A Study to Characterize the Safety and Efficacy of Tafamidis Once Daily in the Treatment of Transthyretin Amyloid Cardiomyopathy in Chinese Participants
Phase: PHASE4
Conditions: Transthyretin Amyloid Cardiomyopathy
Sponsor: Pfizer

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1, 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1
A S T U D Y T O C H A R A C T E R I Z E T H E S A F E T Y A N D EF FI C A C Y O F T A F A MI DI S
O N C E D AI L Y I N T H E T R E A T M E N T O F T R A N S T H Y R E TI N A M Y L O I D 
C A R DI O M Y O P A T H Y I N C H I N E S E P A R TI CI P A N T S
I n vesti g ati o n al Pr o d uct N u m ber:
P F -0 6 2 9 1 8 2 6
I n vesti g ati o n al Pr o d uct (St u d y 
I nter ve nti o n) N a me:
T afa mi dis free aci d
U nite d St ates ( U S) I n vesti g ati o n al Ne w 
Dr u g (I N D) N u m ber:
( N/ A)
E ur o pe a n Cli nic al Tri als D at a b ase 
( E u dr a C T) N u m ber:
( N/ A)
Pr ot oc ol N u m ber:
B 3 4 6 1 0 7 7
P h ase:
4
S h ort Title: A st u d y t o assess t he s afet y a n d effic ac y of t af a mi dis i n C hi nese 
p artici p a nts wit h A T T R -C M
T his d oc u me nt a n d acc o m pa n yi n g materials c o ntai n c o nfi de ntial i nf or mati o n bel o n gi n g t o Pfizer.  E xce pt as 
ot her wise a gree d t o i n writi n g, b y acce pti n g or re vie wi n g t hese d oc u me nts, 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 otifie d.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 2
Pr ot oc ol A me n d me nt S u m m ar y of C h a n ges T a ble
D oc u me nt Hist or y
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
Ori gi nal pr ot oc ol
2 8 J u ne 2 0 1 9
N ot a p plica ble ( N/ A)
A me n d me nt 1
2 6
M arc h 2 0 2 1
S h ort Title: 
T he s h ort title was m o difie d as A st u dy t o 
assess t he s afety a n d effic acy of t af a mi dis 
i n C hi nese p artici p a nts wit h A T T R -C M t o 
be m ore c o nsiste nt wit h t he pr ot oc ol title.
I n vesti g ati o n al Pr o d uct N u m ber:
P F - 0 6 2 9 1 8 2 6- 0 0 was c h a n ge d t o 
P F - 0 6 2 9 1 8 2 6 f or c orrecti o n.
wit h or wit h o ut Tr o p o ni n T or wit h or 
wit h o ut T n T was delete d i n t he secti o ns 
bel o w.

1. 3. Sc he d ule of Acti vities ( S O A)

8. S T U D Y A S S E S S M E N T S A N D
P R O C E D U R E S

9. 4. 3. 2 T nI w/ o T n T

T a ble 1 Pr ot oc ol -Re q uire d S afet y 
L a b or at or y Assess me nts

1 0. 1 0 A p pe n di x 1 0: A b bre vi ati o n
R ati o n ale: tr o p o ni n will be teste d at t he 
ce ntral la b f or t his st u d y, a n d o nl y 
Tr o p o ni n I will be teste d.
Secti o n 1. 1 S y n o p sis:

I n C hi n a, i n or der t o f acilit ate A T T R-
C M p atie nt c o nve nie nce, t he pr o p ose d 
cli nic al d osi n g re gi me n is a 6 1 m g 
t af a mi dis s oft c a ps ule or ally o nce 
d aily, wit h or wit h o ut f o o d was 
c h a n ge d t o I n C hi n a, taf a mi dis
me gl u mi ne c a ps ule 2 0 m g o nce d aily 
h as alre a dy bee n a p pr ove d f or t he 
tre at me nt of AT T R - P N i n a d ult 
p atie nts wit h st a ge 1 sy m pt o m atic 
p oly ne ur o p at hy i n Fe br u ary 2 0 2 0; 6 1 
m g t af a mi dis s oft c a ps ule or ally o nce 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 3
D oc u me nt Hist or y
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
d aily w as a p pr ove d i n Se pte m ber 2 0 2 0 
f or t he tre at me nt of A T T R -C M ,
beca use b ot h tafa mi dis 6 1 m g a n d 
tafa mi dis me gl u mi ne 2 0 m g was 
a p pr o ve d i n C hi na.

P ost- st u dy f oll o w- u p (2 8 d ays after 
E n d of St u dy Visit ) was c h a n ge d t o
P ost- tre at me nt f oll o w- u p f or clarity.

We pl a n t o be gi n t he e nr oll me nt wit hi n 
6 m o nt hs of t he a p pr ov al of t af a mi dis 
f or A T T R-C M by C hi n a He alt h 
A ut h ority.  T he e nr oll me nt d ur ati o n is 
1 6 m o nt hs was delete d t o a d d s o me 
fle xi bilit y f or recr uit me nt. T he sa me 
w or di n g was als o delete d i n S ecti o n
4. 1 O ver all Desi g n.

E arly st u dy disc o nti n u ati o n was 
c ha n ge d t o E n d of Tre at me nt t o ali g n 
wit h t he st u d y  e n d p oi nts. T he sa me 
c ha n ge was als o ma de i n Secti o n 1. 3
Sc he d ule of Acti vities ( S O A) a n d 4. 1 
O ver all Desi g n .
Secti o n 1. 3. Sc he d ule of Acti vities 
( S O A):

P ost- st u dy f oll o w- u p (2 8 d ays after 
E n d of St u dy Visit ) was c h a n ge d t o
P ost- tre at me nt f oll o w- u p ( 2 8 + 7 d ays
after l ast d ose ) f or clarity.

E arly st u dy disc o nti n u ati o n was 
c h a n ge t o wit hi n 2 weeks after E n d of 
Tre at me nt f or clarificati o n.

X was a d de d at M o nt h 1 a n d X was 
re m o ve d at M o nt h 12 f or Dis pe nse 
i n vesti gati o nal dr u gs t o be c o nsiste nt 
wit h Secti o n 6. 1
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 4
D oc u me nt Hist or y
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale

Bis p h os p h o n ate was delete d fr o m 
S o A, n ote c, a n d t hr o u g h o ut t he 
pr ot oc ol

I n n ote c, d oc u me nte d previ o usly was 
c h a n ge d t o d oc u me nte d wit hi n 5 ye a
rs of e nr oll me nt. If gre ater t h a n 5 
ye ars, bi o psy or r a di o n ucli de b o ne 
sci nti gr a p hy ( 9 9 m Tc-P Y P) m ust be 
re pe ate d at t he i nvesti g ative site t o 
e ns ure t he dia g n osis m ore acc urate .

I n n ote g, wit hi n 5 ye ars of e nr oll me nt
was a d de d at t he e n d of t his se nte nce 
t o e ns ure t he dia g n osis is m ore 
acc urate.
Secti o n 5. 2 E xcl usi o n criteri a:
( or v acci ne) was a d de d after Previ o us 
a d mi nistr ati o n wit h a n i nvesti g ati o n al 
dr u g i n ite m 4 f or clarificati o n.
Secti o n 6. 1. 1 A d mi nistr ati o n: s o me 
s pecific i nstr ucti o ns of tafa mi dis 
a d mi nistrati o n relate d pr oce d ures a n d 
n otes were m o ve d here fr o m Secti o n 8 
wit h s o me mi n or re visi o ns f or clarit y 
p ur p ose.
Secti o n 6. 5 C o nc o mit a nt T her a p y ：

If a p artici p a nt is offere d, i n 
acc or d a nce wit h t he prev aili n g l oc al 
g ui deli nes, a C O VI D - 1 9 v acci ne, it 
s h o ul d be per mitte d. T his w o ul d be 
rec or de d as a c o nc o mit a nt me dic ati o n 
a n d st a n d ar d A E c ollecti o n a n d 
re p orti n g pr ocesses w o ul d be f oll o we d
was a d de d at t he e n d of t hir d 
para gra g h i n t his secti o n f or 
clarificatio n .

Per mitte d N S AI Ds i ncl u de was 
c h a n ge d t o C hr o nic use ( gre ater t h a n 
4 ti mes/ m o nt h) of N S AI Ds bef ore t he 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 5
D oc u me nt Hist or y
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
st u dy is pr o hi bite d exce pt t he f oll o wi n g 
per mitte d N S AI Ds i n ite m 1. Beca use 
s o me N S AI Ds ca n affect t he 
P har mac o ki netic a n d 
P har mac o d y na mic res ults of tafa mi dis.

T o pic al o p ht h al mic N S AI Ds 
a d mi nistere d w hile t he p atie nt’s n as al 
p u nct u m is occl u de d are als o 
per mitte d was a d de d i n ite m 1 of 
Pr o hi bite d T her a pies t o a d d s o me 
fle xi bilit y f or c o nc o mita nt t hera pies.

Ite m 3 of Pr o hi bite d T her a pies was 
u p d ate d as A d diti o n ally, t he use of 
difl u nis al, t a ur o urs o de oxyc h ol ate a n d 
d oxycycli ne or a ny ot her T T R 
st a bilizi n g a ge nt or ex peri me nt al 
i nterve nti o ns f or tr a nst hyreti n a myl oi d 
c ar di o my o p at hy wit hi n 3 0 d ays pri or 
t o t he st u dy e ntry a n d/ or d uri n g st u dy 
p artici p ati o n is n ot per mitte d. Beca use 
t he use of difl u nisal or a n y  ot her T T R 
sta bilizi n g a ge nt or e x peri me ntal 
i nter ve nti o ns f or A T T R -C M wit hi n 3 0 
da y s pri or t o t he st u d y e ntr y or d uri n g 
t he st u d y is als o pr o hi bite d.

5. Use of a ny d os a ge f or m of t af a mi dis 
bef ore t he st u dy is pr o hi bite d was 
a d de d i n Pr o hi bite d T her a pies . 
Beca use t his st u d y  w o ul d o nl y i ncl u de 
tafa mi dis nai ve patie nts as me nti o ne d 
i n secti o n 4. 1 O verall Desi g n. Beca use 
a n y pri or use of tafa mi dis bef ore t he 
st u d y partici pati o n ma y affect t he 
assess me nts relate d t o t he st u d y  
e n d p oi nts.
S ecti o n 7. 1 Disc o nti n u ati o n of St u d y 
I nter ve nti o n：
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 6
D oc u me nt Hist or y
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale

If st u dy i nterve nti o n is defi nitively 
disc o nti n ue d, t he p artici p a nt will 
re m ai n i n t he st u dy t o be ev al u ate d f or 
t he E n d of Tre at me nt visit ( wit hi n 2 
weeks after t he E n d of Tre at me nt 
d ate) .  See t he S o A f or d at a t o be 
c ollecte d at t he ti me of disc o nti n u ati o n 
of st u dy i nterve nti o n a n d f oll o w -u p f or 
a ny f urt her ev al u ati o ns t h at nee d t o be 
c o m plete d. w as a d de d per t he ne w 
te m plate.

I n t he eve nt of E arly St u dy 
Disc o nti n u ati o n, t he site st aff will 
f oll o w- u p o n t he p artici p a nt’s vit al 
st at us 1 2 m o nt hs ( or e arly st u dy 
disc o nti n u ati o n) fr o m b aseli ne was 
c h a n ge d t o I n t he eve nt of e arly St u dy 
I nterve nti o n Disc o nti n u ati o n, t he site 
st aff will f oll o w- u p o n t he p artici p a nt’s 
vit al st at us at M o nt h 1 2 fr o m b aseli ne 
( or at E arly St u dy Disc o nti n u ati o n 
visit f or a p artici p a nt w h o wit h dr a ws 
c o nse nt f or a ny f urt her c o nt act) f or 
clarificati o n p ur p ose.

I n t he eve nt of disc o nti n u ati o n of st u dy 
i nterve nti o n, it m ust be d oc u me nte d o n 
t he a p pr o pri ate C R F/i n t he me dic al 
rec or ds w het her t he p artici p a nt is 
disc o nti n ui n g f urt her recei pt of st u dy 
i nterve nti o n or als o fr o m st u dy 
pr oce d ures, p osttre at me nt st u dy 
f oll o w-u p, a n d/ or f ut ure c ollecti o n of 
a d diti o n al i nf or m ati o n. was a d de d per 
t he ne w te m plate.

Q Tc B was delete d t hr o u g h o ut t he 
pr ot oc ol , beca use i n t he ne w te m plate 
Q Tc B was n ot rec o m me n de d t o use.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 7
D oc u me nt Hist or y
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
Secti o n 7. 2. P artici p a nt 
Disc o nti n u ati o n/ Wit h dr a w al Fr o m t he 
St u d y:

T he criteria f or wit h dra w fr o m t he 
st u d y a n d t he data ma na ge me nt f or 
t hese partici pa nts was c h a n ge d as per 
u p date d te m plate.

At t he ti me of disc o nti n ui n g fr o m t he 
st u dy, if p ossi ble, a n e arly 
disc o nti n u ati o n visit s h o ul d be 
c o n d ucte d. See t he S o A f or 
assess me nts t o be c ollecte d at t he ti me 
of st u dy disc o nti n u ati o n a n d f oll o w u p 
a n d f or a ny f urt her ev al u ati o ns t h at 
nee d t o be c o m plete d. T he e arly 
disc o nti n u ati o n visit a p plies o nly t o 
p artici p a nts w h o are 
e nr olle d/r a n d o mize d a n d t he n are 
pre m at urely wit h dr a w n fr o m t he st u dy.
was delete d , beca use t he re q uire me nt 
was a d de d i n Secti o n 7. 1 i n t he e ve nt 
of e n d of treat me nt. 
A Ne w Secti o n 7. 2. 1 Wit h dr a wl of 
c o nse nt was a d de d as per u p date d 
te m plate.
Secti o n 8. S T U D Y A S S E S S M E N T S 
A N D P R O C E D U R E S ：

S u g geste d c hr o n ol o g y of e ve nts was 
a d de d w here m ulti ple pr oce d ures are 
sc he d ule d at t he sa me n o mi nal ti me 
p oi nt(s) relati ve t o d osi n g t o clarif y t he 
a p pr o priate se q ue nce.

P ost- st u dy f oll o w- u p i n t his secti o n
was b ot h c h a n ge d t o P ost- tre at me nt 
f oll o w- u p, f or clarificati o n p ur p ose. 

