An Open Label, Observational, Prospective Registry of Participants With Sickle Cell Disease (SCD) Treated With Oxbryta® (Voxelotor)
Conditions: Sickle Cell Disease
Sponsor: Pfizer

O x br yta ® ( V o xel ot or)®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T versi o n 1. 0 , 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n-I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 
0 1 -A u g -2 0 2 3
Pa ge 1 of 6 4
N O NI N T E R V E N TI O N A L ( N I) S T U D Y P R O T O C O L
St u d y Inf or m ati o n
Title
A n O pe n La bel, O bser vati o nal, Pr os pecti ve Re gistr y  of 
Partici pa nts Wit h Sic kle Cell Disease ( S C D) Treate d 
Wit h O x br y ta ® ( V o xel ot or)® ( V o xel ot or)
Pr ot oc ol n u m ber
C 5 3 4 1 0 1 9/ G B T 
Pr ot oc ol versi o n i de ntifier
1. 0
D ate
1 0 Oct o ber 2 0 2 3
E u P ost A ut h oriz ati o n St u d y 
( P A S) re gister n u m ber
T B D
Acti ve s u bst a nce
O x br y t a® ( V o xel ot or)®
Me dici n al pr o d uct
O x br y ta ® ( V o xel ot or) ® ( v o xel ot or) ta blets f or oral use 
O x br y ta ® ( V o xel ot or) ® ( v o xel ot or) ta blets f or oral 
s us pe nsi o n
Rese arc h q uesti o n a n d 
o bjecti ves
T he pri mar y  o bjecti ve is t o gat her l o n g ter m data o n 
O x br y ta ® ( V o xel ot or)® i n a real-w orl d setti n g. T he 
f oll o wi n g are cate g ories of i nterest i n partici pa nts wit h 
S C D treate d wit h O x br yta ® ( V o xel ot or):

Cli nic al o utc o mes, as assesse d b y cli nical a n d 
la b orat or y assess me nts of he mat ol o gical para meters 
a n d e n d or ga n da ma ge, a n d rate of si g nifica nt cli nical 
e ve nts

Healt hcare res o urce utilizati o n

Healt h -relate d q uality of life ( H R Q o L), as assesse d 
b y  partici pa nts, pare nts/care gi vers, a n d cli nicia ns 

Assess t he safet y a n d t olera bilit y of O x br yta ® 
( V o xel ot or)®
A ut h or
 M D
Pfizer, I nc.
Tele p h o ne:
E mail: 
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)
P P D
P P D
P P D
P P D

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 2 of 6 4
T his d oc u me nt c o ntai ns c o nfi de ntial i nf o r mati o n bel o n gi n g t o Pfizer. E xce pt as ot her w ise a gree d t o i n writi n g, 
b y acce pti n g or re vie wi n g t his d oc u me nt, y o u a gree t o h ol d t his i nf or mati o n i n c o nfi de nce a n d n ot c o p y or 
discl ose it t o ot hers (e xce pt w here re q uire d b y a p plica ble la w) or use it f or u na ut h orize d p ur p oses. I n t he e ve nt 
of a n y act ual or s us pecte d breac h of t his o bli gati o n, Pfizer m ust be pr o m ptl y n ot ifie d.
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 3 of 6 4
1. T A B L E O F C O N T E N T S
1. T A B L E O F C O N T E N T S .......................................................................................................3
LI S T O F FI G U R E S ................................................................................................................... 6
A P P E N DI C E S ........................................................................................................................... 6
2. LI S T O F A B B R E VI A T I O N S................................................................................................ 7
3. R E S P O N SI B L E P A R TI E S .................................................................................................. 1 0
4. A B S T R A C T ......................................................................................................................... 1 1
5. A M E N D M E N T S A N D U P D A T E S ..................................................................................... 1 7
6. MI L E S T O N E S ..................................................................................................................... 1 8
7. R A TI O N A L E A N D B A C K G R O U N D ................................................................................ 1 9
7. 1. I ntr o d ucti o n ............................................................................................................. 1 9
7. 1. 1. Disease Bac k gr o u n d ................................................................................... 1 9
7. 1. 2. O x br y ta ® (V o xel ot or )® (V o xel ot or) .......................................................... 1 9
8. R E S E A R C H Q U E S TI O N A N D O BJ E C TI V E S ................................................................. 2 0
8. 1. O bjecti ves a n d E n d p oi nts ........................................................................................ 2 0
8. 1. 1. O bjecti ves ................................................................................................... 2 0
8. 1. 1. 1 . Pri mar y O bjecti ve .....................................................................2 0
8. 1. 1. 2. Effecti ve ness E n d p oi nt Meas ures ............................................. 2 0
8. 1. 1. 3. Safet y E n d p oi nt Meas ures ......................................................... 2 1
9. R E S E A R C H M E T H O D S .................................................................................................... 2 2
9. 1. St u d y  Desi g n........................................................................................................... 2 2
9. 1. 1. St u d y  Pla n................................................................................................... 2 2
9. 1. 1. 1. O verall St u d y  Desi g n................................................................ 2 2
9. 2. Setti n g ...................................................................................................................... 2 3
9. 2. 1. D urati o n of St u d y  Partici pati o n.................................................................. 2 3
9. 2. 1. 1. E n d of St u d y .............................................................................. 2 3
9. 3. St u d y  P o p ulati o n..................................................................................................... 2 3
9. 3. 1. I n c l usi o n Criteria ........................................................................................ 2 4
9. 3. 2. E xcl usi o n Criteria ....................................................................................... 2 5
9. 4. Varia bles .................................................................................................................. 2 6
9. 5. Treat me nt of Partici pa nts ........................................................................................ 2 9
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 4 of 6 4
9. 5. 1. Descri pti o n of O x br y ta ® ( V o xel ot or) ........................................................ 2 9
9. 5. 2. C o nc o mita nt Me dicati o ns ........................................................................... 2 9
9. 6. Data S o urces ............................................................................................................ 3 0
9. 7. St u d y  Data C ollecti o n ............................................................................................. 3 0
9. 8. St u d y  Size................................................................................................................ 3 0
9. 9. Data Ma na ge me nt ................................................................................................... 3 1
9. 9. 1. Case Re p ort F or ms ( C R Fs)/ Data C ollecti o n T o ols ( D C Ts)/ Electr o nic 
Data Rec or d ..................................................................................................... 3 1
9. 9. 2. Rec or d Rete nti o n ........................................................................................ 3 1
9. 1 0. Data A nal ys is ........................................................................................................ 3 2
9. 1 1. Statistics ................................................................................................................ 3 2
9. 1 1. 1. A nal y sis P o p ulati o n ..................................................................................3 2
9. 1 1. 2. Sa m ple Size ..............................................................................................3 2
9. 1 1. 3. Effecti ve ness E n d p o i nt Meas ures A nal ys es ............................................. 3 2
9. 1 1. 4. Safet y A nal ys is......................................................................................... 3 3
9. 1 2. Q ualit y  C o ntr ol...................................................................................................... 3 3
9. 1 2. 1. Data Q ualit y Ass ura nce ............................................................................ 3 3
9. 1 2. 2. S o urce D oc u me nts .................................................................................... 3 4
9. 1 2. 3. Esse ntial D oc u me ntati o n Re q uire me nts ................................................... 3 4
9. 1 3. Stre n gt h s a n d Li mitati o ns of t he Researc h Met h o ds ............................................. 3 4
9. 1 4. Ot her As pects ........................................................................................................ 3 4
9. 1 4. 1. Fi na ncial Discl os ure ................................................................................. 3 4
9. 1 4. 2. St u d y  a n d Site Start a n d Cl os ure ..............................................................3 4
9. 1 4. 2. 1. First Act of Recr uit me nt .......................................................... 3 4
9. 1 4. 2. 2. Site Cl os ure ............................................................................. 3 5
9. 1 4. 2. 3. St u d y  Ter mi nati o n................................................................... 3 5
1 0. P R O T E C TI O N O F H U M A N P A R T I CI PA N T S ...............................................................3 6
1 0. 1. Patie nt I nf or mati o n ................................................................................................ 3 6
1 0. 2. Patie nt C o nse nt ...................................................................................................... 3 6
1 0. 3. Patie nt Wit h dra wal ................................................................................................ 3 7
1 0. 3. 1. Partici pa nt I D N u m ber .............................................................................. 3 7
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 5 of 6 4
1 0. 3. 2. Eli gi bilit y  Assess me nt.............................................................................. 3 7
1 0. 3. 3. Me dical Hist or y , De m o gra p hic Data, a n d I ns ura nce I nf or mati o n ........... 3 7
1 0. 3. 4. S C D Ge n ot y pe .......................................................................................... 3 7
1 0. 3. 5. P h y sical E xa mi nati o n ............................................................................... 3 7
1 0. 3. 6. Effecti ve ness Data .................................................................................... 3 8
1 0. 3. 6. 1. Cli nical O utc o mes ................................................................... 3 8
1 0. 3. 6. 2. Healt hcare Res o urce Utilizati o n .............................................. 4 0
1 0. 3. 6. 3. Healt h -Relate d Q ualit y  of Life ( H R Q o L)............................... 4 0
1 0. 4. Pati e nt Wit h dra wal ................................................................................................ 4 1
1 0. 4. 1. Disc o nti n uati o n of O x br y ta ® ( V o xel ot or) a n d Partici pa nt 
Disc o nti n uati o n ................................................................................................ 4 1
1 0. 4. 1. 1. Wit h dra wal of C o nse nt ............................................................ 4 1
1 0. 4. 1. 2. Earl y Disc o nti n uati o n of O x br yta ® ( V o xel ot or) .................... 4 1
1 0. 4 . 1. 3. Lost t o F oll o w U p ...................................................................4 2
1 0. 5. I nstit uti o nal Re vie w B oar d (I R B)/I n de pe n de nt Et hics C o m mittee (I E C) ............ 4 2
1 0. 6. Et hical C o n d uct of t he St u d y ................................................................................ 4 2
1 0. 7. Re g ulat or y , Et hical, a n d St u d y O versi g ht C o nsi derati o ns.................................... 4 2
1 0. 7. 1. Re g ulat or y  a n d Et hical C o nsi derati o ns .................................................... 4 2
1 0. 7. 2. I nf or m e d C o nse nt a n d Asse nt Pr ocess ..................................................... 4 3
1 0. 7. 3. Data Pr otecti o n ......................................................................................... 4 4
1 1. M A N A G E M E N T A N D R E P O R TI N G O F A D V E R S E E V E N T S/ A D V E R S E 
R E A C TI O N S ......................................................................................................................4 6
1 1. 1. H u ma n Re vie w of U nstr uct ure d Data ................................................................... 4 6
1 1. 2. Patie nts S ur ve y Assessi n g H R Q o L ....................................................................... 4 7
1 1. 3. Pfizer Trai ni n g Re q uire me nts: .............................................................................. 4 7
1 1. 4. Re g ulat or y  A ge nc y, Instit uti o nal Re vie w B oar d, a n d Site Re p orti n g .................. 4 8
1 2. P L A N S F O R DI S S E M I NA TI N G A N D C O M M U NI C A TI N G S T U D Y R E S U L T S ........4 8
1 2. 1. Disse mi nati o n of St u d y  Data................................................................................. 4 8
1 2. 2. P u blicati o n P olic y ................................................................................................. 4 8
1 3. R E F E R E N C E S ..................................................................................................................4 9
1 4. LI S T O F T A B L E S .............................................................................................................5 0
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 6 of 6 4
1 5. LI S T O F FI G U R E S ........................................................................................................... 5 0
A N N E X 1. LI S T O F S T A N D A L O N E D O C U M E N T S.......................................................... 5 0
A N N E X 2. E N C E P P C H E C K LI S T F O R S T U D Y P R O T O C O L S......................................... 5 0
A N N E X 3. A D DI TI O N A L  I N F O R M A TI O N......................................................................... 5 0
LI S T O F FI G U R E S
Fi g ure 1:
St u d y  Sche ma ........................................................................................... 2 3
Fi g ure 2.
E nr oll me nt Pr ocess Fl o w .......................................................................... 2 5
A P P E N DI C E S
A p pe n di x 1. Sc he d ule of Acti vities ......................................................................................... 5 1
A p pe n di x 2. Healt h -Relate d Q ualit y  of Li fe Meas ures........................................................... 5 3
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 7 of 6 4
2. LI S T O F A B B R E VI A TI O N S
A b bre vi ati o n
Def i niti o n
A C A
a nteri or cere bral arter y
A C R
al b u mi n/creati ni ne rati o
A C S
ac ute c hest s yn dr o me
A E
a d verse e ve nt
A L T
ala ni ne a mi n otra nsferase
A N C
a bs ol ute ne utr o p hil c o u nt
A S T
as partate a mi n otra nsferase
C GI C
Cli nical Gl o bal I m pressi o n of C ha n ge
C R O 
Cl i nical Researc h Or ga nizati o n
C R F
case re p ort f or m
C F R
C o de of Fe deral Re g ulati o n
C K D -E PI
C hr o nic Ki d ne y  Disease E pi de mi ol o g y C olla b orati o n
e C R F
electr o nic case re p ort f or m
E D
e mer ge nc y de part me nt
E D C
electr o nic data ca pt ure
e G F R
esti mate d gl o mer ular filtrati o n rat
H E R
electr o nic healt h rec or ds
E S A
er yt hr o p oieti n -sti m ulati n g a ge nt
F D A
( U S) F o o d a n d Dr u g A d mi nistrati o n
G C P
G o o d Cli nical Practice
H b
he m o gl o bi n
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 8 of 6 4
A b bre vi ati o n
Def i niti o n
H b F
fetal he m o gl o bi n
H b S
sic kle he m o gl o bi n
H R Q o L
healt h -relate d q ualit y of life
I C A
inter nal car oti d arter y
I CF
I nf or me d c o nse nt f or m
I C H
I nter nati o nal C o nfere nce o n Har m o nizati o n
I C U
i nte nsi ve care u nit 
II D
I nacti ve I n gre die nt Data base
I RB
I nstit uti o nal Re vie w B oar d
L D H
lactate de hy d r o ge nase
M C A
mi d dle cere bral arter y
M C V
mea n c o r p usc ular v ol u me
M C H C
mea n c or p usc ular he m o gl o bi n c o nce ntrati o n
Me d D R A
Me dical Dicti o nar y  f or re g ulat or y Acti vities
N CI  C T C A E
Nati o nal Ca ncer I nstit ute C o m m o n Ter mi n ol o g y 
Criteria f or A d verse E ve nts
N P R S
N u merical Pai n Rati n g Scale
N S AI D
n o nster oi dal a nti-i nfla m mat or y dr u g
PI
Pri nci pal I n vesti gat or 
P GI C
Patie nt Gl o bal I m pressi o n of C ha n ge
P H
p ul m o nar y  h yperte nsi o n 
P Q C
Pr o d uct Q ualit y  C o m plai nt
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 9 of 6 4
A b bre vi ati o n
Def i niti o n
P R O MI S
Patie nt- Re p orte d O utc o mes Meas ure me nt 
I nf or mati o n S yste m
Q o L
q ualit y  of life
R B C
re d bl o o d cel l
S A E
seri o us a d verse e ve nt
S C D
sic kle cell disease
S O A
sc he d ule of acti vities
S O C
sta n dar d of care
S p O 2
p ulse o xi metr y
S U S A R
seri o us u ne x pecte d a d verse reacti o n
T A M M V
ti me-a vera ge d ma xi m u m mea n vel ocit y
TI A
tra nsie nt isc he mic attac k
T 2 * M RI
T 2 -wei g hte d ma g netic res o na nce i ma gi n g
T C D
tra nscra nial d o p pler
TI B C
t otal ir o n bi n di n g ca pacit y
U S
U nite d States
U S PI
U nite d States Prescri bi n g I nf or mati o n
V O C
vas o -occl usi ve crisis
W B C
w hite bl o o d cell
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 1 0 of 6 4
3. R E S P O N SI B L E P A R TI E S
Pri nci p al I n vesti g at or (s) of t he Pr ot oc ol
N a m e, D e gree(s)
J o b Title
Affili ati o n
A d dress
Da vi d P ur die , P h D 
Se ni or Direct or, 
Rare Disease
Pfizer, I nc.
Sa n Fra ncisc o, C A
Mic helle X u, M D
Me dical Scie nce 
Direct or
Pfizer, I nc.
Sa n Fra ncisc o, C A
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 1 1 of 6 4
4. A B S T R A C T
St u d y 
N u m ber
G B T 4 4 0 -4 R 2
St u d y T itle
A n O pe n La bel, O bser vati o nal, Pr os pecti ve Re gistr y  of Partici pa nts Wit h 
Sic kle Cell Disease ( S C D) Treate d Wit h O x br y ta ® ( V o xel ot or)®
( V o xel ot or)
S h ort Title
O x br y ta ® ( V o xel ot or) Pr o d uct Re gistr y
S p o ns or
Pfizer, I nc.
Ne w Y or k, N Y 
U nite d States
St u d y 
Descri pti o n
T his re gistr y  is a n o bser vati o nal st u d y desi g ne d t o e val uate t he effect of 
O x br y ta ® ( V o xel ot or) i n i n di vi d uals wit h S C D. T his re gistr y is i nte n de d t o 
be nefit a n d s u p p ort i nterests of partici pa nts, cli nicia ns, re g ulat or y  b o dies, 
pa y ers, a n d i n d ustr y  b y o btai ni n g l o n git u di nal data o n O x br yta ® 
( V o xel ot or).
N u m ber of 
St u d y Sites
T he st u d y  will be c o n ducte d at a p pr o xi matel y  3 5 sites i n t he U S
N u m ber of 
P artici p a nts
A p pr o xi matel y  5 0 0 eli gi ble partici pa nts will be e nr olle d i n t his st u d y
Tre at me nt
T his re gistr y  is a n o bser vati o nal st u d y t o e val uate t he effects of O x br y ta ® 
( V o xel ot or) i n i n di vi d uals wit h S C D. Partici pa nts will recei ve treat me nt 
wit h O x br y ta ® ( V o xel ot or) as prescri be d b y t heir p h ysicia n, as part of t heir 
us ual care. Partici pa nts will be treate d a n d e val uate d per sta n dar d of care 
( S O C) a n d at t he p hys icia n’s discreti o n. T here are n o pre -defi ne d treat me nt 
re q uire me nts. 
O bjecti ves
Pri m ar y
T he pri mar y  o bjecti ve is t o gat her l o n g ter m data o n O x br yta ® ( V o xel ot or) 
i n a real-w orl d setti n g. T he f oll o wi n g are cate g ories of i nterest i n 
partici pa nts wit h S C D treate d wit h O x br y ta ® ( V o xel ot or):

