Clinical trial NCT04549363
Conditions: Multiple Myeloma
Keywords: Belantamab mafodotin Impression cytology Superficial keratectomy Relapsed/Refractory multiple myeloma
Sponsor: GlaxoSmithKline
Start date: 2020-12-21; Completion date: 2022-11-21
Enrollment: 16 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will be available to any participant who has received or is currently receiving belantamab mafodotin treatment through either a clinical trial, an access program, or a physician prescription. Participants do not need to be on active treatment. The purpose of this study is to gain a more complete understanding of the pathophysiology of the corneal events seen in some participants with relapsed/refractory multiple myeloma (RRMM) treated with belantamab mafodotin. A superficial corneal epithelial tissue specimen will be obtained by performing impression cytology (IC) or superficial keratectomy (SK) procedure in participants treated with belantamab mafodotin. The procedure will only be performed in one eye, most affected by the corneal epithelial changes. This specimen will undergo pathologic examination and composition analysis.

Detailed description:

Arms: arm 1: IC will be performed on some participants who received or are receiving treatment with belantamab mafodotin for RRMM and have objective evidence of keratopathy with corneal deposits on slit-lamp and/or confocal microscopy examination and who do not agree to undergo SK. arm 2: SK will be performed on some participants who received or are receiving treatment with belantamab mafodotin for RRMM and have objective evidence of keratopathy with corneal deposits on slit-lamp and/or confocal microscopy examination.
Interventions: intervention 1: Belantamab mafodotin
Intervention descriptions: intervention 1: Belantamab mafodotin is a first-in-class immunoconjugate that targets B cell maturation antigen (BCMA), which is highly expressed on malignant plasma cells.

Protocol documents:
Prot_000.pdf: 
 
 
 
 
                                                         PROTOCOL 
 
 
Study ID: 214098 
 
Official Title of Study: Characterization of Corneal Epithelial Changes in Participants 
Treated with Belantamab Mafodotin (GSK2857916) 
 
Date of Document: 04-Feb-2021 
 
NCT ID: NCT04549363 
 
 


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GlaxoSmithKline group of companies 
 
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TITLE PAGE 
Protocol Title: Characterization of Corneal Epithelial Changes in Participants Treated 
with Belantamab Mafodotin (GSK2857916) 
Protocol Number: 214098 
Protocol Amendment: 02 
Compound Number or Name: GSK2857916 (Belantamab Mafodotin) 
Brief Title: Characterization of Corneal Epithelial Changes in Participants Treated with 
Belantamab Mafodotin (GSK2857916) 
Study Phase: IIIB 
Sponsor Name and Legal Registered Address:  
GlaxoSmithKline Research & Development Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
IND: 119333 
EudraCT: n/a 
NCT:  
Approval Date: 04-FEB-2021  
 
 
 
 
 
Copyright 2021 the GlaxoSmithKline group of companies. All rights reserved. 
Unauthorized copying or use of this information is prohibited. 
 


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SPONSOR SIGNATORY: 
Protocol Title: Characterization of Corneal Epithelial Changes in Participants Treated 
with Belantamab Mafodotin (GSK2857916) 
Protocol Number: 214098 
Protocol Amendment: 02 
Compound Number or Name: GSK2857916 (Belantamab Mafodotin) 
 
 
 
 
 
 
 
 
 
 
 
Roxanne Cacioppo, PhD 
Global Medical Lead, Belantamab Mafodotin 
 
Date 
 


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document Type 
Document Number 
Date 
Amendment 2 
TMF-11824254 
04-FEB-2021 
Amendment 1.    
2020N434638_01 
28-JUL-2020 
Original Protocol-  
2020N434638_00 
20-May-2020 
 
Amendment 2: 04-FEB-2021 
Overall Rationale for the Amendment:  
 
The protocol has been amended to allow the inclusion of patients receiving belantamab 
mafodotin through a Physician prescription.  
 
Section # and Name 
Description of Change 
Brief Rationale 
Title Page 
Deleted “companion” study from 
protocol title 
This protocol has 
been amended to 
allow both trial 
participants and 
patients on 
commercial 
prescriptions.  It is no 
longer exclusively a 
companion study.  
1.1 Synopsis  
Objectives and Endpoints: updated 
Exploratory endpoint 
 
Overall Design:  Allow Inclusion of 
patients receiving belantamab 
mafodotin through a Physician 
prescription 
 
Brief Summary: Clarification of 
steroid treatment 
Clarification 
 
 
Expand pool of 
eligible patients 
 
 
 
Clarification 
1.2 Schema 
Updated to remove symptom 
requirement 
Clarification 
1.3 Schedule of 
Activities 
Added data collection, clarified 
procedural footnotes 
Clarification 
2.2 Background 
Clarification of steroid treatment 
 
Reference to inclusion of patients 
receiving belantamab mafodotin 
through a Physician prescription 
Clarification 
3 Objectives and 
Endpoints 
Updated Exploratory endpoint 
Clarification 
4.1 Overall Design 
Allow Inclusion of patients 
receiving belantamab mafodotin 
through a Physician prescription 
 
Updated design criteria 
Expand pool of 
eligible patients 
 
 
Clarification 


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Section # and Name 
Description of Change 
Brief Rationale 
4.2 Study Procedures 
Clarified that the target eye for the 
procedure is the one with the greater 
number of MECs 
Clarification 
5.1 Inclusion Criteria 
Patients with superficial punctate 
keratopathy and no evidence of 
MEC’s are not eligible 
 
Deleted reference to Grade 2 or 3 
CTCAE v 5.0 
Clarification 
5.2 Exclusion Criteria 
Added restriction on concurrent 
medication that might affect the 
cornea 
 
Added exclusion for any patient with 
decreased corneal sensation 
Safety 
 
 
 
 
 
Safety 
 
6.2 Patient Selection 
Considerations 
Added Section on patient selection 
criteria 
Safety 
6.4 Superficial 
Keratectomy 
procedure 
Clarification of steroid treatment 
Clarification 
6.9 Imaging 
Procedures 
Added Section to clarify imaging 
procedures 
Clarification 
6.10 Concomitant 
Therapy 
Added restriction on concurrent 
medication that might affect the 
cornea 
Safety 
8.1.3 Time Period and 
Frequency for 
Collecting AE and 
SAE Information 
Clarification of AE/SAE collection, 
collect related AE/SAE only 
Clarification 
8.1.5 Follow-up of 
Aes and SAEs 
Clarification of AE/SAE collection, 
collect related AE/SAE only 
Clarification 
8.3 Data Collection 
Added section on data collection 
Clarification 
10.2.5 Reporting of 
SAEs to GSK 
Added contact email 
Clarification 
Whole Document  
Removed any instance of 
“companion” or “companion study” 
This protocol has 
been amended to 
allow both trial 
participants and 
patients on 
commercial 
prescriptions.  It is no 
longer exclusively a 
companion study. 
 


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5  
 
T A B L E O F C O N T E N T S  
P A G E  
TI T L E P A G E  ................................................................................................................... 1  
S P O N S O R SI G N A T O R Y:  ............................................................................................... 2  
P R O T O C O L A M E N D M E N T S U M M A R Y O F C H A N G E S T A B L E  ..................................... 3  
T A B L E O F C O N T E N T S  .................................................................................................. 5  
1  
P R O T O C O L  S U M M A R Y  .......................................................................................... 7  
1. 1.  
S y n o p si s  ....................................................................................................... 7  
1. 2.  
S c h e m a  ...................................................................................................... 1 2  
1. 3.  
S c h e d ul e of A cti viti e s ( S o A)  ........................................................................ 1 3  
2.  
I N T R O D U C TI O N .................................................................................................... 1 5  
2. 1.  
St u d y R ati o n al e  .......................................................................................... 1 5  
2. 2.  
B a c k gr o u n d  ................................................................................................ 1 5  
2. 3.  
B e n efit s a n d Ri s k s  ...................................................................................... 2 0  
2. 3. 1.  
B e n efit A s s e s s m e nt  ..................................................................... 2 0  
2. 3. 2.  
O v er all B e n efit/ Ri s k C o n cl u si o n  ................................................... 2 1  
3.  
O B J E C TI V E S A N D E N D P O I N T S ........................................................................... 2 1  
4.  
S T U D Y D E SI G N  .................................................................................................... 2 2  
4. 1.  
O v er all D e si g n  ............................................................................................ 2 2  
4. 2.  
St u d y Pr o c e d ur e s  ....................................................................................... 2 2  
4. 3.  
E n d of St u d y D efi niti o n  ............................................................................... 2 5  
5.  
S T U D Y P O P U L A TI O N  ........................................................................................... 2 5  
5. 1.  
I n cl u si o n Crit eri a ......................................................................................... 2 5  
5. 2.  
E x cl u si o n Crit eri a  ........................................................................................ 2 5  
6.  
S T U D Y I N T E R V E N TI O N( S ) A N D C O N C O MI T A N T T HE R A P Y  .............................. 2 6  
6. 1.  
St u d y I nt er v e nti o n( s) A d mi ni st er e d  ............................................................. 2 6  
6. 2.  
P ati e nt S el e cti o n C o n si d er ati o n s  ................................................................ 2 6  
6. 2. 1.  
S el e cti o n of Ri g ht or L eft e y e f or t h e pr o c e d ur e  ........................... 2 6  
6. 2. 2.  
S el e cti o n of S K or I C pr o c e d ur e  ................................................... 2 6  
6. 3.  
I m pr e s si o n C yt ol o g y Pr o c e d ur e .................................................................. 2 7  
6. 8.  
s B C M A S a m pl e C oll e cti o n a n d A n al y si s  ..................................................... 2 9  
6. 9.  
I m a gi n g Pr o c e d ur e s .................................................................................... 2 9  
6. 1 0.  C o n c o mit a nt T h er a p y .................................................................................. 2 9  
7.  
DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L  .................................................................... 3 0  
7. 1.  
P arti ci p a nt Di s c o nti n u ati o n/ Wit h dr a w al fr o m t h e St u d y  ............................... 3 0  
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7.2. 
Lost to Follow-up ........................................................................................ 30 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 31 
8.1. 
Safety Assessments ................................................................................... 31 
8.1.1. 
Vital Signs .................................................................................... 31 
8.1.2. 
Adverse Events (AEs), Serious Adverse Events (SAEs), 
and Other Safety Reporting ......................................................... 31 
8.1.3. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 32 
8.1.4. 
Method of Detecting AEs and SAEs ............................................. 32 
8.1.5. 
Follow-up of AEs and SAEs ......................................................... 32 
8.1.6. 
Regulatory Reporting Requirements for SAEs ............................. 33 
8.1.7. 
Cardiovascular and Death Events ................................................ 33 
8.2. 
Biomarkers ................................................................................................. 33 
8.3. 
Data Collection ........................................................................................... 34 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 34 
9.1. 
Participant Information ................................................................................ 34 
9.2. 
Sample Size Determination ........................................................................ 34 
9.3. 
Analysis Methods ........................................................................................ 34 
10. APPENDICES ........................................................................................................ 36 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 36 
10.1.1. 
Regulatory and Ethical Considerations ........................................ 36 
10.1.2. 
Financial Disclosure ..................................................................... 36 
10.1.3. 
Informed Consent Process .......................................................... 37 
10.1.4. 
Data Protection ............................................................................ 37 
10.1.5. 
Dissemination of Clinical Study Data ........................................... 38 
10.1.6. 
Data Quality Assurance ............................................................... 38 
10.1.7. 
Source Documents ...................................................................... 39 
10.1.8. 
Study and Site Start and Closure ................................................. 40 
10.1.9. 
Publication Policy ......................................................................... 40 
10.2. 
Appendix 2: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ....................................... 42 
10.2.1. 
Definition of AE ............................................................................ 42 
10.2.2. 
Definition of SAE .......................................................................... 43 
10.2.3. 
Definition of Cardiovascular Events ............................................. 44 
10.2.4. 
Recording and Follow-up of AEs and SAEs ................................. 45 
10.2.5. 
Reporting of SAEs to GSK ........................................................... 47 
10.3. 
Appendix 3: History of protocol changes ..................................................... 49 
10.4. 
Appendix 4: Abbreviations and Trademarks ................................................ 50 
11. REFERENCES ....................................................................................................... 52 
 


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1 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title:  
Characterization of Corneal Epithelial Changes in Participants Treated with Belantamab 
Mafodotin (GSK2857916) 
Brief Title:  
Characterization of Corneal Epithelial Changes in Participants Treated with Belantamab 
Mafodotin (GSK2857916) 
Rationale: 
Multiple myeloma (MM) is an incurable hematologic malignancy, and despite advances 
in treatment, there remains a high unmet need to find effective novel therapies to treat 
this devastating disease. Belantamab mafodotin is a first-in-class immunoconjugate that 
targets B cell maturation antigen (BCMA), which is highly expressed on malignant 
plasma cells. Belantamab mafodotin comprises a humanized IgG antibody conjugated to 
the microtubule-disrupting agent monomethyl auristatin F (MMAF). Belantamab 
mafodotin has demonstrated clinically meaningful single-agent activity (overall response 
rate [ORR] 31% at the 2.5 mg/kg dose and median duration of response [DOR] not 
reached at a median follow-up of 6.3 months) in patients who are refractory to anti-CD38 
monoclonal antibody, an immunomodulatory drug (IMiD), and proteasome inhibitor. 
Patients who receive belantamab mafodotin often display corneal changes, which are 
associated with subjective and objective changes in vision. On slit-lamp exam, these 
changes appear as microcyst-like epithelial changes (MECs), . These adverse events 
(AEs) have been reported with other MMAF-containing antibody therapies, including 
SGN-75,  SGN-CD19A, and ABT-414 The exact mechanism has not been confirmed, but 
a toxic effect mediated through MMAF’s inhibition of tubulin polymerization within 
basal epithelial cells is thought to play a major role. Similar corneal findings by slit-lamp 
examination have been described in patients treated with high-dose cytarabine, although 
these are thought to represent actual microcysts. Confirmatory corneal histology is 
lacking to support and confirm a working explanatory theory for the belantamab 
mafodotin–related corneal AEs.  
DREAMM-2 is an ongoing phase 2, open-label, two-arm clinical trial investigating two 
doses of belantamab mafodotin (2.5 mg/kg, n=97, and 3.4 mg/kg, n=99, every 3 weeks), 
in which 2.5 mg/kg was recommended to be the effective dose as the monotherapy dose 
for future use in patients with RRMM. Keratopathy of any grade (defined as changes to 
the corneal epithelium) was reported in 75% of patients. Furthermore, 22% experienced 
blurred vision (defined as blurred vision, including diplopia, decreased visual acuity, and 
vision impairment) and 14% experienced dry eye symptoms (defined as dry eye, ocular 
discomfort, eye pruritis, and foreign body sensation in the eyes) in the 2.5 mg/kg cohort. 
Grade 1 or 2 keratopathy occurred in 41 (43%), while Grade 3 keratopathy occurred in 26 
(27%), Grade 1 or 2 blurred vision occurred in 17 (18%), and Grade 3 blurred vision in 4 


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(4%) patients. These events led to dose reductions in 22 (23%) patients and delays in 45 
(47%) patients. Of the 45 patients with treatment delays due to keratopathy, 31 (69%) 
reinitiated treatment, with a median time to treatment reinitiation of 83 days (range 28–
146).  Higher belantamab mafodotin Ctau was associated with probability of developing 
keratopathy and OEF (ocular eye findings) and inversely correlated to time of onset.  
Grading of corneal events was performed using the Common Terminology Criteria for 
Adverse Events (CTCAE) v4.03 as well as the GSK Grading Scale. 
The mechanism of corneal events in patients treated with belantamab mafodotin is 
thought to be related to MMAF uptake into the transient amplifying cells in the basal 
epithelium. These cells have mitotic activity, and, furthermore, daughter cells migrate 
anteriorly as they differentiate into wing cells and terminal superficial epithelial cells. 
These processes are microtubule dependent and can be disrupted by potent tubulin 
inhibitors such as MMAF. We further hypothesize the following:  these damaged cells 
then eventually undergo apoptosis and become pyknotic, which may appear as MECs in a 
pre-apoptotic state; they are eventually extruded from the epithelium; the corneal surface 
is secondarily affected both by these anatomic abnormalities and alterations in superficial 
in the epithelial cell replenishment. 
 
The current management guidelines for belantamab mafodotin–related corneal events 
include the use of preservative-free lubricant eye drops, dose reductions, and dose delays. 
The efficacy of steroid eye drops was systematically evaluated in a randomized ocular 
substudy in the DREAMM-2 study, and the results revealed that empiric topical 
corticosteroid therapy conferred no benefit as prophylaxis for corneal events.  A more 
complete understanding of the pathophysiology of the corneal events seen in these 
patients could help confirm the current hypothesis and inform management of these AEs. 
The direct analysis of corneal epithelial cells in affected patients is paramount to 
furthering this understanding.  
In order to perform a direct analysis of affected corneal epithelial cells, we will collect 
corneal tissue specimens using either of the following procedures:  impression cytology 
(IC) or superficial keratectomy (SK).   Patients with epithelial corneal microcyst like 
changes, meeting study entry criteria, will be enrolled in this study to collect corneal 
epithelium tissue for analysis. Imaging of the corneal epithelial lesions will be obtained 
from slit-lamp examination and/or confocal microscopy, and the grade, and appearance 
will be correlated with the pathologic samples.  
 