T he s pecific pr oce d ures f or e ver y  visit 
was delete d beca use t he pr oce d ures 
f or e ver y visit were alrea d y i n S O A or 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 8
D oc u me nt Hist or y
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
m o ve d t o Secti o n 6. 1. 1 A d mi nistrati o n 
f or clarity.
T he para gra g h of bl o o d c ollecti o n v ol u me 
was u p d ate d as T he t ot al pl a n ne d per 
pr ot oc ol bl o o d s a m pli n g v ol u me f or 
i n divi d u al p artici p a nts i n t his st u dy is 
a p pr oxi m ately 2 8 0 m L, i ncl u di n g p ote nti al 
a d diti o n al bl o o d s a m ples t ake n f or s afety 
assess me nts at ti mes s pecifie d by 
i nvesti g at or. A d diti o n al bl o o d s a m ples 
m ay be t ake n f or s afety assess me nts w he n 
re q uire d f or m a n a ge me nt of a dverse 
eve nts, pr ovi de d t he t ot al v ol u me t ake n 
d uri n g t he st u dy d oes n ot excee d 5 5 0 m L 
d uri n g a ny peri o d of 5 6 c o nsec utive d ays. 
I n exce pti o n al circ u mst a nces, s uc h as 
me dic al e mer ge ncies, t his v ol u me m ay be 
excee de d a n d will n ot c o nstit ute a pr ot oc ol 
devi ati o n i n s uc h circ u mst a nces. Secti o n
8. 3. A d verse E ve nts a n d Seri o us 
A d verse E ve nts:
E ac h p artici p a nt/le g ally a ut h orize d 
re prese nt ative will be q uesti o ne d a b o ut t he 
occ urre nce of A Es i n a n o nle a di n g m a n ner 
was a d de d as per u p date d te m plate.
Secti o n 8. 3. 1. Ti me Peri o d a n d 
Fre q ue nc y f or C ollecti n g A E a n d S A E 
I nf or m ati o n:
T he secti o n was u p d ate d per t he ne w 
pr ot oc ol te m plate wit h m ore s pecific 
re q uire me nt t o defi ne t he peri o d a n d 
pr ocess f or c ollecti n g A E a n d S A E 
i nf or mati o n.
Secti o n 8. 3. 1. 1. Re p orti n g S A Es t o 
Pfizer S afet y:
T he secti o n was u p d ate d per t he ne w 
pr ot oc ol te m pl ate wit h m ore s pecific 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 9
D oc u me nt Hist or y
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
re q uire me nt t o re p ort S A Es t o Pfizer 
Safet y .
Secti o n 8. 3. 1. 2. Rec or di n g N o nseri o us 
A Es a n d S A Es o n t he C R F:
All n o nseri o us A Es a n d S A Es occ urri n g i n a 
p artici p a nt d uri n g t he active c ollecti o n peri o d, 
w hic h be gi ns after o bt ai ni n g i nf or me d c o nse nt 
as descri be d i n Secti o n 8. 3. 1, will be rec or de d 
o n t he A E secti o n of t he C R F was a d de d as 
per u p date d te m plate.
D uri n g t he active c ollecti o n peri o d, b ot h 
n o nseri o us A Es a n d S A Es are rec or de d o n t he 
C R F was c h a n ge d t o T he i nvesti g at or is t o 
rec or d o n t he C R F all directly o bserve d a n d 
all s p o nt a ne o usly re p orte d A Es a n d S A Es 
re p orte d by t he p artici p a nt as per u p d ate d 
te m pl ate.
Secti o n 8. 3. 4. Re g ul at or y Re p orti n g 
Re q uire me nts f or S A Es:
a n i nvesti g at or s afety re p ort was c h a n ge d t o
S U S A Rs as per u p date d te m plate.
i nvesti g at or’s br oc h ure was c h a n ge d t o
S R S D(s) as per u p date d te m plate.
Secti o n 8. 3. 5. 1. E x p os ure D uri n g 
Pre g n a nc y:
T he w h ole secti o n was u p d ate d per t he 
ne w pr ot oc ol te m plate wit h m ore s pecific 
re q uire me nt t o re p ort a n d ma na ge a n E D P 
for i n vesti gat ors.
Secti o n 8. 3. 5. 2. E x p os ure D uri n g 
Bre astfee di n g:
T his ne w secti o n was a d de d per t he ne w 
pr ot oc ol te m plate wit h ver y  s pecific 
re q uire me nt t o re p ort a n d ma na ge a n 
e x p os ure d uri n g breastfee di n g f or 
i n vesti gat ors.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 0
D oc u me nt Hist or y
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
Secti o n 8. 3. 5. 3. Occ u p ati o n al E x p os ure:
T he w h ole secti o n was u p d ate d per t he 
ne w pr ot oc ol te m plate wit h m ore s pecific 
re q uire me nt t o re p ort a n d ma na ge a n 
occ u pati o nal e x p os ure f or i n vesti gat ors.
Ne w secti o ns were a d de d as per u p date d 
te m plate as f oll o wi n g:

Secti o n 8. 3. 8. A dverse Eve nts of 
S peci al I nterest

Secti o n 8. 3. 8. 1. L ac k of Effic acy

Secti o n 8. 3. 9. Me dic al Device 
Deficie ncies

Secti o n 8. 3. 9. 1. Ti me Peri o d f or 
Detecti n g Me dic al Device 
Deficie ncies 

Secti o n 8. 3. 9. 2. F oll o w u p of Me dic al 
Device Deficie ncies

Secti o n 8. 3. 9. 3. Pr o m p t Re p orti n g of 
Device Deficie ncies t o S p o ns or

Secti o n 8. 3. 9. 4. Re g ul at ory Re p orti n g 
Re q uire me nts f or Device Deficie ncies
Secti o n 8. 3. 1 0. Me dic ati o n Err ors:
be n otifie d wit hi n i m me di ately was 
c h a n ge d t o be n otifie d wit hi n 2 4 h o urs as 
per u p date d te m plate.
Secti o n 8. 4 Tre at me nt of O ver d ose : T he 
w h ole secti o n was u p d ate d per t he ne w 
pr ot oc ol te m plate .
Secti o n 8. 5 P h ar m ac o ki netics: or f or 
ot her i nter n al ex pl or at ory p ur p oses was 
delete d , beca use n o e x pl orat or y tests will 
be d o ne i n t his st u d y .
Secti o n 8. 6 P h ar m ac o d y n a mics:
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 1
D oc u me nt Hist or y
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale

T he act u al d ate a n d ti me ( 2 4 -h o ur 
cl ock ti me) of e ac h s a m ple will be 
rec or de d was a d de d f or clarificati o n.

as well as f or ot her i nter n al 
ex pl or at ory p ur p oses was delete d ,
beca use n o e x pl orat or y tests will be
d o ne i n t his st u d y .
Secti o n 8. 1 0 B i o ps y D oc u me nt ati o n of 
A m yl oi d:

Or ot her a n alysis c a n be utilize d 
t o c o nfir m t he de p osit of a myl oi d was 
a d de d be hi n d C o n g o re d st ai n , t o a d d 
s o me fle xi bilit y f or t he acce pta ble 
bi o ps y  a nal ysis met h o ds f or t he 
c o nfir mati o n of a m yl oi d de p ositi o n .

F or p ur p oses of t his st u dy, a n existi n g 
bi o psy res ult will be c o nsi dere d v ali d if 
it is d oc u me nte d i n writi n g a n d t he 
bi o psy w as perf or me d wit hi n 5 ye ars of 
st u dy e nr oll me nt.  If t he bi o psy is n ot 
v ali d, it will be re pe ate d as a scree ni n g 
pr oce d ure at t he i nvesti g ati o n al site.
w as a d de d as t he last para gra p h of t his 
secti o n t o e ns ure t he dia g n osis is m ore 
acc urate.
S ecti o n 9. 4. 2 P h ar m ac o d y n a mics 
A n al yses: T T R C o nce ntr ati o n a n d T T R 
St a biliz ati o n: 

T he secti o n title was c h a n ge d fr o m
T T R St a biliz ati o n t o
P h ar m ac o dy n a mics A n alyses: T T R 
C o nce ntr ati o n a n d T T R St a biliz ati o n ,
beca use T T R co nce ntrati o n is als o 
a nal ys e d i n t he st u d y.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 2
D oc u me nt Hist or y
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale

T he c o nte nt of all t he 1 st t o 3r d
para gra p h was delete d , a n d T he T T R 
c o nce ntr ati o n a n d perce nt T T R 
st a biliz ati o n will be deter mi ne d .
Decl ari n g a p artici p a nt t o h ave bee n 
“st a bilize d ” is defi ne d as perce nt 
st a biliz ati o n is e q u al t o or m ore t h a n 
3 2 %. was a d de d as t he detaile d 
calc ulati o n met h o ds is n ot nee de d i n 
pr ot oc ol .

