a viewable audit 
trail that shows the original data as well as the reason for the change, name of the 
person making the change, and date of the change. 
7.5   
RETENTION OF RECORDS 
Records and documents pertaining to the conduct of this study and the distribution of 
IMP, including eCRFs, ePRO data (if applicable), 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.   


 
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80/Protocol GX29455, Version 3 
No records may be disposed of without the written approval of the Sponsor.  Written 
notification should be provided to the Sponsor prior to transferring any records to 
another party or moving them to another location. 
8.   
ETHICAL CONSIDERATIONS 
8.1   
COMPLIANCE WITH LAWS AND REGULATIONS 
This study will be conducted in full conformance with the ICH E6 guideline for Good 
Clinical Practice and the principles of the Declaration of Helsinki, or the laws and 
regulations of the country in which the research is conducted, whichever affords the 
greater protection to the individual.  The study will comply with the requirements of the 
ICH E2A guideline (Clinical Safety Data Management:  Definitions and Standards for 
Expedited Reporting).  Studies conducted in the United States or under a U.S. 
Investigational New Drug (IND) application will comply with U.S. FDA regulations and 
applicable local, state, and federal laws.   
8.2   
INFORMED CONSENT 
The Sponsor’s sample Informed Consent Form (and ancillary sample Informed Consent 
Forms such as a Child’s Assent or Caregiver
's 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. 
The Informed Consent Form will contain a separate section that addresses the use of 
remaining mandatory samples and the collection of the optional aqueous humor samples 
from the randomized study patients for exploratory research.  The investigator or 
authorized designee will explain to each patient the objectives of the exploratory 
research.  Patients will be told that they are free to refuse to participate and may 
withdraw their specimens at any time and for any reason during the storage period.  
A separate, specific signature will be required to document a patient
's agreement to 
allow any remaining specimens and the collection of the optional aqueous humor 
samples to be used for exploratory research.  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 


 
Lampalizumab—Genentech, Inc. 
81/Protocol GX29455, Version 3 
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. 
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. 
8.3   
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 and reviewed and approved by the IRB/EC before the study is initiated.  
In addition, any patient recruitment materials must be approved by the IRB/EC.  
The Principal Investigator is responsible for providing written summaries of the status of 
the study to the IRB/EC annually or more frequently in accordance with the requirements, 
policies, and procedures established by the IRB/EC.  Investigators are also responsible 
for promptly informing the IRB/EC of any protocol amendments (see Section 9.6). 
In addition to the requirements for reporting all adverse events to the Sponsor, 
investigators must comply with requirements for reporting serious adverse events to the 
local health authority and IRB/EC.  Investigators may receive written IND safety reports 
or other safety-related communications from the Sponsor.  Investigators are responsible 
for ensuring that such reports are reviewed and processed in accordance with health 
authority requirements and the policies and procedures established by their IRB/EC, and 
archived in the site’s study file.  
8.4   
CONFIDENTIALITY 
The Sponsor maintains confidentiality standards by coding each patient enrolled in the 
study through assignment of a unique patient identification number.  This means that 
patient names are not included in data sets that are transmitted to any Sponsor location. 


 
Lampalizumab—Genentech, Inc. 
82/Protocol GX29455, Version 3 
Patient medical information obtained by this study is confidential and may be disclosed 
to third parties only as permitted by the Informed Consent Form (or separate 
authorization for use and disclosure of personal health information) signed by the patient, 
unless permitted or required by law. 
Medical information may be given to a patient’s personal physician or other appropriate 
medical personnel responsible for the patient’s welfare, for treatment purposes. 
Data generated by this study must be available for inspection upon request by 
representatives of the U.S. FDA and other national and local health authorities, Sponsor 
monitors, representatives, and collaborators, and the IRB/EC for each study site, as 
appropriate. 
8.5   
FINANCIAL DISCLOSURE 
Investigators will provide the Sponsor with sufficient, accurate financial information in 
accordance with local regulations to allow the Sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate health authorities.  
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study (i.e., LPLV). 
9.   
STUDY DOCUMENTATION, MONITORING, AND 
ADMINISTRATION 
9.1   
STUDY DOCUMENTATION 
The investigator must maintain adequate and accurate records to enable the conduct of 
the study to be fully documented, including but not limited to the protocol, protocol 
amendments, Informed Consent Forms, and documentation of IRB/EC and 
governmental approval.  In addition, at the end of the study, the investigator will receive 
the patient data, including an audit trail containing a complete record of all changes to 
data. 
9.2   
PROTOCOL DEVIATIONS 
The investigator should document and explain any protocol deviations.  The investigator 
should promptly report any deviations that might have an impact on patient safety and 
data integrity to the Sponsor and to the IRB/EC in accordance with established IRB/EC 
policies and procedures. 
9.3   
SITE INSPECTIONS 
Site visits will be conducted by the Sponsor or an authorized representative for 
inspection of study data, patients’ medical records, and eCRFs.  The investigator will 
permit national and local health authorities, Sponsor monitors, representatives, and 
collaborators, and the IRBs/ECs to inspect facilities and records relevant to this study. 


 
Lampalizumab—Genentech, Inc. 
83/Protocol GX29455, Version 3 
9.4   
ADMINISTRATIVE STRUCTURE 
This research study is being sponsored by Genentech Inc, South San Francisco 
California.  Genentech will perform vendor management, data management, statistical 
programming, data analysis, safety and regulatory activities.  A CRO will be responsible 
for study management and will assist with data management.  An IxRS will be used for 
patient randomization and for management of study drug requests and shipments.  
A central laboratory will be used for most laboratory assessments and for storage of 
other laboratory samples (i.e., anti-lampalizumab antibody serum samples) prior to being 
shipped to Sponsor or its designee for analysis.  Data will be recorded by an EDC 
system using eCRFs (see Section 5.4.2.2) or forwarded to the Sponsor electronically 
(e.g., central laboratory data).  A central reading center will be used for ocular imaging 
analyses (e.g., FAF, near infrared, CFP, FA) which will be forwarded to the Sponsor 
electronically. 
9.5   
PUBLICATION OF DATA AND PROTECTION OF TRADE 
SECRETS 
Regardless of the outcome of a trial, the Sponsor is dedicated to openly providing 
information on the trial to healthcare professionals and to the public, both at scientific 
congresses and in peer-reviewed journals.  The Sponsor will comply with all 
requirements for publication of study results.  For more information, refer to the Roche 
Global Policy on Sharing of Clinical Trials Data at the following Web site: 
http://www.rochetrials.com/pdf/RocheGlobalDataSharingPolicy.pdf 
The results of this study may be published or presented at scientific congresses.  For all 
clinical trials in patients involving an IMP for which a marketing authorization application 
has been filed or approved in any country, the Sponsor aims to submit a journal 
manuscript reporting primary clinical trial results within 6 months after the availability of 
the respective clinical study report.  In addition, for all clinical trials in patients involving 
an IMP for which a marketing authorization application has been filed or approved in any 
country, the Sponsor aims to publish results from analyses of additional endpoints and 
exploratory data that are clinically meaningful and statistically sound. 
The investigator must agree to submit all manuscripts or abstracts to the Sponsor prior 
to submission for publication or presentation.  This allows the Sponsor to protect 
proprietary information and to provide comments based on information from other 
studies that may not yet be available to the investigator. 
In accordance with standard editorial and ethical practice, the Sponsor will generally 
support publication of multicenter trials only in their entirety and not as individual center 
data.  In this case, a coordinating investigator will be designated by mutual agreement. 