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9  
 
O bjecti ves a n d E n d p oi nts:  
 
O bjecti ves  
E n d p oi nts  
Pri m ar y:  T o c haracterize c or neal 
e pit helial c ha n ges i n partici pa nt s treate d 
wit h bela nta ma b maf o d oti n  
Pri m ar y:  Pat h ol o gic c h aracteristics a n d 
c o m p ositi o n of c or neal e pit helial c ha n ges 
o btai ne d b y i m pressi o n c yt ol o g y (I C) or 
S K i n partici pa nt s treate d wit h 
bela nta ma b maf o d oti n  
Sec o n d ar y:  
•  T o c orrel ate cli nical d ata, 
i ncl u di n g vis ual ac uit y a n d 
s y m pt o ms, as well as gra de a n d 
a p peara nce of c or neal c h a n ges o n 
i ma gi n g, wit h hist o pat h ol o gic 
fi n di n gs 
•  Safet y pr ofile of t h e I C or S K 
pr oce d ure  
Sec o n d ar y:  
•  Res ults of a nal ysis of 
cli nical/i ma gi n g data wit h 
hist o pat h ol o gic fi n di n gs  
•  A Es ass ociate d wit h t he I C or S K 
pr oce d ure  
 
O ver all Desi g n:  
T his st u d y will be a vaila ble t o a n y p artici pa nt w h o has recei ve d or is c urre ntl y recei vi n g 
bela nta ma b maf o d oti n treat me nt t hr o u g h eit her a cli nical trial, (i ncl u di n g a n i n vesti gat or -
s p o ns ore d st u d y [I S S], or a n access pr o gra m) or a P h ysicia n prescri pti o n ; patie nts d o n ot 
nee d t o be o n acti ve treat me nt as l o n g as t h e y meet i ncl usi o n criteria.  
Brief S u m m a r y:  
T he p ur p ose of t his st u d y is t o c h aract erize c or neal e pit helial c ha n ges i n partici pa nts wit h 
R R M M treate d wit h bela nta ma b maf o d oti n. St u d y details i ncl u de:  
•  St u d y D urati o n: a p pr o xi matel y 4 wee ks  
•  Visit Fre q ue n c y:  eac h patie nt will ha ve a t otal of 5 visits.  A d diti o nal f oll o w u p 
visits ma y b e re q uire d i n t he e ve nt of del a y i n heali n g fr o m t he o c ular 
pr oce d ures.  
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1 0  
 
I m pr essi o n c yt ol o g y will be perf or me d o n s o me p atie nts w h o recei ve d or are recei vi n g 
treat me nt wit h bela nta ma b maf o d oti n f or rel a pse d/refract or y M M ( R R M M) a n d ha ve 
o bjecti ve e vi de nce of kerat o pat h y wit h c or neal M E Cs  o n slit -la m p a n d/ or c o nf ocal 
micr osc o p y e x a mi nati o n. Partici pa nts wit h Gra de 2 or 3 C T C A E c or neal s y m pt o ms, i n 
a d diti o n t o e vi de nce of c or neal de p osits, will ha ve t he o pti o n t o u n der g o S K i nstea d of 
i m pressi o n c yt ol o g y as a p ote ntial mea ns t o re d uce t heir  s y m pt o ms.  All p artici pa nts 
e nr olle d ar e eli gi ble f or i m pressi o n c yt ol o g y. T h ose w h o are s y m pt o matic ma y c h o ose t o 
u n der g o S K o nl y.  E ac h partici pa nt  will o nl y ha v e o ne c or neal pr o ce d ure (i m pressi o n 
c yt ol o g y or S K ).  
I m pr essi o n c yt ol o g y is a mi ni mall y i n vasi ve pr oce d ure t hat i n v ol ves t he a p plicati o n of 
cell ul ose acetate filter pa per t o t he oc ular s urface t o c ollect s u perfi cial cell l a yers f or 
hist ol o gic, i m m u n o hist ol o gic, or m olec ular a nal ysis. T he pr oce d ure is perf or m e d b y a 
trai ne d o p ht hal m ol o gist or oc ular p at h ol o gist i n t he e ye cli nic wit h or wit h o ut t o pical 
a nest hesia, a n d m ulti ple sa m ples ca n be o bt ai ne d i n o ne sitti n g.  
T he st u d y e ye will be t he o ne t hat a p pears t o ha ve a great er n u m ber of M E Cs. If b ot h 
e yes a p pe ar e q ual i n ter ms of e pit helial c ha n ges, t he e ye wit h t he w orse vis u al ac uit y will 
be selecte d; if b ot h e yes ha ve t he sa me vis u al ac uit y, t he n t he i n vesti gat or ca n select 
eit her e ye.  F oll o wi n g t o pical a nest hesia, a n e yeli d s pec ul u m, will be place d. Ne xt, t he 
filter pa per will be presse d t o a prei de ntifie d re gi o n o n t he c or neal s urface of t he st u d y 
e ye wit h a glass r o d ( or si milar i nstr u me nt) f or 5 – 1 0 sec o n ds. T he filter pa pers o btai ne d 
fr o m t he pr oce d ure will c o ntai n e pit helial la yers fr o m areas of t h e c orn ea wit h micr oc yst -
li ke c ha n ges a n d will be a nal yze d t hr o u g h hist ol o gic tec h ni q ues. T he filter pa per will be 
place d o n a gl ass sli de a n d c o ver sli p place d o n t o p. T he e ye s p ec ul u m will be re m o ve d 
a n d a t o pical a nti bi otic dr o p (e. g. p ol ytri m) will be prescr i be d f or partici pa nt  use f or 7 
da ys.  
S u perficial keratect o m y  is a met h o d t o re m o ve a n area of f ull-t hic k ness c or neal 
e pit heli u m.  T he pr oce d ure is perf or me d b y a n o p ht hal m ol o gist, ta kes 1 5 – 3 0 mi n utes t o 
c o m plete, a n d ma y b e c o n d ucte d i n t he e ye cli nic. W hi le i n s o me cases t his pr oce d ure is 
perf or me d i n a n o perati n g r o o m, o nl y partici pa nt s w h o are a ble t o u n der g o t he pr oce d ure 
i n t he cli nic s h o ul d be selecte d f or it.    
T he st u d y e ye will be sel ecte d usi n g t he criteria d escri be d a b o ve. F oll o wi n g t o pical 
a nest hesia (s u c h as pr o p aracai n e h y dr oc hl ori d e 0. 5 %) a n d a dr o p of p o vi d o ne i o di ne 5 % 
f or a ntise psis, a n e yeli d s pec ul u m will be place d . T he e ye will t he n be vis u alize d usi n g a 
slit-la m p or o perati n g micr osc o pe i n a pr oce d ure r o o m. T he c or neal e pit heli u m of i nterest 
(t he re gi o n t hat c o nt ai ns t he M E Cs) will be caref ull y re m o v e d usi n g eit her a Wec k-
Cel/ dr y cell ul ose s p o n ge or s mall bla de; J e weler or 0. 1 2 f orce ps ma y be re q uire d i n s o me 
cases. T he tiss ue will be s u b mitte d i n f or mali n f or hist ol o gic a nal ysis. Care s h o ul d be 
ta ke n t o mi ni mize cr us h artefact t o t he e pit heli u m a n d t o a v oi d da ma ge t o B o w ma n la yer. 
P ost pr oce d ure, a n ot her dr o p of p o vi d o ne i o di ne 5 % will be place d, f oll o we d b y a dr o p of 
bala nce d s alt s ol uti o n or t o pical a nest hetic (t o w as h o ut a n y resi d ua l p o vi d o ne-i o di ne). A 
ba n da ge c o ntact le ns will be place d. It is rec o m me n de d t hat a t o pical a nti bi otic a n d a 
t o pical ster oi d ( or a fi x e d c o m bi nati o n of b ot h ) is prescri be d 4 ti mes p er da y, eac h , f or at 
least o ne wee k  ( or l o n ger), u ntil t he e pit helial defec t is d oc u me nte d as heale d a n d t he 
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ba n da ge c o ntact le ns is n o l o n ger re q uir e d  i n t he assess me nt of treati n g O p ht hal m ol o gist .  
T he t o pical a nti bi otic ma y be disc o nti n ue d o nce t h e e pit helial defect has heale d.  T he 
t o pical ster oi d s h o ul d be ta pere d off o ver t he f oll o wi n g t w o wee ks.   
 
T he e x pecte d ti me f or c or neal r e -e pit helializati o n is 7 – 1 0 da ys . T h e pr oce d ure ca n ca us e 
s o me pai n t o t he partici p a nt b ut is ge nerall y safe a n d well t olerate d. Pai n, if a n y, ca n b e 
ma na ge d b y t he use of artificial tears, aceta mi n o p he n, a n d narc otics, if nee de d. T he 
ba n da ge c o ntact le ns s h o ul d be hel pf ul i n re d uci n g t he  n ee d f or pai n me dicati o n. I n 
partici pa nt s wit h s y m pt o matic bl urre d visi o n, t he pr oce d ure ma y res ult i n te m p orar y 
vis ual i m pr o ve me nt. T he pr oce d ure ma y als o be c o m plicate d b y a n i nfecti o n or 
w orse ni n g visi o n. A n oc ular pat h ol o gist will be c o ns ulte d t o dete r mi ne t he a p pr o priate 
testi n g of tiss ue sa m ple. 
N o n -i n vasi ve pre-pr oce d ure i ma gi n g will als o be o btai ne d f or all partici pa nt s, re gar dless 
of pr oce d ure c o h ort. A nt eri or se g me nt slit -la m p p h ot o gra p h y will be o btai ne d, as will 
c o nf ocal micr osc o p y (if a vaila bl e), pri or t o i m pressi o n c yt ol o g y or S K.  
O nl y areas wit h micr oc yst -li ke c ha n ges s h o ul d be sa m ple d. All eff ort s h o ul d be ma de t o 
a v oi d or mi ni miz e i ntr usi o n i nt o t he li m b us, if p ossi ble. T he tiss ue deri ve d fr o m S K 
sa m pli n g s h o ul d be place d i n a f or mali n s ol uti o n f or tra nsfer t o t he pat h ol o g y la b orat or y. 
A n oc ular pat h ol o gist s h o ul d e x a mi ne t he s peci me n t o deter mi ne t he c o m p ositi o n of t he 
de p osits.  
N u m ber of P artici p a nts:  
I n t his st u d y u p t o 2 5 partici pa nt s wit h M E Cs o n slit-la m p a n d/ or c o nf ocal micr osc o p y 
e x a mi nati o n res ulti n g fr o m bela nta ma b maf o d oti n treat me nt of R R M M will be e nr olle d. 
Partici pa nt s ma y b e e nr olle d fr o m a n y acti ve res earc h or access pr o gra m , or P h ysicia n 
pr escrip ti o n, a n d d o n ot nee d t o be o n acti ve treat me nt. Partici pa nt s will be i de ntifie d b y 
t he treati n g M M p h ysi cia n a n d referre d t o a n o p ht hal m ol o gist, w h o will perf or m t he S K 
or I C  pr oce d ure. O n ce a t otal of 5 partici pa nt sa m ples fr o m t he s u perficial keratect o m y 
pr oce d ure  ha v e yi el de d e val ua ble materi al f or pat h ol o gic e x a mi nati o n a n d c o m p ositi o n 
a nal ysis of t he c or neal e pit helial c ha n ges, f urt h er e nr oll me nt will cease.  
D at a M o nit ori n g/ Ot her C o m mittee:  N o  
 
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1.2. 
Schema 
 
 
 
Patients with RRMM 
receiving treatment with 
Belantamab Mafodotina
n = 10-25b
Key Eligibility Criteria
•
diagnosed with MECs on 
slit-lamp examination or 
confocal microscopy, in at 
least one eye
•
If undergoing superficial 
keratectomy (SK) no contra-
indication to SK procedure
1. Superficial keratectomy (preferred) or 
Impression cytology 
2. Corneal deposit samples collected for 
pathologic evaluation, histology and 
composition
Screening and 
Consent
Confirmatory 
Imagingc
a Patients on a DREAMM clinical trial, the compassionate use program, or a Physician Prescription are eligible.
b Up to 25 patients will be enrolled.  The goal is to obtain 5 evaluable SK pathologic samples.  Once 5 evaluable SK samples are obtained, enrollment will cease.
c An ophthalmic examination that includes best-corrected visual acuity, slit-lamp examination, and confocal microscopy (if available) must be performed prior to the 
impression cytology or keratectomy procedure to document site and size of corneal epithelial changes and to correlate imaging with pathologic findings. The slit-lamp 
examination must include orbit/lid/adnexa, conjunctiva, sclera, cornea, anterior chamber, iris, lens, and anterior vitreous. Confirmatory anterior segment photography is 
also required unless acceptable corneal images are available from an examination performed <14 days prior to impression cytology or SK. 
Patient follow 
up for safety
CCI
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1. 3.  
S c h e d ul e of A cti viti e s ( S o A)  
Pr o ce d ure  
Scree ni n g  Pre – I C or S K 
pr oce d ure  
I C or S K pr oce d ure  
( d a y of pr oce d ure) 
P ost – I C or S K 
pr oce d ure e 
S afet y f oll o w -u p  
( u p t o 1 w ee k after 
S K pr oce d ure)  
S afet y f oll o w -
u p  
( 2 w ee ks after 
S K pr oce d ure) f 
A d diti o n al f oll o w -
u p at 
o p ht h al m ol o gist’s  
discreti o n g  
I nf or me d c o nse nt 
X  
 
 
 
 
 
 
Eli gi bilit y criteria  
X  
 
 
 
 
 
 
Slit -la m p e xa mi nati o n a n d 
c o nf ocal micr osc o p y (if 
a vaila ble) a wit h i ma gi n g  
 
X  
 
 
X d  
 
 
S nelle n e ye test  a 
 
 
X  
 
X  
X  
 
C or neal tiss ue sa m pli n g c 
 
 
X  
 
 
 
 
P at h ol o g y re vie w of c or neal 
sa m ple 
 
 
 
X  
 
 
 
O p ht hal m ol o g y p ost -
pr oce d ure c hec k u p  
 
 
 
 
 
 
X  
Vital si g ns ( p ulse a n d bl o o d 
press ure)  
 
 
X  
 
 
 
 
A Es/ S A Es  
 
 
X  
X  
X  
X  
 
Data C ollecti o n h 
X  
X  
X  
X  
X  
X  
X  
Bl o o d  C ollecti o n j 
 
 
X  
 
 
 
 
A E, a d verse e ve nt;
I C, i m pressi o n c yt ol o g y; S A E, seri o us a d verse e ve nt; S K, s u perficial keratect o m y.  
aA n o p ht hal mic e xa mi nati o n t hat i ncl u des best -c orrecte d vis ual ac uit y, slit -la m p e xa mi nati o n, a n d c o nf ocal micr osc o p y (if a vaila ble) m ust b e perf or me d pri or t o t he 
i m pressi o n c yt ol o g y or kerate ct o m y pr oce d ure t o d oc u me nt site a n d size of c or neal e pit helial c ha n ges a n d t o c orrelate i ma gi n g wit h pat h ol o gic fi n di n gs. T he slit -
la m p e xa mi nati o n m ust i ncl u de or bit/li d/a d ne xa, c o nj u ncti va, sclera, c or nea, a nteri or c ha m ber, iris, le ns, a n d a nteri or vitr eo us. C o nfir mat or y a nteri or se g me nt 
p h ot o gra p h y is als o re q uire d  u nless acce pta ble c or neal i ma ges are a vaila ble fr o m a n e xa mi nati o n perf or me d < 1 4 da ys pri or t o i m pressi o n c yt ol o g y or S K.  It is 
rec o m me n de d t hat t he i ma gi n g e xa mi nati o n be perf or me d at least 2 4 h rs pri or t o t he pr oce d ure. 
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cG S K ma y st ore sa m ples f or u p t o 3 years after t he e n d of t he st u d y t o ac hie ve st u d y o bj ecti ves. A d diti o nall y, wit h partici pa nts’ c o nse nt, sa m ples ma y be use d f or 
f urt her researc h b y G S K or ot hers s uc h as u ni versities or ot her c o m pa nies t o c o ntri b ute t o t he u n dersta n di n g of t he pat h o p h ys i ol o g y of bela nta ma b maf o d oti n–
ass ociate d kerat o pat h y, t he de vel o p me nt of relate d or ne w treat me nts, or researc h met h o ds.  
d Preferre d ti mi n g f or f oll o w -u p slit -la m p e xa mi nati o n is 2 4– 4 8 h o urs p ost S K pr oce d ure b ut m ust be perf or me d wit hi n 1 wee k after S K pr oce d ure. Safet y f oll o w -u p 
after i m pressi o n c yt ol o g y is n ot re q uir e d u nless t he partici p a nt is e x perie nci n g disc o mf ort or a n A E.  
eT he A E/ S A E f oll o w u p i m me diatel y after t he P ost – I C or S K pr oce d ure ca n b y d o ne b y p h o ne, i n t he 2 4-4 8 h o urs p ost -pr oce d ure.  
fT he partici pa nt s h o ul d be ree xa mi ne d 2 wee ks after t he S K pr oce d ure  if t he e pit helial defe ct d oes n ot heal c o m pletel y i n t he first f oll o w-u p. Ot her wise, t his f oll o w -
u p is n ot re q uire d.  
gI n t he e ve nt t he c or nea has n ot heale d at 2 wee ks, a d diti o nal f oll o w-u p s h o ul d be c o n d ucte d at t he o p ht hal m ol o gist’s discreti o n u ntil hea li n g is c o nfir me d. 
hMi ni mal a d diti o nal data will be c ollecte d t o a de q uatel y c haracterize t he de vel o p me nt of t he c or neal e pit helial c ha n ges i n par tici pati n g patie nts  See S ecti o n 8. 3 . 
 
 
 
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2.  
I N T R O D U C TI O N 
2. 1.  
St u d y R ati o n al e  
T he maj orit y of patie nts w h o recei ve bela nt a ma b maf o d oti n dis pla y micr oc yst -li ke 
e pit helial c ha n ges  ( M E Cs) o n slit -la m p e x a mi nati o n a n d/ or e x perie nce s y m pt o ms 
i ncl u di n g bl urre d visi o n a n d dr y e ye, w hic h are rec o g nize d A Es ass ociate d wit h M M A F-
c o ntai ni n g a nti b o d y t hera pies, i ncl u di n g S G N -7 5 [Ta n nir , 2 0 1 4] , S G N-C D 1 9 A, a n d 
A B T -4 1 4 [Rear d o n , 2 0 1 7] , b ut t he e x act mec ha nis m has n ot bee n f ull y el u ci date d. 
Si milar c or neal fi n di n gs b y slit -la m p e x a mi nati on ha ve bee n descri be d i n p atie nts treate d 
wit h hi g h -d ose c yt ara bi n e [G ut h off , 2 0 1 0] . T he s pecific c or neal A E ( micr oc yst-li ke 
e pit helial c ha n ges) see n wit h bela nta ma b maf o d oti n t hera p y has n ot bee n re plicate d i n 
precli nical m o dels, a n d c o nfir mat or y c or neal hist ol o g y is lac ki n g t o s u p p ort a n d c o nfir m 
t he w or ki n g e x pla nat or y t he or y f or t his c or neal t o xicit y. 
T he p ur p ose of t his st u d y is t o gai n a m ore c o m plete u n dersta n di n g of t he 
pat h o p h ysi ol o g y of t he c or neal e v e nts see n i n s o me patie nts treate d wit h bela nta ma b 
maf o d oti n. T o d o t his, i m pressi o n c yt ol o g y or S K will be e m pl o ye d i n t his st u d y t o 
c ollect c or n eal e pit heli u m wit h e pit helial c ha n ges f or pat h ol o gic e x a mi nati o n a n d 
c o m p ositi o n a nal ysis.  
2. 2.  
B a c k gr o u n d  
M M is a n i nc ura ble mali g na n c y t hat acc o u nts f or 1 % of all ca n ce rs a n d 1 0 % of all 
he mat ol o gic m ali g na n cies. W orl d wi de, a p pr o xi matel y 1 0 3, 0 0 0 ne w cas es are dia g n ose d 
a n n uall y, a n d i n t he U S A, 3 2, 2 7 0 ne w cas es a n d 1 2, 8 3 0 deat hs are esti mate d t o occ ur i n 
2 0 2 0 [Sie gel , 2 0 1 6] . Des pite si g nifica nt a d va nces i n treat me nt o pti o ns, i ncl u di n g 
he mat o p oietic ste m cell tra ns pla nt, a n d n o vel t hera pies li ke sec o n d - a n d (t hir d-ge nerati o n 
pr oteas o me i n hi bit ors,  (I Mi Ds), a n d t he rece nt a d diti o n of m o n ocl o nal a nti b o dies, m ost 
patie nts wit h M M will ulti matel y de vel o p resista nce t o e xisti n g t hera pies a n d rela pse 
[K u mar , 2 0 0 4][ Raj k u mar , 2 0 1 6] . Eac h rela pse re q uires sal va ge t hera p y, a n d t here is 
ofte n a decreasi n g res p o nse d urati o n wit h eac h s u bse q ue nt li ne of sal va ge t hera p y, a n d 
ulti matel y patie nts bec o me resista nt t o or i n eli gi ble f or a v aila ble treat me nt re gi me ns. 
T heref ore, t here is a n ur ge nt nee d t o de vel o p alter nati ve treat me nts wit h n o vel 
mec ha nis ms of acti o n t hat pr o vi de a s ustai ne d res p o nse i n patie nts wit h resista nce t o 
e xisti n g t hera pies [A n ders o n , 2 0 1 6] . 
Bela nta m a b maf o d oti n is a n o vel, h u ma nize d (I g G 1) a nti b o d y -dr u g c o nj u gate t hat is 
bei n g d e vel o pe d f or t he treat me nt of M M. T he p are nt a nti -B C M A a nti b o d y is c o nj u gate d 
t o t he microt u b ule i n hi bit or, M M A F. Bela nta m a b maf o d oti n bi n ds t o B C M A, a tar get 
wi del y e x presse d o n mali g na nt plas ma cells i n M M. T he n or mal f u ncti o n of B C M A is t o 
pr o m ote cell s ur vi val b y tra ns d ucti o n of si g n als fr o m t w o k n o w n li ga n ds: B cell 
acti vati n g fact or fr o m  t he t u m or necr osis fact or fa mil y ( B A F F/ B L y S) a n d A P RI L, a 
pr oliferati o n -i n d uci n g li ga n d. Bel a nta ma b maf o d oti n bi n ds t o B C M A, is i nter nalize d, a n d 
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releases free cys-MMAF, which disrupts the microtubule network, leading to cell cycle 
arrest and apoptosis. Belantamab mafodotin also mediates antibody-dependent cell-
mediated cytotoxicity effector function directed toward BCMA-expressing cells.  
Clinical data from the phase 1, first-in-human trial, Study BMA117159 (DREAMM-1) in 
patients with RRMM (Part 2, n=35 patients treated at the 3.4 mg/kg starting dose) has 
demonstrated an ORR of 60% (95% confidence interval [CI] 42.1%–76.1%), with: 
• 5 (15%) patients achieving a stringent complete response (sCR) or a complete 
response (CR); 
• 14 (40%) achieving a very good partial response (VGPR); 
• 2 (6%) achieving a partial response (PR).  
The median time to first response was 1.2 months (95% CI 0.7–1.4); responses were 
maintained and generally deepened over time. The median progression-free survival 
(PFS) was 12.0 months (95% CI 3.1–not estimable) and the median DOR was 14.3 
months (95% CI 10.6–not estimable). In patients refractory to both immunomodulators 
and proteasome inhibitors, median PFS was 7.9 months (95% CI 2.3–not estimable); in 
patients without prior daratumumab treatment, median PFS was 15.7 months (95% CI 
2.3–not estimable). Overall, belantamab mafodotin was well tolerated and the AEs were 
manageable [Trudel, 2019]. All patients experienced at least one AE, most commonly 
thrombocytopenia (22/35; 63%), blurred vision (18/35; 51%), and cough (14/35; 40%). 
Grade 3 or 4 AEs were reported in 29 (83%) patients, the most common of which were 
thrombocytopenia (Grade 3, 9/35 [26%]; Grade 4, 3/35 [9%]) and anemia (Grade 3, 6/35 
[17%]); no Grade 5 AEs were reported. Serious AEs (SAEs) were reported in 17/35 
(49%) patients, most commonly pneumonia (3/35; 9%), lung infection (2/35; 6%), and 
infusion-related reactions (2/35; 6%). Seven (20%) patients experienced SAEs related to 
study treatment, most commonly infusion-related reactions (2/35; 6%). Four patients died 
during the study, all due to progression of MM. Four (11%) patients had AEs that led to 
permanent discontinuation of study treatment, each due to thrombocytopenia; 
keratopathy; fatigue and cough; and increased alanine aminotransferase (ALT), aspartate 
aminotransferase, and blood creatine phosphokinase. These results suggested that 
belantamab mafodotin demonstrated a manageable safety profile and positive clinical 
activity in patients with heavily pretreated RRMM. GSK has initiated (or plans to initiate) 
further clinical studies to evaluate belantamab mafodotin as monotherapy or in 
combination in participants with relapsed/refractory or newly diagnosed MM. 
In the phase 2 pivotal study 205678 (NCT03525678, DREAMM-2), belantamab 
mafodotin was further evaluated as monotherapy in patients with RRMM at doses of 2.5 
mg/kg and 3.4 mg/kg Q3W. This was a two-arm, randomized study in patients who had 
failed at least three prior lines of antimyeloma therapy, including an anti-CD38 antibody, 
and who were refractory to an IMiD and a proteasome inhibitor (n=97 in the 2.5 mg/kg 
cohort and n=99 in the 3.4 mg/kg cohort) [Lonial, 2020]. As of June 21, 2019 (the 
primary analysis data cutoff date), 30/97 patients (31%; 97.5% CI 20.8–42.6) in the 2.5 
mg/kg cohort and 34/99 patients (34%; 97.5% CI 23.9–46.0) in the 3.4 mg/kg cohort 