T he last para gra g h was u p d ate d as All 
p h ar m ac o dy n a mic a n alyses will be
perf or me d o n t he P D p o p ul ati o n .  T T R 
c o nce ntr ati o n a n d perce nt st a biliz ati o n 
will be s u m m arize d descri ptively as 
c o nti n u o us me as ures, by visit, f or 
over all, by T T R ge n oty pe, a n d by 
N Y H A b aseli ne cl assific ati o n. T he 
pr o p orti o n of p artici p a nts w h o ac hieve 
T T R st a biliz ati o n (ie, w h o h as bee n 
st a bilize d) a n d its 9 5 % c o nfi de nce 
i nterv al will be c alc ul ate d a n d 
s u m m arize d, as c ate g oric al me as ure, 
at e ac h p ost -b aseli ne ti me p oi nt, f or 
over all, by T T R ge n oty pe, a n d by 
N Y H A b aseli ne cl assific ati o n to a d d i n 
t he descri pti ve a nalys is of T T R 
c o nce ntrati o n a n d perce nt sta bilizati o n.  
S ecti o n 1 0. 3 A p pe n di x 3: A d verse 
E ve nts: Defi niti o ns a n d Pr oce d ures f or 
Rec or di n g, E v al u ati n g, F oll o w -u p, a n d 
Re p orti n g:
i nvesti g ati o n al pr o d uct was c h a n ge d t o 
st u dy i nterve nti o n i n t he w h ole secti o n per 
t he ne w te m plate, t he sa me c ha n ge wa s 
als o ma de i n Secti o n 1 0. 4 a n d 1 0. 5 .
Secti o n 1 0. 3. 1. Defi niti o n of A E:
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 3
D oc u me nt Hist or y
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
A n y  a b n or mal la b orat or y test res ults t hat 
meet s o me of t he c o n diti o ns w hic h m ust 
be rec or de d as a n A E was a d de d i n t his 
secti o n per t he ne w pr ot oc ol te m plate.
Secti o n 1 0. 3. 2. Defi niti o n of S A E:
S us pecte d tra ns missi o n via a Pfizer 
pr o d uct was a d de d as a n S A E i n ite m f. 
ot her sit u ati o ns per t he u p date d te m plate.
Secti o n 1 0. 3. 3. Rec or di n g/ Re p orti n g a n d 
F oll o w u p of A Es a n d/ or S A Es:
N o ne was c h a n ge d t o All A Es/ S A Es 
ass oci ate d wit h ex p os ure d uri n g 
pre g n a ncy or bre astfee di n g. Occ u p ati o n al 
ex p os ure is n ot rec or de d as per u p date d 
te m plate.
N ote:  I ncl u de all S A Es ass oci ate d wit h 
ex p os ure d uri n g pre g n a ncy or 
bre astfe e di n g. I ncl u de all A Es/ S A Es 
ass oci ate d wit h occ u p ati o n al ex p os ure 
was a d de d as per u p date d te m plate.
Secti o n 1 0. 4 . 4 C o ntr ace pti o n Met h o ds:
All t he c o nte nt u n der t he title of 
C ollecti o n of Pre g n a nc y I nf or m ati o n
was delete d be ca use t his wa s all i ncl u de d 
i n t he ne w a d de d S ecti o n 8. 3. 5. 1 
E x p os ure D uri n g Pre g n a nc y .
A ne w S ecti o n 1 0. 1 0 A p pe n di x 
1 0: Alter n ati ve Me as ures D uri n g P u blic 
E mer ge ncies was a d de d per t he 
re q uire me nt of ne w pr ot oc ol te m plate.
Gel ati n i n t he dr u g na mes was all detele d
i n t he pr ot oc ol t o be c o nsiste nt wit h t he 
a p pr o ve d la bel of T afa mi dis 6 1 m g a n d 
Tafa mi dis me gl u mi ne 2 0 m g .
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 4
D oc u me nt Hist or y
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
E dit ori al, gr a m m atic al, f or m atti n g, a n d
a d mi nistr ati ve c h a n ges were m a de 
t hr o u g h o ut t he d oc u me nt.
T his a me n d me nt i nc or p orates all re visi o ns t o date, i ncl u di n g a me n d me nts ma de at t he
re q uest of c o u ntr y healt h a ut h orities a n d I R Bs/ E Cs.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 5
T A B L E O F C O N T E N T S
LI S T O F T A B L E S ...............................................................................................................2 0
LI S T O F FI G U R E S .............................................................................................................2 0
1. P R O T O C O L  S U M M A R Y...............................................................................................2 1
1. 1. S y n o psis ..................................................................................................................2 1
1. 2. Sc he ma ....................................................................................................................2 5
1. 3. Sc he d ule of Acti vities ( S o A) ...................................................................................2 6
2. I N T R O D U C TI O N ...........................................................................................................2 9
2. 1. St u d y  Rati o nale .......................................................................................................2 9
2. 2. Bac k gr o u n d .............................................................................................................2 9
2. 2. 1. Cli nical O ver vie w .......................................................................................3 0
2. 3. Be nefit/ Ris k Assess me nt................................ .........................................................3 4
3. O BJ E C TI V E S, E S TI M A N D S, A N D E N D P OI N T S................................ .......................3 5
4. S T U D Y D E SI G N .............................................................................................................3 5
4. 1. O verall Desi g n .........................................................................................................3 5
4. 2. Scie ntific Rati o nale f or St u d y  Desi g n.....................................................................3 6
4. 3. J ustificati o n f or D ose ..............................................................................................3 6
4. 4. E n d of St u d y  Defi niti o n ..........................................................................................3 8
5. S T U D Y P O P U L A T I ON................................ ..................................................................3 8
5. 1. I ncl usi o n Criteria .....................................................................................................3 9
5. 2. E xcl u si o n Criteria....................................................................................................4 0
5. 3. L ifest yle C o nsi derati o ns..........................................................................................4 1
5. 3. 1. C o ntrace pti o n ..............................................................................................4 1
5. 4. Scree n Fail ures ........................................................................................................4 1
6. S T U D Y I N T E R V E N TI O N ..............................................................................................4 1
6. 1. St u d y  Inter ve nti o n(s) A d mi nistere d ........................................................................4 2
6. 1. 1. A d mi nistrati o n ............................................................................................4 3
6. 2. Pre parati o n/ Ha n dli n g/ St ora ge/ Acc o u nta bilit y ........................................................4 5
6. 2. 1. Pre parati o n a n d Dis pe nsi n g ........................................................................4 6
6. 3. Meas ures t o Mi ni mize Bias: Ra n d o mizati o n a n d Bli n di n g .....................................4 6
6. 3. 1. All ocati o n t o I n vesti gati o nal Pr o d uct .........................................................4 6
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 6
6. 4. St u d y  Inter ve nti o n C o m plia nce ...............................................................................4 6
6. 5. C o nc o mita nt T hera p y ..............................................................................................4 7
6. 5. 1. Resc ue Me dici ne .........................................................................................4 8
6. 6. D ose M o dificati o n ...................................................................................................4 8
6. 7. I nter ve nti o n After t he E n d of t he St u d y ..................................................................4 8
7. DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L .......................................................................4 8
7. 1. Disc o nti n uati o n of St u d y  Inter ve nti o n ....................................................................4 8
7. 1. 1. Te m p orar y  Disc o nti n uati o n........................................................................4 9
7. 1. 2. Rec halle n ge .................................................................................................4 9
7. 2. Partici pa nt Disc o nti n uati o n/ Wit h dra wal Fr o m t he St u d y .......................................4 9
7. 2. 1. Wit h dra wal of C o nse nt ...............................................................................5 0
7. 3. L o st t o F oll o w- u p....................................................................................................5 0
8. S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S ...........................................................5 1
8. 1. Efficac y  Assess me nts..............................................................................................5 2
8. 2. Safet y Assess me nts .................................................................................................5 2
8. 2. 1. P h y sical E xa mi nati o ns ................................................................................5 2
8. 2. 2. Vital Si g ns ..................................................................................................5 3
8. 2. 3. Electr ocar di o gra ms..................................................................................... 5 3
8. 2. 4. Ec h ocar di o gra ms ........................................................................................5 4
8. 2. 5. Cli nical Safet y  La b orat or y Assess me nts....................................................5 4
8. 2. 6. B o d y Mass I n de x/ M o difie d B o d y Mass I n de x ........................................... 5 5
8. 2. 7. H os pitalizati o n Deter mi nati o n ....................................................................5 5
8. 2. 8. Pre g na nc y  Testi n g ......................................................................................5 6
8. 3. A d v erse E ve nts a n d Seri o us A d verse E ve nts.......................................................... 5 6
8. 3. 1. Ti me Peri o d a n d Fre q ue nc y  f or C ollecti n g A E a n d S A E I nf or mati o n.......5 6
8. 3. 1. 1. Re p orti n g S A Es t o Pfizer Safet y ...............................................5 7
8. 3. 1. 2. Rec or di n g N o nseri o us A Es a n d S A Es o n t he C R F................... 5 7
8. 3. 2. Met h o d of Detecti n g A Es a n d S A Es ..........................................................5 7
8. 3. 3. F oll o w -u p of A Es a n d S A Es .......................................................................5 7
8. 3. 4. Re g ulat or y Re p orti n g Re q uire me nts f or S A Es ...........................................5 8
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 7
8. 3. 5. E x p os ure D uri n g Pre g na nc y  or Breastfee di n g, a n d Occ u pati o nal 
E x p os ure ..........................................................................................................5 8
8. 3. 5. 1. E x p os ure D uri n g Pre g na nc y ......................................................5 8
8. 3. 5. 2. E x p os ure D uri n g Breastfee di n g ................................................6 0
8. 3. 5. 3. Occ u pati o nal E x p os ure .............................................................6 0
8. 3. 6. Car di o vasc ular a n d Deat h E ve nts ...............................................................6 1
8. 3. 7. Disease -Relate d E ve nts a n d/ or Disease - Relate d O utc o mes N ot 
Q ualif yi n g as A Es or S A Es ..............................................................................6 1
8. 3. 8. A d verse E ve nts of S pecial I nterest............................................................. 6 1
8. 3. 8. 1. Lac k of Efficac y ........................................................................6 1
8. 3. 9. M e dical De vice Deficie ncies ......................................................................6 1
8. 3. 9. 1. Ti me Peri o d f or Detecti n g Me dical De vice Deficie ncies .........6 1
8. 3. 9. 2. F oll o w u p of Me dical De vice Deficie ncies............................... 6 1
8. 3. 9. 3. Pr o m pt Re p orti n g of De vice Deficie ncies t o S p o ns or ..............6 1
8. 3. 9. 4. Re g ulat or y  Re p orti n g Re q uire me nts f or De vice 
Deficie ncies .......................................................................................6 1
8. 3. 1 0. Me dicati o n Err ors .....................................................................................6 1
8. 4. Treat me nt of O ver d ose................................ ............................................................6 2
8. 5. P har mac o ki netics ....................................................................................................6 3
8. 6. P har mac o d y na mics ..................................................................................................6 3
8. 7. Ge netics ...................................................................................................................6 4
8. 7. 1. S pecifie d Ge n etics ......................................................................................6 4
8. 7. 2. Ba n ke d Bi os peci me ns f or Ge netics ............................................................6 4
8. 8. Bi o mar kers ..............................................................................................................6 4
8. 8. 1. S pecifie d Ge ne E x pressi o n ( R N A) Researc h .............................................6 4
8. 8. 2. S pecifie d Pr otei n Researc h .........................................................................6 4
8. 8. 3. S pecifie d Meta b ol o mic Researc h ...............................................................6 4
8. 9. Healt h Ec o n o mics ...................................................................................................6 5
8. 1 0. Bi o ps y  D oc u me ntati o n of A m yl oi d ......................................................................6 6
9. S T A TI S TI C A L C O N SI D E R A TI O N S ............................................................................ 6 6
9. 1. Esti ma n ds a n d Statistical H y p ot heses .....................................................................6 6
9. 2. Sa m ple Size Deter mi nati o n .....................................................................................6 6
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 8
9. 3. P o p ulati o ns f or A nal ysis .........................................................................................6 6
9. 4. Statistical A nal y ses .................................................................................................6 7
9. 4. 1. S afet y A nal ys es ..........................................................................................6 7
9. 4. 1. 1. Treat me nt E mer ge nt A d verse E ve nt .........................................6 7
9. 4. 1. 2. Electr ocar di o gra m A nal y ses......................................................6 7
9. 4. 1. 3. B o d y Mass I n de x/ M o difie d B o d y  Mass I n de x
.........................6 8
9. 4. 1. 4. Ot her Safet y Assess me nts .........................................................6 8
9. 4. 2. P har mac o d y na mics A nal yses: T T R C o nce ntrati o n a n d T T R 
Sta bilizati o n .....................................................................................................6 8
9. 4. 3. A nal y s es f or Efficac y E n d p oi nts................................................................6 8
9. 4. 3. 1. N T -Pr o B N P ..............................................................................6 8
9. 4. 3. 2. T nI .............................................................................................6 8
9. 4. 3. 3. 6 Mi n ute Wal k ...........................................................................6 9
9. 4. 3. 4. Ne w Y or k Heart Ass ociati o n Classificati o n .............................6 9
9. 4. 4. Q ualit y  of Life A nal y ses.............................................................................6 9
9. 4. 4. 1. Ka nsas Cit y  Car di o m yo pat h y Q uesti o n naire O verall 
Sc ore ..................................................................................................6 9
9. 4. 4. 2. E Q - 5 D-5 L ..................................................................................6 9
9. 4. 4. 3. 1 2 -Ite m S h ort F or m S ur ve y ( S F-1 2) .........................................7 0
9. 4. 5. P har mac o ki netic Data .................................................................................7 0
9. 5. I nteri m A nal ys es .....................................................................................................7 0
9. 5. 1. Data M o nit ori n g C o m mittee .......................................................................7 0
1 0. S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L C O N SI D E R A TI O N S 7 1
1 0. 1. A p pe n di x 1: Re g ulat or y , Et hical, a n d St u d y O versi g ht C o nsi derati o ns...............7 1
1 0. 1. 1. Re g ulat or y a n d Et hical C o nsi derati o ns ....................................................7 1
1 0. 1. 1. 1. Re p orti n g of Safet y  Iss ues a n d Seri o us Breac hes of t he 
Pr ot oc ol or I C H G C P .........................................................................7 1
1 0. 1. 2. Fi na ncial Discl os ure .................................................................................7 2
1 0. 1. 3. I nf or me d C o nse nt Pr ocess ........................................................................7 2
1 0. 1. 4. Data Pr otecti o n .........................................................................................7 3
1 0. 1. 5. Di sse mi nati o n of Cli nical St u d y Data ......................................................7 3
1 0. 1. 6. Data Q ualit y Ass ura nce ............................................................................7 5
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 9
1 0. 1. 7. S o urce D oc u me nts ....................................................................................7 6
1 0. 1. 8. St u d y  a n d Site Cl os ure..............................................................................7 6
1 0. 1. 9. P u blicati o n P olic y..................................................................................... 7 7
1 0. 1. 1 0. S p o ns or’s Q ualifie d Me dical Pers o n nel .................................................7 8
1 0. 2 . A p pe n di x 2: Cli nical La b orat or y  Tests.................................................................7 9
1 0. 3. A p pe n di x 3: A d verse E ve nts: Defi niti o ns a n d Pr oce d ures f or Rec or di n g, 
E val uati n g, F oll o w -u p, a n d Re p orti n g ......................................................................8 0
1 0. 3. 1. Defi niti o n of A E .......................................................................................8 0
1 0. 3. 2. Defi niti o n of S A E .....................................................................................8 1
1 0. 3. 3. Rec or di n g/ Re p orti n g a n d F oll o w- u p of A Es a n d/ or S A Es .......................8 3
1 0. 3. 4. Re p orti n g of S A Es.................................................................................... 8 6
1 0. 4. A p pe n di x 4: C o ntrace pti ve G ui da nce a n d C ollecti o n of Pre g na nc y 
I nf or mati o n ................................................................................................................8 7
1 0. 4. 1. Male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria.................................... 8 7
1 0. 4. 2. Fe male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria .................................8 7
1 0. 4. 3. W o ma n of C hil d beari n g P ote ntial ( W O C B P) ..........................................8 8
1 0. 4. 4. C o ntrace pti o n Met h o ds .............................................................................8 8
1 0. 5. A p pe n di x 5: Ge netics................................ ............................................................9 0
1 0. 6. A p pe n di x 6: L i ver Safet y: S u g geste d Acti o ns a n d F oll o w-u p Assess me nts ........9 1
1 0. 7. A p pe n di x 7: E C G Fi n di n gs of P ote ntial Cli nical C o ncer n................................... 9 3
1 0. 8. A p pe ni d x 8: Ne w Y or k Heart Ass ociati o n Classificati o n ................................ ....9 5
1 0. 9. A p pe n di x 9: Healt h Ec o n o mics .............................................................................9 6
1 0. 9. 1. T he Ka nsas Cit y Car di o m y o pat h y Q uesti o n naire O verall Sc ore .............9 6
1 0. 9. 2. E ur o Q o L 5 Di me nsi o ns 5 L e vels ( E Q- 5 D-5 L ) ...................................... 1 0 1
1 0. 9. 3. 1 2 -Ite m S h ort F or m S ur ve y ( S F- 1 2).......................................................1 0 4
1 0. 1 0. A p pe n di x 1 0 : Alter nati ve Meas ures D uri n g P u blic E mer ge ncies .....................1 0 7
1 0. 1 0. 1. Eli gi bilit y ..............................................................................................1 0 7
1 0. 1 0. 2. Tel e healt h Visits ...................................................................................1 0 7
1 0. 1 0. 3. Alter nati ve Facilities f or Safet y Assess me nts ......................................1 0 8
1 0. 1 0. 3. 1. La b orat or y  Testi n g..............................................................1 0 8
1 0 . 1 0. 3. 2. Ima gi n g ................................................................................1 0 9
1 0. 1 0. 3. 3. Electr ocar di o gra ms................................ ..............................1 0 9
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 2 0
1 0. 1 0. 4. St u d y  Inter ve nti o n ................................................................................1 0 9
1 0. 1 0. 5. H o me Healt h Visits ...............................................................................1 1 0
1 0. 1 0. 6. A d verse E ve nts a n d Seri o us A d verse E ve nts....................................... 1 1 0
1 0. 1 0. 7. Efficac y  Assess me nts ...........................................................................1 1 0
1 0. 1 0. 8. I n de pe n de nt O versi g ht C o m mittees .....................................................1 1 0
1 0. 1 1. A p pe n di x 1 1: A b bre viati o ns .............................................................................1 1 1
1 1. R E F E R E N C E S ............................................................................................................1 1 5
LI S T O F T A B L E S
Ta ble 1.
Pr ot oc ol -Re q uire d Safet y L a b orat or y Assess me nts .................................7 9
Ta ble 2.
Pr ot oc ol -Re q uire d Safet y L a b orat or y Assess me nts per mitte d at a 
l ocal la b orat or y.......................................................................................1 0 8
LI S T O F FI G U R E S
Fi g ure 1.
Scatter Pl ot of T T R Perce nt Sta bilizati o n vs Tafa mi dis: T T R M olar 
Rati o b y  Treat me nt i n St u d y B 3 4 6 1 0 4 0...................................................3 2
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 2 1
1. P R O T O C O L S U M M A R Y 
1. 1. S y n o psis 
S h ort Title: A st u d y t o assess t he s afet y a n d effic ac y of t af a mi dis i n C hi nese 
p artici p a nts wit h A T T R -C M
R ati o n ale
Tra nst h y reti n a myl oi d car di o m y o pat h y ( A T T R-C M) occ urs w he n tra nst h yreti n ( T T R) 
a m yl oi d fi brils i nfiltrate t he m yocar di u m, lea di n g t o de p osits of e xtracell ular a m y l oi d.  
De p ositi o n of tra nst h y reti n fi brils occ urs bet wee n t he m yocar dial cells a n d pr o d uces a 
t hic ke ni n g a n d stiffe ni n g of t he m yo c ar dial tiss ue.  T his i nfiltrati o n of t he m y ocar di u m 
res ults i n diast olic d ysf u ncti o n pr o gressi n g t o restricti ve car di o m yo pat h y , c o n gesti ve heart 
fail ure, a n d ulti mately deat h.  T here is a hi g h u n met nee d t o treat tra nst h yreti n a m yl oi d 
car di o m y o pat h y, w hic h is a life t hreate ni n g, rare disease.  O nly 6 0 C hi nese car diac 
a m yl oi d osis case re p orts were p u blis he d fr o m 2 0 0 2-2 0 1 7, a n d A T T R -C M is e xtre mel y  rarely 
re p orte d.1 -7  O ne of 6 0 cases was dia g n ose d as A T T R -C M, 6 2 of t he m were j ust s us pecte d 
o ne. 2
Tafa mi dis is c o nsi dere d as a disease m o dif y i n g t hera p y f or T T R a myl oi d diseases.  It bi n ds 
t o t he t h yr o xi ne bi n di n g sites o n t he T T R tetra mer, t here b y pre venti n g desta bilizati o n i nt o t he 
m o n o meric f or m w hic h ca n f or m a m yl oi d fi brils de p osite d i nt o t he e xtracell ular s pace.  
A T T R -C M is liste d i n 1 st C hi nese Rare Disease list release d i n 2 0 1 8 u n der I di o pat hic 
Car di o m y o pat h y cate g or y.  Base d o n C hi na re g ulat or y  re g ulati o n o n e nc o ura ge me nt f or rare 
disease me dicati o n de vel o p me nt, Pfizer pla ns t o bri d ge t he pi v otal st u d y  efficac y a n d safet y 
data a n d Ja pa nese p har mac o ki netic ( P K) data t o a p pl y  f or c o n diti o nal a p pr o val wit h a p ost 
a p pr o val c o m mit me nt st u d y  desi g n. 
S t u d y B 3 4 6 1 0 1 6 ( F x 1 A-1 0 5) was a P hase 1 st u d y of 2 0 m g of tafa mi dis me gl u mi ne P K i n 
mil d or m o derate he patic i m pair me nt partici pa nts a n d a ge, wei g ht, a n d ge n der -matc he d 
healt h y  v ol u nteers.  T he res ults i n dicate d d osa ge a dj ust me nt is n ot necessar y i n participa nts 
wit h mil d t o m o derate he patic i m pair me nt.  St u d y  B 3 4 6 1 0 0 9 was a P hase 1 st u d y t o e val uate 
t he safety, t olera bilit y , P K a n d p har mac o dy na mics ( P D) of P F -0 6 2 9 1 8 2 6 ( tafa mi dis 
me gl u mi ne) after si n gle oral a d mi nistrati o n of 2 0 m g a n d 4 0 m g  tafa mi dis me gl u mi ne s oft 
ca ps ules t o Ja pa nese a n d Wester n healt h y partici pa nts.  Mea n P K para meters a n d P D res ults 
( T T R perce nt sta bilizati o n) of Ja pa nese partici pa nts were si milar t o t h ose i n Wester n 
partici pa nts s u g gesti n g t hat t here are n o P K a n d P D differe nces base d o n et h nicit y .
T he p ote ntial f or e nz y m atic a n d tra ns p orter me diate d tafa mi dis dr u g - dr u g i nteracti o n ( D DI) 
was e val uate d at t he pr ojecte d cli nical tafa mi dis d oses of 2 0 m g/ da y  tafa mi dis me gl u mi ne 
a n d 6 1 m g/ da y  tafa mi dis free aci d d oses i n m ulti ple n o ncli nical a n d o ne cli nical dr u g-dr u g 
i nteracti o n ( D DI) st u dy ( B 3 4 6 1 0 1 8 [ F x 1 A - 1 0 9]).
Res ults fr o m t hese st u dies ha ve f o u n d t hat 
t he p ote ntial f or cli nicall y si g nifica nt P K dr u g-dr u g i nteracti o ns wit h tafa mi dis is l o w . 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 2 2
Base d u p o n t he T T R % s ta bilizati o n data fr o m St u d y  B 3 4 6 1 0 4 0, a P hase 1, ra n d o mize d, 
d o u ble -bli n d, cr oss o ver, asce n di n g d ose escalati o n st u d y  t o assess t he safet y a n d P K of 
tafa mi dis me gl u mi ne d oses greater t ha n 1 2 0 m g as oral s ol uti o n i n healt h y partici pa nts, 
tafa mi dis me gl u mi n e d oses of 2 0 a n d 8 0 m g  were use d i n t he i nter nati o nal P hase 3 pi v o tal 
st u d y B 3 4 6 1 0 2 8 . St u d y  B 3 4 6 1 0 2 8 was a P hase 3, m ultice nter, i nter nati o nal, 3-ar m, parallel 
desi g n, place b o -c o ntr olle d, ra n d o mize d st u d y wit h a 3 0 m o nt h d o u ble -bli n d treat me nt p hase, 
t o deter mi ne t he efficac y , safety, a n d t olera bilit y of tafa mi dis me gl u mi ne i n A T T R-C M 
patie nts wit h eit her varia nt or wil d -t ype T T R. A cli nicall y  rele va nt, statisticall y si g nifica nt 
( p = 0. 0 0 0 6) re d ucti o n of 3 0 % i n all-ca use m ortalit y a n d fre q ue nc y of car di o vasc ular 
(C V )-relate d h os pitalizati o ns at 3 0 m o nt hs was de m o nstrate d f or patie nts treate d wit h 
tafa mi dis me gl u mi ne c o m pare d t o t h ose treate d wit h place b o.  T his be nefit was f urt her 
reflecte d c o nsiste ntl y a n d r o b ustl y i n ke y sec o n dar y a n d e x pl orat or y a nal ys es.  Tafa mi dis 
treat me nt was ge nerall y safe a n d well t olerate d i n t he st u d y partici pa nt p o p ulati o n, wit h a n 
a vera ge a ge of 7 4, wit h fe w d ose re d ucti o ns a n d a si milar fre q ue nc y  of treat me nt-e mer ge nt 
a d verse e ve nts ( T E A E s) a n d seri o us T E A Es bet wee n t he treat ment gr o u ps .  T he maj orit y  of 
t he a d verse e ve nts (A Es ) were mil d or m o derate i n se verit y a n d disc o nti n uati o n d ue t o A Es, 
b ot h per ma ne nt a n d te m p orar y, were less c o m m o n i n t he tafa mi dis gr o u ps t ha n i n t he 
place b o gr o u p .  T he res ults of pi v otal P hase 3 st u d y  B3 4 6 1 0 2 8 de m o nstrate d t hat c o m para ble 
treat me nt effects were o bser ve d f or t he pri mar y a nal yses (all-ca use m ortalit y a n d t he 
fre q ue nc y of car di o vasc ular-relate d h os pitalizati o ns) a n d sec o n dar y a nalys es (i ncl u di n g T T R 
sta bilizati o n at M o nt h 1) w he n a nalyz e d b y d ose ( 2 0 m g a n d 8 0 m g).  P ost h oc a nal ys es of 
car diac bi o mar ker data pr o g n ostic of s ur vi val ( N T -pr o B N P) a n d C V relate d h os pitalizati o ns 
( Tr o p o ni n I) fa v or t he 8 0 m g d ose.  St u d y  B 3 4 6 1 0 2 8 e nr olle d 1 7 ( of 4 4 1) partici pa nts i n 
Ja pa n ( 5 partici pa nts i n t he place b o gr o u p, 2 partici pa nts i n t he tafa mi dis me gl u mi ne 2 0 m g  
gr o u p, te n partici pa nts i n t he tafa mi dis me gl u mi ne 8 0 m g gr o u p).  T he s u b-a nal ys is of
pri mar y  a n d ke y sec o n dar y e n d p oi nt data fr o m t hese Ja pa nese partici pa nts i n dicate n o 
a p pare nt tre n ds t hat de viate d fr o m t he o verall test p o p ulati o n .
A rece nt a nal ys is of a vaila ble s ur vi val data fr o m St u d y B 3 4 6 1 0 4 5, a n o n g oi n g, l o n g-ter m 
e xte nsi o n st u d y f or partici pa nts pre vi o usl y e nr olle d i n st u d y B 3 4 6 1 0 2 8, s u g gest a mea ni n gf ul 
1 0. 2 % re d ucti o n i n ris k of deat h ( Hazar d rati o 0. 8 9 7 6, 9 5 % CI  0. 5 7 1 1, 1. 4 1 0 8) i n patie nts o n 
8 0 m g c o m pare d t o 2 0 m g of tafa mi dis me gl u mi ne o ver t he l o n ger peri o d of treat me nt
( p = 0. 6 3 9 5).  T hese res ults s u p p orte d t he d ose rec o m me n dati o n of 8 0 m g tafa mi dis 
me gl u mi ne .
T hese p oi nts s u m mariz e t he e vi de nce s u p p orti n g t he e x pectati o n t hat t he tafa mi dis
me gl u mi ne cli nical pr ofile i n t he C hi nese p o p ulati o n will be c o nsiste nt wit h t he gl o bal 
p o p ulati o n a n d is lar gely deri ve d fr o m e x perie nce wit h Ja pa nese patie nts.
T o facilitate patie nt c o n ve nie nce , t he sp o ns or has de vel o pe d a si n gle 6 1 m g tafa mi dis free 
aci d (calle d as tafa mi dis i n t he te xts hereafter, P F -0 6 2 9 1 8 2 6) s oft ca ps ule , i nstea d of 4 2 0 m g  
tafa mi dis me gl u mi ne s oft gel ca ps ules ( o ne ca ps ule c o ntai ns 1 2. 2 m g tafa mi dis, t he acti ve 
p har mace utical i n gre die nt).  A si n gle 8 0 m g tafa mi dis me gl u mi ne s oft gel ca ps ule is 
tec h nically n ot feasi ble beca use of a c o nce ntrati o n -de pe n de nt gelli n g of tafa mi dis 
me gl u mi ne.  A bi oe q ui vale nce ( B E) stu d y , B 3 4 6 1 0 5 6, was c o n d ucte d a n d s h o we d 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 2 3
bi oe q ui vale nce bet wee n 8 0 m g ( 4 x 2 0 m g) tafa mi dis me gl u mi ne wit h 6 1 m g tafa mi dis at 
stea d y-state.
Tafa mi dis me gl u mi ne ca ps ule 2 0 m g o nce dail y has alrea d y  bee n a p pr o ve d i n t he E ur o pea n 
U ni o n f or t he treat me nt of Tr a nst h yreti n A m yl oi d P ol y ne ur o pat h y  (A T T R - P N) i n a d ult 
patie nts wit h sta ge 1 s y m pt o matic p ol y ne ur o pat h y i n 2 0 1 1.  In Ja pa n , tafa mi dis me gl u mi ne
2 0 m g s oft ca ps ule o nce dail y has als o bee n a p pr o ve d b y  t he Mi nistr y of Healt h, La b or a n d 
Welfare ( M H L W) t o dela y
t he peri p heral ne ur ol o gical i m pair me nt of tra nst h yreti n fa milial 
a m yl oi d p oly ne ur o pat h y i n Se pte m ber 2 0 1 3 , a n d tafa mi dis me gl u mi ne 4 x 2 0 m g s oft 
ca ps ule o nce dail y a p pr o ve d t o dela y t he pr o gressi o n of A T T R -C M i n Marc h 2 0 1 9.
Tafa mi dis me gl u mi ne 4 x 2 0 m g o nce dail y a n d tafa mi dis 6 1 m g ha ve bee n a p pr o ve d i n t he 
U nite d States i n Ma y 2 0 1 9 f or t he treat me nt of t he car di o my o pat h y of wil d t y pe or here ditar y 
tra nst h yreti n-me diate d a m y l oi d osis i n a d ults t o re d uce car di o vasc ular m ortalit y a n d 
car di o vasc ul ar-relate d h os pitalizati o n. T afa mi dis has bee n a p pr o ve d i n E ur o pe i n Fe br uar y 
2 0 2 0 f or t he treat me nt of A T T R -C M . I n C hi na, tafa mi dis me gl u mi ne ca ps ule 2 0 m g o nce 
dail y , wit h or wit h o ut f o o d, has alrea d y bee n a p pr o ve d f or t he treat me nt of A T T R - P N i n 
a d ult patie nts wit h sta ge 1 s y m pt o matic p ol y ne ur o pat h y i n Fe br uar y 2 0 2 0 ; 6 1 m g tafa mi dis 
s oft ca ps ule orall y  o nce dail y, wit h or wit h o ut f o o d , was a p pr o ve d i n Se pte m ber 2 0 2 0 f or t he 
treat me nt of A T T R -C M .
T he safet y pr ofile of tafa mi dis me gl u mi ne f or t he treat me nt of A T T R-C M has bee n e val uate d 
i n 3 7 7 A T T R-C M patie nts i n t he pi v otal P hase 3 St u d y  B 3 4 6 1 0 2 8 a n d its o n g oi n g l o n g-ter m 
e xte nsi o n ( LT E) St u d y B 3 4 6 1 0 4 5, as well as i n t he P hase 2 St u d y  B 3 4 6 1 0 2 5 a n d t he 
ass ociate d o n g oi n g L T E, St u d y B 3 4 6 1 0 2 6 ( data pro vi de d f or b ot h o n g oi n g L T Es t hr o u g h 
c ut off date of 0 1 A u g ust 2 0 1 8).  Tafa mi dis safet y data are als o prese nte d fr o m 1 7 P hase 1 
st u dies 3 4 8 healt h y partici pa nts, as well as a P hase 1 st u d y i n partici pa nts wit h he patic 
i m pair me nt.  A d diti o nal s u p p orti ve safet y data are pr o vi de d fr o m 5 cli nical st u dies (c ut off 
date 0 3 Ja n uar y 2 0 1 7) i n v ol vi n g A T T R- P N patie nts ( n = 1 3 7) a n d p ost -mar keti n g data (c ut off 
date 0 1 A u g ust 2 0 1 8), as well as safet y data fr o m tafa mi dis -treate d patie nts e nr olle d i n St u d y 
B 3 4 6 1 0 0 1 ( Tra nst h yr eti n -Ass ociate d A m yl oi d osis O utc o mes S ur ve y  [ T H A O S]; c ut off date 
0 1 A u g ust 2 0 1 8).  
Tafa mi dis was s h o w n t o be safe a n d well -t olerate d.  N o a d verse dr u g reacti o ns were 
i de ntifie d wit h tafa mi dis a d mi nistrati o n i n t he A T T R-C M patie nt p o p ulati o n. 
C hi na Healt h A ut h orit y  has pr o vi de d g ui da nce o n t he desi g n of t he p ost a p pr o val 
c o m mit me nt st u d y.  A pr os pecti ve o bser vati o n al, si n gle-ar m c o h ort st u d y was s u g geste d t o 
e val uate a d verse e ve nts. T he st u d y  is to c ollect T E A Es o bser v e d i n pre vi o us A T T R -C M 
st u dies, defi ne d as A Es wit h a s mall n u meric hi g her i nci de nce o bser ve d i n t he tafa mi dis 
treat me nt gr o u p c o m pare d wit h place b o; n ote d as A Es of cli nical i m p orta nce f or treat me nt 
wit h tafa mi dis.
T he p ur p ose of t his st u d y is t o c ollect safet y, descri pti ve efficac y , P K a n d P D of tafa mi dis 
data i n C hi nese A T T R -C M patie nts, f oll o wi n g t he a p pr o val of tafa mi dis 6 1 m g s oft ca ps ule 
orall y  o nce daily, wit h or wit h o ut f o o d , f or A T T R-C M i n dicati o n i n C hi na .
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 2 4
O bjecti ves, Esti m a n ds, a n d E n d p oi nts
O bjecti ves
Esti m a n ds
E n d p oi nts
Pri m ar y: 
Pri m ar y:
Pri m ar y: 