 
Lampalizumab—Genentech, Inc. 
84/Protocol GX29455, Version 3 
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements.  Any formal publication 
of the study in which contribution of Sponsor personnel exceeded that of conventional 
monitoring will be considered as a joint publication by the investigator and the 
appropriate Sponsor personnel. 
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of data from this study will become and remain the exclusive and unburdened 
property of the Sponsor, except where agreed otherwise. 
9.6   
PROTOCOL AMENDMENTS 
Any protocol amendments will be prepared by the Sponsor.  Protocol amendments will 
be submitted to the IRB/EC and to regulatory authorities in accordance with local 
regulatory requirements. 
Approval must be obtained from the IRB/EC and regulatory authorities (as locally 
required) before implementation of any changes, except for changes necessary to 
eliminate an immediate hazard to patients or changes that involve logistical or 
administrative aspects only (e.g., change in Medical Monitor or contact information). 


 
Lampalizumab—Genentech, Inc. 
85/Protocol GX29455, Version 3 
10.   
REFERENCES 
de Jong PT. Age-related macular degeneration. N Engl J Med 2006;355:1474−85. 
Do DV, Pieramici DJ, van Lookeren Campagne M, et al. A phase Ia dose-escalation 
study of the anti-factor D monoclonal antibody fragment FCFD4514S in patients 
with geographic atrophy. Retina 2014;34:313−20.  
Fritsche LG, Chen W, Schu M, et al. Seven new loci associated with age-related 
macular degeneration. Nat Genet 2013;45:433−9, 439e1−2.  
Holz FG, Bindewald-Wittich A, Fleckenstein M, et al., FAM-Study Group. Progression of 
geographic atrophy and impact on fundus autofluorescence patterns in age-related 
macular degeneration. Am J Ophthalmol 2007;143:463−72. 
Holz FG, Schmitz-Valckenberg S, Fleckenstein M. Recent developments in the 
treatment of age-related macular degeneration. J Clin Invest 2014a;124:1430−8. 
Holz FG, Strauss EC, Schmitz-Valckenberg S, et al. Geographic atrophy: clinical 
features and potential therapeutic approaches. Ophthalmology 
2014b;121:1079−91. 
Lim LS, Mitchell P, Seddon JM, et al. Age-related macular degeneration. Lancet 
2012;379:1728−38. 
Loyet KM, Deforge LE, Katschke KJ Jr, et al. Activation of the alternative complement 
pathway in vitreous is controlled by genetics in age-related macular degeneration. 
Invest Ophthalmol Vis Sci 2012;53:6628−37. 
Rohrer B, Guo Y, Kunchithapautham K, et al. Eliminating complement factor D reduces 
photoreceptor susceptibility to light-induced damage. Invest Ophthalmol Vis Sci 
2007;48:5282−9. 
Scholl HP, Charbel Issa P, 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;27:204−10. 
van de Ven JP, Nilsson SC, Tan PL, et al. A functional variant in the CFI gene confers a 
high risk of age-related macular degeneration. Nat Genet 2013;45:813−7.  
Yates JR, Sepp T, Matharu BK et al. Complement C3 variant and the risk of age-related 
macular degeneration. N Engl J Med 2007;357:553−61.  
 


 
Lampalizumab—Genentech, Inc. 
86/Protocol GX29455, Version 3 
Appendix 1   
Study Flowchart Safety Run-In Assessment:  Screening, Day 1 through Hiatus a 
and Early Termination 
Note:  After completion of baseline visits, safety run-in assessment patients will have study visits every 2 weeks according to the 
Week X schedule shown below (i.e., Week 2, Week 4, Week 6, etc.) until notification by the Sponsor that the hiatus has begun.  
Thereafter, the safety run-in patients will continue Q2W visits according to Appendix 2 with the exception of the optional anterior 
chamber (aqueous humor) sampling (i.e., patients in the safety run-in will not participate in the optional anterior chamber 
sampling). 
Baseline 
 Week X 
Visits  Screening 
Day 1 
 +1 
Day
 + 7 
Days  Week X
 + 1 
Day
 +7 
Days
Early Term b 
Assessment Window (Days) 
−21 to −1   
NA   
(±
 0)   
(±
 2)   
(+ 4)    (±
 0)   
(±
 2)   
(+ 7) 
Written informed consent 
x   
   
   
   
   
   
 
 
Review of inclusion and exclusion criteria 
x   
x   
   
   
   
   
 
 
Site to contact IxRS (as applicable) c 
x   
x   
   
   
x   
   
 
x 
Medical and surgical history including 
tobacco history 
d  
x   
   
   
   
   
   
 
 
Demographic information 
x   
   
   
   
   
   
 
 
Physical examinatione 
x   
   
   
   
   
   
 
x 
Vital signs e  
x   
x   
   
   
   
   
 
x 
Central laboratory samples (hematology, 
coagulation, serum chemistry, and urinalysis) f 
x   
   
   
   
   
   
 
x 
Serum anti-lampalizumab antibody sample 
PRE-treatment f 
   
x   
   
   
x
f 
   
 
x 
Serum PK sample for lampalizumab 
concentration PRE-treatment f 
   
x   
   
   
x
f 
   
 
x 
Serum PK sample for lampalizumab 
concentration POST-treatment f 
   
x   
   
 
 
  
    
 
AH50 samples PRE-treatment f 
   
x   
   
   
x
f   
   
 
x 
Serum pregnancy test f, g  
x   
   
   
   
   
   
 
x 


Appendix 1   
Study Flowchart Safety Run-In Assessment:  Screening, Day 1 through Hiatus a  
and Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
87/Protocol GX29455, Version 3 
Baseline 
 Week X 
Visits  Screening 
Day 1 
 +1 
Day
 + 7 
Days  Week X
 + 1 
Day
 +7 
Days
Early Term b 
Assessment Window (Days) 
−21 to −1   
NA   
(±
 0)   
(±
 2)   
(+ 4)    (±
 0)   
(±
 2)   
(+ 7) 
Urine pregnancy test f, g 
   
x   
   
   
x   
   
 
 
CFI biomarker whole blood sample f 
x   
   
   
   
   
   
 
 
Biomarker whole blood clinical genotyping  
sample f 
   
x   
   
   
   
   
 
 
BCVA testing (starting at 4 m) h 
x   
x   
   
   
x   
   
 
x 
Intraocular pressure 
x   
x   
   
   
x   
   
 
x 
Slit-lamp examination  
x   
x   
   
   
x   
   
 
x 
Dilated binocular indirect ophthalmoscopy  
x   
x   
   
   
x   
   
 
x 
FAF and NI j 
x   
   
   
   
   
   
 
x 
Fundus photography j 
x   
   
   
   
   
   
 
x 
Fluorescein angiography j 
x   
   
   
   
   
   
 
x 
Pre- and post-treatment antimicrobials (if 
applicable) k 
   
x   
   
   
x   
   
 
 
Administration of study drug 
   
x   
   
   
x   
   
 
 
Post-treatment finger counting and 
IOP measurement 
l 
   
x   
   
   
x   
   
 
 
Follow-up call m 
  
   
x   
x   
   
x   
x 
 
Concomitant medications n 
x   
x   
   
   
x   
   
 
x 
Adverse events o 
   
x   
   
   
x   
   
 
x 
Concurrent ocular procedures p 
   
x   
   
   
x   
   
 
x 
 
BCVA =
 best corrected visual acuity; FAF
 =
 fundus autofluorescence; IOP
 =
 intraocular pressure; IxRS = Interactive Voice and Web System; 