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achieved an overall response.  At the 2.5 mg/kg dose, median duration of response 
[DOR] not reached at a median follow-up of 6.3 months). 
The most common Grade 3–4 AEs in the safety population were keratopathy (in 26/95 
[27%] patients in the 2.5 mg/kg cohort and 21/99 [21%] patients in the 3.4 mg/kg cohort), 
thrombocytopenia (19 [20%] and 33 [33%]), and anemia (19 [20%] and 25 [25%]). A 
total of 38/95 (40%) patients in the 2.5 mg/kg cohort and 47/99 (47%) patients in the 3.4 
mg/kg cohort reported SAEs. Two deaths were potentially treatment related (one case of 
sepsis in the 2.5 mg/kg cohort and one case of hemophagocytic lymphohistiocytosis in 
the 3.4 mg/kg cohort). Overall, both dose levels, 2.5 mg/kg and 3.4 mg/kg, have a 
positive benefit/risk profile. The dose of 2.5 mg/kg had a lower incidence of AEs, less 
frequent dose delays and reductions, and similar efficacy as the 3.4 mg/kg dose as 
measured by ORR. Based on benefit/risk assessment, a dose of 2.5 mg/kg Q3W has been 
recommended as the monotherapy dose of belantamab mafodotin for patients with 
RRMM in fourth-line or higher settings. 
Keratopathy of any grade (defined as changes to the corneal epithelium documented by 
slit-lamp examination and/or confocal microscopy) was reported in 75% of patients. 
Furthermore, 22% experienced blurred vision (defined as blurred vision, including 
diplopia, decreased visual acuity, and vision impairment) and 14% experienced dry eye 
(defined as dry eye, ocular discomfort, eye pruritis, and foreign body sensation in the 
eyes) in the 2.5 mg/kg cohort. Grade 1 or 2 keratopathy occurred in 41 (43%), Grade 3 
keratopathy in 26 (27%), Grade 1 or 2 blurred vision in 17 (18%), and Grade 3 blurred 
vision in 4 (4%) patients. These events led to dose reductions in 22 (23%) patients and 
delays in 45 (47%) patients. Dose reductions started at week 13 while dose delays started 
at week 4 for keratopathy. Of the 45 patients with treatment delays due to keratopathy, 31 
(69%) reinitiated treatment, with a median time to treatment reinitiation of 83 days (range 
28–146). Higher belantamab mafodotin Ctau was associated with probability of 
developing keratopathy and OEF and inversely correlated to time of onset.  Grading of 
corneal events was performed using the Common Terminology Criteria for Adverse 
Events (CTCAE) v4.03 as well as the GSK Grading Scale. 
The mechanism of corneal events in patients treated with belantamab mafodotin is likely 
related to MMAF uptake into the corneal epithelial cells and eventual exposure to the 
basal epithelial stem cells that are located in the basal epithelial layer of the cornea 
[Donaghy, 2016]. These cells have mitotic activity, and, furthermore, daughter cells 
migrate anteriorly as they differentiate into wing cells and terminal superficial epithelial 
cells. Both processes are microtubule dependent and can be disrupted by potent tubulin 
inhibitors such as MMAF. The most affected basal epithelial cells die and fail to 
transition into functional wing cells. These damaged cells eventually undergo apoptosis 
and become pyknotic. They are extruded from the epithelium, and in that process, they 
appear microcyst-like on examination. The superficial corneal surface is secondarily 
affected both by these anatomic abnormalities and alterations in superficial corneal cell 
replenishment and tear film stability. 
The current management guidelines for belantamab mafodotin-related corneal events 
include the use of preservative-free lubricant eye drops, dose reductions, and dose delays. 
The efficacy of steroid eye drops was systematically evaluated in a randomized ocular 


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substudy in the DREAMM-2 study, and the results revealed that empiric topical 
corticosteroid therapy conferred no benefit as prophylaxis for corneal events.  
Corneal histopathologic samples in patients treated with belantamab mafodotin with this 
epitheliopathy are lacking, therefore, data is unavailable to support and confirm a 
working explanatory theory for the belantamab mafodotin–related corneal AEs. (Refer to 
the Investigator Brochure for pre-clinical findings regarding corneal events) 
[Investigator's brochure V8.0, GSK Version Number 8, Document Number  
2013N175128_08]. A more complete understanding of the pathophysiology of the 
corneal events seen in these patients is needed. To do this, superficial keratectomy or 
impression cytology for any patients meeting study entry criteria, will be employed in 
this study to collect corneal epithelium with epithelial changes documented by slit-lamp 
examination and/or confocal microscopy for analysis. Images from slit-lamp examination 
and/or confocal microscopy at the time of patient enrollment will be obtained. Pathologic 
results will be correlated with the images to describe size, location, grade, and appearance 
of the epithelial lesions. 
The study eye will be the one that that appears have a greater number of MECs. If both 
eyes appear equal in terms of epithelial changes, the eye with the worse visual acuity will 
be selected; if both eyes have the same visual acuity, then the investigator can select 
either eye.   
Impression cytology is a technique used to diagnose a variety of ocular surface disorders 
and involves the application of cellulose acetate filter paper to collect superficial layers of 
the ocular surface for analysis. The procedure is performed by a trained ophthalmologist 
in the eye clinic with or without topical anesthesia and multiple samples can be obtained 
in one sitting. 
Following topical anesthesia, an eyelid speculum, will be placed. Next, the filter paper 
will be pressed to a preidentified region on the corneal surface of the study eye with a 
glass rod (or similar instrument) for 5–10 seconds. The filter papers obtained from the 
procedure will contain epithelial layers from areas of the cornea with microcyst-like 
changes and will be analyzed through histologic techniques. The filter paper will be 
placed on a glass slide and cover slip placed on top. The eye speculum will be removed 
and a topical antibiotic drop (e.g. polytrim) will be prescribed for 4 times a day for 7 
days.  
Superficial keratectomy is a method to remove an area of full-thickness corneal 
epithelium.  The procedure is performed by an ophthalmologist, takes 15–30 minutes to 
complete, and may be conducted in the eye clinic. While in some cases this procedure is 
performed in an operating room, only patients who are able to undergo the procedure in 
the clinic should be selected for it.    
The study eye will be selected using the criteria described above. Following topical 
anesthesia (such as proparacaine hydrochloride 0.5%) and a drop of povidone iodine 5% 
for antisepsis, an eyelid speculum will placed. The eye will then be visualized using a 
slit-lamp or operating microscope in a procedure room. The corneal epithelium of interest 
(the region that contains the MECs) will be carefully removed using either a Weck-
Cel/dry cellulose sponge or small blade; Jeweler or 0.12 forceps may be required in some 


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1 9  
 
cases. T he tiss ue will be s u b mitte d i n f or mali n f or hist ol o gic a nal ysis. Care s h o ul d be 
ta ke n t o mi ni mize cr us h artefact t o t he e pit heli u m a n d t o a v oi d da ma ge t o B o w ma n la yer. 
P ost pr oce d ure, a n ot her dr o p of p o vi d o ne i o di ne 5 % will be place d , f oll o we d b y a dr o p of 
bala nce d s alt s ol uti o n or t o pical a nest hetic (t o w as h o ut a n y resi d ual p o vi d o ne -i o di ne). A 
ba n da ge c o ntact le ns will be place d. It is rec o m me n de d t hat a t o pical a nti bi otic a n d a 
t o pical ster oi d ( or a fi x e d c o m bi nati o n of b ot h) is prescri be d 4 ti mes p er da y, eac h, f or at 
least o ne wee k ( or l o n ger), u ntil t he e pit helial defect is d oc u me nte d as heale d a n d t he 
ba n da ge c o ntact le ns is n o l o n ger re q uir e d i n t he assess me nt of treati n g O p ht hal m ol o gist .  
T he t o pical a nti bi otic ma y be disc o nti n ue d o nce t h e e pit helial defect has heale d.  T he 
t o pical ster oi d s h o ul d be ta pere d off o ver t he f oll o wi n g t w o wee ks.   
T he e x pecte d ti me f or c or neal r e -e pit helializati o n is 7 – 1 0 da ys [As h b y , 2 0 1 4] . T he 
pr oce d ure ca n ca us e s o me pai n t o t he patie nt b ut is ge n erall y safe a n d well t olerate d. 
Pai n, if a n y, ca n be m a na ge d effecti vel y b y t he us e of artifici al tears, acet a mi n o p he n, a n d 
narc otics, if nee de d. T h e ba n da ge c o ntact le ns s h o ul d be hel pf ul i n re d uci n g t he nee d f or 
pai n me dicati o n. I n patie nts wit h s y m pt o matic bl urre d visi o n, t he pr oce d ure ma y res ult i n 
te m p orar y vis ual i m pr o v e me nt. T he pr oce d ure ma y als o be c o m plicate d b y a n i nfecti o n 
or w orse ni n g visi o n. A n oc ular pat h ol o gist will be c o ns ulte d t o deter mi ne t he a p pr o pri ate 
testi n g of tiss ue sa m ple. 
It is c o m m o n t o e x perie n ce var yi n g d e grees of dis c o mf ort be gi n ni n g 3 0– 9 0 mi n utes 
f oll o wi n g t he s urger y as t he t o pical a nest hesi a dr o ps be gi n t o wear off. Ma n y patie nts 
descri be t his se nsati o n as feeli n g li ke a n e yelas h is i n t he e ye or l o d ge d b e n eat h t he 
c o ntact le ns. T his rarel y l asts m ore t ha n a fe w da ys a n d is a n or mal part of t he heali n g 
pr ocess. W ater y e yes, a r u n n y n ose, li g ht se nsiti vit y, a n d e ye re d ness ma y occ ur d uri n g 
t he earl y p ost o perati ve p eri o d. T his is n or mal a n d is ca use d b y t he p osts ur gical e ye 
irritati o n.  
F or b ot h t he i m pressi o n c yt ol o g y a n d S K c o h orts, n o n -i n vasi ve i ma gi n g i n cl u di n g 
a nteri or se g me nt slit -la m p p h ot o gra p h y a n d c o nf ocal micr osc o p y (if a vaila ble) will be 
o btai ne d pri or t o t he pr oce d ure t o c orrelat e i ma gi n g a n d p at h ol o gi cal fi n di n gs. 
C o nfir mat or y a nteri or s e g me nt p h ot o gra p h y is als o re q uire d u nless acce pta ble c or neal 
i ma ges are a vaila ble fr o m a n e x a mi nati o n perf or me d < 1 4 da ys pri or t o i m pressi o n 
c yt ol o g y or S K.  
T his  st u d y will be a vaila ble t o a n y p atie nt w h o has recei v e d or is c urre ntl y recei vi n g 
bela nta ma b maf o d oti n treat me nt t hr o u g h eit her a cli nical trial  (i ncl u di n g a n i n vesti gat or-
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s p o ns ore d st u d y [I S S], or a n access pr o gra m) or a P h ysicia n prescri pti o n; t he y d o n ot 
nee d t o be o n acti ve treat me nt as l o n g as t h e y meet i ncl usi o n criteria.  
 
2. 3.  
B e n efit s a n d Ri s k s  
P ai n:  
T he S K pr oce d ure ca n ca use pai n t o t he partici pa nt b ut is ge nerall y s afe a n d well 
t olerate d. Pai n ca n b e ma na ge d b y t he use of artifi cial tears or a ba n d a ge c o ntact le ns 
I nfecti o n:  
T he S K pr oce d ure carri es a ris k of i nfecti o n a n d re q uires pr o p h ylactic a nti bi otics. 
I nfecti o us keratitis occ urs i n 2 % of patie nts [V o , 2 0 1 5] . T hese data are fr o m patie nts w h o 
u n der we nt e pit helial d e bri de me nt a n d dia m o n d b urr p olis hi n g of t he B o w m a n’s 
me m bra ne ( n = 9 1 e yes).  
Del a ye d He ali n g:  
I n t his st u d y, it is a ntici pate d t hat S K-i n d uce d e pit helial defect will heal wit hi n 7 da ys 
wit h t he use of a ba n d a ge c o ntact le ns.  
 
T y pic all y, h eali n g occ urs i n 2 da ys f or a 3 – 4 m m ce ntral e pit helial de bri d e me nt [Sta 
Iglesi a , 2 0 0 0] [ Wils o n , 2 0 0 4] [ Par k , 2 0 1 9] . Te m p orar y scarri n g/s u be pit helial haze ca n 
occ ur i n 2 1 % of e yes at 1 m o nt h p ost pr oce d ure a n d i n 9 % of e yes at last f oll o w -u p a n d is 
n ot vis uall y si g nifica nt. N o c o m plicati o ns res ulti n g i n i m paire d visi o n at fi nal f oll o w -u p 
ha ve bee n re p orte d [V o , 2 0 1 5] [ M ur ueta -G o ye n a , 2 0 1 8] . 
C o m or bi dities s uc h as dia betes a n d dr y e ye ca n si g nifica ntl y d ela y t he heali n g pr ocess 
a n d ma y re q uir e a dj u va nt t hera p y (e. g., ba n da ge c o ntact le ns).  
2. 3. 1.  
B e n efit A s s e s s m e nt  
I n p artici pa nts  wit h ce ntral c or neal de p osits, t he S K pr oce d ure ma y or ma y n ot be 
t hera pe utic. A n y i m pr o ve me nt i n vis ual ac uit y will be d oc u me nte d via a S nelle n e ye test 
pre - a n d p ost -pr oce d ure as detaile d i n t he S o A.  Alt h o u g h t his pr oc e d ure is bei n g 
perf or me d pri maril y f or dia g n ostic p ur p os es, a n i m pr o ve me nt i n visi o n, at least 
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te m p oraril y, is a p ote ntial be nefit. F or a n y gi ve n patie nt it is n ot p ossi ble t o pre dict 
w het her a n i m pr o ve me nt i n visi o n will occ ur or n ot.  
2. 3. 2.  
O v er all B e n efit/ Ri s k  C o n cl u si o n  
A p pr oac h es t o mi ni mize ris k i ncl u de s u p p orti ve care wit h t he perf or m a nce of t he S K, 
utilizati o n of a p ost -pr oce d ure ba n d a ge c o ntact le ns al o n g wit h t o pical a nti bi otics a n d a 
ster oi d, a n d cl ose m o nit ori n g.  
T he scie ntific dat a t hat will be o btai ne d fr o m t his st u d y will pr o vi de critic al i nf or mati o n 
o n t he pat h ol o gic n at ure of t he c or neal e pit helial c ha n ges, w hic h ma y i nf or m p ote ntial 
miti gati n g tr eat me nts f or partici pa nts  s ufferi n g fr o m c or neal s y m pt o ms w hile recei vi n g 
treat me nt f or R R M M wit h belanta ma b maf o d oti n.  
 