Cli nical o utc o mes, as assesse d b y cli nical a n d la b orat or y assess me nts 
of he mat ol o gical para meters a n d e n d - or ga n da ma ge, a n d rate of 
si g nifica nt cli nical e ve nts

Healt hcare res o urce utilizati o n

Healt h -relate d q uality of life ( H R Q o L), as assesse d b y partici pa nts, 
pare nts/care gi vers, a n d cli nicia ns 

Safet y  a n d t olera bilit y of O x br yta ® ( V o xel ot or)
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 1 2 of 6 4
O utc o me 
Me as ures
Effecti ve ness

C ha n ge fr o m pre -O x br y ta ® ( V o xel ot or) treat me nt peri o d i n t he 
f oll o wi n g he mat ol o gic para meters c orres p o n di n g t o treat me nt wit h 
O x br y ta ® ( V o xel ot or): 

He m o gl o bi n ( H b)

He m ol y sis meas ures, i ncl u di n g % retic ul oc ytes, a bs ol ute 
retic ul oc ytes, bilir u bi n (t otal, direct, a n d i n direct)

Meas ures of ir o n o verl oa d, i ncl u di n g ferriti n, ir o n, t otal ir o n bi n di n g 
ca pacit y ( TI B C), T 2-wei g hte d ma g netic res o na nce i ma gi n g 
( T 2 * M RI) 

C ha n ge fr o m pre -O x br y ta ® ( V o xel ot or) treat me nt peri o d i n re nal 
f u ncti o n, as meas ure d by t he f oll o wi n g:

Creati ni ne ( Ser u m)

Al b u mi n uri a ( uri ne al b u mi n/creati ni ne rati o [ A C R]) 

He m o gl o bi n uria ( uri ne di pstic k p ositi ve f or bl o o d + 1 or greater 
a n d ≤ 2 R B C b y  hi g h p o wer fiel d)

Ser u m c y stati n C

Esti mate d gl o mer ular filtrati o n rat (e G F R) calc ulate d usi n g t he 
C hr o nic Ki d ne y  Disease E pi de mi ol o g y C olla b orati o n ( C K D -E PI) 
e q uati o n

Rate of si g nifica nt S C D -relate d cli nical e ve nts, f or e xa m ple 
vas o - occl usi ve crisis ( V O C), ac ute c hest sy n dr o me ( A C S), pria p is m, 
str o ke, a n d tra nsie nt isc he mic attac k ( TI A), c hr o nic or e n d sta ge 
ki d ne y  disease, ir o n o verl oa d, le g ulcers, car diac malf u ncti o n, a n d 
p ul m o nar y  h yperte nsi o n ( P H)

Treat me nt i nitiati o n or m o dificati o n of S C D- relate d me dicati o ns 
(e g h y dr o x y urea, criza nli z u ma b, L-gl uta mi ne, o pi oi ds [i n dail y  
m or p hi ne e q ui vale nts], ir o n c helati n g a ge nts, er y t hr o p oiesis-
sti m ulati n g a ge nts [ E S As], n o nster oi dal a nti-i nfla m mat or y dr u gs 
[ N S AIDs], f olic aci d, a n d pe nicilli n)

C ha n ge fr o m pre -O x br y ta ® ( V o xel ot or) treat me nt peri o d in 
healt hcare res o urce utilizati o n: rates of o ut patie nt visits (i ncl u di n g 
i nf usi o n ce nter, ac ute care, or tele me dici ne visit), e mer ge nc y 
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 1 3 of 6 4
de part me nt ( E D) visits, h os pitalizati o ns (i ncl u di n g t otal le n gt h of 
sta y, a n d ti me i n i nte nsi ve care u nit [IC U], if a p pl ica ble), ac ute a n d 
c hr o nic R B C tra nsf usi o ns, h o me o x y ge n s u p ple me ntati o n, a n d re nal 
dial y sis 

C ha n ge fr o m pre-O x br y ta ® ( V o xel ot or) treat me nt peri o d i n t he 
f oll o wi n g H R Q o L meas ures:

Patie nt- Re p orte d O utc o mes Meas ure me nt I nf or mati o n S y ste m 
( P R O MIS Pe diatric -3 7 v 2. 0 -Pr ofile; Pare nt Pr o x y v 2. 0 Pr ofile - 3 7 
a n d 4 9 v 2. 1 Pr ofile)

Patie nt Gl o bal I m pressi o n of C ha n ge ( P GI C)

Cli nical Gl o bal I m pressi o n of C ha n ge ( C GI C)

Ot her meas ures: Ac ute pai n i nte nsit y  as meas ure d b y N u merical 
Pai n Rati n g Scale ( N P R S) a n d a n y o bjecti ve meas ure of e xercise 
t olera nce
S afet y

R ate a n d se verit y of seri o us a d verse e ve nts ( S A Es) a n d a d verse 
e ve nts ( A Es) of i nterest

R ate of A Es lea di n g t o d ose m o dificati o n or disc o nti n uati o n of 
O x br y ta ® ( V o xel ot or)

Pre g na nc y o utc o mes a n d fertilit y
St u d y Desi g n
A n y  partici pa nt w h o is c urre ntly ta ki n g O x br yta ® ( V o xel ot or) or has bee n 
prescri be d a n d will i nit iate treat me nt wit h O x br yta ® ( V o xel ot or), is eli gi ble 
t o partici pate. Eli gi ble partici pa nts will recei ve treat me nt wit h O x br yta ® 
( V o xel ot or) as prescri be d b y t heir p hys icia n, as part of t heir us ual care. 
Partici pa nts will be treate d a n d e val uate d per S O C a n d at t he p h ys icia n’s 
discreti o n.
Partici pa nts will be i ntr o d uce d t o t he st u d y  b y t heir healt h care tea m a n d will 
si g n t he i nf or me d c o nse nt f or m (I C F) or asse nt pri or t o a n y data c ollecti o n 
f or t he st u dy.
T his st u d y  will c ollect data t hat are rec or de d i n the partici pa nts’ me dical 
rec or ds a n d ot her sec o n dar y data s o urces s uc h as I ns ura nce a n d P har mac y 
Clai ms. St u d y  data will be c ollecte d at re g ular i nter vals a n d e ntere d i n case 
re p ort f or ms ( C R Fs) via a n electr o nic data ca pt ure ( E D C) sys te m b y t he 
st u d y staff.
Partici pa nts will be f oll o we d f or u p t o 5 ye ars after t heir first d ose of 
O x br y ta ® ( V o xel ot or) treat me nt, or u ntil t he y wit h dra w t heir c o nse nt t o 
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 1 4 of 6 4
par tici pate, or are disc o nti n ue d fr o m t he st u d y. Treat me nt, i ncl u di n g 
i nterr u pti o ns a n d restarti n g treat me nt, will c o nti n ue at t he discreti o n of t he 
treati n g p hys icia n, a n d t here are n o pre-defi ne d treat me nt re q uire me nts. 
Partici pa nts ma y  recei ve a n y a d diti o nal me dicati o ns prescri be d b y t heir 
treati n g p hys icia n or ha ve a n y me dical i nter ve nti o ns t hat are dee me d 
a p pr o priate b y t he treati n g p h ys icia n or st u d y d oct or. T he partici pa nt or 
treati n g p hys icia n ma y disc o nti n ue O x br yta ® ( V o xel ot or) at a n y ti me. 
Partici pa nts w h o disc o nti n ue treat me nt wit h O x br yta ® ( V o xel ot or) earlier 
t ha n 5 years will c o nti n ue t o be f oll o we d o n st u d y t o c ollect cli nical a n d 
healt h -relate d q ualit y of life ( H R Q o L) o utc o mes f or u p t o 5 years after t heir 
first d ose of O x br yta ® ( V o xel ot or) treat me nt. 
Partici pa nt safet y a n d t olera bilit y will be assesse d t hr o u g h o ut t he st u d y data 
c ollecti o n peri o d b y  t he st u d y d oct or a n d re p orte d t o t he S p o ns or.
D ur ati o n of 
St u d y 
P artici p ati o n
T he a p pr o xi mate d urati o n of st u d y  partici pati o n f or a n i n di vi d ual partici pa nt 
i ncl u des a n o bser vati o n peri o d of u p t o 5 years after t he first d ose of 
O x br y ta ® ( V o xel ot or) treat me nt.
E n d of St u d y
T he e n d of st u d y is defi ne d as t he date of t he last data c ollecti o n ti me p oi nt of 
t he last partici pa nt bei n g f oll o we d.
St u d y 
P o p u l ati o n
I ncl usi o n Criteri a: 
Partici pa nts w h o meet all t he f oll o wi n g criteria will be eli gi ble f or 
e nr ollme nt:
1.
Willi n g a n d a ble t o pr o vi de writte n i nf or me d c o nse nt (a ge d ≥1 8 
ye ars), pare ntal/ g uar dia n c o nse nt a n d partici pa nt asse nt (a ge d ≥1 2 t o 
< 1 8 y ears) per l ocal re g ulati o ns, or pe diatric partici pa nts (a ge d 4 t o 
< 1 2 y ears) wit h pare ntal/ g uar dia n c o nse nt pe r I nstit uti o nal Re vie w 
B oar d (I R B) p olic y  a n d re q uire me nts, c o nsiste nt wit h IC H g ui deli nes
2.
Male or fe male partici pa nts wit h d oc u me nte d dia g n osis of sic kle cell 
disease (all ge n ot y p es) 
3.
U n der g oi n g treat me nt wit h O x br y ta ® ( V o xel ot or) acc or di n g t o t he 
O x br y t a® ( V o x el ot or) U S PI
E xcl usi o n Criteri a: 
Partici pa nts meeti n g a n y of t he f oll o wi n g criteria will n ot be eli gi ble f or 
st u d y e nr oll me nt:
1.
C urre nt partici pati o n i n a n i n vesti gati o nal cli nical trial or e x pa n de d 
access pr o gra m, i n w hic h t he partici pa nt ma y  be recei vi n g v o xel ot or 
treat me nt
2.
Me dical, ps yc h ol o gical, or be ha vi oral c o n diti o n t hat, i n t he o pi ni o n 
of t he st u d y  d oct or, w o ul d c o nf o u n d or i nterfere wit h e val uati o n of 
safety a n d/ or effecti ve ness of t he st u d y dr u g, pre ve nt c o m plia nce 
wit h t he st u d y  pr ot oc ol; precl u de i nf or me d c o nse nt; or re n der t he 
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 1 5 of 6 4
partici pa nt u na ble/ u nli kel y  t o c o m ply wit h t he st u d y pr oce d ures
St atistic al 
Met h o ds
A n al ysis P o p ul ati o n
Effecti ve ness a n d safet y a nal ys es will pri maril y be base d o n t he treate d 
p o p ulati o n, defi ne d as all partici pa nt s recei vi n g at least o ne d ose of 
O x br y ta ® ( V o xel ot or). 
S a m ple Size
T he sa m ple size is selecte d t o pr o vi de a n esti mati o n of t he relati o ns hi p 
bet wee n c ha n ge i n H b a n d si g nifica nt cli nical e ve nts, f or e xa m ple V O Cs, 
str o ke, TI A, a n d P H t hat partici pa nts e x perie nce o ver t he 5 years of t he 
st u d y. T he t otal sa m ple size of a p pr o xi matel y 7 5 0 partici pa nts is e x pecte d t o 
be e nr olle d i n t he st u d y. 
Effecti ve ness A n al yses
C ha n ge fr o m pre -O x br y ta ® ( V o xel ot or) treat me nt peri o d i n H b, he m ol ysis 
meas ures, meas ures of ir o n o verl oa d, a n d re nal f u ncti o n o ver ti me will be 
s u m marize d descri pti vel y. 
A n n ualize d rate of si g nifica nt S C D -relate d cli nical e ve nts, f or e xa m ple 
V O C, A C S, pria pis m, str o ke, TI A, c hr o nic or e n d sta ge ki d ne y  disease, ir o n 
o verl oa d, le g ulcers, car diac malf u ncti o n, P H, a n d R B C tra nsf usi o ns will be 
calc ulate d. T he ass ociati o n bet wee n c ha n ge i n H b a n d he m ol y sis mar ker a n d 
rates of S C D-relate d cli nical e ve nts will be e val uate d. 
Rates of o ut patie nt visits (i ncl u di n g i nf usi o n ce nter, ac ute care, or
tele me dici ne visit), E D visits, h os pitalizati o ns, ac ute a n d c hr o nic R B C 
tra nsf usi o ns, h o me o xy g e n s u p ple me ntati o n, a n d re nal dial ys is will be 
s u m marize d wit h a si milar a p pr oac h as rate of S C D-relate d cli nical e ve nts. 
T he t otal c ost ass ociate d wit h cli nical i nter ve nti o ns will be s u m marize d 
descri pti vel y. 
H R Q o L  meas ures o ver ti me will be s u m marize d descri pti vely. Pr o p orti o n of 
partici pa nts wit h i m pr o ve d H R Q o L meas ures will be calc ulate d a n d t he 
ass ociate d 9 5 % Cl o p per - Pears o n E xact c o nfi de nce i nter vals will be 
c o nstr ucte d as ap pr o priate.
As a p pr o priate, rates of S C D- relate d cli nical e ve nts, healt hcare res o urce 
utilizati o n, t otal c ost ass ociate d wit h cli nical i nter ve nti o ns (if a vaila ble) a n d 
H R Q o L  w hile o n O x br yta ® ( V o xel ot or) treat me nt will be c o m pare d wit h 
t he c orres p o n din g me as ures i n t he 1 2 m o nt hs pri or t o t he first d ose of 
O x br y ta ® ( V o xel ot or) treat me nt. Si milar c o m paris o ns ma y be perf or me d 
bet wee n t he s u b gr o u p of partici pa nts w h o disc o nti n ue O x br y ta ® ( V o xel ot or) 
treat me nt b ut re mai n i n t he st u d y a n d t h ose partici pa nts w h o r e mai n o n 
O x br y ta ® ( V o xel ot or).
S afet y A n al ysis
S A Es a n d pr ot oc ol -s pecifie d A Es will be classifie d acc or di n g t o Me dical 
Dicti o nar y  f or Re g ulat or y Acti vities ( Me d D R A). T he t otal n u m ber wit h 
perce nta ge a n d se verit y of A Es will be ta b ulate d b y s ys te m or gan cla ss a n d 
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 1 6 of 6 4
preferre d ter m a n d b y relati o ns hi p t o O x br y ta ® ( V o xel ot or) treat me nt.
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 1 7 of 6 4
5. A M E N D M E N T S A N D U P D A T E S
N o ne.
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 1 8 of 6 4
6. MI L E S T O N E S
Milest o ne
Pl a n ne d D ate
Start of data c ollecti o n 
0 2 Fe b r uar y 2 0 2 2
E n d of data c ollecti o n
3 1 J a nua r y 2 0 3 0
Fi nal st u d y re p ort
3 0 A p ril 2 0 3 0
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 1 9 of 6 4
7. R A TI O N A L E A N D B A C K G R O U N D
T his n o ni nter ve nti o nal st u d y  is desi g nate d as a P A S S a n d is c o n d ucte d v ol u ntaril y b y Pfizer.
7. 1. I ntr o d ucti o n
7. 1. 1. Dise ase B ac k gr o u n d
Sic kle cell disease ( S C D) is a n i n herite d bl o o d dis or der ca use d b y a p oi nt m utati o n i n t he 
β gl o bi n ge ne res ulti n g i n t he f or mati o n of sic kle he m o gl o bi n ( H b S), w hic h p ol y merizes i n 
t he de o xy ge nate d state a n d lea ds t o re d bl o o d cell ( R B C) sic kli n g. T he disease is mar ke d b y 
t he pat h o p h ysi ol o gic feat ures of he m olyt ic a ne mia, vas o- occl usi o n, a n d pr ogressi ve 
e n d-or ga n da ma ge, wit h a cli nical c o urse c haracterize d b y  life-l o n g disa bilit y a n d early 
deat h .2 ,4 I n a d diti o n t o u n pre dicta ble a n d rec urre nt vas o-occl usi ve pai n e pis o des, he m ol y tic 
a ne mia directl y da ma ges bl o o d vessels, res ulti n g i n a s yste mic vasc ul o pat h y t hat lea ds t o 
c hr o nic a n d pr o gressi ve tiss ue a n d or ga n i nj ur y .3 Wit h i m pr o ve d s ur vi val i n c hil dre n, t he 
nat ura l hist or y of S C D has s hifte d fr o m a disease of c hil d h o o d t o a chr o nic, de bilitati n g 
disease of y o u n g a n d mi d dle -a ge d a d ults. C u m ulati ve i nj ur y t o m ulti ple or ga n s yste ms fr o m 
re peate d e pis o des of R B C sic kli n g, vas o-occl usi o n, a n d c hr o nic he m ol y tic a ne mia e xert a 
hi g h cli nical b ur de n i n t he a gi n g a d ult, si g nifica ntl y i m pacti n g q ualit y of life ( Q o L) a n d 
o verall f u ncti o ni n g .7
7. 1. 2. O x br yt a ® ( V o xel ot or )® (V o xel ot or)
V o xel ot or ( pre vi o usl y  G B T 4 4 0) is a n H b S p oly m erizati o n i n hi bit or t hat bi n ds t o H b S wit h a 
1: 1 st oic hi o metr y a n d e x hi bits prefere ntial partiti o ni n g t o R B Cs. V o xel ot or bi n ds c o vale ntl y  
a n d re versi bl y t o t he N-ter mi nal vali ne of o ne of t he α c hai n of he m o gl o bi n ( H b) a n d 
all ostericall y i ncreases H b S-o x y ge n ( O 2) affin it y,1 sta bilizi n g t he o x yhe m o gl o bi n state a n d 
i n hi biti n g p ol ymerizati o n .5 T he v o xel ot or bi n di n g site ,3 is dista nt fr o m heme p oc kets a n d it 
ca n t heref ore i ncrease O 2 affi nit y wit h o ut stericall y bl oc ki n g t he release of O2. 
I n N o ve m ber 2 0 1 9, O x br yta ® ( V o xel ot or)® was a p pr o ve d i n t he U S b y  t he F oo d a n d Dr u g 
A d mi nistrati o n ( F D A) f or t he treat me nt of S C D i n a d ults a n d pe diatric p atie nts 1 2 years of 
a ge a n d ol der. T his i n dicati o n was a p pr o ve d u n der accelerate d a p pr o val base d o n i ncrease i n 
H b. I n Dece m ber 2 0 2 1, t he i n dicati o n was e x pa n de d t o i ncl u de pe diatric partici pa nts 4 y ears 
of a ge a n d ol der. T his i n dicati o n was a n e xte nsi o n of t he accelerate d a p pr o val of O x br yta ® 
( V o xel ot or) base d o n i ncrease i n H b. I n a d diti o n, a ne w d osa ge f or m was als o a p pr o ve d f or 
t his patie nt p o p ulati o n. V o xel ot or c o nti n ues t o be e val uate d i n o n g oi n g cli nical 
st u dies/e x pa n de d access pr o gra ms e x pl ori n g t he safety, t olera bilit y , p har mac o ki netics, 
p har mac o d y n a mics, a n d treat me nt res p o nse i n pe diatric a n d a d ult partici pa nts wit h S C D as 
well as i n cli nical p har mac ol o g y st u dies i n healt h y  a d ult patie nts. 
I nf or mati o n re gar di n g n o ncli nical st u dies, cli nical st u dies, a n d safet y is a vaila ble i n t he 
O x br y ta ® ( V o xel ot or) U S prescri bi n g i nf or mati o n (O x br y ta ® ( V o xel ot or)® U S PI ).6
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 2 0 of 6 4
8. R E S E A R C H Q U E S TI O N A N D O B J E C TI V E S
8. 1. O bjecti ves a n d E n d p oi nts
T he f oll o wi n g o bjecti ves a n d o utc o me m eas ures will be e val uate d if t he data are a vaila ble.
8. 1. 1. O bjecti ves
8. 1. 1. 1. Pri m ar y O bjecti ve
T he pri mar y  o bjecti ve is t o gat her l o n g ter m data o n O x br yta ® ( V o xel ot or) i n a real-w orl d 
setti n g. T he f oll o wi n g are cate g ories of i nterest i n partic i pa nts wit h S C D treate d wit h 
O x br y ta ® ( V o xel ot or):