T o c haracterize t he safet y pr ofile 
of tafa mi dis o nce dail y f or t he 
treat me nt of C hi nese A T T R -C M 
patie nts i n cli nical practice.

N ot a p plica ble.

I nci de nce of treat me nt-e mer ge nt 
a d verse e ve nts.
Sec o n d ar y: 
Sec o n d ar y: 

T o c haracterize t he descri pti ve 
efficac y of tafa mi dis o nce dail y i n 
C hi nese A T T R -C M patie nts 

T o c haracterize tafa mi dis P D i n 
C hi nese A T T R -C M patie nts.

T o c haracterize t he i mpact o n
q ualit y of life of tafa mi dis o nce 
dail y f or t he treat me nt of C hi nese 
A T T R -C M patie nts .

T o c haracterize tafa mi dis P K i n 
C hi nese A T T R -C M patie nts.

N ot a p plica ble.

Assess me nt of 6 -M W T, N T -pr o 
B N P at sc he d ule d visits.

T T R sta bilizati o n a n d T T R 
c o nce ntrati o n at Baseli ne ( pre 
d osi n g) o n Da y 1, at M o nt hs 1, 6, 
a n d 1 2 ( or E n d of Treat me nt 
( E O T)). 

Ka nsas Cit y Car di o m y o pat h y 
Q uesti o n naire o verall s u m mar y 
sc ores, E Q-5 D - 5 L i n de x sc ores a n d 
E Q -5 D V A S sc ores, 1 2 -Ite m S h ort 
F or m S ur ve y ( S F - 1 2) sc ores, at Da y 
1, M o nt hs 6, 1 2 ( or E n d of 
Treat me nt ( E O T)).