Appendix 1   
Study Flowchart Safety Run-In Assessment:  Screening, Day 1 through Hiatus a  
and Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
88/Protocol GX29455, Version 3 
NA =
 not applicable; NI
 =
 near infrared; PK = pharmacokinetic; Term = termination.    
Notes:  All ocular assessments are to be performed for both eyes unless noted otherwise.  All assessments are to be performed on the same 
day, except those at screening. 
a Genentech will inform the sites when the third evaluable patient has cleared the follow-up visit after the third study drug injection and the 
initiation and termination dates for the hiatus in the study drug treatment.  Patients will not receive any study treatment during the hiatus; after 
the hiatus, safety run-in assessment patients will follow the same treatment and scheduled visits as randomized study patients in the Q2W 
treatment arm (Appendix 2) for the remainder of their participation in the study (until the Week 24 visit).  
b  Patients who withdraw early from the study will have early termination visit 30 (+
 7) days after the last study treatment. 
c At screening, contact the IxRS (or if not available, contact the study team) to obtain patient screening number prior to assessments.  Prior to 
Day 1 visit, contact IxRS (if not available, you will receive confirmation directly from the study site monitor) to verify a patient’s biomarker 
eligibility.  On Day 1, contact IxRS for patient study number and study treatment kit assignment after all assessments are performed; at the 
remaining scheduled study treatment visits, obtain study treatment kit assignment after all visit assessments were performed.  At the early 
termination visit, contact the IxRS to request that patient’s status be changed to “early termination.”  At the final study visit, contact IxRS to 
request to change patient status to “completed.” 
d Significant medical and surgical history, including chronic and ongoing conditions (e.g., trauma, cancer, and ophthalmic history); tobacco use.   
e A targeted physical examination should include an evaluation of the head, eyes, ears, nose, throat, and cranial nerves.  Vital signs consist of 
blood pressure, pulse, respiration, and temperature; perform pre-treatment.  
f Obtain prior to fluorescein angiography (if applicable).  Collect PRE-treatment serum antibody at Weeks 4, 8, 16, and 24; PRE-treatment  
serum PK at Weeks 2, 4, 8, 16, and 24; and PRE-treatment AH50 samples at Weeks 2, 4, 8, 16, and 24.  Consult the Central Laboratory 
Manual for detailed description of the laboratory assessments.  
g  Collect serum sample at screening visit from women of childbearing potential.  If positive, do not enroll the patient in the study. Perform urine 
pregnancy test prior to each study treatment starting at Day 1 visit for women of childbearing potential.  If positive, collect a sample for the 
serum pregnancy test and forward to the central laboratory for analysis.  If the serum pregnancy test is positive, discontinue the patient from 
study treatment.  
h The VA examiner will be masked to the patient’s treated (study) eye and treatment assignment and will perform only the visual acuity 
(including refraction) assessments.  VA examiner is not allowed to perform any other tasks involving direct patient care. 
i Pre-injection IOP and IOP measurement at non-treatment visits will be measured prior to dilation. 
j FAF, and NI images, fluorescein angiograms, and fundus photographs (as applicable) will be forwarded to the central reading center (refer to 
the Central Reading Center Manual).   
k If applicable, before and after treatment, ensure that the patient self-administered antimicrobials as per the investigator’s discretion.  
 


Appendix 1   
Study Flowchart Safety Run-In Assessment:  Screening, Day 1 through Hiatus a  
and Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
89/Protocol GX29455, Version 3 
l  Finger-counting test followed by hand-motion and light-perception tests (when necessary) will be performed by the investigator within 
15 minutes post-study treatment.  At study treatment visits, IOP measurement will be obtained 60 (±
 10) minutes post-treatment in the study eye 
only.  If there are no safety concerns at 60 (±
 10) minutes, the patient will be discharged from the clinic.  If the IOP is increased ≥
 10 mmHg from 
pre-treatment measurement, the patient will remain in the clinic and will be treated in accordance with the investigator’s clinical judgment prior to 
the patient’s discharge.  
m Subsequent to the initial treatment visit, patients will receive a telephone call 1 day and 7 (± 2) days after each treatment visit to solicit adverse 
events.  If warranted, patients will be asked to return for unscheduled visit to assess possible adverse events. 
n Record any concomitant medications used by the patient within 7 days preceding Day 1 and through the conclusion of the patient’s study 
participation or early termination visit (i.e., any prescription medications or over
 −
 the-counter preparations other than protocol-specified 
procedural medications, and pre-treatment and post-treatment medications, such as proparacaine). 
o Adverse events will be recorded starting on Day 1 after the study treatment through the last study visit.  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.   
p 
Record all concurrent ocular procedures performed on the study or non-study eye. 
 


 
Lampalizumab—Genentech, Inc. 
90/Protocol GX29455, Version 3 
Appendix 2   
Study Flowchart for Randomized Study:  Q2W Arms:  Screening, Day 1, Week 2 through Week 24, 
and Early Termination 
Day 
Week  
Visits  Screening 
1   
2   4   6   8   10   12   14   16   18   20   22   24 
Assessment Windows (Days) 
−28 to −1   NA 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
Early 
Term a 
+  7 
Written informed consent 
x   
   
                                    
 
Review of inclusion and exclusion criteria   
x   
x   
                                    
 
Site to contact IxRS (as applicable) b 
x   
x   
x   x   x   x   x   x   x   x   x   x   x   x   
x 
Medical and surgical history including 
tobacco history 
c  
x    
      
  
  
  
  
  
  
  
  
  
  
    
 
Demographic information 
x   
   
                                    
 
Physical examination d 
x    
      
  
  
  
  
  
  
  
  
  
  
x    x 
Vital signs  d  
x    
x      
  
  
  
  
  
  
  
  
  
  
x    x 
Central laboratory samples (hematology, 
coagulation, serum chemistry, and 
urinalysis) e 
x    
      
  
  
  
  
  
  
  
  
  
  
x    x 
Serum anti-lampalizumab antibody sample 
PRE-treatment e 
 
x   
   x      x            x            x   
x 
Serum PK sample for lampalizumab 
concentration PRE-treatment e 
 
x   
x   x      x            x            x   
x 
Serum PK sample for lampalizumab 
concentration POST-treatment e 
 
x      
  
  
  
  
  
  
  
  
  
  
    
 
Optional anterior chamber (aqueous humor) 
sample PRE-treatment e 
 
x   
   x      x                           
 
AH50 samples PRE-treatment e 
   
x   
x   x      x            x            x   
x 
Serum pregnancy test e, f  
x    
      
  
  
  
  
  
  
  
  
  
  
x    x 
 


Appendix 2   
Study Flowchart for Randomized Study:  Q2W Arms:  Screening, Day 1, Week 2 through Week 24, 
and Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
91/Protocol GX29455, Version 3 
Day 
Week  
Visits  Screening 
1   
2   4   6   8   10   12   14   16   18   20   22   24 
Assessment Windows (Days) 
−28 to −1   NA 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
Early 
Term a 
+ 7 
Urine pregnancy test e, f 
   
x   
x   x   x   x   x   x   x   x   x   x   x      
 
CFI biomarker whole blood sample e    
x    
      
  
  
  
  
  
  
  
  
  
        
 
Biomarker whole blood clinical genotyping  
sample e 
    
x      
  
  
  
  
  
  
  