Cli nical o utc o mes, as assesse d b y cli nical a n d la b orat or y  assess me nts of 
he mat ol o gical para meters a n d e n d or ga n da ma ge, a n d rate of si g nifica nt cli nical 
e ve nts

Healt hcare res o urce utilizati o n

Healt h -related q ualit y of life ( H R Q o L) , as assesse d b y partici pa nts, 
pare nts/care gi vers, a n d cli nicia ns

Assess t he safet y a n d t olera bilit y of O x br yta ® ( V o xel ot or) O x br yta ® 
( V o xel ot or) O utc o me Meas ures
8. 1. 1. 2. Effecti ve ness E n d p oi nt Me as ures

C ha n ge fr o m pre-O x br y ta ® ( V o xel ot or) treat me nt peri o d i n t he foll o wi n g 
he mat ol o gic para meters c orres p o n di n g t o treat me nt wit h O x br y ta ® ( V o xel ot or): 

H b

He m ol y sis meas ures, i ncl u di n g % retic ul oc ytes, a bs ol ute retic ul oc ytes, bilir u bi n 
(t otal, direct, a n d i n direct)

Meas ures of ir o n o verl oa d, i nc l u di n g ferriti n, ir o n, t otal ir o n bi n di n g ca pacit y 
( TI B C), T 2-wei g hte d ma g netic res o na nce i ma gi n g ( T 2 * M RI)  

C ha n ge fr o m pre -O x br y ta ® ( V o xel ot or) treat me nt peri o d i n re nal f u ncti o n, as 
meas ure d b y t he f oll o wi n g:

Creati ni ne ( Ser u m)

Al b u mi n uria ( uri ne al b u mi n/creati ni ne rati o [ A C R])

He m o gl o bi n uria ( uri ne di pstic k p ositi ve f or bl o o d + 1 or greater a n d ≤2 R B C b y  
hi g h p o wer fiel d)
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 2 1 of 6 4

Ser u m c y stati n C

Esti mate d gl o mer ular filtrati o n rat (e G F R) calc ulate d usi n g t he C hr o nic Ki d ne y 
Disease E pi de mi ol o g y  C olla b orati o n ( C K D-E PI) e q uati o n

Rate of si g nifica nt S C D -relate d cli nical e ve nts, f or e xa m ple vas o -occl usi ve crisis ( V O C), 
ac ute c hest s y n dr o me ( A C S), pria p is m, str o ke, c hr o nic or e n d sta ge ki d ne y disease ir o n 
o verl oa d, le g ulcers, car diac malf u ncti o n, a n d p ul m o nar y  h yperte nsi o n ( P H)

Treat me nt i nit iati o n or m o dificati o n of S C D-relate d me dicati o ns 
(e g, h y dr o x y urea, criza nliz u ma b, L -gl uta mi ne, o pi oi ds [i n dail y m or p hi ne 
e q ui vale nts], ir o n c helati n g a ge nts, er y t hr o p oiesis-sti m ulati n g a ge nts [ E S As], 
n o nster oi dal a nti -i nfla m mat or y dr u gs [ N S AIDs], f olic a ci d, a n d pe nicilli n)

C ha n ge fr o m pre -O x br y ta ® ( V o xel ot or) treat me nt peri o d i n healt hcare res o urce 
utilizati o n: ra te of o ut patie nt visits (i ncl u di n g i nf usi o n ce nter, ac ute care, or 
tele me dici ne visit), e mer ge nc y de part me nt ( E D) visits, h os pitalizati o ns (i ncl u di n g 
t otal le n gt h of sta y a n d ti me i n i nte nsi ve care u nit [IC U], if a p plica ble), ac ute a n d 
c hr o nic R B C tra nsf us i o ns, h o me o x yge n s u p ple me ntati o n, a n d re nal dial y sis 

C ha n ge fr o m pre -O x br y ta ® ( V o xel ot or) treat me nt peri o d i n t he f oll o wi n g H R Q o L 
meas ures: 

Patie nt- Re p orte d O utc o mes Meas ure me nt I nf or mati o n S y ste m ( P R O MI S)

Patie nt Gl o bal I m pressi o n of C ha n ge ( P GI C)

Cli n ical Gl o bal Im pressi o n of C ha n ge ( C GI C)

Ot her meas ures: Ac ute pai n i nte nsit y  as meas ure d b y N u merical Pai n Rati n g 
Scale ( N P R S) a n d a n y o bjecti v e meas ure of e xercise t olera nce
8. 1. 1. 3. S afet y E n d p oi nt Me as ures

Rate a n d se verit y  of seri o us a d verse e ve nts ( S A Es) a n d a d verse e ve nts ( A Es) of 
i nterest

Rate of A Es lea di n g t o d ose m o dificati o n or disc o nti n uati o n of O x br y ta ® ( V o xel ot or)