P K: plas ma c o nce ntrati o ns of 
tafa mi dis at M o nt hs 1, 6, a n d 1 2 ( or 
E O T). 
O ver all Desi g n
T his is a nati o nal, m ulti -ce nter, si n gle -ar m st u d y, o pe n -la bel t o patie nts wit h s ym pt o matic 
A T T R -C M w h o are tafa mi dis naï ve.  T his st u d y  is t o o btai n safet y, descri pti ve efficac y, P K 
a n d P D data f or tafa mi dis 6 1 m g s oft ca ps ule orall y  o nce daily, wit h or wit h o ut f o o d.  
Partici pa nts wit h Ne w Year Heart Ass ociati o n ( N Y H A ) class greater t ha n or e q ual t o III 
s h o ul d n ot ma ke u p m ore t ha n 1/ 3 of all e nr olle d partici pa nts 
I n vesti gat ors will c o nfir m t he eli gi bilit y of eac h partici pa nt t o meet i ncl usi o n/e xcl usi o n 
criteria. Partici pa nt eli gi bilit y f or partici pati o n i n t he st u d y will recei ve tafa mi dis 6 1 m g 
o nce dail y or 1 2 m o nt hs f oll o wi n g t he assess me nt as t he scree ni n g a n d baseli ne, m o nt h 1, 3, 
6, 9 a n d 1 2 visits ( or E n d of Treat me nt visit ).
Patie nts will c o nti n ue t o recei ve t heir c urre nt me dicati o ns a n d all ot her sta n dar d care f or t heir 
disease.  T he use of per mitte d c o nc o mita nt me dicati o n m ust be i n acc or da nce wit h a p pr o ve d 
tafa mi dis pac ka ge i nsert.  C o nc o mita nt me dicati o n n ot per mitte d i n t his st u d y is descri be d i n 
Secti o n 6. 5 .
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 2 5
Partici pa nts will c o m plete pr ot oc ol re q uire d tests a n d pr oce d ures as descri be d i n sc he d ule of 
acti vities. A fi nal st u d y  re p ort will be c o m plete d a p pr o xi matel y 3 years after t he date of t he 
first tafa mi dis patie nt e nr oll me nt i n t he st u d y.
Sc he d u le d Visits: Da y 1, M o nt hs 1, 3, 6, 9, 1 2 ( or E n d of Treat me nt ) a n d a P ost -treat me nt 
f oll o w- u p.
N u m ber of P artici p a nts
A t least 5 3 partici pa nts nee d t o be treate d.  Refer t o Secti o n 9. 2 f or detaile d i nf or mati o n o n 
sa m ple size deter mi nati o n.
I nter ve nti o n Gr o u ps a n d D ur ati o n
T otal d urati o n of st u d y  partici pati o n f or eac h partici pa nt recei vi n g tafa mi dis o nce daily wit h 
a p pr o ve d d ose is 1 2 m o nt hs ( or Earl y St u d y Disc o nti n uati o n).  F oll o w -u p visit dates s h o ul d 
be base d o n t he date of t he Baseli ne visit.
D at a M o nit ori n g C o m mittee: 
T he st u d y  will n ot use an d ata m o nit ori n g c o m mittee ( D M C).  
St atistic al Met h o ds
In or der t o attai n a n 8 0 % pr o ba bilit y of o bser vi n g at least 1 partici pa nt ha vi n g a n e ve nt f or 
T E A E s wit h i nci de nce rate of 3 %, at least 5 3 partici pa nts nee d t o be treate d.
Descri pti ve a nal ys es will be perf or me d.
1. 2. Sc he m a
N ot a p plica ble.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 2 6
1. 3. Sc he d ule of Acti vities ( S o A)
T he S o A ta ble pr o vi des a n o ver vie w of t he pr ot oc ol visits a n d pr oce d ures.  Refer t o t he 
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S secti o n of t he pr ot oc ol f or detaile d 
i nf or mati o n o n eac h pr oce d ure a n d assess me nt re q uire d f or c o m plia nce wit h t he pr ot oc ol. 
T he i n vesti gat or ma y  sc he d ule visits ( u n pla n ne d visits) i n a d diti o n t o t h ose liste d i n t he S o A 
ta ble, i n or der t o c o n d uct e val uati o ns or assess me nts re q uire d t o pr otect t he well-bei n g of t he 
partici pa nt. 
Pr oce d ure/ Assess me nt
Scree ni n g
B aseli ne 
visit 
M o nt h
a
D a y -4 5 t o 
D a y 0
D a y 1
1
(± 1
wee
k)
3
(Tel
e p h
o ne
visit
± 2 
wee
ks )
6
(± 2 
wee k
s)
9
(Tel
e p h
o ne
visit
± 2 
wee
ks)
1 2
(± 2 wee ks)
( or wit h i n 2 
wee ks after
E n d of 
T re at me nt )
P ost -
tre at me nt
f oll o w-u p
(2 8 + 7 d a ys 
after l ast
d ose )
I nf or me d C o nse nt
X
Me dic al Hist or y 
X
Re vie w e ntr a nce criteri a
X  
X
F ull p h ysic al e x a mi n ati o n
X
Brief p h ysic al e x a mi n ati o n
X  
X
X 
X
Hei g ht
X
Wei g ht
X  
X  
X  
X
X
1 2 Le a d E C G
X  
X  
X
X 
X
Vit al si g ns b
X  
X  
X  
X
X
Ec h oc ar di o gr a m
X
X
X 
T iss ue bi o ps y or r a di o n ucli de 
b o ne sci nti gr a p h y  ( 9 9 m Tc -
P Y P) c
X
L a b or at or y s a m ples
H e m at ol o g y
X
X  
X
X
Ser u m C he mistr y
X
X  
X
X
C o a g ul ati o n (I N R, P T , 
A P T T, FI B )
X
X  
X
X
T h yr oi d -sti m ul ati n g h or mo n e , 
t ot al T h yr o xi ne 4 a n d free 
T h yr o xi ne 4
X  
X  
X
X
Reti n ol Bi n di n g Pr otei n
X
X
X
C o ntr ace pti o n c hec k d
X
X  
X  
X  
X
X
P re g n a nc y test ( o nl y f or 
W O C B P )e
X
X
X
Ser ol o g y ( H Bs A g, a nti - H C V,
a nti -T P a n d a nti -HI V)
X
Ser u m/ uri ne test f or pri m ar y 
a m yl oi d osis ( A L)
X
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 2 7
Pr oce d ure/ Assess me nt
Scree ni n g
B aseli ne 
visit 
M o nt h
a
D a y -4 5 t o 
D a y 0
D a y 1
1
(± 1
wee
k)
3
(Tel
e p h
o ne
visit
± 2 
wee
ks )
6
(± 2 
wee k
s)
9
(Tel
e p h
o ne
visit
± 2 
wee
ks)
1 2
(± 2 wee ks)
( or wit h i n 2 
wee ks after
E n d of 
T re at me nt )
P ost -
tre at me nt
f oll o w-u p
(2 8 + 7 d a ys 
after l ast
d ose )
M ass s pectr o metr y /
Im m u n o hist oc he mistr y
f
X
G e n ot y pi n g g
X
Uri n al ysis
X
X  
X
X
N T – pr o B N P, Tr o p o ni n I
X
X
X
6- M W T
X
X
X
T T R st a biliz ati o n, T T R 
c o nce ntr ati o n h
X  
X  
X
X
T af a m i dis c o nce ntr ati o nsi
X  
X
X
K C C Q j
X
X 
X
E Q -5 D -5 L k
X
X 
X
S F -1 2 k
X
X 
X
N Y H A cl assific ati o n
X  
X
X 
X
C o nc o m it a nt tre at me nts
X  
X  
X  
X  
X  
X  
X
S eri o us a n d n o nseri o us a d verse 
e ve nt m o nit ori n g
X  
X  
X  
X  
X  
X  
X
X
H os pit aliz ati o n deter m i n ati o n
X  
X  
X  
X  
X  
X
D oc u me nt ati o n of vit al st at us
X  
X  
X  
X  
X  
X
Rec or d ti m e of d osi n g
X  
X  
X
X
Rec or d d osi n g a d here nce
X  
X
X
Dis pe nse i n vesti g ati o n al dr u gs
X  
X  
X
a.
Visits, if a p plica ble, are t y picall y defi ne d wit h res pect t o t he Baseli ne visit a n d i n acc or da nce wit h 
e x pectati o ns o n t he sta n dar d of care a n d/ or  re q uire d pr oce d ures f or t he st u d y.
b.
S y st olic a n d diast olic bl o o d press ure (se mis u pi ne at least 5 mi n utes pri or t o assess me nt). p ulse rate, 
res pirat or y rate a n d b o d y te m perat ure
c.
Bi o ps y or ra di o n ucli de b o ne sci nti gra p h y ( 9 9 m Tc-P Y P) f or a m yl oi d d oc u me ntati o n m ust be perf or me d at 
Scree ni n g or ha ve bee n perf or me d a n d d oc u me nte d wit hi n 5 years of e nr oll me nt. If greater t ha n 5 years, 
bi o ps y or ra di o n ucli de b o ne sci nti gra p h y ( 9 9 m Tc -P Y P) m ust be re peate d at t he i n vesti gati ve site . 
d.
Refer t o A p pe n di x 4 f or C o ntrace pti ve G ui da nce a n d C ollecti o n of Pre g na nc y I nf or mati o n.
e.
F or w o m e n of c hil d beari n g p ote ntial. R efer t o A p pe n di x 4 f or W o m a n of C hil d beari n g P ote ntial 
( W O C B P).
f.
F or t h ose a bse nce of a varia nt T T R ge n ot y pe, a bse nce of ra di o n ucli de b o ne sci nti gra p h y ( 9 9 m Tc -P Y P) 
a n d prese nce of a m yl oi d de p osits i n bi o ps y tiss ue.
g.
Re peat n ot re q uire d if t here is d oc u me ntati o n of ge n ot y pi n g res ult c o nfir mi n g t he T T R ge ne m utati o n 
wit hi n 5 years of e nr oll me nt.
h.
T T R sta bilizati o n a n d T T R c o nce ntrati o n: baseli ne ( Da y 1) sa m ple: c ollect pre -d ose d uri n g t he cli nic visit.  
M o nt h 1 sa m ple: c ollect pre -d ose a n d at 3 h o urs ( ± 1. 5 h o urs ) p ost-d ose . M o nt h 6 sa m ple: c ollecte d at 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 2 8
Pr oce d ure/ Assess me nt
Scree ni n g
B aseli ne 
visit 
M o nt h
a
D a y -4 5 t o 
D a y 0
D a y 1
1
(± 1
wee
k)
3
(Tel
e p h
o ne
visit
± 2 
wee
ks )
6
(± 2 
wee k
s)
9
(Tel
e p h
o ne
visit
± 2 
wee
ks)
1 2
(± 2 wee ks)
( or wit h i n 2 
wee ks after
E n d of 
T re at me nt )
P ost -
tre at me nt
f oll o w-u p
(2 8 + 7 d a ys 
after l ast
d ose )
7 h o urs ( ± 2. 5 h o urs) p ost -d ose . M o nt h 1 2 sa m ple: c ollect at 1 h o ur ( ± 3 0 mi n utes) p ost -d ose , or E n d of 
Treat me nt sa m ple: c ollect at ti me d uri n g t he cli nic visit.  Please refer t o Secti o n 8. 6 f or details.
i.
Tafa mi dis c o nce ntrati o ns: M o nt h 1 tafa mi dis c o nce ntrati o n sa m ple: c ollect pre -d ose a n d at 3 h o urs 
( ± 1. 5 h o urs) p ost -d ose; M o nt h 6 tafa mi dis c o nce ntrati o n sa m ple: c ollect at 7 h o urs ( ± 2. 5 h o urs) p ost -d ose; 
M o nt h 1 2 sa m ple: c ollect at 1 h o ur ( ± 3 0 mi n utes) p ost -d ose , or E n d of Treat me nt sa m ple: c ollect at ti me 
d uri n g t he cli nic visit .  Please refer t o Sect i o n 8. 5 f or details.
j.
Ka nsas Cit y Car di o m y o pat h y Q uesti o n naire ( K C C Q) s h o ul d be c o m plete d bef ore t he E Q -5 D -5 L. 
k.
E ur o Q o L -5 Di me nsi o ns ( E Q -5 D -5 L) a n d S F-1 2 t o be c o m plete d after t he K C C Q.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 2 9
2. I N T R O D U C TI O N
2. 1. St u d y R ati o n ale 
A T T R -C M is liste d i n 1 st C hi nese Rare Disease list release d i n 2 0 1 8 u n der I di o pat hic 
Car di o m y o pat h y cate g or y.  Base d o n C hi na re g ulat or y  re g ulati o n o n e nc o ura ge me nt f or rare 
disease me dicati o n de vel o p me nt, Pfizer pla ns t o bri d ge t he pi v otal efficac y a n d safet y data 
a n d Ja pa nese p har mac o ki netic ( P K) data t o a p pl y  f or c o n diti o nal a p pr o val wit h a p ost 
a p pr o val c o m mit me nt st u d y desi g n. 
Tafa mi dis is a s mall m olec ule t hat has bee n de m o nstrate d t o sta bilize tra nst h yreti n. 
me gl u mi ne 2 0 m g s oft ca ps ule ta ke n orall y o nce dail y has alrea d y  bee n a p pr o ve d i n t he 
E ur o pea n U ni o n f or t he treat me nt of Tra nst h yreti n A m yl oi d P ol y ne ur o pat h y ( A T T R - P N) i n 
a d ult patie nts wit h sta ge 1 s ym pt o matic p ol y ne ur o pat h y i n 2 0 1 1.  In Ja pa n , tafa mi dis
me gl u mi ne 2 0 m g s oft ca ps ule o nce dail y has als o bee n a p pr o ve d b y t he Mi nistr y  of Healt h, 
La b or a n d Welfare ( M H L W) t o dela y  t he peri p heral ne ur ol o gical i m pair me nt of tra nst h yreti n 
fa milial a m yl oi d p oly ne ur o pat h y i n Se pte m ber 2 0 1 3 , a n d tafa mi dis me gl u mi ne 4 x 2 0 m g
o nce dail y a p pr o ve d t o dela y t he pr o gressi o n of Tra nst hyr eti n A m yl oi d Car di o m y o pat h y 
( AT T R -C M) i n Marc h 2 0 1 9.  Tafa mi dis me gl u mi ne 4 x 2 0 m g o nce dail y a n d tafa mi dis 6 1 
m g ha ve bee n a p pr o ve d i n t he U nite d States i n Ma y 2 0 1 9 f or t he treat me nt of t he 
car di o m y o pat h y of wil d t y pe or here ditar y tra nst h yreti n-me diate d a m yl oi d osis i n a d ults t o 
re d uce car di o vasc ular m ortalit y a n d car di o vasc ular-relate d h os pitalizati o n. Tafa mi dis has 
bee n a p pr o ve d i n E ur o pe i n Fe br uar y  2 0 2 0 f or t he treat me nt of A T T R -C M. I n C hi na, 
tafa mi dis me gl u mi ne ca ps ule 2 0 m g o nc e dail y has alrea d y bee n a p pr o ve d f or t he treat me nt 
of A T T R -P N i n a d ult patie nts wit h sta ge 1 s y m pt o matic p ol y ne ur o pat h y  in Fe br uar y  2 0 2 0; 
6 1 m g tafa mi dis s oft ca ps ule orall y  o nce dail y was a p pr o ve d i n Se pte m ber 2 0 2 0 f or t he 
treat me nt of A T T R-C M .
T he p ur p o se of t he st u d y is t o c ollect safety, descri pti ve efficac y , P K , a n d P D of tafa mi dis 
data i n C hi nese A T T R -C M patie nts, f oll o wi n g t he a p pr o val of tafa mi dis 6 1 m g f or A T T R-
C M i n dicati o n i n C hi na.
2. 2. B ac k gr o u n d 
A T T R -C M occ urs w he n tra nst h y reti n ( T T R) a myl oi d fi b rils i nfiltrate t he m y ocar di u m, 
lea di n g t o de p osits of e xtracell ular a myl oi d.  De p ositi o n of tra nst h y reti n fi brils occ urs 
bet wee n t he m y o car dial cells a n d pr o d uces a t hic ke ni n g a n d stiffe ni n g of t he m y ocar dial 
tiss ue.  T his i nfiltrati o n of t he m yocar di u m r es ults i n diast olic d ysf u ncti o n pr o gressi n g t o 
restricti ve car di o my o pat h y, c o n gesti ve heart fail ure, a n d ulti mately deat h.  T here is a h i gh 
u n met nee d t o treat tra nst h yreti n a m yl oi d car di o m yo pat h y , w hic h is a life t hreate ni n g, rare 
disease .  O nl y 6 0 C hi nes e car diac a m yl oi d osis case re p orts were p u blis he d fr o m 2 0 0 2- 2 0 1 7, 
a n d A T T R -C M is e xtre mel y  rarel y re p orte d.1 -7  O ne of 6 0 cases w as dia g n ose d as A T T R -
C M, 6 2 of t he m were j ust s us pecte d o ne. 2
C hi na Healt h A ut h orit y  has release d g ui da nce o n P A C st u d y  desi g n of t he p ost a p pr o val 
c o m mit me nt st u d y.  A pr os pecti ve o bser vati o n st u d y , si n gle-ar m c o h ort st u d y is s u g geste d t o 
e val uate a d verse e ve nts a n d ot her relate d safet y  ris ks.  T he st u d y  is to c ollect T E A Es t hat 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 3 0
were o bser v e d i n pre vi o us A T T R -C M st u dies, defi ne d as A Es wit h a s mall n u meric hi g her 
i nci de nce o bser ve d i n t he tafa mi dis treat me nt gr o u p c o m pare d wit h place b o; n ote d as A Es of 
cli nical i m p orta nce f or treat me nt wit h tafa mi dis.
2. 2. 1. Cli nic al O ver vie w
Tafa mi dis is a n oral s mall m olec ule, u n der de vel o p me nt b y  Pfizer, as a disease m o dif yi n g 
t hera p y f or T T R a myl oi d diseases.  It bi n ds t o t he t h y r o xi ne bi n di n g sites o n t he T T R 
tetra mer, t here by pre ve nti n g desta bilizati o n i nt o t he m o n o meric f or m w hic h ca n de p osit as 
a m yl oi d fi brils i n t he e xtracell ular s pace.  It has bee n de m o nstrate d t o bi n d selecti vely t o 
T T R (als o referre d t o as pre- al b u mi n) i n h u ma n bl o o d a n d sl o w fi bril f or mati o n i n vitr o.  I t 
bi n ds t o t he 2 t h y r o xi ne bi n di n g sites wit h ne gati ve c o o perati vit y, e x hi biti n g diss ociati o n 
c o nsta nts of 2 n M [ K d 1] a n d 1 5 4 n M [ K d 2] a n d ki neticall y sta bilizi n g t he T T R tetra mer w he n 
b o u n d ( Se kiji ma 2 0 0 9). 3
St u d y  F x 1 A-1 0 5 ( B 3 4 6 1 0 1 6) was a P hase 1 st u d y of tafa mi dis me gl u mi ne P K i n mil d or 
m o derate he patic i m pair me nt partici pa nts a n d a ge, wei g ht, a n d ge n der -matc he d healt h y  
v ol u nteers.  T he res ults i n dicate d d osa ge a dj ust me nt is n ot necessar y  i n partici pa nts wit h 
mil d t o m o derate he patic i m pair me nt.  St u d y  B3 4 6 1 0 0 9 was a P hase 1 St u d y t o e val uate t he 
safety, t olera bilit y, P K a n d p har mac o d y n a mics ( P D) of P F-0 6 2 9 1 8 2 6 ( tafa mi dis me gl u mi ne) 
after si n gle oral a d mi nistrati o n of 2 0 m g a n d 4 0 m g tafa mi dis me gl u mi ne s oft ca ps ules t o 
Ja pa nese a n d Wester n healt h y partici pa nts.  Mea n P K para meters a n d P D res ults ( T T R 
perce nt sta bilizati o n) of Ja pa nese partici pa nts were si milar t o t h ose i n Wester n partici pa nts 
t h us s u g gesti n g n o si g nifica nt et h nic differe nces i n P K a n d P D.
T he p ote ntial f or e nz y m atic a n d tra ns p orter me diat e d tafa mi dis dr u g-dr u g i nteracti o n ( D DI) 
was e val uate d at t he pr ojecte d cli nical tafa mi dis d oses of 2 0 m g/ da y  tafa mi dis me gl u mi ne 
a n d 6 1 m g/ da y  tafa mi dis free aci d (calle d as tafa mi dis i n t he te xts hereafter) d oses i n 
m ulti ple n o ncli nical a n d o ne cli nical dr u g -dr u g i nteracti o n ( D DI) st u d y  ( F x 1 A- 1 0 9 
[ B 3 4 6 1 0 1 8]).  Res ults fr o m t hese st u dies ha ve f o u n d t hat t he p ote ntial of cli nicall y 
si g nifica nt P K dr u g-dr u g i nteracti o ns wit h tafa mi dis is l o w. 
St u d y  F x - 0 0 2 (B 3 4 6 1 0 1 5 ) was a P hase 1 st u d y  desi g ne d t o e val uate t he safet y, t olera bility, 
a n d p har mac o ki netics of orall y  a d mi nistere d tafa mi dis i n healt h y male a n d fe male v ol u nteers 
at si n gle d oses u p t o 1 2 0 m g a n d 3 m ulti ple escalati n g d oses ( 1 5, 3 0 a n d 6 0 m g) a d mi nistere d 
as s ol uti o n i n c o m paris o n t o place b o o nce dai l y o ver 1 4 da ys.  St u d y F x 1 A-1 0 9 was a 
P hase 1 st u d y  i n healt h y v ol u nteers desi g ne d t o e val uate t he c yt oc hr o me P 4 5 0 i n d ucti o n 
p ote ntial of tafa mi dis 2 0 m g a d mi nistere d f or 1 4 da y s.  I n F x-0 0 2, t he mea n (sta n dar d 
de viati o n) ma xi m u m o bser ve d dr u g c o nce ntratio n ( C ma x ) val ue o n Da y  1 4 f or t he 6 0 m g 
s ol uti o n was 4. 4 0 ( 1. 1 6) g/ m L.  T he mea n (sta n dar d de viati o n) C ma x o n Da y  1 4 f or t he 
2 0 m g ca ps ule was 2. 6 6 ( 0. 5 5) g/ m L i n F x 1 A- 1 0 9.
T here were n o d ose -li miti n g safety or t olera bilit y iss ues n ote d d uri n g t he P hase 1 pr o gra m i n 
healt h y  partici pa nts u p t o a si n gle d ose of 4 8 0 m g or m ulti ple d oses u p t o 6 0 m g.  F urt her, a 
si n gle oral d ose of 2 0 m g tafa mi dis was well t olerate d by partici pa nts wit h m o derate or mil d 
he patic i m pair me nt.  D uri n g St u d y  B 3 4 6 1 0 4 5, 2 patie nts ex perie nce d a n ac ute o ver d ose. 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 3 1
B ot h i n v ol ve d t he acci de ntal i n gesti o n of a si n gle tafa mi dis d ose of 1 6 0 m g wit h o ut t he 
occ urre nce of a n y ass ociate d a d verse e ve nts .
St u d y  B 3 4 6 1 0 4 0 was a P hase 1, ra n d o mize d, d o u ble -bli n d, cr oss o ver, asce n di n g d ose 
escalati o n st u d y t o assess t he safety a n d p har mac o ki netics of tafa mi dis d oses greater t ha n 
1 2 0 m g as oral s ol uti o n i n healt h y partici pa nts.  Si n gle d oses of tafa mi dis me gl u mi ne u p t o 
4 8 0 m g were well t olerate d i n t he st u d y  p o p ulati o n of healt h y a d ult Asia n me n.
T he tra nst hyreti n ( T T R) % sta bilizati o n data fr o m St u d y  B 3 4 6 1 0 4 0 (Fi g ure 1 ) s u g gest t hat a 
platea u is ac hie ve d as t he m olar rati o ( M R) of tafa mi dis: T T R plas ma c o nce ntrati o n 
i ncreases.  Base d u p o n t he data a vaila ble pri or t o c o n d ucti n g St u d y B 3 4 6 1 0 4 0, it was 
belie ve d t hat e x p os ures ac hie ve d f oll o wi n g a tafa mi dis d ose of 2 0 m g o nce dail y  ( Q D) were 
s ufficie nt t o a p pr oac h t he T T R % sta bilizati o n platea u.  T he data fr o m St u d y B 3 4 6 1 0 4 0 
s u g gest t hat d oses hi g her t ha n 2 0 m g pr o vi de a greater de gree of sta bilizati o n, as meas ure d 
b y  t he
  W hile t he l o n g-ter m ris k-be nefit of d oses hi g her 
t ha n 2 0 m g Q D is u n k n o w n, it is reas o na ble t o p ost ulate t hat greater T T R sta bilizati o n has 
t he p ote ntial t o pr o vi de a d diti o nal efficac y.
I n or der t o calc ulate m olar rati os at vari o us tafa mi dis e x p os ures, a T T R c o nce ntrati o n m ust 
be ass u me d.  Mea n T T R c o nce ntrati o ns o bser ve d at baseli ne i n St u d y  F x-0 0 5 ( B3 4 6 1 0 2 0)
( 2 4. 7 m g/ d L) a n d i n patie nts wit h V 1 2 2I m utati o ns i n St u d y F x 1 B- 2 0 1 ( 1 3. 5 m g/ d L) a n d t he 
Tra nst h yreti n A m yl oi d Car diac St u d y ( T R A C S) ( 1 4. 9 m g/ d L) are ass u me d f or t he 
calc ulati o ns t hat f oll o w: a 2 0 m g Q D tafa mi dis d ose at stea d y state pr o d uces a me a n M R i n 
t he ra n ge of 1. 2 t o 3. 2 fr o m mea n mi ni m u m dr u g c o nce ntrati o n at stea d y state ( Cmi n,ss ) t o 
ma xi m u m dr u g c o nce ntrati o n at stea d y state ( C ma x,ss ), w hic h is bel o w t he platea u re gi o n of 
t he data de picte d i n (Fi g ure 1 ).  Mea n Cmi n,ss t o Cma x,ss f oll o wi n g tafa mi dis d oses of 8 0 m g are 
e x pecte d t o pr o d uce M R val ues of 3. 5 t o 9. 6, w hic h are a p pr oac hi n g or o n t he platea u re gi o n 
of T T R % sta bilizati o n.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)
C CI