  
  
        
 
BCVA testing (starting at 4 m) g 
x   
x   
x   x   x   x   x   x   x   x   x   x   x   x   
x 
Intraocular pressure
 h 
  
x   
x   
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   x   
x 
Dilated binocular indirect ophthalmoscopy    
x   
x   
x   x   x   x   x   x   x   x   x   x   x   x   
x 
FAF and NI i 
x    
      
  
  
  
  
x    
  
  
  
  
x    
x 
Fundus photography i  
x    
      
  
  
  
  
x    
  
  
  
  
x    
x 
Fluorescein angiography i 
x    
      
  
  
  
  
  
  
  
  
  
  
x    
x 
Pre- and post-treatment topical 
antimicrobials (if applicable) j 
   
x   
x   x   x   x   x   x   x   x   x   x   x      
 
Administration of study drug or sham 
injection   
   
x   
x   x   x   x   x   x   x   x   x   x   x      
 
Post-treatment finger counting and 
IOP measurement 
k 
   
x   
x   x   x   x   x   x   x   x   x   x   x      
 
Concomitant medications l 
x   
x   
x   x   x   x   x   x   x   x   x   x   x   x   
x 
Adverse events m 
   
x   
x   x   x   x   x   x   x   x   x   x   x   x   
x 
Concurrent ocular procedures n 
   
x   
x   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   x      
 
 


Appendix 2   
Study Flowchart for Randomized Study:  Q2W Arms:  Screening, Day 1, Week 2 through Week 24, 
and Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
92/Protocol GX29455, Version 3 
BCVA =
 best corrected visual acuity; FAF
 =
 fundus autofluorescence; IOP
 =
 intraocular pressure; IxRS = Interactive Voice and Web System; 
NA =
 not applicable; NI
 =
 near infrared; PK = pharmacokinetic.    
Notes:  All ocular assessments are to be performed for both eyes unless noted otherwise.  All assessments are to be performed on the same day, 
except those at screening. 
a For patients who withdraw early from the study, early termination visit assessments will be performed 30 (+7) days after the last study treatment. 
b At screening, contact the IxRS to obtain patient screening number prior to assessments.  Prior to Day 1 visit, contact IxRS to verify a patient’s 
biomarker eligibility.  On Day 1, contact IxRS for patient study number and study treatment kit assignment after all assessments are performed; at 
the remaining scheduled study treatment visits, obtain study treatment kit assignment after all visit assessments were performed.  At the early 
termination visit, contact the IxRS to request that patient’s status be changed to “early termination.”  At the final study visit, contact IxRS to 
request to change patient status to “completed.” 
c Significant medical and surgical history, including chronic and ongoing conditions (e.g., trauma, cancer, and ophthalmic history); tobacco use.  
d A targeted physical examination should include an evaluation of the head, eyes, ears, nose, throat, and cranial nerves.  Vital signs consist of 
blood pressure, pulse, respiration, and temperature; perform pre-injection.  
e Obtain prior fluorescein angiography (if applicable). Consult the Central Laboratory Manual for detailed description of the laboratory assessments. 
f   Collect serum sample at screening visit from women of childbearing potential, including those who have had a tubal ligation.  If positive, do not 
enroll the patient in the study.  Perform urine pregnancy test prior to each study treatment starting at Day 1 visit for women of childbearing 
potential, including those who have had tubal ligation.  If positive, collect a sample for the serum pregnancy test and forward to the central 
laboratory for analysis.  If the serum pregnancy test is positive, discontinue the patient from study treatment. 
g The VA examiner will be masked to the patients’ treated (study) eye and treatment arm (drug vs. sham) assignment and will perform only the VA 
(including refraction) assessments.  VA examiner is not allowed to perform any other tasks involving direct patient care. 
h Pre-injection IOP and IOP measurement at non-treatment visits will be measured prior to dilation. 
i FAF, and NI images, fluorescein angiograms, and fundus photographs (as applicable) will be forwarded to the central reading center (refer to the 
Central Reading Center Manual).   
j If applicable, before and after study treatment, ensure that the patient self-administered antimicrobials as per the investigator’s discretion.   
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 treatment.  At study treatment visits, IOP measurement will be obtained 60 (±
 10) minutes post-study treatment in the study eye only.  
If there are no safety concerns at 60 (±
 10) minutes, the patient will be discharged from the clinic.  If the IOP is increased ≥
 10 mmHg from 
pre-treatment measurement, the patient will remain in the clinic and will be treated in accordance with the investigator’s clinical judgment prior to 
the patient’s discharge. 
l Record any concomitant medications used by the patient within 7 days preceding Day 1 and through the conclusion of the patient’s study 
participation or early termination visit (i.e., any prescription medications or over-the-counter preparations other than protocol-specified procedural 
medications, and pre-treatment and post-treatment medications, such as proparacaine).  
 


Appendix 2   
Study Flowchart for Randomized Study:  Q2W Arms:  Screening, Day 1, Week 2 through Week 24, 
and Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
93/Protocol GX29455, Version 3 
m Adverse events will be recorded starting on Day 1 after the study treatment through the last study visit.  Adverse events assessed by the 
physician as related to study drug should be followed until event resolves or the event is assessed as irreversible, chronic, or stable, even if 
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 treatment visit, patients treated with study drug or sham will receive a telephone call 3 (±1) days after each treatment 
visit to solicit adverse events. 


 
Lampalizumab—Genentech, Inc. 
94/Protocol GX29455, Version 3 
Appendix 3   
Study Flowchart for Randomized Study:  Q4W Arms:  Screening, Day 1, Week 4 through Week 24, 
and Early Termination 
Day 
Week  
Visits  Screening 
1   
4   8   12   16   20   24 
Assessment Windows (Days) 
−28 to −1   NA 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
Early Term a 
+ 7
 
Written informed consent 
x   
   
                  
 
Review of inclusion and exclusion criteria 
x   
x   
                  
 
Site to contact IxRS (as applicable) b 
x   
x   
x   x   x   x   x   x   
x 
Medical and surgical history including tobacco history c  
x    
      
  
  
  
        
 
Demographic information 
x   
   
                  
 
Physical examination d 
x   
   
               x   
x 
Vital signs d  
x   
x   
               x   
x 
Central laboratory samples (hematology, coagulation, serum chemistry, 
and urinalysis)e 
x   
   
               x   
x 
Serum anti-lampalizumab antibody sample PRE-treatment e 
   
x   
x   x      x      x   
x 
Serum PK sample for lampalizumab concentration PRE-treatment 
e 
   
x   
x   x      x      x   
x 
Serum PK sample for lampalizumab concentration POST-treatment e 
    
x      
  
  
  
        
 
Optional anterior chamber (aqueous humor) sample PRE-treatment e   
   
x   
x   x               
 
AH50 samples PRE-treatment e 
   
x   
   x      x      x   
x 
Serum pregnancy test e, f  
x   
   
               x   
x 
Urine pregnancy test e,f 
   
x   
x   x   x   x   x      
 
CFI biomarker whole blood sample e 
x    
      
  
  
  
        
 
Biomarker whole blood clinical genotyping  sample e 
    
x      
  
  
  
        
 
BCVA testing (starting at 4 m) g 
x   
x   
x   x   x   x   x   x   
x 
Intraocular pressure
h 
  
x   
x   
x   x   x   x   x   x   
x 


Appendix 3   
Study Flowchart for Randomized Study:  Q4W Arms:  Screening, Day 1, Week 2 through Week 24, 
and Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
95/Protocol GX29455, Version 3 
Day 
Week  
Visits  Screening 
1   
4   8   12   16   20   24 
Assessment Windows (Days) 
−28 to −1   NA 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
Early Term a 
+ 7
 