Pre g na nc y  o utc o mes a n d fert ilit y
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 2 2 of 6 4
9. R E S E A R C H M E T H O D S 
9. 1. St u d y D esi g n
9. 1. 1. St u d y Pl a n
9. 1. 1. 1. O ver all St u d y Desi g n
T his re gistr y  is a n o bser vati o nal st u d y desi gne d t o e val uate t he effect of O x br y ta ® 
( V o xel ot or) i n i n di vi d uals wit h S C D. T his re gistr y is i nte n de d t o be nefit a n d s u p p ort i nterests 
of par tici pa nts, cli nicia ns, re g ulat or y b o dies, pa yers, a n d i n d ustr y b y o btai ni n g l o n git u di nal 
data o n O x br y ta ® ( V o xel ot or). A p pr o xi matel y 5 0 0 S C D partici pa nts w h o are prescri be d a n d 
treate d wit h O x br yta ® ( V o xel ot or) will be e nr olle d. T he st u d y will be c o n d ucte d at 
a p pr o xi matel y 4 5 sites i n t he U S. 
A n y  partici pa nt w h o is c urre ntly ta ki n g O x br yta ® ( V o xel ot or) or has bee n p rescri be d a n d 
will i nitiate treat me nt wit h O x br y ta ® ( V o xel ot or), is eli gi ble t o partici pate. Eli gi ble 
partici pa nts will recei ve treat me nt wit h O x br y ta ® ( V o xel ot or) as prescri be d b y t heir 
p h y sicia n, as part of t heir us ual care. Partici pa nts will be treate d a n d e val uate d per sta n dar d 
of care ( S O C) a n d at t he p h y sicia n’s discreti o n.
Partici pa nts will be i ntr o d uce d t o t he st u d y  b y t heir healt h care tea m a n d will si g n t he 
i nf or me d c o nse nt f or m (I C F) or asse nt pri or t o a n y data c ollecti o n f or t he st u d y.
T his st u d y will c ollect data t hat are rec or de d i n t he partici pa nts’ me dical rec or ds a n d ot her 
sec o n dar y data s o urces s uc h as I ns ura nce a n d P har mac y Claims. St u d y  data will be c ollecte d 
at re g ular i nter vals a n d e ntere d i n case re p ort f or ms ( C R Fs) via a n electr o n ic data ca pt ure 
( E D C) sys te m b y t he st u d y staff.
Re gar dless of h o w l o n g partici pa nts ha ve bee n o n O x br y ta ® ( V o xel ot or) w he n t he y e nr oll i n 
t he st u dy, partici pa nts will be f oll o we d f or u p t o 5 years after t heir first d ose of O x br yta ® 
( V o xel ot or) treat me nt, or u ntil t he y  wit h dra w t heir c o nse nt t o partici pate, or are disc o nti n ue d 
fr o m t he st u d y. Treat me nt, i ncl u di n g i nterr u pti o ns a n d restarti n g treat me nt, will c o nti n ue at 
t he discreti o n of t he treati n g p hys icia n, a n d t here are n o pre-defi ne d treat me nt re q uire m e nts. 
Partici pa nts ma y  recei ve a n y a d diti o nal me dicati o ns prescri be d b y t heir treati n g p h ysicia n or 
ha ve a n y me dical i nter ve nti o ns t hat are dee me d a p pr o priate b y t he treati n g p h y sicia n or st u d y 
d oct or. T he partici pa nt or treati n g p h ys icia n ma y disc o nti n ue O x br y ta ® ( V o xel ot or) at a n y 
ti me. Partici pa nts w h o disc o nti n ue treat me nt wit h O x br yta ® ( V o xel ot or) earlier t ha n 5 years 
will c o nti n ue t o be f oll o we d o n st u d y  t o c ollect cli nical a n d healt h-relate d q ualit y of life 
( H R Q o L) o utc o mes f or u p t o 5 years after t h eir first d ose of O x br yta ® ( V o xel ot or) treat me nt. 
Partici pa nt safet y a n d t olera bilit y will be assesse d t hr o u g h o ut t he st u d y data c ollecti o n peri o d
b y  t he st u d y d oct or a n d re p orte d t o t he S p o ns or.
T he o verall st u d y  desi g n is ill ustrate d i n Fi g ure 1 .
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 2 3 of 6 4
Fi g ure 1:
St u d y Sc he m a 
S O C, sta n dar d of care.
9. 2. Setti n g
9. 2. 1. D ur ati o n of St u d y P artici p ati o n 
T he a p pr o xi mate d urati o n of st u d y  partici pati o n f or a n i n di vi d ual partici pa nt i ncl u des a n 
o bser vati o n peri o d of u p t o 5 y ears after t he first d ose of O x br y ta ® ( V o xel ot or) treat me nt.
9. 2. 1. 1. E n d of St u d y
T he e n d of st u d y is defi ne d as t he date of t h e last data c ollecti o n ti me p oi nt of t he last 
partici pa nt bei n g f oll o we d.
9. 3. St u d y P o p ul ati o n
All partici pa nts at eac h partici pati n g st u d y site w h o ha ve bee n treate d wit h O x br y ta ® 
( V o xel ot or) will be c o nsi dere d f or i ncl usi o n i n t his st u d y.
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 2 4 of 6 4
9. 3. 1. I ncl usi o n Criteri a
E vi de nce of a pe rs o nall y si g ne d a n d date d i nf or me d c o nse nt d oc u me nt i n dicati n g t hat t he 
patie nt ( or a le gall y  acce pta ble re prese ntati ve) has bee n i nf or me d of all perti ne nt as pects of 
t he st u d y.
Partici pa nts w h o meet all t he f oll o wi n g criteria will be eli gi b le f or e nr oll ment i n t his st u d y :
1.
Willi n g a n d a ble t o pr o vi de writte n i nf or me d c o nse nt (a ge d ≥1 8 y ears), 
pare ntal/ g uar dia n c o nse nt a n d partici pa nt asse nt (a ge d ≥1 2 t o < 1 8 ye ars) per l ocal 
re g ulati o ns, or pe diatric partici pa nts (a ge d 4 t o < 1 2 y ears) wit h pa re ntal/ g uar dia n
c o nse nt per I nstit uti o nal Re vie w B oar d (I R B) p olic y  a n d re q uire me nts, c o nsiste nt 
wit h I C H g ui deli nes
2.
Male or fe male partici pa nts wit h d oc u me nte d dia g n osis of sic kle cell disease (all 
ge n ot y p es) 
3.
Partici pa nts w h o are c urre ntl y ta ki n g O x br yt a® ( V o xel ot or) o r ha ve bee n prescri be d 
a n d will i nitiate treat me nt wit h O x br yta ® ( V o xel ot or) acc or di n g t o t he O x br yta ® 
( V o xel ot or) U S PI
W he n partici pa nts ha ve bee n prescri be d O x br y ta ® ( V o xel ot or) a n d dee me d eli gi ble t o 
partici pate i n t he re gistr y st u d y  base d o n t he i ncl usi o n/e xcl usi o n criteria, t he y  will be 
e nr olle d i n t he st u d y re gar dless of w het her t he y ha ve starte d ta ki n g O x br yta ® ( V o xel ot or). 
After e nr oll me nt i nt o t he st u d y , it is rec o m me n de d t hat t he site perf or m t he pre-O x br y ta ® 
( V o xel ot or) partici pa nt assess me nts as s o o n as p ossi ble. O nce t he first d ose of O x br yta ® 
( V o xel ot or) treat me nt has bee n a d mi nistere d, t he partici pa nts will be f oll o we d f or u p t o 
5 ye ars. Patie nt e nr oll me nt pr ocess fl o w is i n Fi g ure 2 .
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 2 5 of 6 4
Fi g ure 2.
E nr oll me nt Pr ocess Fl o w
9. 3. 2. E xcl usi o n Criteri a
Partici pa nts meeti n g a n y of t he f oll o wi n g criteria will n ot be eli gi ble f or e nr oll me nt i n t his 
st u d y:
1.
C urre nt partici pati o n i n a n i n vesti gati o nal cli nical trial or e x pa n de d access pr o gra m , i n
w hic h t he partici pa nt ma y be recei vi n g O x br y ta ® ( V o xel ot or).
2.
Me dical, ps yc h o l o gical, or be ha vi oral c o n diti o n t hat, i n t he o pi ni o n of t he st u d y 
d oct or, w o ul d c o nf o u n d or i nterfere wit h e val uati o n of safet y a n d/ or effecti ve ness of 
t he st u d y dr u g, pre ve nt c om plia nce wit h t he st u d y pr ot oc ol; precl u de i nf or me d 
c o nse nt; or re n der t he pa rtici pa nt u na ble/ u nli kel y t o c o m pl y wit h t he st u d y 
pr oce d ures.
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 2 6 of 6 4
9. 4. V ari a bles
V ari a ble
R ole
D at a s o urce(s)
O per ati o n al defi niti o n
I n de x date
St u d y peri o d
Case re p ort f or m
I nf or m c o nsent date
I n de x year
St u d y peri o d
Case re p ort f or m
I nf or m c o nse nt date
Pr e -O x br yta
St u d y peri o d
Case re p ort f or m
Baseli ne: t he m ost rece nt 
o bser vati o n bef ore 
recei vi n g O x br yta 
P ost -O x br yta
St u d y peri o d
Case re p ort f or m
F oll o w u p peri o d u p t o 
5 years
E n d of Treat me nt
St u d y peri o d
Case re p ort f or m 
Ca pt ure d fr o m e n d of 
treat me nt f or m
E n d of St u d y
St u d y peri o d
Case re p ort f or m
Ca pt ure d fr o m e n d of st u d y 
f or m
A ge
De m o gra p hics
Case re p ort f or m
A ge at i n de x year
Se x
De m o gra p hics
Case re p ort f or m
Ca pt ure d fr o m t he i nf or m 
c o nse nt a n d eli gi bilit y f or m
Race/ Et h nicit y 
De m o gra p hics
Case re p ort f or m
Ca pt ure d fr o m t he i nf or m 
c o nse nt a n d eli gi bilit y f or m
S C D ge n ot y pe
S C D disease hist or y
Case re p ort f or m
Ca pt ure d fr o m S C D disease 
hist or y f or m
H y dr o x y urea use
S C D di sease hist or y
Case re p ort f or m
Ca pt ure d fr o m S C D disease 
hist or y f or m
Hei g ht
Baseli ne c haracteristics
Case re p ort f or m
Ca pt ure d fr o m P h ysical 
e xa mi nati o n f or m
Wei g ht
Baseli ne c haracteristics
Case re p ort f or m
Ca pt ure d fr o m P h ysical 
e xa mi nati o n f or m
Pr e - Ox br yta S C D 
c o m plicati o ns
Me dical hist or y 
Case re p ort f or m
Ca pt ure d fr o m Pre -O x br yta 
treat me nt f or m
C o nc o mita nt Me dicati o ns 
C o nc o mita nt Me dicati o ns
Case re p ort f or m
Ca pt ure d fr o m c o nc o mita nt 
me dicati o ns f or m
He m o gl o bi n
Effecti ve ness e n d p oi nt 
meas ures - He mat ol o g y
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt -He mat ol o g y 
f or m
Retic ul oc yte c o u nt ( %)
Effecti ve ness e n d p oi nt 
meas ures – He mat ol o g y
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt -He mat ol o g y 
f or m
Retic ul oc yte c o u nt 
Effecti v e ness e n d p oi nt 
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 2 7 of 6 4
V ari a ble
R ole
D at a s o urce(s)
O per ati o n al defi niti o n
(a bs ol ute)
meas ures – He mat ol o g y
assess me nt -He mat ol o g y 
f or m
W hite bl o o d cells ( W B C)
Effecti ve ness e n d p oi nt 
meas ures – He mat ol o g y
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt -He mat ol o g y 
f or m
A bs ol ute n e utr o p hil c o u nt 
( A N C)
Effecti ve ness e n d p oi nt 
meas ures – He mat ol o g y
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt -He mat ol o g y 
f or m
Mea n c or p usc ular v ol u me 
( M C V)
Effecti ve ness e n d p oi nt 
meas ures – He mat ol o g y
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt- He mat ol o g y 
f or m
Mea n c or p usc ular 
he m o gl o bi n c o nce ntrati o n 
( M C H C)
Effecti ve ness e n d p oi nt 
meas ures – He mat ol o g y
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt -He mat ol o g y 
f or m
Platelets
Effecti ve ness e n d p oi nt 
meas ures – He mat ol o g y
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt -He mat ol o g y 
f or m
As partate A mi n otra nsferase 
( A S T)
Effecti ve ness e n d p oi nt 
meas ures – He mat ol o g y
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt -He mat ol o g y 
f or m
Ala ni ne A mi n otra nsferase 
( A L T)
Effecti ve nes s e n d poi nt 
meas ures – He mat ol o g y
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt -He mat ol o g y 
f or m
Lactate De h y dr o ge nase 
( L D H)
Effecti ve ness e n d p oi nt 
meas ures - He mat ol o g y
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt -He mat ol o g y 
f or m
Bilir u bi n ( T otal )
Effecti ve ness e n d p oi nt 
meas ures - C he mistr y
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt -C he mistr y f or m
Bilir u bi n ( Direct)
Effecti ve ness e n d p oi nt 
meas ures - C he mistr y
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt -C he mistr y f or m
Bilir u bi n (I n direct)
Effecti ve ness e n d p oi nt 
meas ures - C he mistr y
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt -C he mistr y f or m
Creati ni ne
Effecti ve ness e n d p oi nt 
meas ures – C he mistr y
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt -C he mistr y f or m
Ferriti n
Effecti ve ness e n d p oi nt 
meas ures – C he mistr y
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt -C he mistr y f or m
Ir o n
Effecti ve ness e n d p oi nt 
meas ures – C he mistr y
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt -C he mistr y f or m
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 2 8 of 6 4
V ari a ble
R ole
D at a s o urce(s)
O per ati o n al defi niti o n
Ser u m c ystati n C
Effect i ve ness e n d p oi nt 
meas ures – C he mistr y
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt -C he mistr y f or m
T otal Ir o n Bi n di n g Ca pacit y 
( TI B C)
Effecti ve ness e n d p oi nt 
meas ures – C he mistr y
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt -C he mistr y f or m
T 2 * M RI
Effecti ve ness e n d p oi nt 
meas ures – C he mistr y
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt -C he mistr y f or m
Uri ne Al b u mi n
Effecti ve ness e n d p oi nt 
meas ures – Re nal f u ncti o n
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt - Re nal f u ncti o n 
f or m
Uri ne Creati ni ne
Effecti ve ness e n d p oi nt 
meas ures – Re nal f u ncti o n
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt - Re nal f u ncti o n 
f or m
Al b u mi n Creati ni ne Rati o 
( A C R)
Effecti ve ness e n d p oi nt 
meas ures – Re nal f u ncti o n
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt - Re nal f u ncti o n 
f or m
He m o gl o bi n uria
Effecti ve ness e n d p oi nt 
meas ures – Re nal f u ncti o n
Case re p ort f or m
Ca pt ure d fr o m la b orat or y 
assess me nt - Re nal f u ncti o n 
f or m
G F R
Effecti ve ness e n d p oi nt 
meas ures – Re nal f u ncti o n
Case re p ort f or m
Ca pt ur e d fr o m la b orat or y 
assess me nt - Re nal f u ncti o n 
f or m
Tra nsf usi o ns
Safet y e n d p oi nt meas ures 
Case re p ort f or m 
Ca pt ure d fr o m tra nsf usi o ns 
f or m
Healt hcare Res o urce 
Utilizati o n
Effecti ve ness e n d p oi nt 
meas ures
Case re p ort f or m
Ca pt ure d fr o m Healt hcare 
Res o urce Utilizati o n f or m
P R O MI S
Effecti ve ness e n d p oi nt 
meas ures
Case re p ort f or m
Ca pt ure d fr o m P R O MI S 
f or m
Patie nt Gl o bal I m pressi o n 
of C ha n ge ( P GI- C)
Effecti ve ness e n d p oi nt 
meas u res
Case re p ort f or m
Ca pt ure d fr o m Patie nt 
Gl o bal I m pressi o n of 
C ha n ge ( P GI -C) f or m
Cli nical Gl o bal I m pressi o n 
of C ha n ge ( C GI - C) 
Effecti ve ness e n d p oi nt 
meas ures
Case re p ort f or m 
Ca pt ure d fr o m Cli nical 
Gl o bal I m pressi o n of 
C ha n ge ( C GI -C) f or m
Pai n Scale
Effecti ve ness e n d p oi nt 
meas ures
Case re p ort f or m 
Ca pt ure d fr o m Pai n Scale 
f or m
S he e ha n Disa bilit y Scale
Effecti ve ness e n d p oi nt 
meas ures
Case re p ort f or m
Ca pt ure d fr o m S hee ha n 
Disa bilit y Scale f or m
E xercise T olera nce
Effecti ve ness e n d p oi nt 
Case re p ort f or m
Ca pt ure d fr o m E xercise 
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 2 9 of 6 4
V ari a ble
R ole
D at a s o urce(s)
O per ati o n al defi niti o n
meas ures
T olera nce f or m
Pre g na nc y Testi n g a n d 
Fertilit y
S afet y e n d p oi nt meas ures
Case re p ort f or m
Ca pt ure d fr o m 
Pre g na nc y Testi n g a n d 
Fertilit y f or m
S C D 
C o m plicati o ns/ A d verse 
E ve nts
Safet y e n d p oi nt meas ures
Case re p ort f or m
Ca pt ure d fr o m S C D 
C o m plicati o ns/ A d verse 
E ve nts Q uesti o n f or m
Pre g na nc y 
Safet y e n d p oi nt meas ures
Case re p ort f or m
Ca pt ure d fr o m Pre g na nc y 
N otificati o n a n d O utc o me 
f or ms 
O x br yta P h ysicia n 
A d mi nistrati o n
E x p os ure meas ures
Case re p ort f or m
Ca pt ure d fr o m O x br yta 
P h ysicia n A d mi nistrati o n 
f or m
O x br yta Partici pa nt 
A d here nce
E x p os ure meas ures
Case re p ort f or m
Ca pt ure d fr o m O x br yta 
Partici pa nt A d here nce f or m
9. 5. Tre at me nt of P artici p a nts
T his re gistr y is a n o bser vati o nal st u d y t o e val uate t he effects of O x br y ta ® ( V o xel ot or) i n 
i n di vi d uals wit h S C D. Partici pa nts will recei ve treat me nt wit h O x br y ta ® ( V o xel ot or) as 
prescri be d b y t heir p h ys icia n, as part of t heir us ual care. Partici pa nts will be treate d a n d 
e val uate d per S O C a n d at t he p h y sicia n’s discreti o n. T here are n o pre-defi ne d treat me nt 
re q uire me nts.
9. 5. 1. Descri pti o n of O x br yt a ® ( V o xel ot or)
O x br y ta ® ( V o xel ot or) is a he m o gl o bi n S p ol ymerizati o n i n hi bit or i n dicate d f or t he treat me nt 
of S C D i n a d ults a n d pe diatric patie nts 4 years of a ge a n d ol der .
Refer t o t he O x br y ta ® ( V o xel ot or) U S prescri bi n g i nf or mati o n (O x br y ta ® ( V o xel ot or)®
U S PI )6 f or details o n t he d osa ge, a d mi nistrati o n, f or m ulati o n, pac ka gi n g, st ora ge, a n d 
ha n dli n g of O x br y ta ® ( V o xel ot or).
9. 5. 2. C o nc o mit a nt Me dic ati o ns
A c o nc o mita nt me dicati o n is defi ne d as a n y prescri pti o n or o ver -t he-c o u nter pre parati o n, 
i nclu di n g vita mi ns a n d s u p ple me nts. 
Pre -specifie d me dicati o ns f or S C D -relate d c o n diti o ns ta ke n by t he partici pa nt fr o m 
1 2 m o nt hs bef ore scree ni n g t hr o u g h t he e n d of st u d y  partici pati o n ( 5 years after t he first d ose 
of O x br y ta ® ( V o xel ot or) treat me nt or early d isc o nti n uati o n) will be rec or de d i n t he C R F. 
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 3 0 of 6 4
Treati n g p h ys icia ns ma y prescri be t he partici pa nt a n y a d diti o nal me dicati o ns or perf or m 
me dical i nter ve nti o ns t he y  dee m a p pr o priate.
Refer t o t he O x br y ta ® ( V o xel ot or) ® U S PI6 f or details o n c o nc o mita nt me dicati o ns a n d 
c o ntrai n dicati o ns.
9. 6. D at a S o urces 
T he mai n data s o urce is t hr o u g h t he electr o nic data ca pt ure i n t he st u d y , w hile sec o n dar y data 
s o urces ma y i ncl u de i ns ura nce clai ms, electr o nic me dical rec or ds, h os pital a d mi nistrati ve 
data, a n d s pecific rare disease data bases.
9. 7. St u d y D at a C ollecti o n
Data o n partici pa nts will be c ollecte d at re g ular i nter vals a n d e ntere d i nt o t he E D C s y ste m b y 
st u d y pers o n nel at t he st u d y site be gi n ni n g wit h t heir first d ose of c o m mercial O xbr y ta ® 
( V o xel ot or). Data c ollecti o n will i ncl u de t h ose data t hat are rec or de d i n t he partici pa nt’s 
me dical rec or ds/ ot her sec o n dar y  data s o urces a n d base d o n assess me nts perf or me d as part of 
t he partici pa nt’s S O C. St u d y data t hat are n ot a vaila ble i n me dical rec or ds or ot her sec o n dar y 
data s o urces will n ot be s olicite d fr o m partici pa nts. T he data t o be c ollecte d i n t his st u d y  a n d 
tar get ti me p oi nts f or data c ollecti o n a n d e ntr y are s pecifie d i n t he sc he d ule of acti vities 
( S O A) i n A p pe n di x 1 .
T here are n ot a n y re q uire d st u d y pr oce d ures or assess me nts be yo n d t he S O C. T he S O A 
s h o ul d be use d as a g ui de f or w hat data t o enter a n d n ot f or w hat assess me nts t o perf or m. 
T heref ore, if a n assess me nt liste d i n t he sc he d ule of acti vit y of t he pr ot oc ol is c o nsi dere d 
sta n dar d of care, t he sites are as ke d t o e nter t he assess me nt res ult i nt o t he st u d y data base. If 
a n assess me nt is n ot c o n d ucte d as S O C, t he sites ca n j ust lea ve t he rele va nt data fiel ds bla n k.
Si nce Healt h -Relate d Q ualit y  of Life Meas ures ( P R O MIS, P GI C, N P R S a n d C GI C) are n ot 
c o m m o nl y c o n d ucte d as S O C, i n or der t o all o w i m p orta nt q ualit y - of-life data t o be gat here d 
i n t he re gistr y, q uesti o n naires are pr o vi de d t o t he sites a n d partici pa nts, a n d we rec o m me n d 
( b ut n ot re q uire) t he sites t o perf or m t hese assess me nts.
9. 8. St u d y Size
T he sa m ple size is selecte d t o pr o vi de a n esti mati o n of t he relati o ns hi p bet wee n c ha n ge i n H b 
a n d si g nifica nt cli nical e ve nts, f or e xa m ple V O Cs a n d str o ke t hat partici pa nts e x perie nce 
o ve r t he 5 ye ars of t he st u d y. T he t otal sa m ple size of a p pr o xi matel y 5 0 0 partici pa nts is 
e x pecte d t o be e nr olle d.
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 3 1 of 6 4
9. 9. D at a M a n a ge me nt 
St u d y  data will be c ollecte d at re g ular i nter vals a n d e ntere d i n case re p ort f or ms ( C R Fs) via 
a n electr o nic data ca pt ure ( e E D C) s yste m. All data ma na ge me nt a n d data a nal ysis will be 
perf or me d b y U B C usi n g statistical s oft ware S A S ®, S A S I nstit ute I nc., Car y , N C, U S A. 
9. 9. 1. C ase Re p ort F or ms ( C R Fs)/ D at a C ollecti o n T o ols ( D C Ts)/ Electr o nic D at a Rec or d
As use d i n t his pr ot oc ol, t he ter m C R F s h o ul d be u n derst o o d t o refer t o eit her a pa per f or m or 
a n electr o nic data rec or d or b ot h, de pe n di n g o n t he data c ollecti o n met h o d use d i n t his st u d y .
A C R F is re q uire d a n d s h o ul d be c o m plete d f or eac h i ncl u de d patie nt.  T he c o m plete d 
ori gi nal C R Fs are t h e s ole pr o pert y of Pfizer a n d s h o ul d n ot be ma de a vaila ble i n a n y f or m t o 
t hir d parties, e xce pt f or a ut h orize d re prese ntati ves of Pfizer or a p pr o priate re g ulat ory 
a ut h orities, wit h o ut writte n per missi o n fr o m Pfizer. T he i n vesti gat or s hall e ns ure t hat t he 
C R Fsare sec urel y st ore d at t he st u d y  site i n e ncr y pte d electr o nic a n d/ or pa per f or m a n d will 
be [ pass w or d pr otecte d or sec ure d i n a l oc ke d r o o m] t o pre ve nt access b y  u na ut h orize d t hir d 
parties.
T he i n vesti gat or has ulti mate res p o nsi bilit y  f or t he c ollecti o n a n d re p orti n g of all cli nical, 
safety, a n d la b orat or y data e ntere d o n t he C R Fs a n d a n y ot her data c ollecti o n f or ms (s o urce 
d oc u me nts) a n d e ns uri n g t hat t he y  are acc urate, a ut he ntic/ ori gi nal, attri b uta ble, c o m plete, 
c o nsiste nt, le gi ble, ti mel y (c o nte m p ora ne o us), e n d uri n g, a n d a vaila ble w he n re q uire d. T he 
C R Fs m ust be si g ne d b y t he i n vesti gat or or by a n a ut h orize d staff me m ber t o attest t hat t he 
data c o ntai ne d o n t he C R Fsare tr ue. A n y c orrecti o ns t o e ntries ma de i n t he C R Fs or s o urce 
d oc u me nts m ust be date d, i nitiale d, a n d e x plai ne d (if necessar y) a n d s h o ul d n ot o bsc ure t he 
ori gi nal e ntr y .
T he s o urce d oc u me nts are t he h os pital or t he p h ys icia n's c hart.  I n t hese cases, data c ollecte d 
o n t he C R Fs m ust matc h t h ose c harts. 
9. 9. 2. Rec or d Rete nti o n
T o e na ble e val uati o ns a n d/ or i ns pecti o ns/a u dits fr o m re g ulat or y  a ut h orities or Pfizer, t he 
i n vesti gat or a grees t o kee p rec or ds, i ncl u di n g t he i de ntit y of all partici pati n g patie nts 
(s ufficie nt i nf or mati o n t o li n k rec or ds, e g, C R Fs a n d h os pital rec or ds ), all ori gi nal si g ne d 
i nfor me d c o nse nt/asse nt d oc u me nts, c o pies of all C R Fs[/ D C Ts], safet y re p orti n g f or ms, 
s o urce d oc u me nts, detaile d rec or ds of treat me nt dis p ositi o n, a n d a de q uate d oc ume ntati o n of 
rele va nt c orres p o n de nce (e g, letters, meeti n g mi n utes, a n d tele p h o ne call re p orts). T he 
rec or ds s h o ul d be retai ne d b y t he i n vesti gat or acc or di n g t o l ocal re g ulati o ns or as s pecifie d i n 
t he cli nical st u d y a gree me nt ( C S A), w hic he ver is l o n ger. T he i n vesti gat or m ust e ns ure t hat 
t he rec or ds c o nti n ue t o be st ore d sec urely f or s o l o n g as t he y are retai ne d.
If t he i n vesti gat or bec o mes u na ble f or a ny reas o n t o c o nti n ue t o retai n st u d y rec or ds f or t he 
re q uire d peri o d (e g, retire me nt, rel ocati o n), Pfizer s h o ul d be pr os pecti vely n otifie d.  T he 
st u d y rec or ds m ust be tra nsferre d t o a desi g nee acce ptable t o Pfizer, s uc h as a n ot her 
i n vesti gat or, a n ot her i nstit uti o n, or t o a n i n de pe n de nt t hir d party arra n ge d b y Pfizer. 
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 3 2 of 6 4
St u d y  rec or ds m ust be ke pt f or a mi ni m u m of 1 5 years after c o m pleti o n or disc o nti n uati o n of 
t he st u d y, u nless U B C a n d Pfizer ha ve e x pres sl y a gree d t o a differe nt peri o d of rete nti o n via 
a se parate writte n a gree me nt.  Rec or d m ust be retai ne d f or l o n ger t ha n 1 5 y ears or as 
re q uire d by a p plica ble l ocal re g ulati o ns. 
T he i n vesti gat or m ust o btai n Pfizer's writte n per missi o n bef ore dis p osi n g of a n y rec or ds, 
e ve n if rete nti o n re q uire me nts ha ve bee n met.
9. 1 0. D at a A n al ysis 
T here is n ot a se parate statistical a nal ys is pla n ( S A P) f or t his pr ot oc ol. T he detaile d data 
a nal ys is of e n d p oi nt meas ures are descri be d i n t he Secti o n 9. 1 1. 3 a n d Secti o n 9. 1 1. 4 . 
9. 1 1. St atistics
9. 1 1. 1. A n al ysis P o p ul ati o n
Effecti ve ness a n d safet y a nal ys es will pri maril y be base d o n t he treate d p o p ulati o n, defi ne d 
as all partici pa nts recei vi n g at least o ne d ose of O x br y ta ® ( V o xel ot or). 
9. 1 1. 2. S a m ple Size
T he sa m p le size is selecte d t o pr o vi de a n esti mati o n of t he relati o ns hi p bet wee n c ha n ge i n H b 
a n d si g nifica nt cli nical e ve nts, f or e xa m ple V O Cs a n d str o ke t hat partici pa nts e x perie nce 
o ver t he 5 ye ars of t he st u d y. T he t otal sam ple size of a p pr o xi matel y  5 0 0 partici pa nts is 
e x pecte d t o be e nr olle d.
9. 1 1. 3. Effecti ve ness E n d p oi nt Me as ures A n al yses
Baseli ne De m o gra p hic C haracteristics:
Baseli ne de m o gra p hic c haracteristics will be s u m marize d descri pti vel y. 
E n d p oi nts :