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 3 2
Fi g ure 1 .
Sc atter Pl ot of T T R Perce nt St a biliz ati o n vs T af a mi dis: T T R M ol ar R ati o 
b y Tre at me nt i n St u d y B 3 4 6 1 0 4 0
A b bre viati o ns: T T R = tra nst h yreti n; Q D = o nce dail y.
S o urce: B 3 4 6 1 0 4 0 C S R Fi g ure 1 4. 4. 7. 2. 1.
Base d u p o n t he T T R % sta bilizati o n data, tafa mi dis me gl u mi ne d oses of 2 0 a n d 8 0 m g were 
use d i n t he i nter nati o nal P hase 3 pi v otal st u d y  B 3 4 6 1 0 2 8.
St u d y  B 3 4 6 1 0 2 8 was a P hase 3, m ultice nter, i nter nati o nal, 3-ar m, parallel desi g n, place b o -
c o ntr olle d, ra n d o mize d st u d y wit h a 3 0 m o nt h do u ble -bli n d treat me nt p hase, t o deter mi ne t he 
efficac y, safety, a n d t olera bilit y of tafa mi dis me gl u mi ne i n A T T R -C M patie nts wit h eit her 
varia nt or wil d -t ype T T R.  A cli nicall y  rele va nt, statisticall y si g nifica nt ( p = 0. 0 0 0 6) re d ucti o n
of 3 0 % i n all-ca use m ortalit y a n d fre q ue nc y of C V-relate d h os pitalizati o ns at 3 0 m o nt hs was 
de m o nstrate d f or patie nts treate d wit h tafa mi dis me gl u mi ne c o m pare d t o t h ose treate d wit h 
place b o.  T his be nefit was f urt her reflecte d c o nsiste ntl y a n d r o b ustl y i n ke y sec o n dar y a n d 
e x pl orat or y a nal ys es.  Tafa mi dis treat me nt was ge nerall y safe a n d well t olerate d i n t he st u d y 
p artici pa nt p o p ulati o n, wit h a n a vera ge a ge of 7 4, wit h fe w d ose re d ucti o ns a n d a si milar 
fre q ue nc y of T E A Es a n d seri o us T E A Es bet wee n t he treat me nt gr o u ps.  T he maj orit y  of t he 
A Es were mil d or m o derate i n se verit y a n d disc o nti n uati o n d ue t o A Es, b ot h per ma ne nt a n d
te m p orar y, were less c o m m o n i n t he tafa mi dis gr o u ps t ha n i n t he place b o gr o u p.  I n St u d y 
B 3 4 6 1 0 2 8 , p ost h oc a nal yses of car diac bi o mar ker data pr o g n ostic of s ur vi val ( N T-pr o B N P) 
a n d C V relate d h os pitalizati o ns ( Tr o p o ni n I) s u g gest differe ntiati o n bet wee n t he 8 0 m g a n d 
2 0 m g d oses a n d a n a d va nta ge of t he 8 0 m g d ose c o m pare d t o 2 0 m g.  C o m bi ne d wit h 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 3 3
curre nt a nal ys es of t he s ur vi val data of St u d y  B 3 4 6 1 0 4 5, B3 4 6 1 0 2 8’s o n g oi n g e xte nsi o n 
st u d y, 8 0 m g tafa mi dis me gl u mi ne was rec o m me n de d. T o facilitate patie nt c o n ve nie nce , t he 
s p o ns or has de vel o pe d a si n gle 6 1 m g  tafa mi dis (as t he free aci d, P F -0 6 2 9 1 8 2 6 ) s oft ca ps ule, 
i nstea d of 4 2 0 m g tafa mi dis me gl u mi ne s oft ge l ca ps ules i n or der.  A bi oe q ui vale nce ( B E) 
st u d y, B 3 4 6 1 0 5 6, was c o n d ucte d a n d s h o we d bi oe q ui vale nce res ults bet wee n 8 0 m g 
tafa mi dis me gl u mi ne wit h 6 1 m g tafa mi dis. Details o n j ustificati o n f or d ose of 8 0 m g ( 4 x 
2 0 m g) a n d de vel o p me nt of its bi oe q ui vale n t si n gle ca ps ule of 6 1 m g tafa mi dis is prese nte d 
i n Secti o n 4. 3 .  Pfizer c o nsi ders 6 1 m g tafa mi dis o nce dail y ( bi oe q ui vale nt t o 8 0 m g [ 4 x 2 0 
m g] tafa mi dis me gl u mi ne) as t he rec o m me n de d d ose f or patie nts wit h A T T R-C M.
T he pri mar y  a nalys is use d a hierarchical c o m bi nati o n of all -ca use m ortalit y a n d fre q ue nc y  of 
C V -relate d h os pitalizati o ns ( w hic h is defi ne d as t he n u m ber of ti mes a patie nt is h os pitalize d 
[ie, a d mitte d t o a h os pital] f or C V-relate d m or bi dit y) o ver t he d urati o n of t he trial, a p plyi n g 
t he meth o d of Fi n kelstei n -Sc h oe nfel d.
A cli nicall y  rele va nt, statisticall y si g nifica nt ( p = 0. 0 0 0 6) re d ucti o n of 3 0 % i n all-ca use 
m ortalit y  a n d fre q ue nc y of C V-relate d h os pitalizati o ns at 3 0 m o nt hs was de m o nstrate d f or 
patie nts treate d wit h tafa mi dis me gl u mi ne c o m pare d t o t h ose treate d wit h place b o.  T his 
be nefit was f urt her reflecte d c o nsiste ntl y a n d r o b ustl y i n ke y sec o n dar y a n d e x pl orat or y 
a nal ys es. 
St u d y  B 3 4 6 1 0 2 8 e nr olle d 1 7 ( of 4 4 1) partici pa nts i n Ja pa n ( 5 partici pa nts i n t he place b o 
gr o u p, 2 partici pa nts i n t he tafa mi dis me gl u mi ne 2 0 m g gr o u p, te n partici pa nts i n t he 
tafa mi dis me gl u mi ne 8 0 m g gr o u p).  T he s u b-a nal ysis of pri mar y a n d ke y sec o n dar y 
e n d p oi nts data fr o m t hese partici pa nts s u g gest n o a p pare nt tre n ds t hat de viate d fr o m t he 
o verall test p o p ulati o n.
A rece nt a nal ys is of a vaila ble s ur vi val data fr o m St u d y B 3 4 6 1 0 4 5, a n o n g oi n g, l o n g-ter m 
e xte nsi o n st u d y f or partici pa nts pre vi o usl y e nr olle d i n st u d y B 3 4 6 1 0 2 8, s u g gest a mea ni n gf ul 
1 0. 2 % re d ucti o n i n ris k of deat h ( H azar d rati o 0. 8 9 7 6, 9 5 % CI 0. 5 7 1 1, 1. 4 1 0 8) i n patie nts o n 
8 0 m g c o m pare d t o 2 0 m g of tafa mi dis me gl u mi ne o ver t he l o n ger peri o d of treat me nt
( p = 0. 6 3 9 5).  T hese res ults s u p p orte d t he d ose rec o m me n dati o n of 8 0 m g tafa mi dis 
me gl u mi ne .
T hese p oi nts s u m marize d t he e vi de nce s u p p orti n g t he e x pectati o n t hat t he tafa mi dis 
me gl u mi ne cli nical pr ofile i n t he C hi nese p o p ulati o n will be c o nsiste nt wit h t he gl o bal 
p o p ulati o n a n d is lar gel y deri ve d fr o m e x perie nce wit h Ja pa nese patie nts.
T he safet y pr ofile of tafa mi dis me gl u mi ne f or t he treat me nt of A T T R -C M has bee n e val uate d 
i n 3 7 7 A T T R-C M patie nts i n t he pi v otal P hase 3 St u d y  B 3 4 6 1 0 2 8 a n d its o n g oi n g l o n g-ter m 
e xte nsi o n ( LT E) St u d y B 3 4 6 1 0 4 5, as well as i n t he P hase 2 St u d y  B 3 4 6 1 0 2 5 a n d t he 
ass ociate d o n g oi n g L T E, St u d y B 3 4 6 1 0 2 6 ( data pr o vi de d f or b ot h o n g oi n g LT Es t hr o u g h 
c ut off date of 0 1 A u g ust 2 0 1 8).  Tafa mi dis safet y data are als o prese nte d fr o m 1 7 P hase 1 
st u dies 3 4 8 healt h y partici pa nts, as well as a P hase 1 st u d y i n partici pa nts wit h he patic 
i m pair me nt.  A d diti o nal s u p p orti ve safety data are pr o vi de d fr o m 5 cli nical st u dies (c ut off 
date 0 3 Ja n uar y 2 0 1 7) i n v ol vi n g A T T R- P N patie nts ( n = 1 3 7) a n d p ost -mar keti n g data (c ut off 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 3 4
date 0 1 A u g ust 2 0 1 8), as well as safet y data fr o m tafa mi dis -treate d patie nts e nr olle d i n St u d y 
B 3 4 6 1 0 0 1 ( Tra nst h yreti n -Ass ociate d A m yl oi d os is O utc o mes S ur ve y [ T H A O S]; c ut off date 
0 1 A u g ust 2 0 1 8).   
Tafa mi dis treat me nt was ge nerall y safe a n d well t olerate d i n t he st u d y p artici pa nt p o p ulati o n,
wit h a n a vera ge a ge of 7 4,
wit h fe w d ose re d ucti o ns a n d a si milar fre q ue nc y  of T E A Es a n d 
seri o us T E A Es bet wee n t he treat me nt gr o u ps.  T he maj orit y  of t he A Es were mil d or 
m o derate i n se verit y  a n d disc o nti n uati o n d ue t o A Es, b ot h per ma ne nt a n d te m p orar y, were 
less c o m m o n i n t he tafa mi dis gr o u ps t ha n i n t he place b o gr o u p.  N o a d verse dr u g reacti o ns 
were i de ntifie d wit h tafa mi dis a d mi nistrati o n i n t he A T T R -C M patie nt p o p ulati o n.
2. 3. Be nefit/ Ris k Assess me nt
Wit h tafa mi dis treat me nt, C hi nese A T T R- C M patie nts will be e x pecte d t o a v oi d T T R 
desta bilizati o n a n d t here b y  dela y pr o gressi o n of A T T R-C M wit h well t olerate d safet y pr ofile. 
Partici pa nts partici pati n g i n t he st u d y  ma y ha ve t he pr o ba bilit y of e x perie nci n g t he e ve nts 
liste d i n l ocal pr o d uct la bel.
M ore detaile d i nf or mati o n a b o ut t he k n o w n a n d e x pecte d be nefits a n d ris ks a n d reas o na bl y 
e x pecte d a d verse e ve nts ( A Es) of tafa mi dis ma y  be f o u n d i n t he pac ka ge i nsert, w hic h is t he 
si n gle refere nce safety d oc u me nt ( S R S D) f or t his st u d y. 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 3 5
3. O B J E C TI V E S, E S TI M A N D S, A N D E N D P OI N T S
O bjecti ves
Esti m a n ds
E n d p oi nts
Pri m ar y: 
Pri m ar y:
Pri m ar y: 

T o c haracterize t he safet y pr ofile 
of tafa mi dis o nce dail y f or t he 
treat me nt of C hi nese A T T R -C M 
patie nts i n cli nical practice.

N ot a p plica ble.

I nci de nce of treat me nt-e mer ge nt 
a d verse e ve nts.
Sec o n d ar y: 
Sec o n d ar y: 

T o c haracterize t he descri pti ve 
efficac y of tafa mi dis o nce dail y i n 
C hi nese A T T R -C M patie nts. 

T o c haracterize tafa mi dis P D i n 
C hi nese A T T R -C M patie nts.

T o c haracterize t he i mpact o n
q ualit y of life of tafa mi dis o nce 
dail y f or t he treat me nt of C hi nese 
A T T R -C M patie nts .

T o c haracterize tafa mi dis P K i n 
C hi nese A T T R -C M patie nts.

N ot a p plica ble.

Assess me nt of 6 -M W T, N T -pr o 
B N P at sc he d ule d visits.

T T R sta bilizati o n a n d T T R 
c o nce ntrati o n at baseli ne ( pre 
d osi n g) o n Da y 1, at M o nt hs 1, 6, 
a n d 1 2 ( or E n d of Treat me nt 
( E O T)). 

Ka nsas Cit y Car di o m y o pat h y 
Q uesti o n naire o verall s u m mar y 
sc ores, E Q-5 D - 5 L i n de x sc ores a n d 
E Q -5 D V A S sc ores, 1 2 -Ite m S h ort 
F or m S ur ve y ( S F - 1 2) sc ores, at Da y 
1, M o nt hs 6, 1 2 ( or E n d of 
Treat me nt ( E O T)).