Slit-lamp examination  
x   
x   
x   x   x   x   x   x   
x 
Dilated binocular indirect ophthalmoscopy  
x   
x   
x   x   x   x   x   x   
x 
FAF and NI i 
x   
   
      x         x   
x 
Fundus photography i  
x   
   
      x         x   
x 
Fluorescein angiography i 
x   
   
               x   
x 
Pre- and post-treatment antimicrobials (if applicable) j 
   
x   
x   x   x   x   x      
 
Administration of study drug or sham injection    
   
x   
x   x   x   x   x      
 
Post-treatment finger counting and IOP measurement k 
   
x   
x   x   x   x   x      
 
Concomitant medications l 
x   
x   
x   x   x   x   x   x   
x 
Adverse events m 
   
x   
x   x   x   x   x   x   
x 
Concurrent ocular procedures n 
   
x   
x   x   x   x   x   x   
x 
Follow-up call (if applicable) o 
   
x   
x   x   x   x   x      
 
BCVA =
 best corrected visual acuity; FAF
 =
  fundus autofluorescence; IOP
 =
 intraocular pressure; IxRS = Interactive Voice and Web System; 
NA =
 not applicable; NI
 =
 near infrared; PK
 =
 pharmacokinetic.   
Notes:  All ocular assessments are to be performed for both eyes unless noted otherwise.  All assessments are to be performed on the same 
day, except those at screening. 
a For patients who withdraw early from the study, early termination assessments will be performed 30 (
 +
 7) days after the last study treatment. 
b At screening, contact the IxRS to obtain patient screening number prior to assessments.  Prior to the Day 1 visit, contact IxRS to verify a 
patient’s biomarker eligibility. On Day 1, contact IxRS for patient study number and study treatment kit assignment after all assessments are 
performed; at the remaining scheduled study treatment visits, obtain study treatment kit assignment after all visit assessments were 
performed.  At the early termination 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”. 
c Significant medical and surgical history, including chronic and ongoing conditions (e.g., trauma, cancer, and ophthalmic history); tobacco 
use.  


Appendix 3   
Study Flowchart for Randomized Study:  Q4W Arms:  Screening, Day 1, Week 2 through Week 24, 
and Early Termination (cont.) 
Lampalizumab—Genentech, Inc. 
96/Protocol GX29455, Version 3 
Day 
Week  
Visits  Screening 
1   
4   8   12   16   20   24 
Assessment Windows (Days) 
−28 to −1   NA 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
 +
 4 
Early Term a 
+ 7
 
d A targeted physical examination should include an evaluation of the head, eyes, ears, nose, throat, and cranial nerves.  Vital signs consist of 
blood pressure, pulse, respiration, and temperature at all study visits; on days of study treatment administration, perform pre-treatment.  
e Obtain prior to fluorescein angiography (if applicable).  Consult the Central Laboratory Manual for a detailed description of the laboratory 
assessments.  
f   Collect serum sample at screening visit from women of childbearing potential, including those who have had a tubal ligation.  If positive, do 
not enroll the patient in the study. Perform urine pregnancy test prior to each study treatment starting at Day 1 visit for women of 
childbearing potential, including those who have had tubal ligation.  If positive, collect a sample for the serum pregnancy test and forward to 
the central laboratory for analysis.  If the serum pregnancy test is positive, discontinue the patient from study treatment. 
g The VA examiner will be masked to patients’ treated (study) eye and treatment arm (drug vs. sham) assignment and will perform only the VA 
(including refraction) assessments.  VA examiner is not allowed to perform any other tasks involving direct patient care. 
h Pre-treatment IOP and IOP measurement at non-treatment visits (as applicable) will be measured prior to dilation. 
i FAF and NI images, fluorescein angiograms, and fundus photographs (as applicable) will be forwarded to the central reading center (refer to 
the Central Reading Center Manual).   
j If applicable, before and after treatment, ensure that the patient self-administered antimicrobials as per the investigator’s discretion   
k  Finger-counting test followed by hand-motion and light-perception tests (when necessary) will be performed by the investigator within 
15 minutes after study treatment injection.  At study treatment visits, IOP measurement will be obtained 60 (±
 10) minutes post-treatment in 
the study eye only.  If there are no safety concerns at 60 (±
 10) minutes, the patient will be discharged from the clinic.  If the IOP is increased 
≥
 10 mmHg from pre-treatment measurement, the patient will remain in the clinic and will be treated in accordance with the investigator’s 
clinical judgment prior to the patient’s discharge. 
l Record any concomitant medications used by the patient within 7 days preceding Day 1 and through the conclusion of the patient’s study 
participation or early termination visit (i.e., any prescription medications or over
 −
 the-counter preparations other than protocol-specified 
procedural medications, and pre-treatment and post-treatment medications, such as proparacaine). 
m Adverse events will be recorded starting on Day 1 after the study treatment through the last study visit.  Adverse events assessed by the 
physician as related to study drug should be followed until event resolves or the event is assessed as irreversible, chronic, or stable, even if 
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 treatment visit, patients treated with study drug or sham will receive a telephone call 3 (±1) days after each 
treatment visit to solicit adverse events. 
 


 
Lampalizumab—Genentech, Inc. 
97/Protocol GX29455, Version 3 
Appendix 4   
Study Flowchart:  Unscheduled Safety Visit Assessments 
Assessment a 
 
Vital signs (blood pressure, respiration rate, temperature, and pulse)   
x 
Physical exam 
x 
Best corrected visual acuity (4-meter 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 the 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. 
98/Protocol GX29455, Version 3 
Appendix 5   
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 5   
Grading Scale for Assessment of Anterior Chamber Flare or 
Cells and Vitreous Cells (cont.) 
Lampalizumab—Genentech, Inc. 
99/Protocol GX29455, Version 3 
Grading Scale for Vitreous Cells 
Cells in Retro-Illuminated Field   
Description 
Grade 
0 
Clear 
0 
1−20 
Few opacities 
Trace 
21−50 
Scattered opacities 
1 
51−100 
Moderate opacities 
2 
101−250 
Many opacities 
3 
≥ 251 
Dense opacities 
4 
Modified from: Nussenblatt RB, Whitcup SM, Palestine AG. Uveitis: fundamentals 
and clinical practice; 2nd ed. St Louis: Mosby, 1996; 64. 
 