C ha n ge fr o m pre -O x br y ta ® ( V o xel ot or) treat me nt peri o d i n H b , he m ol ysis meas ures, 
meas ures of ir o n o verl oa d, a n d re nal f u ncti o n o ver ti me will be s u m marize d 
descri pti vel y. 

A n n ualize d rate of si g nifica nt S C D -relate d cli nical e ve nts, f or e xa m ple V O C, A C S, 
pria pis m, str o ke, TI A, c hr o nic or e n d sta ge ki d ne y disease, i r o n o verl oa d, le g ulcers, 
car diac malf u ncti o n, a n d P H will be calc ulate d. T he ass ociati o n bet wee n c ha n ge i n 
H b he m ol y sis mar ker a n d rates of S C D-relate d cli nical e ve nts will be e val uate d. 

Rates of o ut patie nt visits (i nc l u di n g i nf usi o n ce nter, ac ute care, or
tele me dici ne visit), E D visits, h os pitalizati o ns, ac ute a n d c hr o nic R B C tra nsf usi o ns, 
h o me o x y ge n s u p ple me ntati o n, a n d re nal dial ys is will be s u m marize d wit h a si milar 
a p pr oac h as i nci de nces of S C D -relate d cli nical e ve nts. T he t otal c ost ass ociate d wit h 
cli nical i nter ve nti o ns will be s u m marize d descri pti vel y . 
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 3 3 of 6 4

H R Q o L  meas ures o ver ti me will be s u m marize d descri pti vely. Pr o p orti o ns of 
partici pa nts wit h i m pr o ve d H R Q o L meas ures will be calc ulate d a n d t he ass ociate d 
9 5 % Cl o p per Pears o n E xact c o nfi de nce i nter va ls will be c o nstr ucte d as a p pr o priate. 

Rates of S C D -relate d cli nical e ve nts, healt hcare res o urce utilizati o n, t otal c ost 
ass ociate d wit h cli nical i nter ve nti o ns (if a vaila ble) a n d H R Q o L w hile o n O x br y ta ® 
( V o xel ot or) treat me nt will be c o m pare d wit h t he c orr es p o n di n g meas ures pri or t o t he 
first d ose of O x br yta ® ( V o xel ot or) treat me nt, as a p pr o priate. 
S u b gr o u p a nal ys is:
Si milar c o m paris o ns ma y be perf or me d bet wee n t he s u b gr o u p of partici pa nts w h o 
disc o nti n ue O x br y ta ® ( V o xelot or) treat me nt b ut re mai n i n t he st u d y  a n d t h ose partici pa nts 
w h o re mai n o n O x br y ta ® ( V o xel ot or). 
Ot her s u b gr o u p or se nsiti vit y  a nalys es ma y be perf or me d.
9. 1 1. 4. S afet y A n al ysis
S A Es a n d pr ot oc ol -s pecifie d A Es will be classifie d acc or di n g t o Me dical Dicti o nar y f or 
Re g ulat or y  Acti vities ( Me d D R A). T he fre q ue nc y of A Es will be ta b ulate d b y sys te m or ga n 
class, preferre d ter m, se verit y, a n d relati o ns hi p t o O x br yta ® ( V o xel ot or) treat me nt.
9. 1 2. Q u alit y C o ntr ol
9. 1 2. 1. D at a Q u alit y Ass ur a nce

All partici pa nt data relati n g t o t he st u d y will be rec or de d i n t he C R F u nless 
tra ns mitte d t o t he S p o ns or or desi g nee electr o nicall y (e g, la b orat or y data). T he st u d y 
d oct or is res p o nsi ble f or verif y i n g t hat data e ntries are acc urate a n d c orrect b y 
p h y sically or electr o nicall y  si g ni n g t he C R F.

G ui d a nce o n c o m pleti o n of C R Fs will be pr o vi de d i n t he C R F c o m pleti o n g ui deli ne.

T he st u d y  d oct or m ust per mit as nee de d st u d y-relate d m o nit ori n g, a u dits, I R B re vie w, 
a n d re g ulator y  a ge nc y i ns pecti o ns a n d pr o vi de direct access t o s o urce data 
d oc u me nts.

M o nit ori n g details will be pr o vi de d i n t he m o nit ori n g pla n .

Rec or ds a n d d oc u me nts, i ncl u di n g si g ne d I C Fs, pertai ni n g t o t he c o n d uct of t his 
st u d y m ust be retai ne d b y t he st u d y d oct or f or 2 years after st u d y c o m pleti o n u nless 
l ocal re g ulati o ns or i nstit uti o nal p olicies re q uire a l o n ger rete nti o n peri o d. N o rec or ds 
ma y  be destr o ye d d uri n g t he rete nti o n peri o d wit h o ut t he writte n a p pr o val of t he 
S p o ns or. N o rec or ds ma y be tra nsferre d t o a n ot her l ocati o n or party wit h o ut writte n 
n otificati o n t o t he S p o ns or.
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 3 4 of 6 4
9. 1 2. 2. S o urce D oc u me nts

S o urce d oc u me nts pr o vi de e vi de nce f or t he e xiste nce of t he partici pa nt a n d 
s u bsta ntiate t he i nte grit y of t he data c ollecte d. S o urce d oc u me nts are file d at t he st u d y 
site.

F or t his st u d y , s o urce data i ncl u des data rec or de d i n t he partici pa nt’s me dical rec or ds 
a n d ot her sec o n dar y data s o urces a n d c ollecte d as part of t he partici pa nt’s us ual 
me dical care.

T he st u d y  d oct or m ust mai ntai n acc urate d oc u me ntati o n (s o urce data) t hat s u p p orts 
t he i nf or mati o n e ntere d i n t he C R F.

St u d y  m o nit ors will c o nfir m t hat data e ntere d i nt o t he C R F b y  a ut h orize d site 
pers o n nel are acc urate, c o m plete, a n d verifia ble fr o m s o urce d oc u me nts.
9. 1 2. 3. Esse nti al D oc u me nt ati o n Re q uire me nts
T he S p o ns or or S p o ns or’s re prese ntati ve will c ollect fr o m t he st u d y site t he re q uire d esse ntial 
re g ulat or y d oc u me nts per I C H g ui da nce pri or t o e nr oll me nt of a n y  partici pa nt i n t he st u d y.
9. 1 3. Stre n gt hs a n d Li mit ati o ns of t he Rese arc h Met h o ds
A p ost mar keti n g pr o d uct re gistr y e na bles r o b ust a n d s yste matic data c ollecti o n o n pr o d uct 
use i n t he real - w orl d setti n g. It ca n als o pr o vi de details o n meas ures s uc h as care patter n, 
l o n g-ter m efficac y a n d safet y w hic h re q uire l o n g -ter m f oll o w u p a n d lar ge n u m ber of 
patie nts. 
D ue t o t he o bser vati o nal st u d y  desi g n, li mitati o ns i ncl u de relia nce o n data i ncl u de d i n 
partici pa n ts’ me dical rec or ds, li mite d m o nit ori n g a n d q ualit y c o ntr ol f or data c ollecti o n, 
p atie nt p o p ulati o n a n d s ta n dar d of care var y a m o n g st u d y sites, a n d s usce pti bilit y t o m ulti ple 
s o urces of bias f or c o m pari n g o utc o mes.
9. 1 4. Ot her As pects
9. 1 4. 1. Fi n a nci al Discl os ure
Fi na n cial Discl os ure state me nts will be ha n dle d i n a se parate a gree me nt a part fr o m t he 
pr ot oc ol, ke pt o n file a n d s u b mitte d, as a p plica ble, wit h a n y s u bseq ue nt lice nse a p plicati o n.
9. 1 4. 2. St u d y a n d Site St art a n d Cl os ure
9. 1 4. 2. 1. First Act of Recr uit me nt
T he st u d y  start date is t he date o n w hic h t he st u d y is o pe n f or recr uit me nt of partici pa nts.
T he first act of recr uit me nt is t he first site o pe n a n d will be t he st u d y  start date.
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 3 5 of 6 4
9. 1 4. 2. 2. Site Cl os ure
St u d y  sites will be cl ose d u p o n st u d y c o m pleti o n. A st u d y site is c o nsi dere d cl ose d w he n t he 
S p o ns or/ C R O has c o nfir me d t hat all partici pa nt data e ntere d i nt o E D C is c o nfir me d fi nal a n d 
si g ne d by t he Pri nci pal I n vesti gat or ( PI); all re q uire d d oc u me nts a n d st u dy s u p plies ha ve 
bee n destr o ye d a n d a st u d y -site cl os ure visit has bee n perf or me d.
T he S p o ns or reser ves t he ri g ht t o cl ose t he st u d y s ite at a ny ti me f or a n y reas o n at t he s ole 
discreti o n of t he S p o ns or. T he st u d y  d oct or ma y als o i nitiate st u d y-site cl os ure at a ny ti me, 
pr o vi de d t here is reas o na ble ca use a n d s ufficie nt n otice is gi ve n i n a d va nce of t he i nte n de d 
ter mi nati o n. 
Reas o ns f or t he earl y cl os ure of a st u d y site b y t he S p o ns or or st u d y d oct or ma y i ncl u de b ut 
are n ot li mited t o:

Fail ure of t he st u d y  d oct or t o c o m pl y wit h t he pr ot oc ol, t he re q uire me nts of t he IR B 
or l ocal healt h a ut h orities, t he S p o ns or's pr oce d ures, or G C P g ui deli nes

I na de q uate or n o recr uit me nt (e val uate d after a reas o na ble a m o u nt of ti me) of 
partici pa nts b y t he st u d y d oct or

E nr oll me nt g oal met earlier t ha n e x pecte d
T he st u d y  d oct or s hall i nf or m t he partici pa nt a n d t he I nstit uti o nal Re vie w B oar ds (I R Bs), of 
a n y site cl os ure.
9. 1 4. 2. 3. St u d y Ter mi n ati o n
T he S p o ns or reser ves t he ri g ht t o ter mi nate t he st u d y  or cl ose t he st u d y site at a n y ti me f or 
a n y reas o n at t he s ole discreti o n of t he S p o ns or. 
Reas o ns f or ter mi nati n g t he st u dy ma y i ncl u de, b ut are n ot li mite d t o t he f oll o wi n g:

Disc o nti n uati o n of f urt her O x br y ta ® ( V o xel ot or) de vel o p me nt
I n a ny i nsta nce of earl y ter mi na ti o n of t he st u d y, t he S p o ns or will n otif y, i n writi n g, t he st u d y 
d oct ors, a n d t he I R Bs, a n d will s pecif y  t he reas o n(s) f or ter mi nati o n.
T he st u d y  d oct or s hall i nf or m t he partici pa nt a n d of a n y  early ter mi nati o n of t he st u d y.
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 3 6 of 6 4
1 0. P R O T E C TI O N O F H U M A N P A R TI CI P A N T S
1 0. 1. P atie nt Inf or m ati o n 
All parties will c o m pl y  wit h all a p plica ble la ws, i ncl u di n g la ws re gar di n g t he i m ple me ntati o n 
of or ga nizati o nal a n d tec h nical meas ures t o e ns ure pr otecti o n of patie nt pers o nal data. S uc h 
meas ures will i ncl u de o mitti n g patie nt na mes or ot her directl y i de ntifia ble data i n a n y 
re p orts, p u blicati o ns, or ot her discl os ures, e xce pt w here re q uire d by a p plica ble la ws. 
T he pers o nal data will be st ore d at t he st u d y  site i n e ncr ypte d electr o nic a n d/ or pa per f or m 
a n d will be pass w or d pr otecte d or sec ure d i n a l oc ke d r o o m t o e ns ure t hat o nl y a ut h orize d 
st u d y staff ha ve access. T he st u d y site will i m ple me nt a p pr o priate tec h nical a n d 
or ga nizati o nal meas ures t o e ns ure t hat t he pers o nal data ca n be rec o vere d i n t he e ve nt of 
disaster. I n t he e ve nt of a p ote ntial pers o nal data breac h, t he st u d y  site s hall be res p o nsi ble 
f or deter mi ni n g w het her a pers o nal data breac h has i n fact occ urre d a n d, if s o, pr o vi di n g 
breac h n otificati o ns as re q uire d b y  la w.
T o pr otect t he ri g hts a n d free d o ms of nat ural pers o ns wit h re gar d t o t he pr ocessi n g of 
pers o nal data, w he n st u d y  data are c o m pile d f or tra nsfer t o Pfizer a n d ot her a uth orize d 
parties, patie nt na mes will be re m o ve d a n d will be re place d b y a si n gle, s pecific, n u merical 
c o de, base d o n a n u m beri n g s ys te m defi ne d b y  Pfizer. All ot her i de ntifia ble data tra nsferre d 
t o Pfizer or ot her a ut h orize d parties will be i de ntifie d b y t his si n gle, patie nt-s pecific c o de. 
T he i n vesti gat or site will mai ntai n a c o nfi de ntial list of patie nts w h o partici pate d i n t he st u d y , 
li n ki n g eac h patie nt’s n u merical c o de t o his or her act ual i de ntit y. In case of data tra nsfer, 
Pfizer will mai ntai n hi g h st a n dar ds of c o nfi de ntialit y a n d pr otecti o n of patie nts’ pers o nal data 
c o nsiste nt wit h t he cli nical st u d y  a gree me nt a n d a p plica ble pri vac y la ws.
T o pr otect t he ri g hts a n d free d o ms of nat ural pers o ns wit h re gar d t o t he pr ocessi n g of 
pers o nal data, w he n st u d y  data are c o m pile d f or tra nsfer t o Pfizer a n d ot her a ut h orize d 
parties, a n y patie nt na mes will be re m o ve d a n d will be re place d b y  a si ngle, s pecific, 
n u merical c o de . All ot her i de ntifia ble data tra nsferre d t o Pfizer or ot her a ut h orize d parties 
will be i de nt ifie d b y t his si n gle, patie nt-s pecific c o de. In case of data tra nsfer, Pfizer will 
mai ntai n hi g h sta n dar ds of c o nfi de ntialit y a n d pr ot ecti o n of patie nts’ pers o nal data c o nsiste nt 
wit h t he C R O S O P a n d a p plica ble pri vac y la ws.
1 0. 2. P atie nt C o nse nt
A si g ne d a n d da te d c o nse nt a n d/ or asse nt f or m (a ge < 1 8 years) will be o btai ne d bef ore a n y 
data c ollecti o n f or t he st u d y . 
F or pe diatric partici pa nts, c o nse nt s h o ul d be o btai ne d fr o m at least o ne pare nt ( or b ot h if it is 
re q uire d per st u dy site p olic y) or t he partici pa nt’ s le gall y a ut h orize d re prese ntati ve. 
As a p plica ble, t he c o nse nt will i ncl u de la n g ua ge f or t he use of de- i de ntificati o n a n d 
t o ke nizati o n tec h n ol o g y t hat will all o w f or t he ac q uisiti o n a n d li n ka ge of t he partici pa nt t o 
t heir healt hcare data t hat e xists i n phar mac y a n d me dical a d mi nistrati ve clai ms data bases.
G ui deli nes f or t he i nf or me d c o nse nt/asse nt pr oces s are o utli ne d i n Secti o n 1 0. 7. 2 .
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 3 7 of 6 4
1 0. 3. P atie nt W it h dr a w al
1 0. 3. 1. P artici p a nt I D N u m ber
U p o n e xec uti o n of c o nse nt/asse nt, all partici pa nts will be gi ve n a u ni q ue partici pa nt I D 
n u m ber. T his n u m ber will be use d t o i de ntif y  t he partici pa nt t hr o u g h o ut t he st u d y a n d m ust 
be use d o n all st u d y  d oc u me ntati o n relate d t o t hat partici pa nt.
1 0. 3. 2. Eli gi bilit y Assess me nt
C o n fir mati o n of eli gi bilit y (all i ncl usi o n/e xcl usi o n criteria) will be perf or me d at pre -
O x br y ta ® (V o xel ot or) treat me nt peri o d. 
1 0. 3. 3. Me dic al Hist or y, De m o gr a p hic D at a, a n d I ns ur a nce I nf or m ati o n
Me dical hist or y  will be rec or de d f or u p t o 1 2 m o nt hs pri or t o t he first d ose of O x br yta ® 
( V o xel ot or) (retr os pecti ve data). Me dical hist or y will i ncl u de all a vaila ble S C D ge n ot y pe 
res ults a n d si g nifica nt me dical hist or y, i ncl u di n g he mat ol o gical para meters.
De m o gra p hics (se x, race, et h nicit y , a n d a ge) a n d S C D c haracteristics will be rec or de d at 
pre -O x br y ta ® ( V o xel ot or) treat me nt peri o d, usi n g t he m ost rece nt data bef ore e nr oll me nt. 
I nf or mati o n o n t he partici pa nt’s i ns ura nce pa y er will als o be c ollecte d (e g, Me dicai d, 
Me dicare, d ual eli gi ble, pri vate, or self -i ns ure d).
1 0. 3. 4. S C D Ge n o t y pe
S C D ge n ot y pe (at pre -O x br y ta ® ( V o xel ot or) treat me nt peri o d) o nl y f or me dical dia g n osis of 
S C D, if a dia g n osis is n ot d oc u me nte d i n t he me dical c hart.
1 0. 3. 5. P h ysic al E x a mi n ati o n
Hei g ht a n d wei g ht will be c ollecte d at t he scree ni n g visit f or all partici pa nts of a ge 1 8 a n d 
a b o ve, a n d at scree ni n g a n d all f oll o w u p visits f or partici pa nts u p t o a ge 1 8. P ulse o xi metr y  
[ % S p O 2] will be c ollecte d f or all partici pa nts at scree ni n g a n d all f oll o w u p visits per S O C.
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 3 8 of 6 4
1 0. 3. 6. Effecti ve ness D at a
1 0. 3. 6. 1. Cli nic al O utc o mes
1 0. 3. 6. 1. 1. L a b or at or y Asses s me nts
T he f oll o wi n g data will be rec or de d o n t he C R F: 
F or pre -O x br y ta ® ( V o xel ot or) Treat me nt Visits, o nl y  t he m ost rece nt res ults fr o m re g ularly 
sc he d ule d o ut patie nt visit will be e ntere d. 
F or p ost -O x br y ta ® ( V o xel ot or) Treat me nt Re g ularl y Sc he d ule d O ut patie nt Visits, all 
a vaila ble res ults d uri n g t he data c ollecti o n peri o d will be e ntere d. 
F or p o st-O x br y ta ® ( V o xel ot or) Ac ute Visits ( E mer ge nc y De part me nt, H os pitalizati o n, Ac ute 
Pai n/I nf usi o n Ce nter), o nl y  t he res ults o n t he da y of prese ntati o n ( or first availa ble res ults 
d uri n g t he visit) a n d da y  of disc har ge will be e ntere d, if a vaila ble. 
T he f oll o wi n g data fr o m t he m ost rece nt res ults will be rec or de d i n t he C R F: 