3.  
O B J E C TI V E S A N D E N D P O I N T S  
O bjecti ves  
E n d p oi nts  
Pri m ar y:  T o c haracterize c or neal 
e pit heli o pat h y i n partici pa nts  treate d wit h 
bela nta ma b maf o d oti n  
Pri m ar y:  Pat h ol o gic c h aracteristics a n d 
c o m p ositi o n of c or neal e pit helial c ha n ges 
o btai ne d b y i m pressi o n c yt ol o g y  (I C) or 
S K i n partici pa nts  treate d wit h 
bela nta ma b maf o d oti n  
Sec o n d ar y:  
•  T o c orrel ate cli nical d ata, 
i ncl u di n g vis ual ac uit y a n d 
s y m pt o ms, as well as gra de a n d 
a p peara nce of c or neal c h a n ges o n 
i ma gi n g, wit h hist o pat h ol o gic 
fi n di n gs 
•  Safet y pr ofile of t h e i m pressi o n 
c yt ol o g y or S K pr o ce d ure  
Sec o n d ar y:  
•  Res ults of a nal ysis of 
cli nical/i ma gi n g data wit h 
hist o pat h ol o gic fi n di n gs  
•  A Es ass ociate d wit h t he 
i m pressi o n c yt ol o g y or S K 
pr oce d ure  
 
 
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4.  
S T U D Y D E SI G N  
4. 1.  
O v er all D e si g n  
•  T his  st u d y is a vaila ble t o a n y p artici pa nt w h o has recei v e d or is c urre ntl y 
recei vi n g bel a nta ma b maf o d oti n treat me nt t hr o u g h a cli nical trial (i ncl u di n g a n 
I S S, or a n access pr o gra m) or a P h ysi cia n pres cri pti o n; t he y d o n ot nee d t o be o n 
acti ve treat me nt as l o n g as t he y meet i ncl usi o n criteria s pecifie d bel o w.  
•  U p t o 2 5 partici pa nts  will c o m plete t he pr oce d ure. O nce a t otal of 5 p artici p a nt 
sa m ples fr o m S K pr oce d ure has  yiel de d e val ua bl e material f or p at h ol o gic 
e x a mi nati o n a n d c o m p ositi o n a nal ysis of t he c or neal e pit heli al c ha n ges, f urt her 
e nr oll me nt will cease.  
•  Eac h patie nt will ha ve a t otal of 3 (I C) t o 6 ( S K)  visits.  A d diti o nal f oll o w u p visits 
ma y b e re q uir e d i n t he e v e nt of dela y i n heali n g fr o m t he oc ular pr oce d ures.  
•  O ne e ye will be t he st u d y e ye. T he st u d y e ye will be t he e ye m ost affecte d wit h 
t he c or neal e pit helial c ha n ges. If b ot h e yes are e q u all y affecte d, t he p o orer-seei n g 
e ye will be sele cte d.  
•  Eac h partici pa nt will o nl y ha v e o ne c or neal pr oce d ure (i m pressi o n c yt ol o g y or 
S K).  All partici pa nts will be as ke d  t o partici p ate i n t he
4. 2.  
St u d y Pr o c e d ur e s  
•  C or neal e pit helial tiss ue will be o btai ne d b y I C or S K fr o m t he st u d y e ye s h o wi n g 
t he greater n u m ber of M E Cs . Re m o val of t he li m bal tiss ue s h o ul d be a v oi de d 
d uri n g t he S K pr o ce d ure, if p o ssi ble. T he sa m ple material will be pr ocesse d a n d 
tra nsferre d t o t he ce ntral la b orat or y. 
•  Assess me nts of t he e pit h elial c ha n ges will be ma de, i ncl u di n g b ut n ot li mite d t o 
hist ol o g y, electr o n micr osc o p y, a n d i m m u n o hist oc he mistr y. See ta ble b el o w f or 
met h o ds t o i n vesti gate t h e c or neal e pit heli u m.  
•  A nteri or se g me nt slit -la m p p h ot o gra p h y of b ot h e yes. 
•  C o nf ocal micr osc o p y, if a vaila ble, i n t he st u d y e ye.  
•  
 
 
 
 
 
 
 
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Name of 
analysisa 
How should the sample 
be fixed/prepared? 
Description of test 
References 
Microscopic 
evaluation/  
histopathology 
 
Tissue fixed in 10% 
neutral buffered formalin 
and embedded in paraffin. 
5 µm sections examined 
microscopically  
Histologic characterization – 
description of cells in the 
epithelium; will show apoptotic 
cells 
[Lee, 2018] 
[Stiefel, 2019]  
Hematoxylin-eosin (H&E) stain: 
hematoxylin is used to illustrate 
nuclear detail (color is related to 
the amount of DNA); eosin is 
used to stain cytoplasm 
[Sampias, 2019] 
Periodic acid-Schiff (PAS) 
stain: used for structures with a 
high proportion of 
carbohydrates (e.g., glycogen, 
glycoproteins, proteoglycans) 
typically found in connective 
tissues, mucus, and basement 
membranes 
[Anderson, 2020]  
Congo red stain: used for 
amyloid epithelial changes 
[Byrwa-Neff, 
2020] 
Masson’s trichome stain: used 
for collagenous connective 
tissue fibers; differentiates 
collagen and smooth muscle; 
used in the detection of diseases 
or changes in connective/muscle 
tissue 
[Anderson, 2020]  
Immunohisto-
chemistry (IHC) 
for IgG 
Tissue samples examined 
by IHC; performed with 
primary antibodies 
Will identify IgG-positive 
intracytoplasmic granules in the 
epithelium; because belantamab 
mafodotin is an IgG1, it could 
show if belantamab mafodotin 
itself is deposited in the 
epithelium 
[Lee, 2018] 
[Stiefel, 2019] 
Electron 
microscopy 
Samples for transmission 
electron microscopy will 
be processed using 
standard techniques: 
tissues will be epoxy 
embedded in standard 
fashion without post 
fixation. Ultrathin sections 
measuring 80 nm will be 
stained with uranyl acetate 
and lead citrate and 
examined in a Zeiss 
EM900 transmission 
electron microscope at 80 
kV  
Used for high-resolution images 
of detailed structures such as 
tissues, cells, organelles, and 
macromolecular complexes 
[Electron 
Microscopy, 
2020] [Stiefel, 
2019]  


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Name of 
analysisa 
How should the sample 
be fixed/prepared? 
Description of test 
References 
Mass 
spectrometry 
(nanoscale liquid 
chromatography 
coupled to tandem 
mass 
spectrometry 
[nano LC-
MS/MS])  
For comprehensive 
methods, see [Karring, 
2012]  
Analysis of peptide mixtures in 
sample-limited situations 
Can be used to identify in-gel 
digested protein spots 
Has been utilized to determine 
the composition of corneal 
epithelial changes associated 
with mutations in TGFBI gene 
[Karring, 2012] 
[Gaspari, 2011]  
aHistologic characterization, H&E, and PAS are required; all other stains and techniques are at the 
investigator’s discretion. 
 
Participants who receive belantamab mafodotin consistently display microcyst-like 
epithelial changes on slit-lamp examination and/or experience symptoms including 
changes in visual acuity, blurred vision, and dry eye, which are recognized AEs 
associated with MMAF-containing antibody therapies, including SGN-75 [Tannir, 2014], 
SGN-CD19A, and ABT-414 [Reardon, 2017], but the exact mechanism is unknown. The 
corneal findings by slit-lamp examination have been described in participants treated 
with high-dose cytarabine [Guthoff, 2010]. The specific corneal AE seen with 
belantamab mafodotin therapy has not been replicated in preclinical models, and 
confirmatory corneal histology is lacking to support and confirm the working explanatory 
theory for this corneal toxicity. 
The mechanism of corneal events in participants treated with belantamab mafodotin is 
unknown, but it is likely related to MMAF uptake into the corneal basal epithelial stem 
cells that are located in the basal epithelial layer of the cornea [Donaghy, 2016]. These 
cells have mitotic activity, and, furthermore, daughter cells migrate anteriorly as they 
differentiate into wing cells and terminal superficial epithelial cells. Both processes are 
microtubule dependent and can be disrupted by potent tubulin inhibitors such as MMAF. 
The leading hypothesis is that the most affected basal epithelial cells die and fail to 
transition into functional wing cells. These damaged cells eventually undergo apoptosis 
and become pyknotic. They are extruded from the epithelium, and in that process, they 
appear microcyst-like on examination. The superficial corneal surface is secondarily 
affected both by these anatomic abnormalities and alterations in superficial corneal cell 
replenishment and tear film stability. 
The current management guidelines for belantamab mafodotin-related corneal events 
include the use of preservative-free lubricant eye drops, dose reductions, and dose delays. 
The efficacy of steroid eye drops was systematically evaluated in a randomized ocular 
substudy in the DREAMM-2 study, and the results revealed that empiric topical 
corticosteroid therapy conferred no benefit. Corneal histopathologic samples in 
participants treated with belantamab mafodotin with this epitheliopathy are lacking. A 
more complete understanding of the pathophysiology of the corneal events seen in these 
participants could help confirm current hypotheses and inform management of these AEs. 
To do this, impression cytology or SK will be employed in this study to collect corneal 
epithelium with deposits for analysis. Advice from a council of corneal ophthalmology 
experts has been sought, and it is recommended that a total of 5 samples with sufficient 


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material for examination will provide confirmatory diagnosis of the underlying pathology 
and composition of these deposits. At least one highly experienced ophthalmic 
pathologist and laboratory will be utilized for tissue analysis. 
4.3. 
End of Study Definition 
The end of the study is defined as the date of the last visit of the last participant in the 
study or last scheduled procedure shown in the SoA for the last participant in the trial. 
A participant is considered to have completed the study if he/she has completed all 
phases of the study including the last visit, as specified in the SoA. 
5. 
STUDY POPULATION 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all the following criteria apply:  
1. Male or female, aged 18 years or older (at the time consent is obtained).  
2. Capable of providing signed written informed consent, which includes 
compliance with the requirements and restrictions listed on the consent form. 
3. Participants with RRMM who have received or are currently receiving treatment 
with belantamab mafodotin AND diagnosed with MECs on slit-lamp examination 
or confocal microscopy, with or without symptoms, in at least one eye. 
a. If patient only had superficial punctate keratopathy with no evidence of 
MEC’s they are not eligible. 
4. If undergoing SK procedure, treating provider has determined there is no 
excessive risk to the participant (see Section 6.2). 
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
 
1. Any serious and or/unstable medical or psychiatric disorder, or other conditions 
that could interfere with the participant’s safety. 
2. Any excess risk of delayed wound healing (e.g., diabetes mellitus). 
3. Do not meet criteria specified by the study or program through which they would 
receive belantamab mafodotin. 
4. Any patient taking concurrent medication that may affect the cornea (i.e. 
amiodarone, some chloroquines). 
5. Any patient with decreased corneal sensation. 
6. Eye infections, including infectious keratopathy, stye, blepharitis, and 
conjunctivitis. 
7. An active uveitis including anterior, posterior, or panuveitis in either eye. 
8. Permanent legal blindness in the fellow (non-study) eye. 


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Note: If the participant’s eyes are equally affected with the MECs, the study eye will be 
the one with lesser visual acuity. 
 
6. 
 STUDY INTERVENTION(S) AND CONCOMITANT 
THERAPY 
6.1. 
Study Intervention(s) Administered 
Impression cytology is a technique used to collect superficial layers from the ocular 
surface through the application of cellulose acetate filter paper. The procedure is 
performed with or without topical anesthesia by an ophthalmologist or ocular pathologist. 
SK is a method to remove a small region of the corneal epithelium down to but not 
including the level of the Bowman’s membrane. This procedure will be performed by an 
ophthalmologist and will be conducted in the eye clinic or hospital under local anesthesia 
with appropriate antisepsis. 
In this study, impression cytology or SK will be employed to collect corneal epithelium 
with epithelial changes for analysis. 
6.2. 
Patient Selection Considerations 
6.2.1. 
Selection of Right or Left eye for the procedure 
The study eye will be the one that appears to have a greater number of MECs. If both 
eyes appear equal in terms of epithelial changes, the eye with the worse visual acuity will 
be selected; if both eyes have the same visual acuity, then the investigator can select 
either eye.   
6.2.2. 
Selection of SK or IC procedure 
The following guidance should be considered before deciding which procedure (IC or 
SK) to perform:  
1) Patients should be assessed carefully for participation in either procedure.  Patient 
eligibility factors to be considered include but are not limited to: excessive risk of 
delayed wound healing, history of concerning ocular or systemic infections, 
ocular condition that may place the patient at increased risk for recovery, social or 
medical circumstances that would make the risk of increased recovery time too 
high 
2) Corneal sensation is checked at the screening visit for this study, and any eyes 
with reduced sensation should be considered ineligible for SK.  
3) For SK, a higher keratopathy disease burden, greater predominance of MECs and 
central corneal location of MECs is preferred.  
 


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6.3. 
Impression Cytology Procedure 
The study eye will be selected using the criteria described above.  Following topical 
anesthesia, an eyelid speculum, will be placed. Next, the filter paper will be pressed to a 
preidentified region on the corneal surface of the study eye with a glass rod (or similar 
instrument) for 5–10 seconds. The filter papers obtained from the procedure will contain 
epithelial layers from areas of the cornea with microcyst-like changes and will be 
analyzed through histologic techniques. The filter paper will be placed on a glass slide 
and cover slip placed on top. The eye speculum will be removed and a topical antibiotic 
drop (e.g. polytrim) will be prescribed for 4 times a day for 7 days.  
6.4. 
Superficial Keratectomy Procedure 
The study eye will be selected using the criteria described above. Following topical 
anesthesia (such as proparacaine hydrochloride 0.5%) and a drop of povidone iodine 5% 
for antisepsis, an eyelid speculum will placed. The eye will then be visualized using a 
slit-lamp or operating microscope in a procedure room. The corneal epithelium of interest 
(the region that contains the MECs) will be carefully removed using either a Weck-
Cel/dry cellulose sponge or small blade; Jeweler or 0.12 forceps may be required in some 
cases. The tissue will be submitted in formalin for histologic analysis. Care should be 
taken to minimize crush artefact to the epithelium and to avoid damage to Bowman layer. 
Post procedure, another drop of povidone iodine 5% will be placed, followed by a drop of 
balanced salt solution or topical anesthetic (to wash out any residual povidone-iodine). A 
bandage contact lens will be placed. 
It is recommended that a topical antibiotic and a topical steroid (or a fixed combination of 
both) is prescribed 4 times per day, each, for at least one week (or longer), until the 
epithelial defect is documented as healed and the bandage contact lens is no longer 
required in the assessment of treating Ophthalmologist.  The topical antibiotic may be 
discontinued once the epithelial defect has healed.  The topical steroid should be tapered 
off over the following two weeks.   
The expected time for corneal re-epithelialization is 7–10 days [Ashby, 2014]. The 
procedure can cause some pain to the participant but is generally safe and well tolerated. 
Pain, if any, can be managed by the use of artificial tears. A bandage contact lens should 
be helpful in reducing the need for pain medication. In participants with symptomatic 
blurred vision, the procedure may result in temporary visual improvement. The procedure 
may also be complicated by an infection or worsening vision. An ocular pathologist will 
be consulted to determine the appropriate testing of tissue sample.  
If the epithelial defect has not healed completely at the day 7 visit, the bandage contact 
lens should be left in place and both the steroid and antibiotic continued. The participant 
should be examined again in approximately 1 week. 
The participant should be re-examined 2 weeks after the SK procedure if the epithelial 
defect does not heal completely in the first follow-up. Otherwise, this follow-up is not 
required. In the event the cornea has not healed at 2 weeks, additional follow-up should 
be conducted at the ophthalmologist’s discretion until healing is confirmed. 


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6.8. 
sBCMA Sample Collection and Analysis 
The BCMA receptor undergoes gamma-secretase mediated cleavage, leading to release 
of the BCMA extracellular domain as soluble BCMA (sBCMA) into the circulation 
[Laurent, 2015].   
Samples will be collected to measure concentrations of sBCMA at a single timepoint, 
prior to IC or SK procedure.  Serum analysis for sBCMA will be performed under control 
of GSK (further details are included in the SRM). Raw data will be archived at the 
bioanalytical site (detailed in the SRM).  
The actual date and time of each blood sample collection will be recorded. Details on 
sBCMA blood sample collection including blood volumes, processing, storage, and 
shipping procedures are provided in the SRM. 
6.9. 
Imaging Procedures 
Slit-lamp examination, and confocal microscopy (if available) must be performed prior to 
the impression cytology or superficial keratectomy procedure to document site and size 
of corneal epithelial changes and to correlate imaging with pathologic findings.   The slit-
lamp examination must include orbit/lid/adnexa, conjunctiva, sclera, cornea, anterior 
chamber, iris, lens, and anterior vitreous. Full anterior segment (slit lamp) examination 
including fluorescein staining of the cornea. 
 
It is recommended that the imaging examination be performed at least 24 hrs prior to the 
procedure. 
Confirmatory anterior segment photography is also recommended, if available.   Anterior 
segment exam includes:, conjunctiva, sclera, cornea, lens and anterior vitreous.  If 
anterior segment photography of the cornea is available, representative images will be 
collected and stored centrally. 
 
6.10. 
Concomitant Therapy 
Any patient taking concurrent medication that may affect the cornea (i.e. amiodarone, 
some chloroquines) should not be enrolled. 
Concomitant use of ophthalmic medications related to allowable underlying ophthalmic 
conditions is permitted. Any medication (including over-the-counter prescription 
medications, vitamins, and/or herbal supplements) that the participant is receiving at the 
time of enrollment, at time of study procedure, and post procedure must be recorded 
along with: 
• Reason for use; 
• Dates of administration including start and end dates; 
• Dosage information including dose and frequency. 
The Medical Monitor should be contacted if there are any questions regarding 
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7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/ WITHDRAWAL 
7.1. 
Participant Discontinuation/Withdrawal from the Study 
• A participant may withdraw from the study at any time at his/her own request or 
may be withdrawn at any time at the discretion of the investigator for safety, 
behavioral, or compliance reasons. This is expected to be uncommon. 
• At the time of discontinuing from the study, if possible, an early discontinuation 
visit should be conducted, as shown in the SoA (Section 1.3). See SoA for data to 
be collected at the time of study discontinuation and follow-up and for any further 
evaluations that need to be completed. 
• The participant will be permanently discontinued both from the study intervention 
and from the study at that time. 
• If the participant withdraws consent for disclosure of future information, the 
sponsor may retain and continue to use any data collected before such a 
withdrawal of consent. 
• If a participant withdraws from the study, he/she may request destruction of any 
samples taken and not tested, and the investigator must document this in the site 
study records. 
7.2. 
Lost to Follow-up 
A participant will be considered lost to follow-up if he/she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or 
should continue in the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, [3] 
telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record. 
• Should the participant continue to be unreachable, he/she will be considered to 
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Discontinuation of specific sites or the study as a whole is handled as part of Appendix 1. 
Discontinuation in this study does not mean the participant has discontinued from the 
associated treatment protocol. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
A signed, written informed consent form (ICF) must be obtained from the participant 
prior to any study-specific procedures or assessments being performed. The timing of 
each assessment is listed in the SoA. 
• Study procedures and their timing are summarized in the SoA (Section 1.3).  
• Protocol waivers or exemptions are not allowed.  
• Immediate safety concerns should be discussed with the sponsor immediately 
upon occurrence or awareness to determine if the participant should continue or 
discontinue study intervention. 
• Adherence to the study design requirements, including those specified in the SoA, 
is essential and required for study conduct. 
• All screening evaluations must be completed and reviewed to confirm that 
potential participants meet all eligibility criteria. The investigator will maintain a 
screening log to record details of all participants screened and to confirm 
eligibility or record reasons for screening failure, as applicable.  
• Procedures conducted as part of the participant’s routine clinical management 
(e.g., blood count) and obtained before signing of ICF may be utilized for 
screening or baseline purposes provided the procedure met the protocol-specified 
criteria and was performed within the time frame defined in the SoA.  
8.1. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.1.1. 
Vital Signs 
Vital signs will consist of 1 pulse and 1 blood pressure measurement.  
Blood pressure and pulse measurements will be assessed with a completely automated 
device. Manual techniques will be used only if an automated device is not available. 
Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest 
for the participant in a quiet setting without distractions (e.g., television, cell phones) 
8.1.2. 
Adverse Events (AEs), Serious Adverse Events (SAEs), and 
Other Safety Reporting 
The definitions of AEs and SAEs can be found in Appendix 2. 