 


 
Lampalizumab—Genentech, Inc. 
100/Protocol GX29455, Version 3 
Appendix 6   
Pre-Injection Procedures for All Patients 
The pre-injection procedure, lampalizumab reconstitution and injection and sham 
injection procedures and post-injection procedures are also described in details in the 
Pharmacy Binder. 
While reconstituting lampalizumab, a sterile field must be used, and any 
personnel must wear a surgical face mask.  Lampalizumab should be administered 
within 2 hours following reconstitution; the prepared dose may be maintained at room 
temperature prior to administration. 
The following procedures will be used to minimize the risk of potential adverse events 
associated with intravitreal (ITV) injections (e.g., endophthalmitis).  Aseptic technique will 
be observed by clinic staff involved in the injection tray assembly, anesthetic 
preparation, and study drug (lampalizumab) preparation and administration.  In addition 
to the procedures outlined below, any additional safety measures in adherence to 
specific institutional policies associated with ITV injections will be observed. 
As per individual site investigator decision, patients may self-administer antimicrobial 
drops prior to treatment and after treatment following each injection (study drug or 
sham). 
The following procedures will be conducted by the physician performing the ITV injection 
of study drug: 
•   Prepare a sterile field with supplies that include the following: 
•  10% povidone iodine swabs, sterile surgical gloves 
•  4 × 4 sterile pads 
•  a pack of sterile cotton-tipped applicators 
•  eyelid speculum 
•  sterile ophthalmic drape 
•  0.5% proparacaine hydrochloride 
•  5% povidone iodine ophthalmic solution 
•  1% or 2% lidocaine for the anesthesia, ophthalmic antimicrobial solution 
(per individual investigator decision), and injection supplies 
•   Instill two drops of 0.5% proparacaine hydrochloride into the study eye 
•   Wait 90 seconds 
•   As per individual investigator decision, instill two drops of antimicrobial drops 
(e.g., ofloxacin ophthalmic solution [Ocuflox
®], trimethoprim-polymyxin B ophthalmic 
solution [Polytrim®], moxifloxacin ophthalmic solution [Vigamox
®], or gatifloxacin 
ophthalmic solution [Zymar®] single-use vial)   


Appendix 6   
Pre-Injection Procedures for All Patients (cont.) 
Lampalizumab—Genentech, Inc. 
101/Protocol GX29455, Version 3 
•   Wait 5 minutes 
•   Instill two more drops of 0.5% proparacaine hydrochloride into the study eye 
•   Wait 90 seconds  
•   Disinfect the periocular skin and eyelid of the study eye in preparation for injection.  
Scrub the eyelid, lashes, and periorbital skin with 10% povidone iodine swabs, 
starting with the eyelid and lashes and continuing with the surrounding periocular 
skin.  Ensure that the eyelid margins and lashes are swabbed, and proceed in a 
systematic fashion, from medial to temporal aspects. 
NOTE: For patients who develop adverse reaction to povidone-iodine, the following approaches 
are permitted:  irrigate the eye with sterile saline after the study treatment (lampalizumab or 
sham) with the aim to rinse away any remaining povidone-iodine or use a limited amount of 
povidone-iodine by placing a swab directly on the treatment site after the lid speculum has been 
placed. 
 


 
Lampalizumab—Genentech, Inc. 
102/Protocol GX29455, Version 3 
Appendix 7   
Preparation and Administration of Lampalizumab Injection 
The drug must be reconstituted using a sterile field while personnel are wearing a 
surgical face mask.  Within 2 hours following dose preparation (reconstitution), 
lampalizumab should be administered; the prepared dose may be maintained at room 
temperature prior to administration.   
Reconstitute the for 10-mg lampalizumab dose as follows: 
1.   Remove the plastic flip-off seal from one vial of lampalizumab lyophilized powder 
(6-cc vial), and swab the top of the vial with an alcohol swab. 
2.   Remove the plastic flip-off seal from one vial of Sterile Water for Injection (SWFI) 
(10-cc vial), and swab the top of the vial with an alcohol swab. 
3.   Using a 1-cc tuberculin syringe, withdraw 0.50 mL of SWFI (10-cc vial) from a vial, 
expel any air bubbles, insert the syringe into the lampalizumab vial, and add. 
4.  Swirl the lampalizumab vial gently until the lyophilized powder dissolves; do not 
shake or vortex the vial vigorously.  Let stand for approximately 5 minutes until 
bubbles dissolve. 
 
Filter the lampalizumab as follows: 
1.   Withdraw 0.2 mL of lampalizumab dose solution through a 19-gauge, 1.5 TW, 5-μm 
filter needle attached to a 1-cc tuberculin syringe. 
2.  After withdrawing lampalizumab in through the filter, remove filter needle; replace 
it with a 30-gauge, 0.5-inch Precision Glide
® needle and expel excess of 
lampalizumab so that the syringe contains 0.1 mL of lampalizumab solution for 
dosing. 


Appendix 7   
Preparation and Administration of Lampalizumab Injection (cont.) 
Lampalizumab—Genentech, Inc. 
103/Protocol GX29455, Version 3 
Table 1   Lampalizumab Reconstitution 
Step   Procedure 
Materials 
Methods 
1  
Reconstitute the lyophilized 
lampalizumab 
Note:  Vials of lampalizumab 
should remain refrigerated 
(2°C-8°C or 36°F−46°F) until 
just prior to reconstitution with 
SWFI. 
•  One vial of lyophilized 
lampalizumab 
•  1-cc tuberculin 
syringes 
•  10-cc vial of SWFI 
•  Alcohol swabs 
Swab the top of lampalizumab 
vial with an alcohol swab after 
removing the flip-top seal. 
Swab the top of SWFI vial with 
an alcohol swab after removing 
the flip-top seal. 
Expel any air bubbles from the 
syringe prior to injecting 
0.50 mL SWFI into 
lampalizumab vial. 
Swirl the lampalizumab vial 
containing the SWFI gently 
until the lyophilized powder 
dissolves.  Do not shake 
vigorously or vortex the 
vials.  Let stand for 
approximately 5 minutes until 
bubbles dissolve. 
2  
Filter the lampalizumab  
•  5-μm filter needle 
(needle is 19-gauge, 
1.5 TW) 
•  1-cc tuberculin 
syringe 
•  30 gauge, 0.5-inch 
Precision Glide 
needle 
 
Withdraw 0.2 mL of 
lampalizumab dose solution 
through a 5-μm filter needle 
attached to a 1-cc tuberculin 
syringe. 
After withdrawing 
lampalizumab in through the 
filter, remove filter needle, 
replace it with a 30-gauge, 
0.5-inch Precision Glide 
needle, expel excess 
lampalizumab so that the 
syringe contains 0.1 mL of 
lampalizumab solution. 
SWFI =
 Sterile Water for Injection. 
 
ADMINISTRATION OF LAMPALIZUMAB 
To administer intravitreal lampalizumab, the treating physician will conduct the following 
procedures: 
•   Put on gloves, place sterile ophthalmic drape to isolate the field, and place the 
speculum underneath the eyelid of the study eye. 
•   Instill two drops of 5% povidone iodine ophthalmic solution in the study eye, 
ensuring that the drops cover the planned injection site on the conjunctiva. 
•   Wait 90 seconds. 


Appendix 7   
Preparation and Administration of Lampalizumab Injection (cont.) 
Lampalizumab—Genentech, Inc. 
104/Protocol GX29455, Version 3 
•   Saturate a sterile, cotton-tipped applicator with 0.5% proparacaine hydrochloride 
drops and hold the swab against the planned intravitreal injection site for 
10 seconds in preparation for the subconjunctival injection of 1% or 2% lidocaine 
hydrochloride solution for injection (without epinephrine). 
•   Inject 1% or 2% lidocaine (without epinephrine) subconjunctivally.  For the patients 
intolerant of lidocaine as evidenced by an associated adverse event, topical 
proparacaine may be permitted after consultation with the Medical Monitor.  
•   Use a sterile 4
 ×
 4 pad in a single wipe to absorb excess liquid and to dry the 
periocular skin. 
•   Instruct the patient to direct gaze away from syringe prior to lampalizumab injection. 
•  Physician will wear surgical face mask and refrain from talking, coughing, or 
sneezing during the injection. 
 