H b (i ncl u di n g % H b F at baseli ne a n d all f oll o w u p visits), w hite bl o o d cells ( W B C), 
a bs ol ute ne utr o p hil c o u nt ( A N C), mea n c or p usc ular v ol u me ( M C V), mea n 
c or p usc ular he m o gl o bi n c o nce n trati o n ( M C H C), Platelets, as partate a mi n otra nsferase 
( A S T), ala ni ne a mi n otra nsferase ( A L T), a n d lactate de h yr o ge nase ( L D H).

He m ol y sis meas ures, i ncl u di n g % retic ulo c y tes, a bs ol ute retic ul oc ytes, bilir u bi n 
(t otal, direct, a n d i n direct)

Meas ures of ir o n o verl oa d (ferriti n, ir o n, TI B C, T 2 * M RI )

Creati ni ne ( Ser u m) 

Al b u mi n uria ( uri ne al b u mi n/creati ni ne rati o [ A C R]) 

He m o gl o bi n uria ( uri ne di pstic k p ositi ve f or bl o o d + 1 or greater a n d ≤ 2 R B C b y  hi g h 
p o wer fiel d)

Ser u m c y stati n C 

e G F R calc ulate d usi n g C K D- E PI e q uati o n
1 0. 3. 6. 1. 2. S C D C o m plic ati o ns
F or t he pre O x br y ta ® ( V o xel ot or) treat me nt S C D c o m plicati o ns, all e ve nts t hat occ urre d 
wit hi n 1 2 m o nt hs pri or t o starti n g O x br y ta ® ( V o xel otor) treat me nt will be rec or de d i n t he 
C R F. 
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 3 9 of 6 4
F or t he p ost - O x br y ta ® ( V o xel ot or) treat me nt S C D c o m plicati o ns, all e ve nts occ urri n g si nce 
t he last c ollecti o n ti me p oi nt will be rec or de d i n t he C R F.
1 0. 3. 6. 1. 3. V as o - Occl usi ve Crises ( V O Cs) a n d Ac ute C hest S y n dr o me ( A C S)
V O C data as d oc u me nte d i n t he partici pa nt’s me dical rec or d will be c ollecte d a n d will 
i nclu de data o n V O C e ve nts, d urati o n, i nte nsit y , a n d ass ociate d i nter ve nti o ns. 
A V O C is defi ne d as a n ac ute e pis o de of pai n t hat:

Has n o me dicall y deter mi ne d ca use ot her t ha n a vas o -occl usi ve e ve nt, a n d 

Res ults i n a visit t o a me dical facilit y ( h os pitalizati o n, e mer ge nc y  de part me nt, ur ge nt 
care ce nter, o ut patie nt cli nic, or i nf usi o n ce nter), or res ults i n a re m ote c o ntact wit h a 
healt hcare pr o vi der; a n d 

Re q uires pare nteral narc otic a ge nts, pare nteral n o nster oi dal a nti- i nfla m mat or y dr u gs 
( N S AI Ds), or a n i ncrease i n treat me nt wit h oral narc otics.
Data relate d t o a n y e ve nts of A C S will be c ollecte d. 
T h e e ve nts ma y ha ve occ urre d i n a me dical setti n g ( h os pital, cli nic, e mer ge ncy r o o m) or at 
h o me.
1 0. 3. 6. 1. 4. Pri a pis m
Occ urre nce of pria pis m e ve nts will be c ollecte d. All data f r o m e ve nts occ urri n g d uri n g t he 
peri o d si nce t he last c ollecti o n ti me p oi nt will be rec or de d i n t he C R F.
1 0. 3. 6. 1. 5. Str o ke a n d Tr a nsie nt Isc he mic Att ac k
Data relate d t o a n y e ve nts of str o ke (Isc he mic, He m orr ha gic, a n d Sile nt), a n d Tra nsie nt 
isc he mic attac k ( TIA), f or e xa m ple, as i de ntifie d via M RI or T C D ( T A M M V meas ures i n 
I C A, M C A, A C A), will be c ollecte d. 
1 0. 3. 6. 1. 6. Le g Ulcers
Data o n le g ulcer(s) assess me nts will be c ollecte d, i ncl u di n g i n f or mati o n o n e xisti n g a n d ne w 
ulcers. 
1 0. 3. 6. 1. 7. C ar di ac M alf u ncti o n a n d P ul m o n ar y H y perte nsi o n
Ca r diac malf u ncti o n, f or e xa m ple, as assesse d by car diac E C H O or car diac cat heterizati o n 
will be c ollecte d. 
Cli nical i n dicat ors of P H (s uc h as t he 6 -mi n ute wal k test, d y s p nea o n e xerti o n, he patic 
c o n gesti o n, etc.) will als o be c ollecte d.
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 4 0 of 6 4
1 0. 3. 6. 1. 8. Ot her S C D C o m plic at i o n
Data o n ot her S C D c o m plicati o ns will be c ollecte d. T his ma y  i ncl u de sic kle cell a ne mia, 
s ple n o me gal y/s ple nect o m y, dact ylitis, c h olelit hiasis/c h olec ystect o m y, a plastic crisis, c hr o nic 
or e n d sta ge ki d ne y  disease (as defi ne d b y G F R < 6 0), ir o n o verl oa d (as dia g n ose d b y T 2 * 
M RI  or R 2 * M RI), p ne u m o nia, reti n o pat h y, a vasc ular necr osis, dee p vei n t hr o m b osis, a n d 
c hr o nic/ac ute pai n.
1 0. 3. 6. 1. 9. R B C Tr a nsf usi o n 
T he hist or y  of R B C tra nsfusi o ns will be c ollecte d. 
1 0. 3. 6. 1. 1 0. S C D -Rel ate d Me dic ati o n Use
A d mi nistrati o n of S C D -relate d me dicati o ns, s uc h as h ydr o x y urea, criza nliz u ma b, L -
gl uta mi ne, o pi oi ds (i n dail y  m or p hi ne e q ui vale nts), ir o n c helati n g a ge nts, E S As, N S AIDs, 
f olic aci d, a n d pe nicilli n, will be c ollecte d.
1 0. 3. 6. 2. He alt hc are Res o urce Utiliz ati o n
Data o n a n y o ut patie nt visits (i ncl u di n g i nf usi o n ce nter, ac ute care, or
tele me dici ne visit), E D visits, h os pitalizati o ns (i ncl u di n g t otal le n gt h of sta y a n d ti me i n I C U, 
if a p plica ble), ac ute a n d c hr o nic R B C tra nsf usi o ns, h o me o x yge n s u p ple me ntati o n, a n d re nal 
dial y sis will be c ollecte d. 
1 0. 3. 6. 3. He alt h -Rel ate d Q u alit y of Life ( H R Q o L)
Data o n H R Q o L meas ures will be c ollecte d a n d c o m plete d b y  t he partici pa nt electr o nically. 
D uri n g a n e ve nt t hat li mits or pre ve nts o n-site S O C visits, t he H R Q o L ca n be c o m plete d 
re m otel y if per mitte d/a p pr o ve d b y the I R Bs . T he q uesti o n naires are pr o vi de d i n A p pe n di x 2 .
1 0. 3. 6. 3. 1. P atie nt Re p orte d O utc o me Me as ure me nt I nf or m ati o n S yste m ( P R O MI S)
T he Nati o nal I nstit ute of Hea lt h self-re p orte d ( or care gi ver-re p orte d) P R O MIS meas ures of 
f u ncti o n, s ym pt o ms, be ha vi ors, a n d f eeli n gs, will be c ollecte d. 
If n ot perf or me d as part of t he partici pa nt’s us ual care, sta n dar dize d P R O MIS f or ms 
Pe diatric - 3 7 v 2. 0-Pr ofile ; Pare nt Pr o x y v 2. 0 Pr ofile-3 7 a n d 4 9 v 2. 1 Pr ofile will be pr o vi de d.
1 0. 3. 6. 3. 2. P atie nt Gl o b al I m pressi o n of C h a n ge ( P GI C)
Data f r o m the self -re p orte d Patie nt Gl o bal Im pressi o n of C ha n ge ( P GI C) will be c ollecte d. 
T he P GI C is a si n gle q uesti o n t hat reflects a partici pa nt's or care gi ver’s belief a b o ut t he 
effecti ve ness of treat me nt wit h O x br y ta ® ( V o xel ot or). P GI C is a 7 -p oi nt scale de picti n g a 
partici pa nt's rati n g of o verall i m pr o ve me nt. Partici pa nts/care gi vers rate t heir c ha n ge as “ ver y  
m uc h i m pr o ve d,” “ m uc h i m pr o ve d,” “ mi ni mall y  i m pr o ve d,” “ n o c ha n ge,” “ mi ni mall y 
w orse,” “ m uc h w orse,” or “ ver y  m uc h w orse”.
If n ot perf or me d as part of t he partici pa nt’s us ual care, t he q uesti o n naire will be pr o vi de d.
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 4 1 of 6 4
1 0. 3. 6. 3. 3. N u meric al P ai n R ati n g Sc ale ( N P R S) 
Data fr o m t he N P R S will be c ollecte d, if it was use d t o assess ac ute pai n i nte nsit y f or V O Cs 
a n d t he res ult was rec or de d as part of t he partici pa nt’s S O C . Partici pa nts will be as ke d 
ver ball y t o c h o ose a w h ole n u m ber fr o m 0 t o 1 0 t hat best descri bes t he se verit y  of pai n 
d uri n g t he last S C D relate d vas o -occl usi ve crisis/ pai n attac k/ pai n crisis, wit h 0 bei n g “ n o 
pai n” a n d 1 0 bei n g “t he w orst pai n i ma gi na ble.”
1 0. 3. 6. 3. 4. Cli nic al Gl o b al I m pressi o n of C h a n ge ( C GI C)
Data fr o m t he C GI C will be c ollecte d. T he C GI C is a brief, sta n d -al o ne assess me nt of t he 
cli nicia n's vie w of t he p artici pa nt's gl o bal f u ncti o ni n g pri or t o a n d after i nitiati n g O x br y ta ® 
( V o xel ot or). T he C GI pr o vi des a n o verall cli nicia n-deter mi ne d s u m mar y  meas ure t hat ta kes 
i nt o acc o u nt all a vaila ble i nf or mati o n, i ncl u di n g a k n o wle d ge of t he partici pa nt's hist or y, 
ps y ch os ocial circ u msta nces, s y m pt o ms, be ha vi or, a n d t he i m pact of t he s y m pt o ms o n t he 
partici pa nt's a bilit y  t o f u ncti o n. C GIC will be c ollecte d, if it d oes n ot i nfl ue nce t he 
partici pa nt’s us ual care.
If n ot perf or me d as part of t he partici pa nt’s us ual care , t he C GI C will be pr o vi de d.
1 0. 3. 6. 3. 5. E xercise T oler a nce
A n y  o bjecti ve meas ures or re p orts of e xercise t olera n ce will be c ollecte d, if t he y were 
rec or de d as part of t he partici pa nt’s S O C. 
1 0. 4. P atie nt Wit h dr a w al
1 0. 4. 1. Disc o nti n u ati o n of O x br yt a ® ( V o xel ot or) a n d P artici p a nt Disc o nti n u ati o n
1 0. 4. 1. 1. Wit h dr a w al of C o nse nt
Partici pa nts a n d/ or t heir care gi ver/ le gally a ut h orize d re prese nt ati ve will be i nf or me d t hat 
partici pati o n is v ol u ntar y a n d t hat t he y  ma y disc o nti n ue O x br yta ® ( V o xel ot or) treat me nt or 
wit h dra w fr o m t he st u d y at a n y ti me a n d f or a n y reas o n. A ny partici pa nt w h o re q uests t o be 
wit h dra w n or w h ose care gi ver /le gall y a ut h orize d re prese ntati ve re q uests wit h dra wal will be 
wit h dra w n fr o m t he st u d y b y t he st u d y d oct or.
1 0. 4. 1. 2. E arl y Disc o nti n u ati o n of O x br yt a ® ( V o xel ot or)
Partici pa nts ma y  be disc o nti n ue d fr o m O x br yta ® ( V o xel ot or) treat me nt b y t he st u d y d oct or 
or treati n g p h y sicia n at a n y ti me a n d f or a ny reas o n.
Partici pa nts w h o are disc o nti n ue d or wit h dra w fr o m O x br y ta ® ( V o xel ot or) treat me nt will 
c o nti n ue t o be f oll o we d f or u p t o 5 y ears after t he first d ose of O x br yta ® ( V o xel ot or) 
treat me nt u nless t he y wit h dra w c o nse nt f or st u d y partici pati o n. 
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 4 2 of 6 4
1 0. 4. 1. 3. L ost t o F oll o w U p

A partici pa nt will be c o nsi dere d l ost t o f oll o w- u p if he or s he re peate dl y fails t o 
ret ur n f or t heir r o uti ne visits per S O C f or ≥1 y ear a n d is u na ble t o be c o ntacte d by t he 
st u d y site.

A partici pa nt w h o is dee me d l ost t o f oll o w -u p a n d later u ne x pecte dl y ret ur ns t o 
t he site f or S O C treat me nt ma y be re-c o nse nte d pri or t o an y  ne w data c ollecti o n. 