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AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant’s legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, 
and reporting events that meet the definition of an AE or SAE and remain responsible for 
following up all AEs related to the study intervention.  
The methods of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 2  . 
8.1.3. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• All SAEs related to the IC or SK procedure only will be collected from the start of 
intervention until the last follow-up visit at the time points specified in the SoA. 
However, any SAEs assessed as related to study participation (e.g., study 
intervention, protocol-mandated procedures, invasive tests) will be recorded from the 
time a participant consents to participate in the study.  
• AEs related to the IC or SK procedure only will be collected from the start of 
intervention until the last follow-up visit at the time points specified in the SoA 
(Section 1.3). 
• Medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will not be collected. 
• SAEs related to the IC and SK procedure will be recorded and reported to the sponsor 
or designee immediately, and under no circumstance should this exceed 24 hours, as 
indicated in Appendix 2 . The investigator will submit any updated SAE data to the 
sponsor within 24 hours of it being available. 
• Investigators are not obligated to actively seek information on AEs or SAEs after the 
conclusion of study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the study, 
and he/she considers the event to be reasonably related to the study intervention or 
study participation, the investigator must promptly notify the sponsor. 
8.1.4. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended 
and nonleading verbal questioning of the participant is the preferred method to inquire 
about AE occurrence.  
8.1.5. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. Related SAEs will be followed until the event is 
resolved, stabilized, or otherwise explained, and the epithelial defect is healed, or the 


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participant is lost to follow-up (as defined in Section 7.2). Further information on follow-
up procedures is given in Appendix 2 . 
8.1.6. 
Regulatory Reporting Requirements for SAEs 
• Prompt notification by the investigator to the sponsor of an SAE is essential so that 
legal obligations and ethical responsibilities toward the safety of participants and the 
safety of a study intervention under clinical investigation are met.  
• The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study intervention under clinical 
investigation. The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, Institutional Review Boards 
(IRB)/Independent Ethics Committees (IEC), and investigators. 
• An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (e.g., summary or listing of SAEs) from the sponsor will 
review and then file it along with the Investigator’s Brochure (IB) and will notify the 
IRB/IEC, if appropriate, according to local requirements. 
• Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 
8.1.7. 
Cardiovascular and Death Events 
For any cardiovascular (CV) events detailed in Appendix 2 and all deaths, whether or not 
they are considered SAEs, specific CV and Death sections of the Case Report Form 
(CRF) will be required to be completed. These sections include questions regarding CV 
(including sudden cardiac death) and non-CV death.  
The CV CRFs are presented as queries in response to reporting of certain CV MedDRA 
terms. The CV information should be recorded in the specific CV section of the CRF 
within 1 week of receipt of a CV Event data query prompting its completion. 
The Death CRF is provided immediately after the occurrence or outcome of death is 
reported. Initial and follow-up reports regarding death must be completed within 1 week 
of when the death is reported. 
8.2. 
Biomarkers 
Cornea tissue samples will be collected to evaluate the composition of microcyst-like 
epithelial changes observed in participants treated with belantamab mafodotin. Samples 
will be collected according to the schedule described in the SoA and, as detailed in the 
laboratory manual, provided separately to sites.  
GSK may store samples for up to 3 years after the end of the study to achieve study 
objectives. Additionally, with participants’ consent, samples may be used for further 
research by GSK or others such as universities or other companies to contribute to the 


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understanding of the pathophysiology of belantamab mafodotin–associated keratopathy, 
the development of related or new treatments, or research methods. 
8.3. 
Data Collection 
Minimal additional data will be collected to adequately characterize the development of 
the corneal epithelial changes in participating patients. 
 
a. Patient Demographics & Disease characteristics 
b. Limited Medical History and prior cancer treatment 
c. Belantamab mafodotin treatment Exposure 
d. Ocular History including the time of development of keratopathy, and the grade. 
 
9. 
STATISTICAL CONSIDERATIONS 
This is an exploratory study, and only descriptive statistics apply. 
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A 
general description of the statistical methods to be used to analyze the safety data is 
outlined below. 
9.1. 
Participant Information 
All-treated population is defined as all participants who are enrolled. All analyses will be 
based on this population. 
9.2. 
Sample Size Determination 
No statistical hypotheses will be tested as part of this protocol. The primary objective of 
this protocol will be assessed through a qualitative evaluation of pathology results. 
A total of 5 evaluable participants should provide sufficient information to make a 
qualitative assessment.  
9.3. 
Analysis Methods 
No formal statistical tests of hypothesis will be performed. All participants who have SK 
in this program will be included in the safety analysis.  
Demographic characteristics and dosing level and duration will be summarized using 
descriptive statistics (i.e., categorical variables will be described by absolute and relative 
frequencies), while continuous variables will be summarized by mean, standard 
deviation, quartiles, minimum, and maximum. The available information on all 
nonserious AEs leading to discontinuation, SAEs, and all other AEs (including AEs of 
special interest) will also be summarized using descriptive statistics. 
All available demographic and safety data will be included in the data listings and 
tabulations. No imputation of values for missing data will be performed. Participants who 


T M F -1 1 8 2 4 2 5 4  
C O N FI D E N TI A L  
 
 
 
2 1 4 0 9 8  
 
3 5  
 
are l ost t o f oll o w -u p will be i ncl u de d i n t he statistical a nal ysis t o t he p oi nt of t heir last 
e x a mi nati o n. All data will be e x a mi ne d usi n g sta n dar d data ma n a ge me nt o perati n g 
pr oce d ures.  
C ha n ges i n c or neal e pit helial fi n di n gs fr o m pre t o p ost pr oce d ure, pat h ol o gical a n d 
res ults i n safet y p o p ulati o n will be ta b ulate d i n a des cri pti ve 
ma n ner.  
 
C CI
C CI


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10. 
APPENDICES 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• This study will be conducted in accordance with the protocol and with: 
▪ Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical 
Guidelines; 
▪ Applicable ICH Good Clinical Practice (GCP) Guidelines; 
▪ Applicable laws and regulations. 
• The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., 
advertisements) must be submitted to an IRB/IEC by the investigator and 
reviewed and approved by the IRB/IEC before the study is initiated.  
• Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants.  
• Protocols and any substantial amendments to the protocol will require health 
authority approval prior to initiation except for changes necessary to eliminate an 
immediate hazard to study participants. 
• The investigator will be responsible for the following: 
▪ Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/IEC. 
▪ Notifying the IRB/IEC of SAEs or other significant safety findings as 
required by IRB/IEC procedures. 
▪ Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), European Medical Device 
Regulation 2017/745 for clinical device research (if applicable), and all 
other applicable local regulations. 
10.1.2. 
Financial Disclosure  
Investigators and subinvestigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory 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. 


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10.1.3. 
Informed Consent Process 
• The investigator or his/her representative will explain the nature of the study to 
the participant and answer all questions regarding the study.  
• Participants must be informed that their participation is voluntary. Participants 
will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance 
Portability and Accountability Act (HIPAA) requirements, where applicable, and 
the IRB/IEC or study center.  
• The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF. 
• Participants must be reconsented to the most current version of the ICF(s) during 
their participation in the study.  
• A copy of the ICF(s) must be provided to the participant. 
Participants who are rescreened are required to sign a new ICF. 
GSK (alone or working with others) may use a participant’s coded study data and 
samples and other information to carry out this study, understand the results of this study, 
learn more about belantamab mafodotin–associated keratopathy, and publish the results 
of these research efforts. 
The ICF contains a separate section that addresses the use of participant data and 
remaining samples for optional further research. The investigator or authorized designee 
will inform each participant of the possibility of further research not related to the 
study/disease. Participants will be told that they are free to refuse to participate and may 
withdraw their consent at any time and for any reason during the storage period. A 
separate signature will be required to document a participant’s agreement to allow any 
participant data and/or remaining leftover samples to be used for further research not 
related to the study/disease. Participants who decline further research will tick the 
corresponding “No” box. 
10.1.4. 
Data Protection 
• Participants will be assigned a unique identifier by the sponsor. Any participant 
records or datasets that are transferred to the sponsor will contain the identifier 
only; participant names or any information that would make the participant 
identifiable will not be transferred.  
• The participant must be informed that his/her personal study-related data will be 
used by the sponsor in accordance with local data protection law. The level of 
disclosure must also be explained to the participant, who will be required to give 
consent for their data to be used as described in the ICF.  


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• The participant must be informed that his/her medical records may be examined 
by Clinical Quality Assurance auditors or other authorized personnel appointed by 
the sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
10.1.5. 
Dissemination of Clinical Study Data 
• Where required by applicable regulatory requirements, an investigator signatory 
will be identified for the approval of the clinical study report (CSR). The 
investigator will be provided reasonable access to statistical tables, figures, and 
relevant reports and will have the opportunity to review the complete study results 
at a GSK site or other mutually agreeable location. 
• GSK will also provide all investigators who participated in the study with a 
summary of the study results and will tell the investigators which treatment their 
patients received. The investigator(s) is/are encouraged to share the summary 
results with the study participants, as appropriate. 
• Under the framework of the SHARE initiative, GSK intends to make anonymized 
participant-level data from this trial available to external researchers for scientific 
analyses or to conduct further research that can help advance medical science or 
improve participant care. This helps ensure the data provided by trial participants 
are used to maximum effect in the creation of knowledge and understanding. 
Requests for access may be made through www.clinicalstudydatarequest.com. 
• Study details will be made available on www.clinicaltrials.gov prior to, during, 
and after the conduct of the study. 
• The procedures and timing for public disclosure of the protocol and results 
summary and for development of a manuscript for publication for this study will 
be in accordance with GSK Policy. 
• A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge. 
10.1.6. 
Data Quality Assurance 
• All participant data relating to the study will be recorded on printed or electronic 
CRF (eCRF) unless transmitted to the sponsor or designee electronically (e.g., 
laboratory data). The investigator is responsible for verifying that data entries are 
accurate and correct by physically or electronically signing the CRF.  
• Guidance on completion of CRFs will be provided in the Study Reference 
Manual. 
• Quality tolerance limits (QTLs) will be predefined in the Monitoring Plan to 
identify systematic issues that can impact participant safety and/or reliability of 
study results. These predefined parameters will be monitored during and at the 


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end of the study, and all deviations from the QTLs and remedial actions taken will 
be summarized in the CSR. 
• The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents.  
• Monitoring details describing strategy including definition of study critical data 
items and processes (e.g., risk-based initiatives in operations and quality such as 
Risk Management and Mitigation Strategies and Analytical Risk-Based 
Monitoring), methods, responsibilities, and requirements, including handling of 
noncompliance issues and monitoring techniques (central, remote, or on-site 
monitoring), are provided in the Monitoring Plan. 
• The sponsor or designee is responsible for the data management of this study 
including quality checking of the data.  
• The sponsor assumes accountability for actions delegated to other individuals 
(e.g., contract research organizations). 
• Records and documents, including signed ICF, pertaining to the conduct of this 
study must be retained by the investigator for 25 years from the issue of the final 
CSR/equivalent summary unless local regulations or institutional policies require 
a longer retention period. No records may be destroyed during the retention 
period without the written approval of the sponsor. No records may be transferred 
to another location or party without written notification to the sponsor.  
10.1.7. 
Source Documents 
• Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
• Data reported on the CRF or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents, or the discrepancies 
must be explained. The investigator may need to request previous medical records 
or transfer records, depending on the study. Also, current medical records must be 
available. 
• The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF. 
• Study monitors will perform ongoing source data verification to confirm that data 
entered into the CRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are 
being protected; and that the study is being conducted in accordance with the 
currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements.  


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10.1.8. 
Study and Site Start and Closure 
First Act of Recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the first site open and will be the study start date. 
Study/Site Termination 
GSK or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
For study termination: 
• Discontinuation of further study intervention.  
For site termination: 
• Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor’s procedures, or GCP guidelines. 
• Inadequate or no recruitment of participants (evaluated after a reasonable amount 
of time) by the investigator. 
• If the study is prematurely terminated or suspended, the sponsor shall promptly 
inform the investigators, the IECs/IRBs, the regulatory authorities, and any 
contract research organization(s) used in the study of the reason for termination or 
suspension, as specified by the applicable regulatory requirements. The 
investigator shall promptly inform the participant and should assure appropriate 
participant therapy and/or follow-up. 
10.1.9. 
Publication Policy 
• The results of this study may be published or presented at scientific meetings. If 
this is foreseen, the investigator agrees to submit all manuscripts or abstracts to 
the sponsor before submission to the scientific meeting or peer-reviewed journal. 
This allows the sponsor to protect proprietary information and to provide 
comments.  


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• The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally 
support publication of multicenter studies only in their entirety and not as 
individual site data. In this case, a coordinating investigator will be designated by 
mutual agreement. 
• Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 
 


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10.2. 
Appendix 2: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.2.1. 
Definition of AE 
AE Definition 
• An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study intervention, whether or not 
considered related to the study intervention. 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a study intervention. 
 
Definition of Unsolicited and Solicited AE 
• An unsolicited AE is an AE that was not solicited using a Participant Diary and that 
is communicated by a participant who has signed the ICF. Unsolicited AEs include 
serious and nonserious AEs. 
• Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses 
requiring a hospitalization, or emergency room visit, or visit to/by a health care 
provider). The participant will be instructed to contact the site as soon as possible 
to report medically attended event(s), as well as any events that, though not 
medically attended, are of participant concern. Detailed information about reported 
unsolicited AEs will be collected by qualified site personnel and documented in the 
participant’s records. 
• Unsolicited AEs that are not medically attended nor perceived as a concern by the 
participant will be collected during interviews with the participants and by review 
of available medical records at the next visit. 
• Solicited AEs are predefined local and systemic events for which the participant is 
specifically questioned, and that are noted by the participant in his/her diary.  
 
Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (e.g., electrocardiography [ECG], radiologic scans, vital 
signs measurements), including those that worsen from baseline, considered 
clinically significant in the medical and scientific judgment of the investigator (i.e., 
not related to progression of underlying disease). 
• Exacerbation of a chronic or intermittent preexisting condition, including either an 
increase in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study intervention administration, even 
though it may have been present before the start of the study. 


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• Signs, symptoms, or the clinical sequelae of a suspected intervention–intervention 
interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae.  
 
Events NOT Meeting the AE Definition  
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition. 
• Medical or surgical procedure (e.g., endoscopy, appendectomy); the condition that 
leads to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present 
or detected at the start of the study that do not worsen. 
10.2.2. 
Definition of SAE 
An SAE is defined as any serious adverse event that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it was more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
• In general, hospitalization signifies that the participant has been admitted 
(usually involving at least an overnight stay) at the hospital or emergency ward 
for observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills 
any other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered 
serious. 
• Hospitalization for elective treatment of a preexisting condition that did not 
worsen from baseline is not considered an AE. 


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d. Results in persistent or significant disability/incapacity 
• The term “disability” means a substantial disruption of a person’s ability to 
conduct normal life functions. 
• This definition is not intended to include experiences of relatively minor 
medical significance, such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (e.g., sprained ankle), that may 
interfere with or prevent everyday life functions but do not constitute a 
substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Other situations: 
• Possible Hy’s law case: ALT ≥3×ULN AND total bilirubin ≥2×ULN (>35% 
direct bilirubin) or international normalized ratio (INR) >1.5 must be reported 
as an SAE. 
• Medical or scientific judgment should be exercised by the investigator in 
deciding whether SAE reporting is appropriate in other situations such as 
significant medical events that may jeopardize the participant or may require 
medical or surgical intervention to prevent one of the other outcomes listed in 
the above definition. These events should usually be considered serious. 
o Examples of such events include invasive or malignant cancers, 
intensive treatment for allergic bronchospasm, blood dyscrasias, 
convulsions, or development of intervention dependency or intervention 
abuse. 
 
10.2.3. 
Definition of Cardiovascular Events 
Cardiovascular (CV) Events Definition: 
Investigators will be required to fill out the specific CV event page of the CRF for the 
following AEs and SAEs: 
• Myocardial infarction/unstable angina 
• Congestive heart failure 
• Arrhythmias 
• Valvulopathy 
• Pulmonary hypertension 
• Cerebrovascular events/stroke and transient ischemic attack 
• Peripheral arterial thromboembolism 
• Deep venous thrombosis/pulmonary embolism 
• Revascularization 


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10.2.4. 
Recording and Follow-up of AEs and SAEs 
AE and SAE Recording 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, and laboratory and diagnostics 
reports) related to the event. 
• The investigator will then record all relevant AE/SAE information. 
• It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the GSK-required form. 
• There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to GSK. 
• The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to one of the following categories:  
• Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities. 
• Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities. 
• Severe: An event that prevents normal everyday activities. An AE that is assessed 
as severe should not be confused with an SAE. Severe is a category used for rating 
the intensity of an event; both AEs and SAEs can be assessed as severe. 
• An event is defined as “serious” when it meets at least one of the predefined 
outcomes as described in the definition of an SAE, NOT when it is rated as severe.  
Assessment of Causality 
The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. 
• A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship, cannot 
be ruled out. 
• The investigator will use clinical judgment to determine the relationship. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 


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• The investigator will also consult the IB and/or Product Information, for marketed 
products, in his/her assessment. 
• For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK. However, it is very 
important that the investigator always makes an assessment of causality for 
every event before the initial transmission of the SAE data to GSK. 
• The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of AEs and SAEs 
• The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This 
may include additional laboratory tests or investigations, histopathologic 
examinations, or consultation with other health care professionals. 
• New or updated information will be recorded in the originally submitted 
documents. 
• The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
 
 


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10.2.5. 
Reporting of SAEs to GSK 
SAE Reporting to GSK via Electronic Data Collection Tool 
• The primary mechanism for reporting SAEs to GSK will be the electronic data 
collection tool. 
• If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) to report the event within 24 hours. 
• The site will enter the SAE data into the electronic system as soon as they become 
available. 
• The investigator or medically qualified subinvestigator must show evidence within 
the eCRF (e.g., check review box, signature, etc.) of review and verification of the 
relationship of each SAE to study intervention/study participation (causality) 
within 72 hours of SAE entry into the eCRF. 
• After the study is completed at a given site, the electronic data collection tool will 
be taken offline to prevent the entry of new data or changes to existing data. 
• If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken offline, then the site can report this information on a paper SAE form (see 
next section) or to the medical monitor by telephone. 
• Contacts for SAE reporting can be found in the Study Reference Manual.  
Complete the SAE form and email it to the GSK Case Management Group (CMG) 
group mailbox: uk.gsk-rd-gcsp-ctsm-admin@gsk.com. 
 
SAE Reporting to GSK via Paper Data Collection Tool 
• Email transmission of the SAE paper data collection tool is the preferred method to 
transmit this information to the medical monitor or the SAE coordinator. 
• In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service. 
• Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE data collection tool within the designated reporting time 
frames. 
• Contacts for SAE reporting can be found in the Study Reference Manual.  
Complete the SAE form and email it to the GSK CMG group mailbox: uk.gsk-rd-
gcsp-ctsm-admin@gsk.com. 
 


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Assessment of Intensity 
• The investigator will make an assessment of intensity for each AE/SAE/device 
deficiency reported during the study and assign it to one of the following 
categories:  
• Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities. 
• Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities. 
• Severe: An event that prevents normal everyday activities. An AE that is assessed 
as severe should not be confused with an SAE. Severe is a category used for rating 
the intensity of an event; both AEs and SAEs can be assessed as severe. 
• An event is defined as “serious” when it meets at least one of the predefined 
outcomes as described in the definition of an SAE, not when it is rated as severe. 
• Other measures to evaluate AEs and SAEs may be utilized (e.g., National Cancer 
Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE]). 
 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE/device deficiency. 
• A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship, cannot 
be ruled out. 
• The investigator will use clinical judgment to determine the relationship. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• The investigator will also consult the IB or Product Information, for marketed 
products in his/her assessment. 
• For each AE/SAE/device deficiency, the investigator must document in the 
medical notes that he/she has reviewed the AE/SAE/device deficiency and has 
provided an assessment of causality. 
• There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK. However, it is very 
important that the investigator always makes an assessment of causality for every 
event before the initial transmission of the SAE data to GSK. 
• The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 


T M F -1 1 8 2 4 2 5 4  
C O N FI D E N TI A L  
 
 
 
2 1 4 0 9 8  
 
4 9  
 
1 0. 3.  
A p p e n di x 3: Hi st or y of pr ot o c ol c h a n g e s  
 
T he Pr ot oc ol A me n d me nt S u m mar y of C ha n ges T a ble f or t he c urre nt a me n d me nt is 
l ocate d directl y b ef ore t he Ta ble of C o nte nts ( T O C). 
 
A me n d me nt 1: 2 8 -J U L -2 0 2 0  
 
O ver all R ati o n ale f or t he A me n d me nt:   
 
T he pr ot oc ol has bee n a me n de d t o u p date te ar fl ui d s peci me n c ollecti o n pr ocess a n d a d d 
a bl o o d sa m ple assess me nt at baseli ne.  
 