Administer lampalizumab as follows: 
•   Insert the needle through an area 3.5−4.0 mm posterior to the limbus, avoiding the 
horizontal meridian and aiming toward the center of the globe.  Rotate the injection 
site at every treatment visit. 
•  Inject the dose solution slowly. 
•   Remove the needle slowly to ensure that all drug solution is in the eye. 
•   Refer to Appendix 9 for detailed post-injection procedures 
 


 
Lampalizumab—Genentech, Inc. 
105/Protocol GX29455, Version 3 
Appendix 8   
Preparation and Administration of Sham Injection 
Genentech will supply all materials for the sham injections. 
The designated physician (a qualified ophthalmologist administering the intravitreal or 
sham injection) will prepare the sham injection as outlined below.    
SHAM PREPARATION 
The preparation process for the sham injection will be identical to the study drug 
injection (see Appendix 6).  A sterile tray will be assembled by study personnel.  The tray 
assembly will be identical for both lampalizumab and sham injections. 
Refer to Appendix 6 for detailed instructions for pre-injection procedures. 
The treating physician will not use a needle for the sham injection (except of lidocaine 
injection given subconjunctivally); the treating physician will discard the lidocaine needle 
and syringes from the sterile tray in the sharps container immediately following each 
sham injection and will return the sham vial in the kit box. 
SHAM ADMINISTRATION 
Patients receiving sham injections do not receive an actual injection.  The procedures for 
cleansing and anesthetizing the study eye will be performed as outlined in Appendix 6.  
The patient should be instructed to direct his or her gaze away from the syringe prior to 
administration of the sham injection.  The treating physician will withdraw the tuberculin 
syringe plunger to the 0.1-mL mark on the syringe, then place the hub of the 
syringe
 −
 without the needle −
 against the pre-anesthetized conjunctival surface.  
The treating physician will then press the syringe hub firmly against the globe and then 
slowly depress the plunger, mimicking the action of an injection. 
It is essential that the procedures of the sham injection, including preparation and the 
sham injection itself, mimic as much as possible those used for the administration of 
lampalizumab.  For subsequent sham injections, follow the same procedure of rotating 
the location of the injection site, as is done with the lampalizumab injections 
(see Appendix 6).  
The treating physician or unmasked technician (if applicable) will discard all injection 
materials (i.e., syringes and needles) in a sharps container immediately following each 
sham injection, and the empty vial will be placed in the kit box.  Refer to Appendix 9 for 
detailed post-injection procedures.  


 
Lampalizumab—Genentech, Inc. 
106/Protocol GX29455, Version 3 
Appendix 9   
Post-Injection Procedures for All Patients 
As per individual investigator decision, immediately following the lampalizumab or sham 
injection, instill two drops of antimicrobial drops (e.g., ofloxacin ophthalmic solution 
[Ocuflox
®], trimethoprim-polymyxin B ophthalmic solution [Polytrim
®], moxifloxacin 
ophthalmic solution [Vigamox®], or gatifloxacin ophthalmic solution [Zymar
®] single-use 
vial). 
The patient will be monitored with a finger-counting test within 15 minutes of the study 
drug or sham treatment by the treating physician. 
Discard the supplies in order to preserve patient’s masking.  Discard all syringes and 
needles in the sharps container. 
The used study drug/sham kit, including the used vial should be stored until Genentech 
representative conducts the study drug accountability and the site is instructed to discard 
or ship to Genentech. 
Any materials that could disclose the identity of study drug or patient treatment 
assignment should be removed from the tray. 
A measurement of IOP in the study eye only will be obtained 60 (±
 10) minutes after 
study treatment.  If there are no safety concerns at the 60 (±
 10) minute measurement, 
the patient may be discharged from the clinic.  If the IOP is increased by ≥
 10 mmHg 
from the pre-treatment measurement at 60 (±
 10) minutes and is of concern to the 
investigator, the patient will remain in the clinic to be treated in accordance with the 
investigator’s clinical judgment prior to discharge.  If applicable, the Adverse Event CRF 
page will be completed. 
As per individual site investigator decision, patients may self-administer antimicrobial 
drops after treatment following each injection (study drug or sham). 


 
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Appendix 10  
Best Corrected Visual Acuity Testing 
SCOPE 
Best corrected visual acuity (BCVA) will be measured by trained and certified personnel 
at the study sites.  The visual acuity (VA) examiner must be masked to each patient’s 
study (treated) eye, treatment arm (study drug vs. sham) assignment.  BCVA will be 
measured at the intervals specified in the protocol (see Section 4.5 of the protocol and 
Appendix 1, Appendix 2, and Appendix 3). 
EQUIPMENT 
The following are needed to conduct the examination: 
•   Examination lane of adequate dimensions to allow testing at required distances 
•   Standard chair with a firm back 
•   Set of three Precision Vision™ or Lighthouse distance acuity charts (modified Early 
Treatment Diabetic Retinopathy Study Charts R, 1, and 2 in the United States) 
•   Retro-Illuminated box 
•   Study frame 
•   Study lens set 
 
TRAINING AND CERTIFICATION 
A VA specifications document, procedure manual, and training materials will be provided 
to the investigational sites, and examiner certification will be obtained.  The VA 
examination room also must be certified before any VA examinations are performed. 
 


 
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Appendix 11  
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 
(see Appendix 1, Appendix 2, and Appendix 3).  Analysis (if applicable) of fundus 
photographs will be performed by the central reading center. 
EQUIPMENT 
See the Central Reading Center Manual. 
PROCEDURE 
The central reading center will provide a study manual and training materials.  The 
fundus photographer and photography equipment will be certified by the reading center 
before any study images are taken.  See the Central Reading Center Manual for further 
details. 
 


 
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109/Protocol GX29455, Version 3 
Appendix 12  
Fluorescein Angiography 
SCOPE 
Fluorescein angiography will be performed at the study sites by trained personnel who 
are certified by the central reading center.  The fluorescein angiograms (FAs) will be 
obtained at the intervals specified in the protocol (see Appendix 1, Appendix 2, and 
Appendix 3).  Analysis (if applicable) of FAs will be performed by the central reading 
center. 
EQUIPMENT 
Digital angiograms must be used while conducting an angiographic evaluation for the 
study. 
Film-based angiography is not acceptable. 
DIGITAL IMAGING SYSTEMS AND CERTIFICATION 
Digital imaging systems are required.  The system and software at the site will be 
certified by the central reading center prior to obtaining any study angiograms.  This 
certification and validation process will ensure that the central reading center will be able 
to correctly calculate the required measurements. 
PROCEDURES 
The central reading center will provide a study manual and training materials.  
Photographers, systems, and software will be certified prior to obtaining angiograms of 
patients. 
 


 
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Appendix 13  
Fundus Autofluorescence 
SCOPE 
Fundus autofluorescence (FAF) will be performed at the study sites by trained personnel 
who are certified by the central reading center.  FAF imaging will be performed for each 
patient at the intervals specified in the protocol (see Appendix 1, Appendix 2, and 
Appendix 3) and will be forwarded to the central reading center.  Analysis (if applicable) 
of FAF images will be performed by the central reading center. 
EQUIPMENT 
Equipment utilized during this study is described in the Central Reading Center Manual.  
The ability to transfer images to electronically exportable digital files is required (i.e., no 
printed FAF images will be sent to the central reading center). 
PROCEDURES AND CERTIFICATION 
The central reading center will provide the study manual and training materials.  
FAF operators, systems, and software will be certified prior to any evaluation of patients. 