A n y  data t hat was misse d d uri n g t he l ost t o f oll o w- u p peri o d will n ot be c ollecte d.
1 0. 5. I nstit uti o n al Re vie w B o ar d (I R B)/I n de pe n de nt Et hics C o m mittee (I E C)
T here m ust be pr os pecti ve a p pr o val of t he st u d y  pr ot oc ol, pr ot oc ol a me n d me nts, a n d ot her 
rele va nt d oc u me nts (e g, i nf or me d c o nse nt f or ms if a p plica ble) fr o m t he rele va nt IR Bs/I E Cs. 
All c orres p o n de nce wit h t he I R B/I E C m ust be retai ne d.  C o pies of I R B/I E C a p pr o vals m ust 
be f or war de d t o Pfizer. 
1 0. 6. Et hic al C o n d uct of t he St u d y
T he st u d y  will be c o n d ucte d i n acc or da nce wit h le gal a n d re g ulat ory re q uire me nts, as well as 
wit h scie ntific p ur p ose, val ue a n d ri g or a n d f oll o w ge nerall y acce pte d researc h practices 
descri be d i n C T 2 4 -WI -G L 0 2 -R F 0 4 .
1 0. 7. Re g ul at or y, Et hic al, a n d St u d y O versi g ht C o nsi der ati o ns
1 0. 7. 1. Re g ul at or y a n d Et hic al C o nsi der ati o ns
T his st u d y wi ll be c o n d ucte d i n acc or da nce wit h t he pr ot oc ol a n d wit h t he f oll o wi n g:

C o nse ns us et hical pri nci ples deri ve d fr o m i nter nati o nal g ui deli nes i ncl u di n g t he 
Declarati o n of Helsi n ki a n d C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical 
Scie nces ( CI O M S) I nter nati o nal Et hical G ui deli nes

A p plica ble I C H G o o d Cli nical Practice ( G C P) G ui deli nes

A p plica ble la ws a n d re g ulati o ns
T he pr ot oc ol, pr ot oc ol a me n d me nts, I C F, Asse nt, a n d ot her rele va nt d oc u me nts (e g, 
a d vertis e me nts) m ust be s u b mitte d t o a n IR B b y t he st u d y  d octor a n d re vie we d a n d a p pr o ve d 
b y  t he I R B bef ore t he st u d y is i nitiate d.
A n y  a me n d me nts t o t he pr ot oc ol will re q uire I R B a p pr o val bef ore i m ple me ntati o n of 
c ha n ges ma de t o t he st u d y desi g n, e xce pt f or c ha n g es necessar y t o eli mi nate a n i m me diate 
hazar d t o st u d y partici pa nts. 
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 4 3 of 6 4
Pr ot oc ols a n d a n y s u bsta ntial a me n d me nts t o t he pr ot oc ol will re q uire healt h a ut h orit y  
a p pr o val pri or t o i nitiati o n e xce pt f or c ha n ges necessar y t o eli mi nate a n i m me diate hazar d t o 
st u d y partici pa nts.
T he st u d y  d oct or will be res p o nsi ble f or t he f oll o wi n g:

Pr o vi di n g writte n s u m maries of t he stat us of t he st u d y  t o t he I R B a n n ually or m ore 
fre q ue ntly i n acc or da nce wit h t he I R B re q uire me nts

N otif y i n g t he I R B of S A Es or ot her si g nifica nt safet y fi n di n gs as re q uire d b y IR B 
pr oce d ures

Pr o vi di n g o versi g ht of t he c o n d uct of t he st u d y at t he site a n d a d here nce t o 
re q uire me nts of 2 1 C F R, I C H g ui deli nes, t he I RB, E ur o pea n re g ulati o n 5 3 6/ 2 0 1 4 f or 
cli nical st u dies (if a p plica ble), E ur o pea n Me dical De v ice Re g ulati o n 2 0 1 7/ 7 4 5 f or 
cli nical de vice researc h (if a p plica ble), a n d all ot her a p plica ble l ocal re g ulati o ns
1 0. 7. 2. I nf or me d C o nse nt a n d Asse nt Pr ocess

T he st u d y  d oct or or his/ her re prese ntati ve will e x plai n t he nat ure of t he st u d y t o t he 
partici pa nt ( or t heir le gall y a ut h orize d re prese ntati ve) a n d a ns wer all q uesti o ns 
re gar di n g t he st u dy.

Partici pa nts m ust be i nf or me d t hat t heir partici pati o n is v ol u ntar y. Partici pa nts ( or 
t heir le gall y a ut h orize d re prese ntati ve) will be re q uire d t o si g n a state me nt of 
i nf or me d c o nse nt t hat meets t he re q uire me nts of 2 1 C F R 5 0, l ocal re g ulati o ns, IC H 
g ui deli nes, Healt h I ns ura nce P orta bilit y , a n d Acc o u nta bilit y Act ( HIP A A) 
re q uire me nts, w here a p plica ble, a n d t he I RB or st u d y  ce nter. 

Partici pa nts u n der 1 8 ye ars of a ge (a n d t heir pare nt or le gall y a ut h orize d 
re prese ntati ve) will revie w t he I C F a n d si g n a n Asse nt F or m, acc or di n g t o l ocal I R B 
g ui deli nes. Partici pa nts w h o i nitia ll y si g n t he asse nt f or m a n d s u bse q ue ntl y le gall y 
bec o me a n a d ult w hile acti vel y  partici pati n g i n t he st u d y ( bef ore t he e n d of st u d y) 
s h o ul d be re-c o nse nte d usi n g t he a d ult I C F s o o n after t heir stat us c ha n ges.

T he me dical rec or d m ust i ncl u de a state me nt t hat writte n i nf or me d c o nse nt was 
o btai ne d bef ore t he partici pa nt was e nr olle d i n t he st u d y  a n d t he date t he writte n 
c o nse nt was o btai ne d. T he a ut h orize d pers o n o btai ni n g t he i nf or me d c o nse nt m ust 
als o si g n t he I C F.

D uri n g a n e ve nt t hat li mits or pre ve nts o n -site S O C visits, t he site ca n o btai n 
c o nse nt/asse nt of a partici pa nt re m otel y , if per mitte d/a p pr o ve d by t he I RBs.

Partici pa nts m ust be re -c o nse nte d t o t he m ost c urre nt versi o n of t he I C F(s) d uri n g 
t heir partici pati o n i n t he st u d y.
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 4 4 of 6 4

A c o p y of t h e si g ne d a n d date d I C F(s) m ust be pr o vi de d t o t he partici pa nt ( or t heir 
le gall y a ut h orize d re prese ntati ve).
T he ori gi nal c o pies of t he si g ne d a n d date d I CF (a n d asse nt f or m , if a p plica ble), m ust be 
retai ne d i n t he i nstit uti o n’s rec or ds a n d are s u bject t o ins pecti o n b y  re prese ntati ves of t he 
S p o ns or, or re prese ntati ves fr o m re g ulat or y  a ge ncies.
Partici pa nts u na ble t o si g n t he I C F ma y  partici pate i n t he st u d y if a le gall y a ut horize d 
re prese ntati ve or wit ness pr o vi des t he c o nse nt (i n acc or da nce wit h t he pr oce dures of I CH-
G C P a n d l ocal re g ulati o ns) a n d t he partici pa nt c o nfir ms his/ her i nterest i n st u d y  
partici pati o n. T he partici pa nt, pare nt, or le gall y a ut h orize d re prese ntati ve w ill be i nf or me d 
t hat he/s he ca n freel y wit h dra w c o nse nt a n d st o p partici pati o n i n t he st u d y at a n y ti me wit h 
n o prej u dice t o f urt her treat me nt. It is t he pare nt or le gall y  a ut h orize d re prese ntati ve’s 
res p o nsi bilit y t o c o m m u nicate t his decisi o n t o t he st u d y d oct or.
I n t he e ve nt of a pre g na nc y i n t he fe male part ner of a male partici pa nt, a pre g na nc y  c o nse nt 
f or m will be pr o vi de d t o t he part ner of t he male partici pa nt t o all o w t he f oll o w-u p of t he 
pre g na nc y .
1 0. 7. 3. D at a Pr otecti o n

Partici pa nts will be assi g ne d a u ni q ue i de ntifier b y  t he S p o ns or. A n y partici pa nt 
rec or ds or datasets t hat are tra nsferre d t o t he S p o ns or will c o ntai n t he i de ntifier o nl y ; 
partici pa nt na mes or a n y i nf or mati o n w hic h w o ul d ma ke t he partici pa nt i de ntifia ble 
will n ot be tra nsferre d.

T he partici p a nt m ust be i nf or me d t hat his/ her pers o nal st u d y-relate d data will be use d 
b y  t he S po ns or i n acc or da nce wit h l ocal data pr otecti o n la w. T he le vel of discl os ure 
m ust als o be e x plai ne d t o t he partici pa nt w h o will be re q uire d t o gi ve c o nse nt f or 
t heir data t o be use d as descri be d i n t he i nf or me d c o nse nt. 

T he partici pa nt m ust be i nf or me d t ha t his/ her me dical rec or ds a n d sec o n dar y data 
s o urces ma y be e xa mi ne d b y st u d y a u dit ors or ot her a ut h orize d pers o n nel a p p oi nte d 
b y  t he S p o ns or, b y a p pr o priate I R B me m bers, an d b y  i ns pect ors fr o m re g ulat or y 
a ut h orities.

Li n ke d P har mac y  & Me dical Clai ms Data:

B y  si g ni n g t he I CF, partici pa nts are a greei n g t o ha ve healt h rec or ds ma de 
a vaila ble as part of t he c ollecti o n of me dical a n d p har mac y  clai ms i n or der t o 
e val uate c o nc o mit a nt me dicati o n a n d cli nical o utc o mes. T his data w o ul d be 
o btai ne d fr o m p har mac y  & medical clai ms data bases t hat ha ve bee n de- i de ntifie d 
a n d t o ke nize d t o matc h t he partici pa nt i n t he st u d y . T his de-i de ntifie d data w o ul d 
be ma p pe d i nt o t he pr oject data base. L o gic c hec ks t o c o nfir m acc urate li n ka ge 
w o ul d be perf or me d b y t he cli nical m o nit ori n g a n d data ma na ge me nt tea ms.
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 4 5 of 6 4

All data s h o ul d be rec or de d, ha n dle d, a n d st ore d i n a wa y  t hat all o ws its acc urate 
re p orti n g, i nter pretati o n, a n d verificati o n. All i nte grate d data w o ul d be prese nte d 
t o t he site i n a 2 1 C F R Part 1 1 c o m plia nt s yste m f or re vie w a n d clarificati o n of 
acc urac y a n d q ualit y.

T he i n vesti gat or/ desi g nee is res p o nsi ble f or ass uri n g t hat all data ( w het her e ntere d 
i nt o t he e C R F or a bstracte d fr o m t he electro nic healt h rec or ds ( E H R) is c o m plete, 
acc urate, a n d t hat e ntr y a n d u p dates are perfor me d i n a ti mel y  ma n ner. T he 
I n vesti gat or m ust certif y t hat t he data e ntere d are c o m plete a n d acc urate.

After fi nal data base l oc k, t he i n vesti gat or will recei ve c o pies of all partici pa nt 
data f or arc hi vi n g at t he i n vesti gati o nal site.
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 4 6 of 6 4
1 1. M A N A G E M E N T A N D R E P O R TI N G O F A D V E R S E E V E N T S/ A D V E R S E 
R E A C TI O N S 
I n t his st u dy, data will be c ollecte d b y t he f oll o wi n g t w o met h o ds 1) H u ma n re vie w of 
U nstr uct ure d Data, a n d 2) S ur ve y  of patie nts t o assess H R Q o L. A Es a n d S A Es re p orti n g 
re q uire me nt f or b ot h met h o ds are descri be d bel o w .
1 1. 1. H u m a n Re vie w of U nstr uct ure d D at a
T his st u d y  pr ot oc ol re q uires h u ma n re vie w of patie nt-le vel u nstr uct ure d data; u nstr uct ure d 
data refer t o ver bati m me dical data, i nc l u di n g te xt-base d descri pti o ns a n d vis ual de picti o ns of 
me dical i nf or mati o n, s uc h as me dical rec or ds, i ma ges of p h ysicia n n otes, ne ur ol o gical sca ns, 
x- ra ys, or narrati ve fiel ds i n a data base. T he re vie wer is o bli gate d t o re p ort a d verse e ve nts 
( A Es) wit h e x plicit attri b uti o n t o a n y  Pfizer dr u g t hat a p pear i n t he re vie wed i nf or mati o n 
( defi ne d per t he patie nt p o p ulati o n a n d st u d y peri o d s pecifie d i n t he pr ot oc ol). E x plicit 
attri b uti o n is n ot i nferre d b y  a te m p oral relati o ns hi p bet wee n dr u g a d mi nistrati o n a n d an A E 
b ut m ust be base d o n a defi nite state me nt of ca usalit y  b y a healt hcare pr o vi der li n ki n g dr u g 
a d mi nistrati o n t o t he A E.
T he re q uire me nts f or re p orti n g safet y e ve nts o n NI S A E Re p ort F or m f or Pr ot oc ols wit h 
Sti p ulate d Acti ve C ollecti o n of A Es t o Pfizer Safet y  are as f oll o ws:

All seri o us a n d n o n -seri o us A Es wit h e x pl icit attri b uti o n t o a n y Pfizer dr u g t hat 
a p pear i n t he re vie we d i nf or mati o n m ust be re p orte d, wit hi n 2 4 h o urs of a ware ness, 
t o Pfizer Safet y usi n g t he NIS A E M Re p ort F or m.

Sce nari os i n v ol vi n g dr u g e x p os ure, i ncl u di n g e x p os ure d uri n g pre g na nc y , e x p os ure 
d ur i n g breast fee di n g, me dicati o n err or, o ver d ose, mis use, e xtra vasati o n, lac k of 
efficac y, a n d occ u pati o nal e x p os ure ass ociate d wit h t he use of a Pfizer pr o d uct m ust 
be re p orte d, wit hi n 2 4 h o urs of a ware ness, t o Pfizer Safet y usi n g t he NI S A E M 
Re p ort F or m.

If a n e m br yo or fet us has bee n e x p ose d t o t he st u d y dr u g, as s o o n as e x p os ure d uri n g 
pre g na nc y  ( E D P) has bee n dia g n ose d, se n d t he E D P s u p ple me ntal f or m wit h t he NI S 
A E M Re p ort F or m wit h t he a p p r o priate fiel ds c o m plete d. 

F or t hese A Es wit h a n e x plicit attri b uti o n or sce nari os i n v ol vi n g e x p os ure t o a Pfizer 
pr o d uct, t he safet y  i nf or mati o n i de ntifie d i n t he u nstr uct ure d data re vie we d is 
ca pt ure d i n t he E ve nt Narrati ve secti o n of t he re p ort f or m, a n d c o nstit utes all cli nical 
i nf or mati o n k n o w n re gar di n g t hese A Es. N o f oll o w-u p o n relate d A Es will be 
c o n d ucte d.
All t he de m o gra p hic fiel ds o n t he NI S A E M Re p ort F or m ma y  n ot necessaril y be c o m plete d, 
as t he f or m desi g nates, si nce n ot all ele m e nts will be a vaila ble d ue t o pri vac y c o ncer ns wit h 
t he use of sec o n dar y data s o urces. W hile n ot all de m o gra p hic fiel ds will be c o m plete d, at t he 
ver y  least, at least o ne patie nt i de ntifier (e g, ge n der, a ge as ca pt ure d i n t he narrati ve fiel d of 
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 4 7 of 6 4
t he f or m) will be re p orte d o n t he NIS A E M Re p ort F or m, t h us all o wi n g t he re p ort t o be 
c o nsi dere d a vali d o ne i n acc or da nce wit h p har mac o vi gila nce le gislati o n. All i de ntifiers will 
be li mite d t o ge neralities, s uc h as t he state me nt “ A 3 5- ye ar -ol d fe male...” or “ A n el de rly 
male...”   Ot her i de ntifiers will ha ve bee n re m o ve d.   
A d diti o nall y , t he o nset/start dates a n d st o p dates f or “Ill ness,” “ St u d y Dr u g,” a n d “ Dr u g 
Na me” ma y  be d oc u me nte d i n m o nt h/ year ( m m m/ y y y y) f or mat rat her t ha n i de ntif yi n g t he 
act ual date of occ urre n ce wit hi n t he m o nt h / year of occ urre nce i n t he da y/ m o nt h/ year 
( D D/ M M M/ Y Y Y Y) f or mat.”
1 1. 2. P atie nts S ur ve y Assessi n g H R Q o L 
T his st u d y  d oes n ot i n v ol ve data c ollecti o n o n i n di vi d ual patie nts b y t heir treati n g healt hcare 
pr ofessi o nals a n d t he q uesti o n naires use d i n t his st u dy d o n ot i nte n d t o i de ntif y  pr o d uct 
safety i nf or mati o n.  H o we ver, t he q uesti o n naire will be c o m plete d b y partici pa nts o nli ne a n d 
via pa per -base d q uesti o n naire, a n d a partici pa nt c o ul d v ol u nteer pr o d uct safet y  i nf or mati o n 
i n free te xt fiel ds, i n bla n k mar gi ns, t o st u d y  pers o n nels, etc.  A n y safet y i nf or mati o n f or a n 
i n di vi d ual patie nt t hat is v ol u nteere d by a st u d y partici pa nt (e. g., t he patie nt hi m/ herself, 
healt h care pr ofessi o nal, la y  pers o n) d uri n g t his researc h m ust be re p orte d as descri be d 
bel o w: 
T he f oll o wi n g safety e ve nts m ust be re p orte d o n t he NI S A E Re p ort fr o m f or Pr ot oc ols 
wit h o ut sti p ulate d acti ve c ollecti o n: seri o us a n d n o n- seri o us a d verse e ve nts ( A Es) w he n 
ass ociate d wit h t he use of t he Pfizer pr o d uct, a n d sce nari os i n v ol vi n g e x p o s ure d uri n g 
pre g na nc y , e x p os ure d uri n g breast fee di n g, me dicati o n err or, o ver d ose, mis use, 
e xtra vasati o n, lac k of efficac y  a n d occ u pati o nal e x p os ure ( all re p ort a ble, re g ar dless of 
w het her ass oci ate d wit h a n A E) , w he n ass ociate d wit h t he use of a Pfizer pr od uct.  
I n the e ve nt t hat a st u d y  partici pa nt v ol u nteers pr o d uct safet y i nf or mati o n, st u d y site staff 
m ust c o m plete t he NI S A E Re p ort fr o m f or Pr ot oc ols wit h o ut sti p ulate d acti ve c ollecti o n of 
A Es a n d s u b mit t o Pfizer wit hi n 2 4 h o urs of bec o mi n g a ware of t he safet y e ve nt.  I ncl u de d i n 
t he c o m pleti o n of t he NI S A E M Re p ort F or m is t he st u d y partici pa nt’s c o ntact i nf or mati o n; 
c o m plete c o ntact i nf or mati o n s h o ul d be o btai ne d s o t hat, o nce t he NI S A E M Re p ort F or m is 
se nt t o Pfizer, t he NIS A E M Re p ort F or m ca n be assesse d a n d pr ocesse d acc or di n g t o 
Pfizer’s sta n dar d o perati n g pr oce d ures, i ncl u di n g re q uests f or f oll o w -u p t o t he st u d y  
partici pa nt. 
1 1. 3. Pfizer Tr ai ni n g Re q uire me nts:
All researc h staff me m bers m ust c o m plete t he f oll o wi n g Pfizer trai ni n g re q uire me nts:

“ Y o ur Re p orti n g Res p o nsi bilities ( Y R R) wit h S u p ple me nt al T o pics. ”
T hese trai ni n gs m ust be c o m plete d b y  researc h staff me m bers pri or t o t he start of data 
c ollecti o n. All trai ni n gs i ncl u de a “ C o nfir mati o n of Trai ni n g State me nt” (f or si g nat ure b y t he 
trai nee) as a rec or d of c o m pleti o n of t he trai ni n g, w hic h m ust be ke pt i n a retrie va ble f or mat. 
C o pies of all si g ne d trai ni n g state me nts m ust be pr o vi de d t o Pfizer. 
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 4 8 of 6 4
Re -trai ni n g m ust be c o m plete d o n a n a n n ual basis usi n g t he m ost c urre nt Y o ur Re p orti n g 
Res p o nsi bilities ( Y R R) wit h S u p ple me ntal T o pics trai ni n g materials. W here Pfizer iss ues a n 
u p date d safet y  trai ni n g pr o gra m, i ncl u di n g d uri n g t he c o urse of a cale n dar yea r, ve n d or s hall 
e ns ure all ve n d or pers o n nel c o m plete t he u p date d safet y trai ni n g wit hi n si xt y ( 6 0) cale n dar 
da y s of iss ua nce b y Pfizer. 
1 1. 4. Re g ul at or y A ge nc y, I nstit uti o n al Re vie w B o ar d, a n d Site Re p orti n g
T he S p o ns or a n d/ or Cli nical Researc h Or ga nizati o n ( C R O) are res p o nsi ble f or n otif y i n g t he 
rele va nt re g ulat or y a ut h orities, ce ntral I nstit uti o nal Re vie w B oar ds (I R Bs), a n d st u d y d oct ors 
of relate d, seri o us u ne x pecte d a d verse reacti o ns ( S U S A Rs) as per l ocal re g ulati o ns. T he 
st u d y d oct or is res p o nsi ble f or n otif yi n g t he l ocal I R Bs of all S A Es t hat occ ur at his or her 
site as re q uire d by l ocal re g ulati o ns, if t his res p o nsi bilit y  resi des wit h t he st u d y d oct or.
1 2. P L A N S F O R DI S S E MI N A TI N G A N D C O M M U NI C A TI N G S T U D Y R E S U L T S
I n t he e ve nt of a n y pr o hi biti o n or restricti o n i m p ose d (e g, cli nical h ol d) b y a n a p plica ble 
co m pete nt aut h orit y i n a n y area of t he w orl d, or if t he i n vesti gat or i s a ware of a ny ne w 
i nf or mati o n w hic h mi g ht i nfl ue nce t he e val uati o n of t he be nefits a n d ris ks of a Pfizer 
pr o d uct , Pfizer s h o ul d be i nf or me d i m me diatel y . 
1 2. 1. Disse mi n ati o n of St u d y D at a
T his st u d y a n d st u d y res ults will be p oste d o n t he U S Nati o nal I nstit utes of Healt h’s we bsite 
w w w. Cli nicaltrials. g o v a n d ot her p u blicl y  accessi ble sites.
1 2. 2. P u blic ati o n P olic y
It is i nte n de d t o p u blis h t he res ults of t he st u dy at re g ular ti me i nter vals (e g, yearl y) o ver t he 
c o urse of t he st u d y. A ut h ors hi p will be deter mi ne d b y  t he G B T Re gistr y  Steeri n g C o m mittee 
a n d i n li ne wit h Inter nati o nal C o m mittee of Me dical J o ur nal E dit ors a ut h ors hi p re q uire me nts.
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 4 9 of 6 4
1 3. R E F E R E N C E S
1.
Eat o n W A, He nr y  E R, H ofric hter J, M ozzarelli A. Is c o o perati ve o x yge n bi n di n g b y  
he m o gl o bi n reall y  u n derst o o d? Nat Str uct Bi ol. 1 9 9 9; 6( 4): 3 5 1– 8.
2.
Gla d wi n M T, Barst RJ, Gi b bs J S R, Hil des hei m M, Sac h de v V, N o uraie M, et al. Ris k 
fact ors f or deat h i n 6 3 2 patie nts wit h sic kle cell disease i n t he U nite d States a n d U nite d 
Ki n g d o m. P L o S O N E. 2 0 1 4; 9( 7):e 9 9 4 8 9. d oi: 1 0. 1 3 7 1/j o ur nal. p o ne. 0 0 9 9 4 8 9.
3.  
Kat o GJ, Gla d wi n M T, Stei n ber g M H. Dec o nstr ucti n g sic kle cell disease: rea p praisal of 
t he r ole of he m olys is i n t he de vel o p me nt of cli nical s u b p he n ot y pes. Bl o o d Re v. 
2 0 0 7; 2 1( 1): 3 7 - 4 7.
4.  
N o uraie M, Lee J S, Z ha n g Y, Ka nias T, Z ha o X, Xi o n g Z. T he relati o ns hi p bet wee n t he 
se verity of he m ol ys is, cli nical ma nifestati o ns a n d ris k of deat h i n 4 1 5 patie nts wit h 
sic kle cell a ne mia i n t he U S a n d E ur o pe. Hae mat ol o gica. 2 0 1 3; 9 8( 3): 4 6 4– 7 2. d oi: 
1 0. 3 3 2 4/ hae mat ol. 2 0 1 2. 0 6 8 9 6 5.
5.  
O kse n ber g D, D uf u K, Patel M P, C h ua n g C, Li Z, X u Q, et al. G B T 4 4 0 i ncreases 
he m o gl o bi n o x y ge n affi nit y , re d uces sic kli n g a n d pr ol o n gs R B C half-life i n a m uri ne 
m o d el of sic kle cell disease. Br J Hae mat ol. 2 0 1 6; 1 7 5( 1): 1 4 1 – 5 3.
6.
O x br y ta ® ( V o xel ot or)® ( v o xel ot or) Ta blets U nite d States Prescri bi ng I nf or mati o n. 
A vaila ble at: htt ps:// hc p. O x br y ta ® ( V o xel ot or).c o m/ p df/ prescri bi n g-i nf or mati o n. p df. 
Accesse d 2 0 Dece m ber 2 0 2 1.
7.
S w a ns o n M E, Gr osse S D, K ul kar ni R. Disa bilit y  a m o n g i n di vi d uals wit h sic kle cell 
disease: literat ure re vie w fr o m a p u blic healt h pers pecti ve. A m J Pre v Me d. 
2 0 1 1; 4 1( 6 S u p pl 4): S 3 9 0 -7. d oi: 1 0. 1 0 1 6/j.a me pre. 2 0 1 1. 0 9. 0 0 6.
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 5 0 of 6 4
1 4. LI S T O F T A B L E S 
N o ne.
1 5. LI S T O F FI G U R E S
Fi g ure 1:
St u d y  Sc he ma
Fi g ure 2.
E nr oll me nt Pr ocess Fl o w
A N N E X 1. LI S T O F S T A N D A L O N E D O C U M E N T S
N o ne .
A N N E X 2. E N C E P P C H E C K LI S T F O R S T U D Y P R O T O C O L S
N ot re q uire d .
A N N E X 3. A D DI TI O N A L I N F O R M A TI O N
N ot a p plica ble .
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 5 1 of 6 4
A p pe n di x 1. Sc he d ule of Acti vities
D at a 
C ollecti o n/ Pr oce d ure
Pre -O x br yt a ® 
( V o xel ot or) 
tre atme nt 
peri o d
St u d y D at a C ollecti o n Peri o d
M o n t h I nter v als
– 1 2 t o 1 
3 
6 
9
1 2 
1 8 
2 4 
3 0 
3 6 
4 2 
4 8 
5 4 
6 0
I nf or me d 
C o nse nt/ Asse nt a
X
Re vie w of eli gi bilit y b
X
Me dical hist or y a n d 
S C D ge n ot y p e c
X
P h ysical e xa mi nati o n 
(i ncl u di n g hei g ht a n d 
wei g ht) a n d vital 
si g nsd
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Cli nical o utc o mes a n d 
i nter ve nti o nse
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Healt h res o urce 
utilizati o n f
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
H R Q o L assess me nts 
( P R O MI S, N P R S, a n d 
e xercise t olera nce) g
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
C GI C a n d P GI C
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
S C D me dicati o ns h
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Safet y data i
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Ser u m pre g na nc y test j
X
Uri ne pre g na nc y test
k
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
C GI C = Cli nical Gl o bal I m pressi o n of C ha n ge; H R Q o L = Healt h -relate d q ualit y of life; P GI C = Patie nt Gl o bal 
I mpressi o n of C ha n ge; P R O MI S = Patie nt -Re p orte d O utc o mes Meas ure me nt I nf or mati o n S yste m; 
N P R S = N u merical Pai n Rati n g Scale.
N O T E: Wit h t he e xce pti o n of i nf or me d c o nse nt/asse nt, all ot her data liste d a b o ve are re q uire d t o be c ollecte d if 
assess me nts are perf or me d as part of t he par tici pa nt’s sta n dar d-of -care; t he data fr o m t hese assess me nts will be 
c ollecte d at t he ti me p oi nts i n dicate d (if a vaila ble) a n d will i ncl u de all data a vaila ble f or t he peri o d bet wee n t he 
ti me p oi nts.
a.
A si g ne d a n d date d c o nse nt a n d/ or asse nt f or m (a ge < 1 8 year s) will be o btai ne d bef ore a n y data c ollecti o n f or t he 
st u d y. F or pe diatric partici pa nts, c o nse nt s h o ul d be o btai ne d fr o m at least o ne pare nt ( or b ot h if it is re q uire d per 
i n vesti gati o nal site p olic y) or t he partici pa nt’s le gall y a ut h orize d re prese ntati ve.
b.
I ncl usi o n a n d e xcl usi o n criteria s h o ul d be re vie we d at t he pre-O x br yta ® ( V o xel ot or) treat me nt peri o d t o e ns ure 
partici pa nt eli gi bilit y is met.
c.
Rec or d a vaila ble si g nifica nt me dical hist or y f or u p t o 1 2 m o nt hs pri or t o t he first d ose of O x br yta ® ( V o xel ot or) 
(retr os pecti ve data) i n t he C R F. Rec or d de m o gra p hics (se x, race, et h nicit y, a n d a ge), a n d S C D c haracteristics 
(i ncl u di n g he mat ol o gical para meters), usi n g t he m ost rece nt data bef ore e nr oll me nt. Rec or d all a vaila ble S C D gen ot y pe 
res ults. Perf or m S C D ge n oty pe (at pre -O x br yta ® ( V o xel ot or) treat me nt peri o d) o nl y f or a me dical dia g n osis of S C D, if 
dia g n osis is n ot d oc u me nte d i n me dical c hart.
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 5 2 of 6 4
d.
P h ysical e xa mi nati o n (i ncl u di n g hei g ht a n d wei g ht) will be c ollecte d at t he scree ni n g visit f or all partici pa nts 1 8 a n d 
a b o ve, a n d at scree ni n g a n d all f oll o w u p visits f or partici pa nts u p t o a ge 1 8. P ulse o xi metr y [ % S p O 2] will be c ollecte d 
f or all partici pa nts at scree ni n g a n d all f oll o w u p visits per sta n dar d of care.
e.
Rec or d a vaila ble cli nical o utc o mes data i ncl u di n g la b orat or y assess me nts, f or e xa m ple: V O Cs, A C S, pria pis m, str o ke, 
TI As, le g ulcers, car diac malf u ncti o n, p ul m o nar y h y perte nsi o n, R B C tra nsf usi o ns, a n d S C D -relate d me dicati o n use 
(see Secti o n 1 0. 3. 6. 1 f or details).
f.
Healt h res o urce utilizati o n i ncl u des a n y o ut patie nt visits (i ncl u di n g i nf usi o n ce nter, ac ute care, or
tele medici ne visit) , E D visits, h os pitalizati o ns (i ncl u di n g le n gt h of sta y, if a p plica ble), ac ute a n d c hr o nic R B C 
tra nsf usi o ns, h o me o x y ge n s u p ple me ntati o n, a n d re nal dial ysis occ urri n g d uri n g t he peri o d bet wee n data c ollecti o n 
ti me p oi nts. 
g.
H R Q o L assess me nts wil l i ncl u de P R O MI S, P GI C, N P R S, C GI C, a n d e xercise t olera nce. Rec or d data fr o m t he m ost 
rece nt assess me nt bef ore eac h c ollecti o n ti me p oi nt. If n ot perf or me d as part of t he partici pa nt’s us ual care, t he 
q uesti o n naires will be pr o vi de d f or t he partici pa nt, pare nt/care gi ver, or cli nicia n t o c o m plete. See Secti o n 1 0. 3. 6. 3 f or 
details. T he q uesti o n naires are pr o vi de d i n A p pe n di x 2 .
h.
Rec or d me dicati o ns f or S C D -relate d c o n diti ons (e g, h y dr o x y urea, criza nliz u ma b, L - gl uta mi ne, o pi oi ds, i n dail y 
m or p hi ne e q ui vale nts, ir o n c helati n g a ge nts, E S As, N S AI Ds, f olic aci d, a n d pe nicilli n) ta ke n b y t he partici pa nt fr o m 
1 2 m o nt hs bef ore s cree ni n g t hr o u g h t he e n d of st u d y partici pati o n ( 5 yea rs after t he first d ose of O x br yta ® ( V o xel ot or) 
treat me nt or earl y disc o nti n uati o n).
i.
Rec or d all seri o us a d verse e ve nts, a d verse e ve nts of i nterest, O x br yta ® ( V o xel ot or) -relate d A Es, ot her safet y e ve nts,
pre g na nc y test res ults, a n d re p orts of fertilit y iss u es occ urri n g d uri n g t he peri o d si nce t he last c ollecti o n ti me p oi nt. See 
Secti o n 1 1 f or defi niti o ns a n d f or details o n rec o di n g a n d re p orti n g A Es a n d safet y e ve nts.
j.
Fe males of c hil d -beari n g p ot e ntial will ha ve a ser u m pre g na nc y test at Scree ni n g.
k.
Uri ne pre g na nc y tests will be perf or me d at sc he d ule d visits f or fe males of c hil d -beari n g p ote ntial. If a uri ne pre g na nc y 
test is p ositi ve, t he res ult m ust be c o nfir me d wit h a ser u m pre gna nc y test. See Secti o n 1 1 .
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 5 3 of 6 4
A p pe n di x 2. He alt h -Rel ate d Q u alit y of L ife Me as ures
Patie nt- Re p orte d O utc o mes Meas ure me nt I nf or mati o n S y ste m ( P R O MI S) – A d ult
Patie nt- Re p orte d O utc o mes Meas ure me nt I nf or mati o n S y ste m ( P R O MI S) – Pe diatric
Patie nt- Re p or te d O utc o mes Meas ure me nt I nf or mati o n S yste m ( P R O MI S) – Pare nt Pr o x y
Patie nt Gl o bal I m pressi o n of C ha n ge ( P GI C)
Cli nical Gl o bal I m pressi o n of C ha n ge ( C GI C )
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 5 4 of 6 4
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)
C O P Y RI G H T E D M A T E RI A L

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 5 5 of 6 4
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)
C O P Y RI G H T E D M A T E RI A L

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 5 6 of 6 4
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)
C O P Y RI G H T E D M A T E RI A L

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 5 7 of 6 4
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)
C O P Y RI G H T E D M A T E RI A L

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 5 8 of 6 4
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)
C O P Y RI G H T E D M A T E RI A L

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 5 9 of 6 4
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)
C O P Y RI G H T E D M A T E RI A L

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 6 0 of 6 4
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)
C O P Y RI G H T E D M A T E RI A L

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 6 1 of 6 4
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)
C O P Y RI G H T E D M A T E RI A L

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 6 2 of 6 4
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)
C O P Y RI G H T E D M A T E RI A L

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 6 3 of 6 4
Patie nt Gl o bal I m pressi o n of C ha n ge ( P GI C)
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

O x br yta ® ( V o xel ot or) ®
C 5 3 4 1 0 1 9/ G B T 4 4 0 4 R 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
P R O S P E C T v ersi o n 1 . 0, 1 0 Oct o ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5 . 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy
0 1- A u g -2 0 2 3   
Pa ge 6 4 of 6 4
Cli nical Gl o bal I m pressi o n of C ha n ge ( C GI C)
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)

D o c u m e nt A p pr o v al R e c or d
D o c u m e nt N a m e:
D o c u m e nt Titl e:
Si g n e d B y:
D at e( G M T)
Si g ni n g C a p a cit y
0 9 0 1 7 7 e 1 9f 8 1 4 2 2 3\ A p pr o v e d\ A p pr o v e d O n: 0 4- J a n- 2 0 2 4 1 4: 5 7 ( G M T)
P P D
P P D
P P D