Secti o n # a n d N a me  
Descri pti o n of C h a n ge  
Brief R ati o n ale  
 
O bjecti ves a n d 
E n d p oi nts, S y n o psis  
A d de d Bl o o d Sa m ple A nal ysis  
A d d A nal ysis of 
bl o o d B C M A le vels  
M ulti ple secti o ns 
U p date d t o i ncl u de bl o o d sa m ple 
c ollecti o n  
A d d A nal ysis of 
bl o o d B C M A le vels  
1. 3 Sc he d ule of 
Assess me nts  
A d de d Bl o o d Sa m ple C ollecti o n  
A d d A nal ysis of 
bl o o d B C M A le vels  
3. 0 O bjecti ves a n d 
E n d p oi nts  
A d de d Bl o o d Sa m ple A nal ysis  
A d d A nal ysis of 
bl o o d B C M A le vels  
4. 2 St u d y Pr oce d ures  
A d de d Tear Fl ui d & Bl o o d Sa m ple 
A nal ysis  
Clarificati o n  
6. 6 Bela nta m a b 
Maf o d oti n P K Sa m pl e 
A nal ysis  
A d de d Secti o n  
Clarificati o n  
6. 7 s B C M A Sa m ple 
C ollecti o n a n d 
A nal ysis  
A d de d Secti o n  
Clarificati o n of 
s pecific la b testi n g 
 
 
C CI


T M F -1 1 8 2 4 2 5 4  
C O N FI D E N TI A L  
 
 
 
2 1 4 0 9 8  
 
5 0  
 
1 0. 4.  
A p p e n di x 4 : A b br e vi ati o n s a n d Tr a d e m ar k s 
A D C  
A nti b o d y -dr u g c o nj u gate  
A E  
A d verse e ve nt  
A L T  
Ala ni ne a mi n otra nsferas e  
A P RI L  
A pr oliferati o n -i n d u ci n g li ga n d 
B A F F  
B -cell acti vati n g fact or fa mil y  
B C M A  
B -cell mat urati o n a nti ge n  
BI B  
Bi oa nal ysis I m m u n o ge ni cit y a n d Bi o mar kers  
B L ys  
B l y m p h oc yt e sti m ul at or  
C D 3 8  
C l uster of differe ntiati o n 3 8 
C F R  
C o de of Fe d eral Re gister  
CI  
C o nfi de nce i nter val  
CI O M S  
C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical Scie nces  
C L W  
Ce ntral La b orat or y W or ks heet  
C M G  
Case Ma na ge m e nt Gr o u p  
C R F  
Case Re p ort F or m  
C S R  
Cli nical st u d y re p ort  
C V  
Car di o vasc ular  
D O R  
D urati o n of Res p o nse  
D R E A M M  
Dri vi n g E x celle nce i n A p pr oac hes t o M ulti ple M yel o ma  
e C R F 
Electr o nic Case Re p ort F or m  
G C P  
G o o d Cli nical Practice  
G S K  
Gla x o S mit h Kli ne  
H & E  
He mat o x yli n -e osi n  
HI P A A  
Healt h I ns ura nce P orta bilit y a n d Acc o u nta bilit y Act  
I B 
I n v esti gat or’s Br oc h ure 
I C 
I m pr essi o n C yt ol o g y 
I C F 
I nf or me d C o nse nt F or m 
I C H 
I nter nati o nal C o u ncil f or Har m o nizati o n of Tec h ni cal Re q uire me nts 
f or P har mace uticals f or H u ma n Use   
I E C 
I n d e pe n de nt Et hics C o m mittee 
I g G 
I m m u n o gl o b uli n G 
I g G 1 
I m m u n o gl o b uli n G 1 
I H C 
I m m u n o hist oc he mistr y 
I Mi D 
I m m u n o m o d ulat or y dr u gs 
I S S 
I n v esti gat or S p o ns ore d St u d y 
k g  
kil o gra m  
M E Cs  
Micr oc yst -li ke e pit helial c ha n ges 
m g  
milli gra m  
M M  
M ulti ple m yel o ma  
M M A F  
M o n o met h yl a uristati n -F  
N CI  
Nati o nal Ca ncer I nstit ute  
O E F  
Oc ular e ye fi n di n gs  
O R R  
O verall Res p o nse Rate  
C CI


T M F -1 1 8 2 4 2 5 4  
C O N FI D E N TI A L  
 
 
 
2 1 4 0 9 8  
 
5 1  
 
P A S  
Peri o dic aci d -Sc hiff  
P F S  
Pr o gressi o n -free S ur vi val 
P R  
Partial Res p o nse  
Q T L  
Q ualit y T olera nce Li mit  
Q 3 W  
E ver y t hree wee ks  
R R M M  
Rela pse d/ Refract or y m ulti ple m yel o ma  
S A E  
Seri o us a d verse e ve nt  
s C R 
Stri n ge nt C o m plete Res p o nse  
S o A  
Sc he d ule of acti vities  
S R M  
St u d y R efere nce Ma n ual  
U L N  
U p per li mit of n or mal  
V G P R  
Ver y G o o d Partial Res p o nse  
 
 
Tr a d e m ar k I nf or m ati o n  
Tr a d e m ark s of t h e Gl a x o S mit h Kli n e 
gr o u p of c o m p a ni e s  
 
Tr a d e m ark s n ot o w n e d by t h e 
Gl a x o S mit h Kli n e gr o u p of c o m p a ni es  
N O N E  
 
C yt ara bi ne  
 
 
P ol ytri m  
 
 
 
 
 
C CI


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11. 
REFERENCES 
Anderson J. An introduction to routine and special staining [Online]. Available: 
https://www.leicabiosystems.com/knowledge-pathway/an-introduction-to-routine-and-
special-staining/] [Accessed April 2020]. 
Anderson KC. 2016. Progress and paradigms in multiple myeloma. Clin Cancer Res, 22, 
5419-5427. 
Ashby BD, Garrett Q, Willcox MDP. 2014. Corneal injuries and wound healing – review 
of processes and therapies. Austin J Clin Ophthalmol, 1, 1017. 
Byrwa-Neff KJ Safety with special stains [Online]. Available: 
https://www.leicabiosystems.com/knowledge-pathway/safety-with-special-stains/] 
[Accessed April 2020]. 
Donaghy H. 2016. Effects of antibody, drug and linker on the preclinical and clinical 
toxicities of antibody-drug conjugates. MAbs, 8, 659-71. 
Electron Microscopy Facility. What is electron microscopy? [Online]. Available: 
https://www.umassmed.edu/cemf/whatisem/] [Accessed April 2020]. 
Gaspari M., Cuda G. (2011) Nano LC–MS/MS: A Robust Setup for Proteomic Analysis. 
In: Toms S., Weil R. (eds) Nanoproteomics. Methods in Molecular Biology (Methods 
and Protocols), vol 790. Humana Press 
GlaxoSmithKline Document Number 2013N175128_08] GSK285916 IB Version 8. 
Effective 06-JUL-2020 
Guthoff T, Tietze B, Meinhardt B, Becher J, Guthoff R. 2010. Cytosine-arabinoside-
induced keratopathy: a model of corneal proliferation kinetics. Ophthalmologica, 224, 
308-11. 
Karring H, Runager K, Thogersen IB, Klintworth GK, Hojrup P, Enghild JJ. 2012. 
Composition and proteolytic processing of corneal deposits associated with mutations in 
the TGFBI gene. Exp Eye Res, 96, 163-70. 
Kumar SK, Therneau TM, Gertz MA, Lacy MQ, Dispenzieri A, Rajkumar SV, et al. 
2004. Clinical course of patients with relapsed multiple myeloma. Mayo Clin Proc, 79, 
867-74. 
Laurent SA, Hoffmann FS, Kuhn PH, et al. Gamma-secretase directly sheds the survival 
receptor BCMA from plasma cells. Nat Commun. 2015;6:7333. 
Lee BA, Lee MS, Maltry AC, Hou JH. 2018. Clinical and histological characterization of 
toxic keratopathy from depatuxizumab mafodotin (ABT-414), an antibody-drug 
conjugate: [RETRACTED]. Cornea. 
Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, et al. 2020. Belantamab 
mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, 
randomised, open-label, phase 2 study. Lancet Oncol, 21, 207-21. 
Mikhael J. 2020. Treatment options for triple-class refractory multiple myeloma. Clin 
Lymphoma Myeloma Leuk, 20, 1-7. 


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Murueta-Goyena A, Canadas P. 2018. Visual outcomes and management after corneal 
refractive surgery: A review. J Optom, 11, 121-9. 
Park M, Richardson A, Pandzic E, Lobo EP, Whan R, Watson SL et al. 2019. Visualizing 
the contribution of keratin-14(+) limbal epithelial precursors in corneal wound healing. 
Stem Cell Reports, 12, 14-28. 
Rajkumar SV. 2016. Multiple myeloma: 2016 update on diagnosis, risk-stratification, and 
management. Am J Hematol, 91, 719-34. 
Reardon DA, Lassman AB, Van Den Bent M, Kumthekar P, Merrell R, Scott AM, et al. 
2017. Efficacy and safety results of ABT-414 in combination with radiation and 
temozolomide in newly diagnosed glioblastoma. Neuro Oncol, 19, 965-75. 
Sampias C, Rolls G. 2019. H&E staining overview: a guide to best practices [Online]. 
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Siegel RL, Miller KD, Jemal A. 2016. Cancer statistics, 2016. CA Cancer J Clin, 66, 7-
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Sta Iglesia DD, Stepp MA. 2000. Disruption of the basement membrane after corneal 
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Stiefel HC, Sandhu RK, Miller AK, Wilson DJ, Chamberlain WD. 2019. 
Characterization of corneal deposition keratopathy in the setting of blood cell dyscrasia 
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relapsed/refractory non-Hodgkin lymphoma or metastatic renal cell carcinoma. Invest 
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Vo RC, Chen JL, Sanchez PJ, Yu F, Aldave AJ. 2015. Long-term outcomes of epithelial 
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Wilson SA, Last A. 2004. Management of corneal abrasions. Am Fam Physician, 70, 
123-8. 
 

SAP_001.pdf: 
Reporting and Analysis Plan 
Study ID: 214098 
Official Title of Study: Characterization of Corneal Epithelial Changes in 
Participants Treated with Belantamab Mafodotin (GSK2857916) 
Date of Document: 12-Oct-2022 
NCT ID: NCT04549363 


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 1 of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
 
 
 
 
 
S T A TI S TI C A L A N A L Y SI S P L A N  
 
Pr ot oc ol n u m ber 2 1 4 0 9 8 –  A me n d me nt 0 2 T M F- 1 1 8 2 4 2 5 4 d ate d 
0 4 F E B 2 0 2 1 
 
C h ar acteriz ati o n of C or ne al E pit heli al C h a n ges i n P artici p a nts 
Tre ate d wit h Bel a nt a m a b M af o d oti n ( G S K 2 8 5 7 9 1 6) 
 
 
 
 
 
 
 
 
 
 
A U T H O R :
V E R SI O N N U M B E R A N D D A T E : V 2. 0 , 1 2 O C T 2 0 2 2 
 
 
 
P P D
P P D


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 2 of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
S T A TI S TI C A L A N A L Y SI S P L A N S I G N A T U R E P A G E  
St atisti cal A nal ysis Pla n V 2. 0 ( Date d 1 2 O C T 2 0 2 2) f or Pr ot oc ol 2 1 4 0 9 8 a me n d me nt 0 2 . 
 
 
N a me 
Si g n at ure 
D ate ( D D M M Y Y Y Y) 
A ut h or: 
Refer t o e Si g nat ur e 
 
  
P ositi o n: 
Bi ostatisticia n Tea m Lea d 
  
C o m p a n y: 
I Q VI A 
 
 
 
 
 
N a me 
Si g n at ure 
D ate ( D D M M Y Y Y Y) 
A ut h or: 
Refer t o e Si g nat ur e 
 
  
P ositi o n: 
Bi ostatisticia n Tea m Lea d 
  
C o m p a n y: 
I Q VI A 
 
 
U p o n  r e vi e w of t his d oc u me nt, t h e u n dersi g n e d a p pr o ves t his versi o n of t h e Statistical A nal ysis Pla n, a ut h orizi n g 
t h at t h e c o nt e nt is acce pta ble f or t h e r e p orti n g of t his st u d y. 
 
N a me 
Si g n at ure 
D ate ( D D M M Y Y Y Y) 
A p pr o ve d B y: 
Refer t o e Si g nat ur e 
 
  
P ositi o n: 
St u d y Lea d Statisticia n  
  
C o m p a n y: 
G S K  
 
 
P P D
P P D
P P D
P P D


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 3 of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
A p pr o ve d B y: 
Refer t o e Si g nat ur e 
 
  
P ositi o n: 
St u d y Lea d Pr o gra m mer 
 
  
C o m p a n y: 
G S K  
 
A p pr o ve d B y: 
Refer t o e Si g nat ur e 
 
  
P ositi o n: 
  
C o m p a n y: 
G S K  
 
A p pr o ve d B y: 
Refer t o e Si g nat ur e 
 
  
P ositi o n: 
Se ni or Bi ostatisticia n Re vie wer 
  
C o m p a n y: 
I Q VI A 
 
P P D
P P D
P P D
P P D


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 4 of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
M O DI FI C A TI O N H I S T O R Y 
 
U ni q ue 
I de ntifie r f or 
t his Versi o n 
D ate of t he 
D oc u me nt 
Versi o n  
A ut h or  
Si g nific a nt C h a n ges fr o m  
Pre v i o us A ut h orize d Versi o n 
1. 0 
0 5 M A Y 2 0 2 1 
N ot A p plica ble –  First Versi o n 
1. 1 
1 2 A U G 2 0 2 1 
Mi n or u p dates t o A p pe n di x 1 –  e nsur e d secti o n 
r efers t o ‘ Pri or/ C o n c o mita nt Oc ul ar 
T her a p y / Me dicati o ns’ a n d t hat r efer e n ces ar e 
t o e n d of st u d y n ot e n d of tr eat me nt. 
1. 2 
1 2 A P R 2 0 2 2 
U p date d t o acc o u nt f or i nteri m a nal ysis (if 5 
S K pa tie nts ar e n ot ac hie ve d b y t h e pla n n e d 
fi n al a n al ysis ti meli n e. 
Defi niti o n of all-tr eate d, I C S K p o p ulati o ns 
u p date d. 
Oc ular hist or y a n d ris k fact ors s u m maries 
r e m o ve d. 
S u m mar y f or m ulti ple m yel o ma disease 
c h ara cteristics r e m o ve d. 
S u m mar y f or hist ol o gic c h ara cterizati o n 
r e m o ve d. 
S u m mar y f or c or n eal i ma gi n g a n d se nsati o n 
r e m o ve d. 
S u m maries f or oc ul ar e xa mi nati o n a n d f oll o w-
u p r e m o ve d. 
A Es a n d S A Es s u m maries t o be pr ese nte d b y 
All- Tr eate d n ot I C S K p o p ulati o n. 
Tear fl ui d s u m mar y u p date d t o pr ese nt 
detecte d/ n ot detecte d ( n ot q ua ntitati ve data). 
1. 3 
0 4 M A Y 2 0 2 2 
C ha n ge d p o p ulati o ns f or pri mar y, safet y a n d 
P P D
P P D
P P D
P P D
P P D


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 5 of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
p har mac o ki n etics a nal yses.  
1. 4 
0 7J U N 2 0 2 2 
A d de d i n p har mac o ki n etics p o p ulati o ns. 
1. 5 
1 3J U N 2 0 2 2 
Re m o ve d P K T E A R, P K P L A S a n d P D BI O 
fr o m r eas o ns f or e xcl usi o n s u m mar y wit hi n 
dis p ositi o n ta ble. Gr a m mar c orr ecti o ns. 
1. 6 
1 5J U N 2 0 2 2 
S A P versi o n a n d date u p date d. Gra m mar 
c orr ecti o ns. 
2. 0 
1 2 O C T 2 0 2 2 
A d diti o n of s u m mar y statistics t o be r e p ort e d 
f or mA b f or plas ma r es ults 
 
 
P P D
P P D


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 6 of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
T A B L E O F C O N T E N T S  
1.  
I N T R O D UC TI O N .............................................................................................................9  
2.  
S T U D Y O B J E C TI V E S ......................................................................................................9  
2. 1.  
Pri m ar y O bjecti ve ................................................................................................................................. 9 
2. 2.  
Se c o n d ar y O bjecti ves ............................................................................................................................ 9 
3.  
S T U D Y D E SI G N ............................................................................................................. 1 0 
3. 1.  
G e ner al Descri pti o n ............................................................................................................................ 1 0 
3. 2.  
Sc he d ule of Acti vities .......................................................................................................................... 1 2 
3. 3.  
C h a n ges t o A n al ysis fr o m Pr ot oc ol ..................................................................................................... 1 4 
4.  
P L A N N E D A N A L Y S E S .................................................................................................. 1 4 
4. 1.  
Fi n al A n al ysis ...................................................................................................................................... 1 4 
5.  
A N A L Y SI S P O P U L A TI O N S .......................................................................................... 1 5 
5. 1.  
All P artici p a nts Scree ne d .................................................................................................................... 1 5 
5. 2.  
All- Tre ate d P o p ul ati o n ........................................................................................................................ 1 5 
5. 3.  
I m pressi o n C yt ol o g y or S u perfici al Ker atect o m y Pr oce d ure P o p ul ati o n .......................................... 1 5 
6.  
G E N E R A L A N D S T A TI S TI C A L C O N SI D E R A TI O N S ............................................... 1 6 
6. 1.  
Refere nce St art D ate a n d St u d y D a y .................................................................................................. 1 6 
6. 2.  
B aseli ne ................................................................................................................................................ 1 7 
6. 3.  
U nsc he d ule d visits ............................................................................................................................... 1 7 
C CI
P P D


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 7 of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
6. 4.  
St atistic al Tests .................................................................................................................................... 1 7 
6. 5.  
Missi n g d at a ........................................................................................................................................ 1 7 
6. 6.  
S oft w are Versi o n ................................................................................................................................. 1 7 
7.  
O U T P U T P R E S E N T A TI O N S ......................................................................................... 1 7 
8.  
DI S P O SI TI O N A N D WI T H D R A W A L S ........................................................................ 1 8 
8. 1.  
Dis p ositi o n ........................................................................................................................................... 1 8 
9.  
D E M O G R A P HI C C H A R A C T E RI S TI C S ...................................................................... 1 8 
9. 1.  
De ri v ati o ns .......................................................................................................................................... 1 9 
1 0.  
O C U L A R HI S T O R Y A N D RI S K F A C T O R S ............................................................. 1 9 
1 1.  
O C U L A R T H E R A P Y ................................................................................................... 1 9 
1 2.  
O C U L A R M E DI C A TI O N ............................................................................................ 2 0 
1 3.  
DI S E A S E C H A R A C T E RI S TI C S ................................................................................. 2 0 
1 4.  
M Y E L O M A T R E A T M E N T ......................................................................................... 2 0 
1 5.  
E X P O S U R E T O B E L A N T A M A B M A F O D O TI N ....................................................... 2 0 
1 6.  
P RI M A R Y E N D P OI N T ................................................................................................ 2 1 
1 7. 1.  
Sec o n d ar y a n d E x pl or at or y Cli nic al E n d p oi nts ............................................................................. 2 1 
1 7. 2.  
Sec o n d ar y S afet y E n d p oi nts ............................................................................................................ 2 2 
1 7. 2. 1.  
A d verse e ve nts .......................................................................................................................... 2 2 
1 7. 2. 2.  
Vital si g ns ................................................................................................................................. 2 3 
1 7. 3. 3.  
Bi o mar kers ................................................................................................................................ 2 4 
A P P E N DI X 1.  P A R TI A L D A T E C O N V E N TI O N S ............................................................ 2 4 
 
 
P P D
C CI
C CI


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 8 of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
A B B R E VI A TI O N S  
 
A D C   
  
  
 
A nti b o d y- Dr u g C o nj u gate 
A E   
  
  
  
A d verse E ve nt 
A T C  
  
  
  
A nat o mic T h er a pe utic Class 
B C M A   
  
  
B- Cell Mat ur ati o n A nti ge n 
G S K   
  
  
  
Gla x o S mit h Kli n e 
I C  
  
  
  
I m pr essi o n c yt ol o g y 
I C S K p o p ul ati o n   
  
I m pr essi o n c yt ol o g y or s u perficial ker atect o m y pr oce d ur e p o p ulati o n 
I S S  
  
  
  
I n vesti gat or- S p o ns or e d St u d y 
m A b  
  
  
  
A nti- B C M A m o n ocl o n al a nti b o d y 
Me d D R A  
  
  
Me dical Di cti o nar y f or Re g ulat or y Acti vities 
M E Cs   
  
  
Micr oc yst-li ke e pit h elial c h a n ges 
M M A F    
  
  
M o n o met h yl A uristati n- F 
P K   
  
  
  
P har mac o ki n etic 
P T   
  
  
  
Pr eferr e d T er m 
S A P   
  
  
  
Statistical A nal ysis Pla n 
S C R  
  
  
  
A ll Partici pa nts Scr ee n e d p o p ulati o n 
S K   
  
  
  
S u perficial ker atect o m y 
W H O 
  
  
  
W orl d Healt h Or ga nizati o n 
 
 
P P D


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 9 of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
1.  IN T R O D U C TI O N  
T his  d oc u m e nt descri bes t h e r ules a n d c o n ve nti o ns t o be use d i n t h e pr ese ntati o n, s u m marizi n g a n d a nal ysis of data 
fr o m parti ci pa nts r ecei vi n g bela nta ma b m af o d oti n ( G S K 2 8 5 7 9 1 6) i n a n ot h er G S K trial or patie nts o n c o m mer cial 
pr escri pti o ns. T his is a n e x pl orat or y st u d y, a n d o nl y descri pti ve statistics a p pl y. 
T his st atisti cal a nal ysis pla n ( S A P) is base d o n pr ot oc ol 2 1 4 0 9 8 a me n d me nt 0 2 ( T M F- 1 1 8 2 4 2 5 4), date d 0 4 Fe br uar y 
2 0 2 1. 
2.  S T U D Y O B J E C TI V E S  
2. 1.  P RI M A R Y O B J E C TI V E  
T h e pri mar y o bjecti ve i s t o c har acterize c or n eal e pit h eli o pat h y i n partici pa nts tr eate d wit h bela nta ma b maf o d oti n. 
2. 2.  S E C O N D A R Y O B J E C TI V E S  
T h e sec o n dar y o bjecti ves ar e: 
 
T o c orr elate cli nical data, i n cl u di n g vis ual ac uit y a n d s y m pt o ms, as well as gra de a n d a p pear a n ce of c or n eal 
c h an ges o n i ma gi n g, wit h hist o pat h ol o gic fi n di n gs. 
 