 
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111/Protocol GX29455, Version 3 
Appendix 14  
Near-Infrared Imaging 
Note:  Near infrared (NI) images are taken to complement the central reading center 
evaluation of fundus autofluorescence images. 
SCOPE 
NI imaging will be performed at the study sites by trained personnel who are certified by 
the central reading center.  NI imaging will be performed for each patient at the intervals 
specified in the protocol (see Appendix 1, Appendix 2, and Appendix 3). 
The NI images of both eyes will be obtained at protocol-specified visits and will be 
forwarded to the central reading center. 
EQUIPMENT 
Equipment utilized during this study is described in the Central Reading Center Manual.  
The ability to transfer images to electronically exportable digital files is required 
(i.e., no printed NI images will be sent to the central reading center). 
PROCEDURES AND CERTIFICATION 
The central reading center will provide the study manual and training materials.  
NI operators, systems, and software will be certified prior to any evaluation of patients. 
 


 
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Appendix 15  
Biological Sample Collection and Shipping Instructions 
BIOLOGICAL SAMPLES 
Biological samples for the assessment of lampalizumab concentrations 
(pharmacokinetics), anti-lampalizumab antibodies, systemic alternative complement 
pathway activity assay, complement factor I whole blood sample, biomarker whole blood 
clinical genotyping sample and laboratory assessment (hematology, serum chemistry, 
coagulation, and urinalysis) samples will be collected at the timepoints specified in 
Appendix 1, Appendix 2, and Appendix 3. 
Refer to the Central Laboratory Manual for detailed sample collection, storage, and 
shipping instructions.  All necessary transfer tubes, Vacutainers™, labels, shipping 
boxes, and forms will be provided by the central laboratory. 
OPTIONAL ANTERIOR CHAMBER (AQUEOUS HUMOR) SAMPLE 
COLLECTION 
The optional aqueous humor paracentesis samples will be collected from patients who 
consent to the procedure and sample acquisition.  An aqueous humor sample will be 
collected before the patient’s study eye treatment visits as indicated in Appendix 1, 
Appendix 2, and Appendix 3.  The aqueous humor sample collection consists of an 
anterior chamber paracentesis (removing approximately 0.1 mL of fluid from the anterior 
chamber of the eye). 
The anterior chamber paracentesis will be performed by a qualified physician by placing 
a drop of topical anesthetic on the cornea, passing a 30-gauge needle through the 
limbus into the anterior chamber and removing 0.1 mL of aqueous fluid.   
Samples will be collected with the kit provided by central laboratory and shipped on dry 
ice to the central laboratory as soon as possible after the draw. 
For administration of study treatment following the collection of the aqueous humor 
sample, the subconjunctival lidocaine anesthetic must be injected into the eye prior to 
study drug/sham injection. 
 


 
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113/Protocol GX29455, Version 3 
Appendix 16  
The cobas® CFI Profile Clinical Trial Assay (CTA) 
The cobas complement factor I (CFI) Profile Clinical Trial Assay (CTA) is a real-time 
polymerase chain reaction (PCR) test developed by Roche Molecular Systems (RMS) to 
identify genotypes of three single−nucleotide polymorphisms (SNPs) associated with 
CFI, complement factor H (CFH), and C2/complement factor B (CFB) in DNA extracted 
from whole blood samples from patients with geographic atrophy (GA) secondary to 
age-related macular degeneration (AMD). The cobas CFI Profile CTA is intended to be 
used as an Investigational-Use-Only assay to characterize the complement factor profile 
of study participants.  It may also be used to stratify research participants for 
randomization or to enrich the study population with CFI biomarker-positive participants 
in specific type clinical studies. 
The cobas CFI Profile CTA consists of two kits and will use the cobas 4800 platform.  
The cobas DNA Sample Preparation Kit (DNA isolation kit) provides the necessary 
components to manually extract genomic DNA from whole blood samples.  The cobas 
CFI Profile CTA contains the necessary PCR master mix, oligonucleotides, cofactor, and 
controls to detect three SNPs associated with CFI, CFH, and C2/CFB. 
Valid cobas Test Results 
 
AMD 
Gene 
chr. 
No. 
Tagging 
SNP 
Tagging 
SNP 
Location
Risk 
Allele
Major 
Allele Risk Hmzy  
Het 
Non-Risk 
Hmzy 
MMx1  CFI  
4   rs4698775 CCDC  
G   
T 
rs4698775 
GG 
rs4698775 
TG 
rs4698775 
TT 
MMx2 
C2/ 
CFB  
6   rs429608  SKIV2L 
G   
G 
rs429608 
GG 
rs429608 
GA 
rs429608 
AA 
MMx3  CFH  
1   rs1329428 CFH  
C   
C 
rs1329428 
CC 
rs1329428 
CT 
rs1329428 
TT 
AMD =
 age-related macular degeneration; C
 =
 complement component; CF
 =
 complement factor; 
chr
 =
 chromosome; het
 =
 heterozygous; hmzy
 =
 homozygous; SNP
 =
 single nucleotide 
polymorphism. 
 
 


Appendix 16 
The cobas® CFI Profile Clinical Trial Assay (CTA) (cont.) 
 
Lampalizumab—Genentech, Inc. 
114/Protocol GX29455, Version 3 
MMx1 
MMx2  
MMx3 
  
CFI 
C2/CFB 
CFH 
Biomarker Status 
rs4698775 GG  
rs429608 GG   
rs1329428 CC 
+ 
rs4698775 GG  
rs429608 GG   
rs1329428 CT 
+ 
rs4698775 GG  
rs429608 GG   
rs1329428 TT 
+ 
rs4698775 GG  
rs429608 GA   
rs1329428 CC 
+ 
rs4698775 GG  
rs429608 GA   
rs1329428 CT 
+ 
rs4698775 GG  
rs429608 GA   
rs1329428 TT 
+ 
rs4698775 GG  
rs429608 AA   
rs1329428 CC 
+ 
rs4698775 GG  
rs429608 AA   
rs1329428 CT 
+ 
rs4698775 GG  
rs429608 AA   
rs1329428 TT 
− 
rs4698775 TG  
rs429608 GG   
rs1329428 CC 
+ 
rs4698775 TG  
rs429608 GG   
rs1329428 CT 
+ 
rs4698775 TG  
rs429608 GG   
rs1329428 TT 
+ 
rs4698775 TG  
rs429608 GA   
rs1329428 CC 
+ 
rs4698775 TG  
rs429608 GA   
rs1329428 CT 
+ 
rs4698775 TG  
rs429608 GA   
rs1329428 TT 
+ 
rs4698775 TG  
rs429608 AA   
rs1329428 CC 
+ 
rs4698775 TG  
rs429608 AA   
rs1329428 CT 
+ 
rs4698775 TG  
rs429608 AA   
rs1329428 TT 
− 
rs4698775 TT  
rs429608 GG   
rs1329428 CC 
− 
rs4698775 TT  
rs429608 GG   
rs1329428 CT 
− 
rs4698775 TT  
rs429608 GG   
rs1329428 TT 
− 
rs4698775 TT  
rs429608 GA   
rs1329428 CC 
− 
rs4698775 TT  
rs429608 GA   
rs1329428 CT 
− 
rs4698775 TT  
rs429608 GA   
rs1329428 TT 
− 
rs4698775 TT  
rs429608 AA   
rs1329428 CC 
− 
rs4698775 TT  
rs429608 AA   
rs1329428 CT 
− 
rs4698775 TT  
rs429608 AA   
rs1329428 TT 
−