T o descri be safet y pr ofile of t h e i m pr essi o n c yt ol o g y (I C) or s u perficial ker atect o m y ( S K ) pr oce d ur e. 
P P D
C CI


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 1 0  of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
3.  S T U D Y D E SI G N  
3. 1.  G E N E R A L D E S C RI P TI O N  
 
T his st u d y is a vaila ble t o a n y partici pa nt w h o h as r ecei ve d or is c urr e ntl y r ecei vi n g bela nta ma b maf o d oti n 
tr eat m e nt t hr o u g h a cli nical trial (i n cl u di n g a n i n vesti gat or- s p o ns or e d st u d y (I S S), or a n access pr o gra m) or a 
P h ysi ci a n pr escri pti o n; t h e y d o n ot n ee d t o be o n acti ve tr eat me nt as l o n g as t h e y meet i n cl usi o n criteria ( See 
pr ot oc ol  a me n d me nt 0 2 ( T M F- 1 1 8 2 4 2 5 4) –  Secti o n 5 S T U D Y P O P U L A TI O N). 
 
U p t o 2 5 partici pa nts will c o m plete t h e pr oce d ur e. O n ce a t otal of 5 partici pa nt sa m ples fr o m S K pr oce d ur e has 
yi e l de d e val ua ble material f or pat h ol o gic e xa mi nati o n a n d c o m p ositi o n a nal ysis of t h e c or n eal e pit h elial 
c h a n ges, f urt h er e nr oll me nt will cease. 
 
E a c h pati e nt will ha ve a t otal of 3 ( I C) to 6 ( S K ) visits. A d diti o n al f oll o w- u p visits ma y be r e q uir e d i n t h e e ve nt 
of del a y i n h eali n g fr o m t h e oc ular pr oce d ur es. 
 
O n e e ye will be t h e st u d y e ye. T h e st u d y e ye will be t h e e ye m ost affecte d wit h t h e c or n eal e pit h elial c h a n ges. 
If b ot h e yes ar e e q uall y affecte d, t h e p o or er-seei n g e ye will be selecte d. 
 
 
I m pr essi o n c yt ol o g y: F oll o wi n g t o pical a n est h esia, a n e yeli d s pec ul u m, will be place d. Ne xt, t h e filter pa per 
wil l be pr esse d t o a pr ei de ntifie d r e gi o n o n t h e c or n eal s urface of t h e st u d y e ye wit h a glass r o d ( or si milar 
i nstr u m e nt) f or 5– 1 0 sec o n ds. T h e filter pa pers o btai n e d fr o m t h e pr oce d ur e will c o ntai n e pit h elial la yers fr o m 
ar eas of t h e c or n ea wit h micr oc yst-li ke c ha n ges a n d will be a nal yze d t hr o u g h hist ol o gic tec h ni q ues.  
 
S u perfi ci al ker atect o m y: F oll o wi n g t o pical a n est h esia (s uc h as pr o para cai n e h y dr oc hl ori de 0. 5 %) a n d a dr o p of 
p o vi d o n e i o di n e 5 % f or a ntise psis, a n e yeli d s pec ul u m will be place d. T h e e ye will t h e n be vis ualize d usi n g a 
slit-l a m p or o perati n g micr osc o pe i n a pr oce d ur e r o o m. T h e c or n eal e pit h eli u m of i nter est (t h e r e gi o n t h at 
c o nt ai ns t h e M E Cs) will be car ef ull y r e m o ve d usi n g eit h er a Wec k- Cel/ dr y cell ul ose s p o n ge or s mall bl a de; 
Je wel er or 0. 1 2 f or ce ps ma y be r e q uir e d i n s o me cases. T h e tiss ue will be s u b mitte d i n f or mali n f or hist ol o gi c 
a n al ysis. 
 
St u d y D ur ati o n: a p pr o xi matel y 4 wee ks. 
 
 
 
P P D
C CI


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 1 1  of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
T a bl e A: St u d y sc h e ma 
 
 
P P D
C CI
C CI
C CI


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 1 2  of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d 
u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
3. 2.  S C H E D U L E O F A C TI VI TI E S  
A E,  a d verse e ve nt; 
I C, i m pr essi o n c yt ol o g y; S A E, seri o us a d verse e ve nt; S K, s u perfi ci al kerat ect o m y. 
P P D
C CI
C CI
C CI


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 1 3  of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d 
u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
a A n  o p ht hal mic e xa mi nati o n t hat i n cl u des best-c orr ecte d vis ual ac uit y, slit-la m p e xa mi n ati o n, a n d c o nf ocal mi cr osc o p y (if a vaila bl e) m ust be perf or m e d pri or t o t h e 
i m pr essi o n c yt ol o g y or keratect o m y pr oce d ur e t o d oc u me nt site a n d size of c or n eal e pit h elial c h a n ges a n d t o c orr el at e i m a gi n g wit h pat h ol o gi c fi n di n gs. T h e slit la m p 
e xa mi nati o n m ust i n cl u de or bit/li d/a d n e xa, c o nj u n cti va, sclera, c or n ea, a nteri or c h a m ber, iris, le ns, a n d a nteri or vitr e o us. C o nfir m at or y a nt eri or se g m e nt p h ot o gra p h y is als o 
r e q uir e d u nl ess acce pta ble c or n eal i ma ges ar e a vaila ble fr o m a n e xa mi nati o n perf or me d < 1 4 da ys pri or t o i m pr essi o n c yt ol o g y or S K. It i s r ec o m m e n de d t hat t h e i m a gi n g 
e xa mi nati o n be perf or me d at least 2 4 hrs pri or t o t h e pr oce d ur e. 
b E xa m pl es of pr eferr e d ter ms ( C T C A E v 5. 0) i n cl u de, b ut ar e n ot li mite d t o, keratitis, e ye dis or der – ot h er, bl urr e d visi o n, dr y e ye, e ye pai n, flas hi n g li g hts, p h ot o p h o bi a, a n d 
wat eri n g e yes. 
c G S K ma y st or e sa m ples f or u p t o 3 years after t h e e n d of t he st u d y t o ac hie ve st u d y o bjecti ves. A d diti o nall y, wit h parti ci pa nts’ c o nse nt, sa m pl es m a y be use d f or f urt h er 
r esear c h b y G S K or ot h ers s uc h as u ni versities or ot h er c o m pa nies t o c o ntri b ute t o t h e u n dersta n di n g of t h e pat h o p h ysi ol o g y of bel a nta ma b m af o d oti n –  ass oci at e d 
ker at o pat h y, t h e de vel o p me nt of r elate d or n e w tr eat me nts, or r esear c h met h o ds. 
d Pr eferr e d ti mi n g f or f oll o w- u p slit-la m p e xa mi nati o n is 2 4 – 4 8 h o urs p ost S K pr oce d ur e b ut m ust be perf or me d wit hi n 1 wee k aft er S K pr oce d ur e. Safet y f oll o w- u p aft er 
i m pr essi o n c yt ol o g y is n ot r e q uir e d u nless t h e partici pa nt is e x perie n ci n g disc o mf ort or a n A E. 
e T h e A E/ S A E f oll o w- u p i m me diatel y after t h e P ost – I C or S K pr oce d ur e ca n be d o n e b y p h o n e, i n t h e 2 4- 4 8 h o urs p ost- pr oce d ur e. 
f T h e parti ci pa nt s h o ul d be r ee xa mi n e d 2 wee ks after t h e S K pr oce d ur e if t h e e pit h elial defect d oes n ot h eal c o m pl et el y i n t h e first f oll o w- u p. Ot h er wise, t his f oll o w- u p is n ot 
r e q uir e d. 
g I n t h e e ve nt t h e c or n ea has n ot h eale d at 2 wee ks, a d diti o n al f oll o w-u p s h o ul d be c o n d ucte d at t h e o p ht hal m ol o gist’s discr eti o n u ntil  h eali n g is c o nfir m e d. 
h Mi ni mal a d diti o nal data will be c ollect e d t o a de q uatel y c h ara cterize t h e de vel o p me nt of t h e c or n eal e pit h elial c ha n ges i n parti ci pati n g pati e nts. 
P P D
C CI


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 1 4  of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
3. 3.  C H A N G E S T O A N A L Y SI S F R O M P R O T O C O L  
I m pr essi o n c yt ol o g y or s u perficial ker atect o m y pr oce d ur e p o p ulati o n (I C S K) a n d e val ua ble i m pr essi o n c yt ol o g y or 
s u perfi ci al ker atect o m y pr oce d ur e p o p ulati o n ( EI C S K) ar e n ot defi n e d i n t h e pr ot oc ol a me n d me nt 0 2 ( T M F-
1 1 8 2 4 2 5 4) b ut ha ve  bee n a d de d si n ce a n e nr olle d partici pa nt ma y n ot u n der g o eit h er i m pr essi o n c yt ol o g y or 
s u perfi ci al ker atect o m y. T h ese p o p ulati o ns ha ve  bee n defi n e d i n Secti o n 5. 3. 
 
4.  P L A N N E D A N A L Y S E S  
A n i nt eri m a nal ysis will be perf or me d o nl y if t h e 5 S K patie nts tar get is n ot met b y t h e pla n n e d Fi n al A nal ysis 
ti m eli n e –  fi n al a n al ysis w o ul d t h e n be c o m pl ete d o n ce t h e fi nal r ecr uit me nt is ac hie ve d. If t h e 5 S K patie nts tar get 
is m et b y t h e pla n n e d Fi nal A nal ysis deli ver y ti me, t h e n n o i nteri m a nal ysis will be p erf or me d, a n d o nl y fi n al 
a n al ysis will be perf or me d. 
Dat a m o nit ori n g c o m mittee a n al ys es ar e n ot pla n n e d. 
4. 1.  F I N A L A N A L Y SI S  
T h e e n d of t h e st u d y is defi n e d as t h e date of t h e last visit of t h e last partici pa nt i n t h e st u d y or last sc h e d ule d 
pr oce d ur e s h o w n i n t h e sc h e d ule of acti vities ( Secti o n 3. 2) f or t h e last partici pa nt i n t h e trial. 
A parti ci pa nt is c o nsi der e d t o ha ve c o m plete d t h e st u d y if h e/s h e has c o m plete d all p hases of t h e st u d y i n cl u di n g t h e 
P P D
C CI


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 1 5  of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
l ast visit, as s pecifie d i n t h e sc h e d ule of acti vities ( Secti o n 3. 2). 
All fi nal, pl a n n e d a nal yses i de ntifie d i n t his S A P will be perf or me d b y I Q VI A Bi ostatistics f oll o wi n g S p o ns or 
A ut h oriz ati o n of t his statistical a nal ysis pla n , o ut p ut te m plates a n d data base l oc k. 
5.  A N A L Y SI S P O P U L A TI O N S  
5. 1.  A L L P A R TI CI P A N T S S C R E E N E D  
A ll parti ci pa nts scr ee n e d p o p ulati o n will c o ntai n all partici pa nts w h o si g n e d i nf or me d c o nse nt. 
5. 2.  A L L - TR E A T E D P O P U L A TI O N  
All-tr eat e d p o p ulati o n is defi n e d as all partici pa nts scr ee n e d w h o ar e e nr olle d ( wit h o ut scr ee n fail ur e). 
5. 3.  IM P R E S SI O N C Y T O L O G Y O R S U P E R FI CI A L K E R A T E C T O M Y 
P R O C E D U R E (I C S K) P O P U L A TI O N  
I C or S K  (I C S K) p o p ulati o n is defi n e d as partici pa nts fr o m all-tr eate d p o p ulati o n w h o h a d a tiss ue sa m ple c oll ect e d 
usi n g I m pr essi o n C yt ol o g y (I C) or S u perficial Ker atect o m y ( S K) pr oce d ur e, w h et h er or n ot t h e s peci me n is 
e val ua bl e. 
5. 4.  E V A L U A B L E IM P R E S SI O N C Y T O L O G Y O R S U P E R FI CI A L 
K E R A T E C T O M Y P R O C E D U R E ( EI C S K) P O P U L A TI O N  
E val ua bl e I C or S K ( EI C S K) p o p ulati o n is defi n e d as partici pa nts fr o m all-tr eate d p o p ulati o n w h o ha d a n e val ua bl e 
tiss ue sa m pl e c ollecte d usi ng I C or S K pr oce d ur e. A tiss ue sa m ple s peci me n will be deter mi n e d t o be e val ua bl e b y 
t h e pat h ol o gist i n t h e pat h ol o g y r e p ort. 
P P D


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 1 6  of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
6.  G E N E R A L  A N D S T A TI S TI C A L  C O N SI D E R A TI O N S  
6. 1 . R E F E R E N C E S T A R T D A T E A N D S T U D Y D A Y  
St u d y Da y will be calc ulate d fr o m t h e r efer e n ce start date a n d will be use d t o s h o w start /st o p da y of assess me nts a n d 
e ve nts.  
Refer e n ce st art date ( Da y 1) is defi n e d as t h e da y of pr oce d ur e (i m pr essi o n c yt ol o g y or s u perficial keratect o m y), a n d 
will a p pear i n e ver y listi n g w h er e a n assess me nt date or e ve nt date a p pears. 
 
 
If t h e dat e of t h e e ve nt is o n or after t h e r efer e n ce start date, t h e n:  
St u d y  Da y = ( date of e ve nt –  r efer e n ce date) + 1. 
 
If t h e dat e of t h e e ve nt is pri or t o t h e r efer e n ce start date, t h e n:  
St u d y  Da y = ( date of e ve nt –  r efer e n ce date).  
P P D
C CI


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 1 7  of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
 
I n case of partial/ missi n g dates, t h e y will be ha n dle d as s pecifie d i n A P P E N DI X 1 . I m p ute d dates will n ot be use d t o 
cal c ul at e st u d y da y of t h e e ve nts a n d will n ot be pr ese nte d i n t h e listi n gs. 
6. 2.  B A S E LI N E  
T h e baseli n e val ue will be t h e latest assess me nt wit h a n o n- missi n g val ue d o n e bef or e t h e I C or S K pr oce d ur e, 
i n cl u di n g t h ose fr o m u nsc h e d ule d visits. If ti me is n ot c ollecte d, Da y 1 assess me nts ar e ass u me d t o be ta ke n pri or t o 
pr oce d ur e a n d use d as baseli n e. 
6. 3.  U N S C H E D U L E D VI SI T S  
U nsc h e d ul e d meas ur e me nts will n ot be i n cl u de d i n ta bles . Listi n gs will i n cl u de sc h e d ule d a n d u nsc h e d ule d visits 
data. 
6. 4.  S T A TI S TI C A L T E S T S  
N o st atisti cal t est will be perf or me d. 
6. 5.  M I S SI N G D A T A 
N o i m p utati o n of val u es f or missi n g data will be perf or me d. 
6. 6.  S O F T W A R E V E R SI O N  
All a nal ys es will be c o n d ucte d usi n g S A S versi o n 9. 4 or hi g h er. 
7.  O U T P U T P R E S E N T A TI O N S  
T h e t e m pl at es pr o vi de d wit h t his S A P descri be t h e pr ese ntati o ns f or t his st u d y a n d t h er ef or e t h e f or mat a n d c o nt e nt 
of t h e s u m m ar y ta bles, fi g ur es, a n d listi n gs t o be pr o vi de d b y I Q VI A Bi ostatistics. 
P P D


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 1 8  of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
S u m mar y st atistics will be s u m marize d b y visit w h e n a p pr o priat e a n d will c o nsist of val ues f or:  
 
n u m ber of partici pa nts, n u m ber of missi n g val ues, mea n, sta n dar d de viati o n, me dia n, l o wer a n d u p per q uartil es, 
mi ni m u m a n d ma xi m u m f or q ua ntitati ve para meters. 
 
n u m ber a n d per ce nta ge of partici pa nts f or q ualitati ve par a meters. Per ce nta ges will be pr ese nte d wit h o n e 
deci m al place. Per ce nta ges c o m p utati o n will de pe n d o n  ta ble str uct ur e a n d will be detaile d i n t h e ta ble f o ot n ot es 
( See O ut p ut te m plates d oc u me nt). 
8.  D I S P O SI TI O N A N D W
I T H D R A W A L S 
All parti ci pa nts w h o pr o vi de i nf or me d c o nse nt will be acc o u nte d f or i n t his st u d y.  
8. 1.  D I S P O SI TI O N 
T h e n u m ber of scr ee n e d partici pa nts, scr ee n fail ur es a n d r eas o ns of scr ee n fail ur e will be pr ese nte d o n all 
parti ci pa nts.  
9.  D E M O G R A P H I C C H A R A C T E RI S TI C S  
De m o gr a p hi c c h ara cteristics will be pr ese nte d o n  t h e all-tr eate d p o p ulati o n. 
T h e f oll o wi n g de m o gra p hic data will be r e p ort e d f or t his st u d y: 
 
A ge ( years) - calc ulate d r elati ve t o year of c o nse nt 
 
Se x 
 
Et h ni cit y 
 
Ra ce  
 
G S K 2 8 5 7 9 1 6 par e nt st u d y or patie nts o n c o m mer cial pr escri pti o ns 
 
De m o gr a p hi c c h ara cteristics will be pr ese nte d i n a ta ble b y met h o d of tiss ue c ollecti o n (im pr essi o n 
P P D
C CI


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 1 9  of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
c yt ol o g y/s u perficial keratect o m y/ n ot c ollect e d). 
  
D e m o gr a p hi c c h ara cteristics will als o be i n cl u de d i n a b y- partici pa nt listi n g. 
9. 1.  D E RI V A TI O N S  
A ge ( years) = Year of c o nse nt –  Year of birt h 
1 0.  O C U L A R H I S T O R Y A N D R I S K F A C T O R S  
T h e f oll o wi n g oc ular hist or y a n d ris k fact ors will be r e p orte d f or t his st u d y: 
 
Pr e vi o us dia g n osis of dr y e ye ( Yes/ N o) 
 
Pr e vi o us dia g n osis of gla uc o ma o n ri g ht/left e ye ( Yes/ N o) 
 
Pr e vi o us dia g n osis of catar act o n ri g ht/left e ye ( Yes/ N o) 
 
Hist or y of catar act s ur ger y o n ri g ht/left e ye ( Yes/ N o) 
 
Hist or y of laser tr eat me nt s ur ger y o n ri g ht/left e ye ( Yes/ N o) 
 
Hist or y of ot h er oc ular s ur ger y o n ri g ht/left e ye ( Yes/ N o) 
 
Hist or y of seri o us e ye tra u ma o n ri g ht/left e ye ( Yes/ N o) 
 
Hist or y of oc ular disease r e q uiri n g me dical tr eat me nt o n ri g ht/left e ye ( Yes/ N o) 
 
Ot h er ( Yes/ N o) 
 
Oc ul ar hist or y a n d ris k fact ors will be i n cl u de d i n a b y- partici pa nt listi n g. 
1 1.  O C U L A R T H E R A P Y  
Oc ul ar t h era pi es will be pr ese nte d i n a b y- parti ci pa nt listi n g o nl y o n  t h e all-tr eate d p o p ulati o n a n d c o de d usi n g 
Me d D R A versi o n 2 5. 0 or a b o ve.  
C o n c o mit a nt oc ular t h era pies will be fla g ge d a n d ar e t h era pies w hic h:  
o  
starte d pri or t o, o n or after t h e date of i nf or me d c o nse nt,  
o  
A N D e n de d o n or after t h e date of i nf or m e d c o nse nt or wer e o n g oi n g at t h e e n d of t h e st u d y. 
P P D


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 2 0  of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
1 2.  O C U L A R M E DI C A TI O N  
Oc ul a r m e di cati o n will be pr ese nte d i n a b y- partici pa nt listi n g o nl y o n  t h e all-tr eate d p o p ulati o n a n d c o de d usi n g 
G S K dr u g di cti o n ar y.  
 
C o n c o mit a nt oc ular me dicati o ns will be fla g ge d a n d ar e me dicati o ns w hic h:  
o  
starte d pri or t o, o n or after t h e date of i nf or me d c o nse nt,  
o  
A N D e n de d o n or after t h e date of i nf or m c o nse nt or wer e o n g oi n g at t h e e n d of t h e st u d y. 
1 3.  D I S E A S E C H A R A C T E RI S TIC S  
T h e f oll o wi n g disease c hara cteristics will be r e p orte d f or t his st u d y: 
 
Ti m e si n ce i nitial dia g n osis of m ulti ple m yel o ma –  calc ulate d r elati ve t o date of scr ee ni n g 
 
St a ge at scr ee ni n g a n d at i nitial dia g n osis (I/II/III/ U n k n o w n) 
 
M yel o m a i m m u n o gl o bi n (I g A/I g D/I g E /Ig G/I g M ) 
 
Li g ht c hai n m yel o ma at scr ee ni n g ( Yes/ N o) a n d t y pe. 
 
Dis ease c h ara cteristics will be i n cl u de d i n a b y- partici pa nt listi n g o n t h e all-tr eate d p o p ulati o n. 
1 4.  M Y E L O M A T R E A T M E N T  
Pri or m yel o m a tr eat me nts will be pr ese nte d i n a b y- partici pa nt listi n g o nl y o n  t h e all-tr eate d p o p ulati o n.  
1 5.  E X P O S U R E  T O B E L A N T A M A B M A F O D O TI N  
T h e f oll o wi n g e x p os ur e i nf or mati o n will be r e p orte d f or t his st u d y: 
 
D urati o n of e x p os ur e ( wee ks) deri ve d b y: (last date of d ose i nta ke –  first date of d os e i nta ke + 1) / 7.  
 
All e x p os ur e i nf or mati o n will be i n cl u de d i n a b y- partici pa nt listi n g o n t h e all-tr eate d p o p ulati o n. 
P P D


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 2 1  of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
1 6.  P RI M A R Y E N D P OI N T  
Dat a  c oll ect e d fr o m “ C or n eal Tiss ue Sa m ple” a n d “ Pat h ol o g y” e C R F pa ges will be pr ese nte d o n t h e EI C S K 
p o p ul ati o n. 
Met h o d of tiss ue c ollecti o n will be pr ese nte d i n a ta ble o n st u d y e ye. 
 “Im m u n o hist oc h e mistr y”, “ E lectr o n micr osc o p y” parts fr o m “P at h ol o g y” eC R F pa ge will be pr ese nte d i n ta bl es b y 
m et h o d of tiss ue c ollecti o n (i m pr essi o n c yt ol o g y/s u perficial ker atect o m y) o n st u d y e ye. 
“A nt eri or se g me nt slit-la m p p h ot o gr a p h y ”  a n d “ Pat h ol o g y c o m me nts” parts fr o m “ pat h ol o g y” e C R F pa ge will be 
pr ese nt e d i n a b y- partici pa nt listi n g. 
 
All C or n eal Tiss ue Sa m ple a n d Pat h ol o g y data will als o be i n cl u de d i n a b y- partici pa nt listi n g o n t h e all-tr eate d 
p o p ul ati o n. 
1 7.  S E C O N D A R Y  A N D E X P L O R A T R Y E N D P OI N T S  
1 7. 1.  S E C O N D A R Y A N D E X P L O R A T O R Y C LI NI C A L E N D P OI N T S  
Dat a c oll ect e d fr o m “ C or n eal s y m pt o m gr a di n g” e C R F pa ge will be pr ese nte d i n a ta ble b y met h o d of tiss ue 
c oll ecti o n (i m pr essi o n c yt ol o g y/s u p erficial keratect o m y) a n d b y visit o n st u d y e ye o n t h e I C S K p o p ulati o n. 
 
Dat a c oll ect e d fr o m “ Oc ular c or n eal e xa mi n ati o n ” e C R F pa ge will be pr ese nte d i n a ta ble b y met h o d of tiss ue 
c oll ecti o n (i m pr essi o n c yt ol o g y/s u p erficial keratect o m y) a n d b y visit o n st u d y e ye o n t h e I C S K p o p ulati o n. 
Safet y f oll o w u p visit is r e q uir e d f or partici pa nts wit h s u perficial keratect o m y pr oce d ur e b ut n ot r e q uir e d f or 
parti ci pa nts wit h i m pr essi o n c yt ol o g y u nless t h e partici pa nt is e x perie n ci n g disc o mf ort or a n A E. At t his visit, t h e 
t a bl e will pr ese nt partici pa nts wit h s u perficial keratect o m y pr oce d ur e a n d partici pa nts wit h i m pr essi o n c yt ol o g y w h o 
ha ve ha d at l east o n e safet y f oll o w- u p visit. 
 
F or b y- visit ta bles, if t w o safet y f oll o w- u p visits ha ve bee n d o n e, t h e latest n o n- missi n g val ue will be c o nsi der e d 
P P D
C CI


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 2 2  of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
o nl y. 
 
All sec o n dar y a n d e x pl orat or y cli nical data will als o be i n cl u de d i n a b y- partici pa nt listi n g o n t h e all-tr eate d 
p o p ul ati o n. U nsc h e d ule d visits will be dis pla ye d i n t h ese listi n gs. 
1 7. 2.  S E C O N D A R Y S A F E T Y E N D P OI N T S  
1 7. 2. 1.  A D V E R S E E V E N T S  
A d verse E ve nts ( A Es) r elate d t o t h e I C or S K pr oce d ur e o nl y will be c ollecte d fr o m t h e start of i nter ve nti o n u ntil t h e 
l ast f oll o w- u p visit at t h e ti me p oi nts s pecifie d i n t h e sc h e d ule of acti vities ( Secti o n 3. 2). 
 
All Seri o us A d verse E ve nts ( S A Es) r elate d t o t h e I C or S K pr oce d ur e o nl y will be c ollecte d fr o m t h e start of 
i nt er ve nti o n u ntil t h e last f oll o w- u p visit at t h e ti me p oi nts s pecifie d i n t h e sc h e d ule of acti vities ( Secti o n 3. 2). 
H o we ver, a n y S A Es assesse d as r elate d t o st u d y partici pati o n (e. g., st u d y i nter ve nti o n, pr ot oc ol- ma n date d 
pr oce d ur es, i n vasi ve tests) will be r ec or de d fr o m t h e ti me a partici pa nt c o nse nts t o partici pate i n t h e st u d y. 
 
A Es a n d S A Es will be pr ese nte d o n  t h e I C S K p o p ulati o n a n d c o de d usi n g Me d D R A versi o n 2 3. 0 or a b o ve. 
 
A n o ver all s u m mar y ta ble of n u m ber of partici pa nts wit hi n eac h of t h e cate g ories descri be d bel o w, will be pr o vi de d 
b y m et h o d of tiss ue c ollecti o n (i m pr essi o n c yt ol o g y/s u perfici al keratect o m y) s u m marizi n g: 
o  
Partici pa nts wit h at least o n e A E  r elate d t o t h e I C or S K pr oce d ur e. 
o  
Partici pa nts wit h at least o n e S A E r elate d t o t h e st u d y partici pati o n or t o t h e I C or S K pr oce d ur e. 
o  
Partici pa nts wit h at least o n e S A E lea di n g t o st u d y disc o nti n uati o n 
o  
Partici pa nts wit h A E lea di n g t o deat h. 
A Es a n d S A Es will be pr ese nte d i n ta bles b y P T a n d s orte d b y d ecr easi n g fr e q ue n cies o n t otal, a n d br o ke n d o w n b y 
m a xi m u m gr a de. A Es will be gra de d acc or di n g t o t h e N CI C o m m o n Ter mi n ol o g y Criteria of A d verse E ve nts ( N CI 
C T C A E) Versi o n 5. 0.  
Parti ci pa nts will be c o u nte d o nl y o n ce f or eac h P T e ve n if t he y h a ve m ulti ple r ec or ds of t h e sa me P T. If a parti ci pa nt 
r e p orts a n A E m or e t h a n o n ce wit hi n t h at  P T, t h e A E wit h t he w orst-case gr a de will be use d i n t h e c orr es p o n di n g 
gra de s u m maries. 
P P D


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 2 3  of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
 
A Es l ea di n g t o Deat h ar e t h ose e ve nts w hic h ar e r ec or de d o n t h e A d verse E ve nts pa ge of t h e par e nt st u d y e C R F as 
at l east o n e of t h e f oll o wi n g criteria: 
o  
A E Ter m: “ Deat h ”  
o  
O utc o me: “ Deat h  r elate d t o a d verse e ve nt” 
o  
Seri o us n ess: Res ults i n deat h 
o  
T o xicit y gr a de ( C T C A E): Gra de 5 
A Es l ea di n g t o deat h will be pr ese nte d i n a b y- partici pa nt listi n g o n t h e all-tr eate d p o p ulati o n. 
 
All sec o n dar y safet y data will als o be i n cl u de d i n a b y- partici pa nt listi n g o n t h e all-tr eate d p o p ulati o n. 
1 7. 2. 2.  V I T A L SI G N S 
Dat a c oll ect e d fr o m “ Vital si g ns” e C R F pa ge  will be pr ese nte d i n a b y- partici pa nt listi n g o nl y o n t h e all-tr eate d 
p o p ul ati o n. 
 
P P D
C CI


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 2 4  of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
1 7. 3. 3.  B IO M A R K E R S  
Bi o m ar ker m eas ur e me nts will be pr ese nte d o n t h e P D Bi o mar ker p o p ulati o n f or: 
 
S ol u bl e B C M A 
All  bi o m ar ker data will be i n cl u de d i n a b y- partici pa nt listi n g o n t h e P D Bi o mar ker p o p ulati o n. 
A P P E N DI X 1.  P A R TI A L D A T E C O N V E N TI O N S  
 
Al g orit h m f or Pri or / C o n c o mita nt Oc ular T h era p y/ Me dicati o ns:  
S T A R T D A T E 
S T O P D A T E 
A C TI O N 
K n o w n 
K n o w n 
If st o p date < i nf or me d c o nse nt date, assi g n as pri or  
If sto p date > = i nf or me d c o nse nt date a n d start date < = e n d of st u d y, assi g n 
as c o n c o mita nt  
If st o p date > = i nf or me d c o nse nt date a n d start date > e n d of st u d y, assi g n as 
p ost st u d y  
P P D
C CI


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 2 5  of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
S T A R T D A T E 
S T O P D A T E 
A C TI O N 
 
Partial 
I m p ute st o p date as latest p ossi ble date (i. e. last da y of m o nt h if da y 
u n k n o w n or 3 1st Dece m ber if da y a n d m o nt h ar e u n k n o w n), t h e n: 
If st o p date < i nf or me d c o nse nt date, assi g n as pri or 
If st o p date > = i nf or me d c o nse nt date a n d start date < = e n d of st u d y, assi g n 
as c o n c o mita nt 
If st o p date > = i nf or me d c o nse nt date a n d start date > e n d of st u d y, assi g n as 
p ost st u d y 
 
 
Missi n g 
 
 
 
If st o p date is missi n g c o ul d n e ver be ass u me d a pri or st u d y 
If start date < = e n d of st u d y, assi g n as c o n c o mita nt 
If start date > e n d of st u d y, assi g n as p ost st u d y 
 
 
 
 
Partial 
K n o w n 
 
 
 
 
 
 
 
 
 
I m p ute start date as earliest p ossi ble date (i. e. first da y of mo nt h if da y 
u n k n o w n or 1st Ja n uar y if da y a n d m o nt h ar e u n k n o w n), t h e n: 
If st o p date < i nf or me d c o nse nt date, assi g n as pri or 
If st o p date > = i nf or me d c o nse nt date a n d start date < = e n d of st u d y, assi g n 
as c o n c o mita nt 
If st o p date > = i nf or me d c o nse nt start date a n d start date > e n d of st u d y, 
assi g n as p ost st u d y 
 
Partial 
I m p ute start date as earliest p ossi ble date (i. e. first da y of mo nt h if da y 
u n k n o w n or 1st Ja n uar y if da y a n d m o nt h ar e u n k n o w n) a n d i m p ute st o p 
date as latest p ossi bl e date (i. e. last da y of m o nt h if da y u n k n o w n or 3 1st 
Dece m ber if da y a n d m o nt h ar e u n k n o w n), t h e n: 
If st o p date < i nf or me d c o nse nt date, assi g n as pri or 
If st o p date > = i nf or me d c o nse nt date a n d start date < = e n d of st u d y, assi g n 
as c o n c o mita nt 
If st o p date > = i nf or me d c o nse nt date a n d start date > e n d of st u d y, assi g n as 
p ost st u d y 
P P D


 
G S K 
P R O T O C O L 2 1 4 0 9 8 a m e n d m e nt 0 2 
 
St ati sti c al A n al y si s Pl a n 
P a g e 2 6  of 2 6  
 
 
D o c u m e nt: 
\\i e e d c-
v n a s c 0 1 \ Bi o s d at a\ G S K\ G S K 2 8 5 7 9 1 6\ U Z A 7 8 7 6 6\ Bi o st ati sti c s\ D o c u m e nt ati o n\S A P \ U Z A 7 8 7 6 6 _ 2 1 4 0
9 8 _ S A P _ v 2. 0 _ 1 2 O C T 2 0 2 2. d o c x 
A ut h or: 
V er si o n N u m b er: 
2. 0 
 
V er si o n D at e:  
1 2 O C T 2 0 2 2 
T e m pl at e N o.:  C S _ T P _ B S 0 1 6 R e vi si o n 6 
R ef er e n c e: C S _ WI _ B S 0 0 5 
Eff e cti v e D at e: 0 2 D e c 2 0 1 9  
 
C o p yri g ht © 2 0 0 9, 2 0 1 0, 2 0 1 2, 2 0 1 6, 2 0 1 8, 2 0 1 9 I Q VI A. All  ri g ht s r e s er v e d. T h e c o nt e nt s of t hi s d o c u m e nt ar e c o nfi d e nti al a n d 
pr o pri et ar y t o I Q VI A H ol di n g s I n c. a n d it s s u b si di ari e s. U n a ut h ori z e d u s e, di s cl o s ur e or r e pr o d u cti o n i s stri ctl y pr o hi bit e d. 
S T A R T D A T E 
S T O P D A T E 
A C TI O N 
 
Missi n g 
I m p ute start date as earliest p ossi ble date (i. e. first da y of mo nt h if da y 
u n k n o w n or 1st Ja n uar y if da y a n d m o nt h ar e u n k n o w n), t h e n: 
If st o p date is missi n g c o ul d n e ver be ass u me d a pri or me dicati o n 
If start date < = e n d of st u d y, assi g n as c o n c o mita nt 
If start date > e n d of st u d y, assi g n as p ost st u d y 
 
 
 
Missi n g 
K n o w n 
If st o p date < i nf or me d c o nse nt date, assi g n as pri or 
If sto p date > = i nf or me d c o nse nt date, assi g n as c o n c o mita nt 
Ca n n ot be assi g n e d as ‘ p ost st u d y’ 
 
Partial 
I m p ute st o p date as latest p ossi ble date (i. e. last da y of m o nt h if da y 
u n k n o w n or 3 1st Dece m ber if da y a n d m o nt h ar e u n k n o w n), t h e n: 
If st o p date < i nf or me d c o nse nt date, assi g n as pri or 
If st o p date > = i nf or me d c o nse nt date, assi g n as c o n c o mita nt 
Ca n n ot be assi g n e d as ‘ p ost st u d y’ 
 
Missi n g 
Assi g n as c o n c o mita nt 
 
P P D


St atistic al A n al ysis Pl a n - Versi o n 2. 0 - 1 3- Oct- 2 0 2 2
Electr o nic Si g n at ure M a nifest ati o n 
T his pa ge is a ma nifestati o n of t he electr o nic si g nat ure(s) use d i n c o m plia nce wit h t he or ga nizati o n's 
electr o nic si g nat ure p olicies a n d pr oce d ures.
P a ge 2 7 - O bject 1 0 0 0 5 5 1 A 0 0 0 0 0 0 0 0 6 D 4 5 E 6 C B
Si g ner F ull 
N a me
Me a ni n g of Si g n at ure
D ate a n d Ti me
D o c u m e n t A p p r o val (I c e r ti f y t ha t I ha v e t h e 
e d u ca ti o n, t rai ni n g a n d e x p e ri e n c e t o p e r f o r m t his 
tas k)
1 2 O c t 2 0 2 2 
2 1: 1 5: 4 4 U T C
D o c u m e n t A p p r o val (I c e r ti f y t ha t I ha v e t h e 
e d u ca ti o n, t rai ni n g a n d e x p e ri e n c e t o p e r f o r m t his 
tas k)
1 2 O c t 2 0 2 2 
2 1: 1 6: 4 1 U T C
D o c u m e n t A p p r o val (I c e r ti f y t ha t I ha v e t h e 
e d u ca ti o n, t rai ni n g a n d e x p e ri e n c e t o p e r f o r m t his 
tas k)
1 2 O c t 2 0 2 2 
2 3: 3 9: 0 3 U T C
D o c u m e n t A p p r o val (I c e r ti f y t ha t I ha v e t h e 
e d u ca ti o n, t rai ni n g a n d e x p e ri e n c e t o p e r f o r m t his 
tas k)
1 3 O c t 2 0 2 2 
0 8: 1 8: 4 8 U T C
D o c u m e n t A p p r o val (I c e r ti f y t ha t I ha v e t h e 
e d u ca ti o n, t rai ni n g a n d e x p e ri e n c e t o p e r f o r m t his 
tas k)
1 3 O c t 2 0 2 2 
0 9: 4 7: 4 4 U T C
D o c u m e n t A p p r o val (I c e r ti f y t ha t I ha v e t h e 
e d u ca ti o n, t rai ni n g a n d e x p e ri e n c e t o p e r f o r m t his 
tas k)
1 3 O c t 2 0 2 2 
1 3: 3 9: 2 1 U T C
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