P K: plas ma c o nce ntrati o ns of 
tafa mi dis at M o nt hs 1, 6, a n d 1 2 ( or 
E O T )). 
4. S T U D Y D E SI G N
4. 1. O ver all Desi g n
T his is a nati o nal, m ulti -ce nter, si n gle -ar m st u d y, o pe n t o patie nts wit h s y m pt o matic 
A T T R -C M w h o are tafa mi dis naï ve.  T his st u d y  is t o o btai n safet y, descri pti o n efficac y, P K 
a n d P D data f oll o wi n g t he a p pr o val of tafa mi dis 6 1 m g s oft ca ps ule orall y o nce dail y, wit h or 
wit h o ut f o o d.  T he p ote ntial site n u m ber will be 5 -1 0 a n d at least 5 3 patie nts will be e nr olle d.  
T he partici pa nts of greater t ha n or e q ual t o N Y H A class III s h o ul d n ot be m ore t ha n 1/ 3 of all 
e nr olle d partici pa nts .
Patie nts will c o nti n ue t o recei ve t heir c urre nt me dicati o ns a n d all ot her sta n dar d care f or t heir 
disease base d o n cli nical practice.  T he use of per mitte d c o nc o mita nt me dicati o n m ust be i n 
acc or da nce wit h tafa mi dis pac ka ge i nsert.  C o nc o mita nt me dicati o n n ot per mitte d i n t his 
st u d y is descri be d i n Secti o n 6. 5 .
T o tal d urati o n of st u d y partici pati o n f or eac h partici pa nt recei vi n g tafa mi dis o nce daily wit h 
a p pr o ve d d ose is 1 2 m o nt hs.  T he f oll o wi n g visit dates after baseli ne visit s h o ul d be base d o n 
t he date of t he Baseli ne visit e xce pt t he p ost-treat me nt f oll o w- u p.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 3 6
Partici pa nts will c o m plete pr ot oc ol re q uire d tests a n d pr oce d ures as descri be d i n Sc he d ule of 
acti vities. A fi nal st u d y  re p ort will be c o m plete d a p pr o xi matel y 3 years after t he date of t he 
first tafa mi dis patie nt e nr oll me nt i n t he st u d y.
Sc he d ule d Visits: Da y  1, M o nt hs 1, 3, 6, 9, 1 2 ( or E n d of Treat me nt ), cli nic visit at Da y 1, 
M o nt h 1, M o nt h 6, M o nt h 1 2, tele p h o ne c o ntact at M o nt h 3 a n d M o nt h 9. 
4. 2. Scie ntific R ati o n ale f or St u d y Desi g n
T his st u d y  is t o c ollect safet y, descri pti ve efficac y P K, a n d P D data f or tafa mi dis o nce dail y 
wit h a p pr o ve d f or m ulati o n.  I nci de nce of treat me nt -e mer ge nt a d verse e ve nts will be c ollecte d 
f or pri mar y e n d p oi nt a nal ysis.  Bl o o d sa m ples a n d s pecial cli nical assess me nts will be 
c ollecte d f or sec o n dar y  e n d p oi nts a nal ysis, i ncl u di n g 6- mi n utes wal k test ( 6- M W T ), N 
Ter mi nal pr o h or m o ne B t y pe Natri uretic Pe pti de ( N T -pr o B N P ), T T R sta bilizati o n, T T R 
c o nce ntrati o n, plas ma c o nce ntrati o ns of tafa mi dis, Ka nsas Cit y  Car dio m y o pat h y  
Q uesti o n naire O verall Sc ore, E ur o Q o L 5 Di me nsi o ns 5 L e vels (E Q -5 D -5 L ) I n de x Sc ore a n d 
E ur o Q o L 5 Di me nsi o ns vis ual a nal o g ue scale (E Q -5 D V A S ) sc ores, 1 2-s h ort ite m s ur ve y 
f or m ( S F-1 2) sc ores at eac h defi ne d visit.  T o c ollect t he P K data will k n o w t he dr u g 
e x p os ure a n d safet y of tafa mi dis i n C hi nese patie nts.
4. 3. J ustific ati o n f or D ose
Base d o n res ults of P hase 3 pi v otal st u d y  B 3 4 6 1 0 2 8 a n d t he bi oe q ui vale nce St u d y  
B 3 4 6 1 0 5 6, gl o ball y , t he pr o p ose d cli nical d osi n g re gi me n is 8 0 m g tafa mi dis me gl u mi ne 
ora ll y (a d mi nistere d as 4 2 0 m g ca ps ules, o ne ca ps ule c o ntai ns 1 2. 2 m g tafa mi dis, t he acti ve 
p har mace utical i n gre die nt ) o nce daily a n d/ or tafa mi dis 6 1 m g ( bi oe q ui vale nt t o t he 
f or m ulati o n/ d osa ge of tafa mi dis me gl u mi ne 8 0 m g (4 x 2 0 m g )) orall y o nce dail y , with or 
wit h o ut f o o d.
T he t hera pe utic i n dicati o n s i n U nite d States Prescri bi n g I nf or mati o n are “ V y n da qel
(tafa mi dis me gl u mi ne) a n d V yn da ma x (tafa mi dis) i n dicate d t o re d uce all ca use m ortalit y  a n d 
car di o vasc ular relate d h os pitalizati o n i n patie nts wit h wil d t y p e or here ditar y tra nst hyr eti n 
a m yl oi d car di o m yo pat h y” .
F or C hi na, i n or der t o facilitate A T T R -C M patie nt c o n ve nie nce , t he p r o p ose d a n d a p pr o ve d 
f or m ulati o n a n d cli nical d osi n g re gi me n is a t afa mi dis 6 1 m g s oft ca ps ule orall y o nce dail y, 
wit h or wit h o ut f o o d.
R ati o n ale of 8 0 m g ( 4 x 2 0 m g) t af a mi dis me gl u mi ne s oft c a ps ules o nce d ail y 
I n pi v otal P hase 3 st u dy B 3 4 6 1 0 2 8 pr ot oc ol, tafa mi dis me gl u mi ne at 2 0 m g a n d 8 0 m g d oses 
were e m pl o y e d a n d c o m pare d wit h place b o.  T he 2 0 m g d ose of tafa mi dis me gl u mi ne ha d 
bee n use d pre vi o usl y  bef ore B 3 4 6 1 0 2 8 i n b ot h p ol yne ur o pat h y  a n d car di o m yo pat h y trials.  A 
ra n ge of tafa mi dis me gl u mi ne e x p os ures ha d bee n assesse d i n cli nical p har mac ol o g y st u dies 
( St u d y F x- 0 0 2, St u d y  B 3 4 6 1 0 4 0, a n d B 3 4 6 1 0 3 1) i n healt h y v ol u nteers t hat i ncl u de d t he 
c o nce ntrati o ns e x pecte d wit h a n 8 0 m g d ose.  T he a d diti o n of t he 8 0 m g d ose i n B 3 4 6 1 0 2 8, 
w hic h was e x pecte d t o res ult i n near ma xi mal T T R sta bilizati o n, w o ul d per mit e x pl orati o n of 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 3 7
a hi g her d ose t o ass ure t hat efficac y  a n d safet y ha d bee n e x pl ored acr oss a ra n ge of 
a de q uatel y se parate d d oses.
T he res ults of pi v otal P hase 3 st u d y  B 3 4 6 1 0 2 8 de m o nstrate d t hat c o m para ble treat me nt 
effects were o bser ve d f or t he pri mar y  a nal yses (all-ca use m ortalit y a n d t he fre q ue nc y of 
car di o vasc ular -relate d h os pitalizati o ns) a n d sec o n dar y a nalys es (i ncl u di n g T T R sta bilizati o n 
at M o nt h 1) w he n a nal yze d b y d ose ( 2 0 m g a n d 8 0 m g).  T o f urt her assess differe nces 
bet wee n tafa mi dis me gl u mi ne 2 0 m g a n d 8 0 m g d oses t o s u p p ort d ose rec o m me n dati o n, 
car diac bi o mar ker data b y d ose i n St u d y B 3 4 6 1 0 2 8 were e x pl ore d a n d e val uate d.  P ost h oc 
a nal ys es of bi o mar ker data pr o g n ostic of s ur vi val ( N T- pr o B N P) a n d C V relate d 
h os pitalizati o ns ( Tr o p o ni n I) s u g gest differe ntiati o n bet wee n t he 8 0 m g a n d 2 0 m g d oses a n d 
a n a d va nta ge of t he 8 0 m g d ose c o m pare d t o 2 0 m g.  I n a d diti o n, t his st u d y  e nr olle d 1 7 ( of 
4 4 1) partici pa nts i n Ja pa n ( 5 partici pa nts i n t he place b o gr o u p, 2 partici pa nts i n t he tafa mi dis 
me gl u mi ne 2 0 m g gr o u p, te n partici pa nts i n t he tafa mi dis me gl u mi ne 8 0 m g gr o u p) a n d a 
s u b-p o p ulati o n re p ort was ge nerate d.  Alt h o u g h t he sa m ple size is li mite d, efficac y  a n d 
safety res ults i n t he Ja pa nese partici pa nts were c o nsiste nt wit h t he res ults fr o m t he o verall 
st u d y p o p ulati o n.
U p o n c o m pleti o n of t he M o nt h 3 0 visit i n St u d y  B 3 4 6 1 0 2 8, patie nts were t o be eli gi ble f or 
treat me nt wit h tafa mi dis i n a se parate o n g oi n g e xte nsi o n st u d y ( B 3 4 6 1 0 4 5), w hic h w o ul d 
per mit t he c ollecti o n of a d diti o nal safet y  a n d efficac y data, a n d w o ul d i ncl u de t he assess me nt 
of h os pitalizati o ns, m ortalit y , a n d ot her o utc o mes relati n g t o disease pr o gressi o n.  F or t he 
p ur p ose of t his st u d y, 3 0 m o nt hs was defi ne d as 9 1 0 da y s.  Eli gi bilit y f or t he e xte nsi o n st u d y 
( B 3 4 6 1 0 4 5) re q uire d patie nt partici pati o n i n St u d y B 3 4 6 1 0 2 8 at least t hr o u g h Da y 8 9 6 
( M o nt h 3 0 mi n us 2 wee ks).  Res ults fr o m B 3 4 6 1 0 4 5 c o nti n ue t o de m o nstrate a si g nifica nt 
re d ucti o n i n all-ca use m ortalit y.  C urre nt a nalys es of t he s ur vi val data fr o m t he o n g oi n g 
St u d y  B 3 4 6 1 0 4 5 i n dicate d a mar gi nal yet mea ni n gf ul 1 0. 2 % re d ucti o n i n ris k of deat h i n 
patie nts o n 8 0 m g c o m pare d t o 2 0 m g of tafa mi dis me gl u mi ne o ver t he l o n ger peri o d of 
treat me nt.
De vel o p me nt a n d r ati o n ale of a si n gle 6 1 m g t af a mi dis s oft c a ps ule, bi oe q ui v ale nt t o 4 
2 0 m g taf a mi dis me gl u mi ne c a ps ules at ste a d y st ate
In or der t o facilitate patie nt c o n ve nie nce , the s p o ns or has de vel o pe d a f or m ulati o n , a sin gle 
6 1 m g tafa mi dis s oft ca ps ule , t hat pr o vi de d patie nts wit h a si n gle oral d osa ge f or m i nstea d of 
4 2 0 m g tafa mi dis me gl u mi ne s oft gel ca ps ules.  A si n gle 8 0 m g tafa mi dis me gl u mi ne s oft 
gel ca ps ule is tec h nicall y n o t feasi ble beca use of a c o nce ntrati o n- de pe n de nt gelli n g of 
tafa mi dis me gl u mi ne.  M ulti ple 
f or ms were scree ne d a n d it was deter mi ne d t hat 
tafa mi dis was t he fa v ore d acti ve p har mace utical i n gre die nt. 
St u d y  B 3 4 6 1 0 5 6 was a n o pe n la bel, ra n d o mize d, 2-peri o d, 2- se q ue nce, cr oss o ver, m ulti ple
d ose pi v otal bi oe q ui vale nce st u d y  i n faste d healt h y v ol u nteers c o m pari n g area u n der t he 
c o nce ntrati o n-ti me c ur ve o ver t he d osi n g i nter val ta u ( A U Cta u), a n d ma xi m u m o bser ve d dr u g 
c o nce ntrati o n ( C ma x ) at stea dy -state, of 6 1 m g tafa mi dis s oft ca ps ules ( Treat me nt A, Test) a n d 
4 × 2 0 m g c o m mercial tafa mi dis me gl u mi ne s oft ca ps ules ( Treat me nt B, Refere nce).  
Bi oe q ui vale nce criteria were met f or t he tafa mi dis 6 1 m g ca ps ule relati ve t o t he tafa mi dis 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)
C CI

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 3 8
me gl u mi ne 4 × 2 0 m g ca ps ules af ter re peate d oral dail y d osi n g f or 7 d a y s ( o n st u d y Da ys 1 
a n d 2, a sec o n d d ose of t he st u d y  me dicati o n was a d mi nistere d a p pr o xi matel y 1 2 h o urs after 
t he first d ose a n d at least after a 2 h o ur fast).  T he rati o of a dj uste d ge o metric mea ns ( 9 0 % 
CI ) of tafa mi dis A U Cta u a n d C ma x were 1 0 2. 2 8 % ( 9 7. 9 9 %, 1 0 6. 7 6 %) a n d 9 4. 1 2 % ( 8 9. 0 9 %, 
9 9. 4 2 %) res pecti vel y, f oll o wi n g a d mi nistrati o n of t he tafa mi dis 6 1 m g ca ps ule relati ve t o 
tafa mi dis me gl u mi ne 4 × 2 0 m g ca ps ules.  T he c orres p o n di n g 9 0 % CIs were c o ntai ne d 
wit hi n t he ( 8 0 %, 1 2 5 %) bi oe q ui vale nce acce pta nce ra n ge. 
St u d y  B 3 4 6 1 0 5 4 assesse d effect of f o o d wit h t he 6 1 m g tafa mi dis s oft ca ps ule f or m ulati o n.  
Base d o n t he rati os of a dj uste d ge o metric mea ns, tafa mi dis (area u n der t he c o nce ntrati o n-
ti me c ur ve fr o m ti me 0 t o i nfi nit y (A U C i nf) a n d C ma x f oll o wi n g a si n gle d ose i ncrease d by 
a p pr o xi matel y 6 % a n d 3 2 % res pecti vel y, f or t he 6 1 m g tafa mi dis ca ps ule fe d vs. faste d.  
Gi ve n t hat tafa mi dis is a d mi nistere d as a c hr o nic me dicati o n a n d t hat o verall e x p os ure was 
n ot differe nt bet w ee n t he fe d a n d faste d treat me nt, t hese data s u p p ort d osi n g wit h o ut re gar d 
t o f o o d.  In a d diti o n, si m ulati o ns usi n g t he p o p ulati o n P K m o del s u g gest t he differe nce i n 
stea d y-state Cma x u n der fe d c o n diti o ns is a p pr o xi matel y  2 % c o m pare d t o faste d c o n diti o ns, 
w hic h is c o nsi dere d n ot t o be cli nicall y  mea ni n gf ul.
He nce, t his st u d y will e m pl o y  tafa mi dis at 6 1 m g, orall y o nce daily, t he a p pr o ve d d ose 
re gi me n.
4. 4. E n d of St u d y Defi niti o n
A partici pa nt is c o nsi dere d t o ha ve c o m plete d t he st u d y  if he/s he has c o m plete d all p hases of 
t he st u d y i ncl u di n g M o nt h 1 2 or Earl y St u d y Disc o nti n uati o n.
T he e n d of t he st u d y is defi ne d as t he date all partici pa nts ha ve c o m plete d t he visits 
sc he d ule d i n t he S o A .
5. S T U D Y P O P U L A TI O N
T his st u d y  ca n f ulfill its o bjecti ves o nl y if a p pr o priate partici pa nts are e nr olle d.  T he 
f oll o wi n g eli gi bilit y criteria are desi g ne d t o select partici pa nts f or w h o m partici pati o n i n t he 
st u d y is c o nsi dere d a p pr o priate.  All rele va nt me dical a n d n o n me dical c o n diti o ns s h o ul d be 
ta ke n i nt o c o nsi derati o n w he n deci di n g w het her a partic ular partici pa nt is s uita ble f or t his 
pr ot oc ol. 
Pr os pecti ve a p pr o val of pr ot oc ol de viati o ns t o recr uit me nt a n d e nr oll me nt criteria, als o 
k n o w n as pr ot oc ol wai vers or e xe m pti o ns, is n ot per mitte d.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 3 9
5. 1. I ncl usi o n Criteri a
Partici pa nts are eli gi ble t o be i ncl u de d i n t he st u d y o nl y if all of t he f oll o wi n g criteria a p pl y :
A ge a n d Se x:
Male a n d fe male partici pa nts, a ge greater t ha n or e q ual t o 1 8
at scree ni n g visit.
T y pe of P artici p a nt a n d Dise ase C h ar acteristics:
Partici pa nts , i n t he o pi ni o n of t he i n vesti gat or, w h o are willi n g a n d a ble t o ta ke tafa mi dis 
a n d c o m pl y wit h all sc he d ule d visits, treat me nt pla n, la b orat or y tests, lifest yle 
c o nsi derati o ns, a n d ot her st u d y pr oce d ures.
Refer t o A p pe n di x 4 f or re pr o d ucti ve criteria f or male (Secti o n 1 0. 4. 1 ) a n d fe male 
(Secti o n 1 0. 4. 2 ) partici pa nts.
Partici p a nt has d oc u me nte d A T T R - C M, w hic h is defi ne d as:
a.
Varia nt A T T R -C M:

prese nce of a varia nt T T R ge n ot y pe ass ociate d wit h car di o m y o pat h y a n d 
prese nti n g wit h a car di o m y o pat h y p he n ot y p e (e g, a hist or y of c o n gesti ve heart 
fail ure);

e vi de nce of car diac i n v ol ve me nt b y  ec h ocar di o gra p h y wit h a n e n d diast olic 
i nter ve ntric ular se ptal wall t hic k ness > 1 2 m m;

prese nce of a m yl oi d i n bi o ps y  tiss ue, s uc h as fat as pirate, sali var y gla n d, 
me dia n ner ve c o n necti ve tiss ue s heat h, or car diac (a m y l oi d de m o nstrate d per 
a p pr o priate sta i n s uc h as C o n g o re d or alci n bl ue stai n) O R ra di o n ucli de b o ne 
sci nti gra p hy ( 9 9 m Tc-P Y P) Sci nti gra p h y .
b.
Wil d -t ype A T T R -C M:

a bse nce of a varia nt T T R ge n ot y p e;

e vi de nce of car diac i n v ol ve me nt b y  ec h ocar di o gra p h y wit h a n e n d diast olic 
i nter ve ntric ular se ptal wall t hic k ness > 1 2 m m;

prese nce of a m yl oi d de p osits i n bi o ps y  tiss ue, s uc h as fat as pirate, sali var y 
gla n d, me dia n ner ve c o n necti ve tiss ue s heat h, or car diac (a m yl oi d 
de m o nstrate d per a p pr o priate stai n s uc h as C o n g o re d or alci n bl ue stai n), wit h 
T T R prec u rs or pr otei n i de ntificati o n b y eit her i m m u n o hist oc he mistr y, mass 
s pectr o metr y O R ra di o n ucli de b o ne sci nti gra p hy ( 9 9 m Tc-P Y P).
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 4 0
Wei g ht:
N ot a p plica ble.
I nf or me d C o nse nt:
Ca pa ble of gi vi n g si g ne d i nf or me d c o nse nt as descri be d i n A p pe n di x 1 , w hic h i ncl u des 
c o m plia nce wit h t he re q uire me nts a n d restricti o ns liste d i n t he i nf or me d c o nse nt 
d oc u me nt (I C D) a n d i n t his pr ot oc ol.
5. 2. E xcl usi o n Criteri a
Partici pa nts are e xcl u de d fr o m t he st u d y if a n y of t he f oll o wi n g criteria a p pl y :
Me dic al C o n diti o ns:
Ot her ac ute or c hr o nic me dical or ps yc hiatric c o n diti o n i ncl u di n g rece nt ( wit hi n t he 
past y ear) or acti ve s uici dal i deati o n or be ha vi or or la b orat or y a b n or malit y t hat ma y 
i ncrease t he ris k ass ociate d wit h st u d y partici pati o n or st u d y i nter ve nti o n 
a d mi nistrati o n or ma y i nterfere wit h t he i nter pretati o n of st u d y res ults a n d, i n t he 
j u d g me nt of t he i n vesti gat or, w o ul d ma ke t he partici pa nt i na p pr o priate f or e ntr y i nt o 
t his st u d y.
Pri or/ C o nc o mit a nt T her a p y:
Partici pa nts w h o ha ve pri or li ver a n d/ or heart tra ns pla nt.
Pa rtici pa nts wit h pri mar y (li g ht c hai n) or sec o n dar y a myl oi d osis.
Pri or/ C o nc urre nt Cli nic al St u d y E x perie nce:
Pre vi o us a d mi nistrati o n wit h a n i n vesti gati o nal dr u g or vacci ne wit hi n 3 0 da y s ( or as 
deter mi ne d b y t he l ocal re q uire me nt) or 5 half -li ves prece di n g t he first d ose of st u d y 
i nter ve nti o n use d i n t his st u d y ( w hic he ver is l o n ger). 
Ot her E xcl usi o ns:
I n vesti gat or site staff me m bers directly i n v ol ve d i n t he c o n d uct of t he st u d y a n d t heir 
fa mil y me m bers, site staff me m bers ot her wise s u per vise d b y t he i n vesti gat or, or 
Pfizer e m pl o y ees, i ncl u di n g t heir fa mil y me m bers, directl y i n v ol ve d i n t he c o n d uct of 
t he st u d y. 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 4 1
5. 3. Lifest yle C o nsi der ati o ns
5. 3. 1. C o ntr ace pti o n  
T he i n vesti gat or or his or her desi g nee, i n c o ns ultati o n wit h t he pa rtici pa nt, will c o nfir m t hat 
t he partici pa nt has selecte d a n a p pr o priate met h o d of c o ntrace pti o n f or t he i n di vi d ual 
partici pa nt a n d his or her part ner(s) fr o m t he per mitte d list of c o ntrace pti o n met h o ds (see 
A p pe n di x 4 Secti o n 1 0. 4. 4 ) a n d will c o nfir m t hat t he partici pa nt has bee n i nstr ucte d i n its 
c o nsiste nt a n d c orrect use.  At ti me p oi nts i n dicate d i n t he sc he d ule of acti vities ( S o A ), t he 
i n vesti gat or or desi g nee will i nf or m t he partici pa nt of t he nee d t o use hi g hl y effecti ve 
c o ntrace pti o n c o nsiste ntl y a n d c orrectl y a n d d oc u me nt t he c o n versati o n a n d t he partici pa nt’s 
affir mati o n i n t he partici pa nt’s c hart ( partici pa nts nee d t o affir m t heir c o nsiste nt a n d c orrect 
use of at least 1 of t he selecte d met h o ds of c o ntrace pti o n).  I n a d diti o n, t he i n vesti gat or or 
desi g nee will i nstr uct t he partici pa nt t o call i m me diatel y if t he selecte d c o ntrace pti o n met h o d 
is disc o nti n ue d or if pre g na nc y is k n o w n or s us pecte d i n t he partici pa nt or part ner.
5. 4. Scree n F ail ures
Scree n fail ures are defi ne d as partici pa nts w h o c o nse nt t o partici pate i n t he cli nical st u d y  b ut 
are n ot su bse q ue ntl y  assi g ne d t o st u d y i nter ve nti o n.  A mi ni mal set of scree n fail ure 
i nf or mati o n is re q uire d t o e ns ure tra ns pare nt re p orti n g of scree n fail ure partici pa nts t o meet 
t he C o ns oli date d Sta n dar ds of Re p orti n g Trials ( C O N S O R T) p u blis hi n g re q uire me nts a n d t o 
res p o n d t o q ueries fr o m re g ulat or y a ut h orities.  Mi ni mal i nf or mati o n i ncl u des de m o gra p h y, 
scree n fail ure details, eli gi bilit y criteria, a n d a n y seri o us a d verse e ve nt ( S A E).
I n di vi d uals w h o rec o ver fr o m ac ute me dical c o n diti o n s ma y, acc or di n g t o t he best me dical 
j u d g me nt of t he i n vesti gat or, be a p pr o priate f or rescree ni n g.
If in di vi d ual s rec o vere d wit hi n 4 5 da ys, t he in di vi d ual i ncl usi o n/e xcl usi o n criteria ma y  n ot 
nee d a re peat pr oce d ure t o rescree n.  It ma y be necessar y t o o btai n inf or me d c o nse nt a gai n 
f or s o me partici pa nts b ut n ot ot hers base d u p o n t he st u d y desi g n, t he me dical c o n diti o n, or 
t he a ge a n d ot her partici pa nt iss ues.  Instit uti o nal re vie w b oar d s (I R Bs)/ et hics c o m mittees
(E Cs ) m a y  als o ha ve s pecific g ui da nces f or t heir sites
6. S T U D Y I N T E R V E N TI O N
St u d y  i nter ve nti o n is defi ne d as a n y i n vesti gati o nal i nter ve nti o n(s), mar kete d pr o d uct(s), 
place b o, or me dical de vice(s) i nte n de d t o be a d mi nistere d t o a st u d y  partici pa nt acc or di n g t o 
t he st u d y pr ot oc ol.
F or t he p ur p oses of t his p r ot oc ol, t he ter m i n vesti gati o nal pr o d uct ma y be use d 
s yn o n y m o usl y  wit h st u d y i nter ve nti o n.  I n vesti gat ors will c o nfir m t he eli gi bilit y of eac h 
partici pa nt t o meet i ncl usi o n/e xcl usi o n criteria.  Partici pa nt eli gi bilit y f or partici pati o n i n t he 
st u d y will recei ve tafa mi dis 6 1 m g (t he a p pr o ve d d ose) orall y o nce dail y wit h or wit h o ut 
f o o d, f or 1 2 m o nt hs f oll o wi n g t he assess me nt as t he scree ni n g a n d baseli ne visits.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 4 2
6. 1. St u d y I nter ve nti o n(s) A d mi nistere d
I nter ve nti o n N a me
Tafa mi dis free aci d
A R M N a m e
Treat me nt
T y pe
I nter ve nti o nal t y pe: Dr u g
D ose F or m ul ati o n
I n acc or da nce wit h C hi na a ut h orit y a p pr o ve d pac ka ge i nsert
U nit D ose Stre n gt h(s)
Milli gra m
D os a ge Le vel(s)
6 1 m g, o nce dail y
R o ute of A d m i nistr ati o n
Oral
I n vesti g ati o n al Me dici n al 
Pr o d uct (I M P) a n d 
N o ni n vesti g ati o n al Me dici n al 
Pr o d uct ( NI M P)
I M P
S o urci n g
Pr o vi de d ce ntrall y b y t he s p o ns or
fr o m C hi na a ut h orit y a p pr o ve d pac ka ge i nsert.
P ac k a gi n g a n d L a beli n g
St u d y i nter ve nti o n will be pr o vi de d wit h a p pr o ve d pac ka ge . 
Refer t o Secti o n 6. 3. 1 f or i n vesti gati o nal pr o d uct all ocati o n.
[ C urre nt/ F or mer N a me(s) or 
Ali as(es)]
Tafa mi dis
St u d y  i nter ve nti o n will be dis pe nse d at baseli ne ( Da y 1), M o nt h 1  a n d M o nt h 6 visits.  
Partici pa nts will be i nstr ucte d t o ta ke t he me dicati o n o n a dail y  basis.  T he y will als o be 
i nstr ucte d t o bri n g all of t heir st u d y me dicati o n bac k t o t he st u d y site, i ncl u di n g use d a n d 
u n use d st u d y  me dicati o n, at eac h sc he d ule d st u dy visit s o t hat t he t ota l a m o u nt of dr u g ta ke n 
ca n be deter mi ne d a n d u n use d me dicati o n c ollecte d b y site pers o n nel.  St u d y i nter ve nti o n 
c o u nt will be perf or me d at eac h sc he d ule d visit f or all partici pa nts.
F or t he p ur p ose of pr o m oti n g d osi n g a d here nce, t he sites will calc ulate t he n u m ber of da y s 
d ose d di vi de d b y  t he n u m ber of da ys partici pati n g i n t he st u d y f or eac h st u d y visit t o pr o vi de 
a meas ure of treat me nt a d here nce.  As part of st u d y  data a nalys is, partici pa nts will be 
c o nsi dere d t o be a d here nt t o t he d osi n g re q uire me nts of t he st u d y if t he y ha ve ta ke n 
me dicati o n per da y  o n at least 8 0 % of t he da ys of st u d y partici pati o n. 
I n t he e ve nt t hat partici pa nts e x perie nce a d verse e ve nts t hat ma y be ass ociate d wit h t he
t olera bilit y of treat me nt wit h tafa mi dis t hat ma y i m pact d osi n g ad here nce, t he y  s h o ul d ret ur n
t o t he cli nic wit h t heir me dicati o n.  If t he i n vesti gat or assesses t hat t he t olera bilit y iss ue is
persiste nt a n d a ntici pate d t o i m pact d osi n g a d here nce a n d t hat t he partici pa nt ’s safety is n ot
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 4 3
c o m pr o mise d b y c o nti n ui n g treat me nt, t he site has t he o pti o n t o disc o nti n ue d osi n g f or t his 
partici pa nt a n d t o ter mi nate st u d y partici pati o n.
Patie nts will c o nti n u o usl y recei ve t heir c urre nt me dicati o ns a n d all ot her sta n dar d care f or 
t heir disease.  T he use of per mitte d c o nc o mita nt me dicati o n m ust be i n acc or da nce wit h 
tafa mi dis la bel.
6. 1. 1. A d mi nistr ati o n
Partici pa nts will s wall o w t he i n vesti gati o nal pr o d uct w h ole, a n d will n ot ma ni p ulate or c he w 
t he i n vesti gati o nal pr o d uct pri or t o s wall o wi n g a n d ta ki n g t he ca ps ules wit h a glass of water.  
Partici pa nts will be i nstr ucte d t o d ose at a c o nsiste nt ti me of da y .  Partici pa nts will be 
i nstr ucte d t o start ta ki n g t heir me dicati o n eac h da y i n t he m or ni n g ( A M d osi n g); h o we ver, it 
is per mitte d f or partici pa nts t o ta ke his/ her me dicati o n i n t he after n o o n or e ve ni n g pri or t o a 
cli nic visit (e g, t he M o nt h 6 visit) w he n t he ti mi n g of P K sa m ple c ollecti o n is pr o hi biti ve f or 
a d here nce wit h A M d osi n g.  Partici pa nts s h o ul d n ot ta ke a n e xtra d ose of me dicati o n i n t he 
e ve nt t hat a d ose fr o m a pre vi o us da y is misse d a n d s h o ul d res u me d osi n g ca ps ules per da y  
fr o m a n i n di vi d ual r o w o n t he st u d y me dicati o n at t he ne xt pla n ne d d osi n g ti me.  Si milarl y, if 
m ulti ple d oses are misse d i n s uccessi o n, t he partici pa nt s h o ul d res u me d osi n g at t he ne xt 
pla n ne d d osi n g ti me wit h o ut ta ki n g a d diti o nal d oses t o ma ke u p f or t h ose d oses t hat were 
misse d.  I nstr ucti o ns o n d osi n g are pr o vi de d o n t he Partici pa nt Dail y D osi n g Diar y . 
At t he e n d of eac h visit, sites will i nstr uct partici pa nts, i n writi n g o n t he fr o nt of t he 
Partici pa nt Dail y  D osi n g Diar y, w he n t o ta ke t heir me dicati o n pri or t o t heir ne xt st u d y visit.  
T his is es peciall y  i m p orta nt if t he ne xt visit has a c ollecti o n of bl o o d sa m ple(s) f or P K 
a nal ys is.
K n o wi n g t he act ual ti me of d osi n g is esse ntial f or a p pr o priate a nal ys is of sa m ples f or T T R 
sta bilizati o n, T T R c o nce ntrati o n, a n d f or tafa mi dis p har mac o ki netic meas ure me nts.  O n t he 
da y  of t he st u d y visit, partici pa nts will write t he act ual ti me t hat t he y t o o k t heir me dicati o n i n 
t he Partici pa nt Dail y D osi n g Diar y a n d t he site staff will rec or d t his d osi n g ti me i n t he case 
re p ort f or m ( C R F).  
O n Da y  1 ( Baseli ne Visit), partici pa nts will be i nstr ucte d t o t a ke t heir first dail y d ose of 6 1 
m g tafa mi dis , after t he c o m pleti o n of t he baseli ne pr oce d ures a n d t o c o nti n ue d osi n g ca ps ules 
eac h da y i n t he m or ni n g ( A M d osi n g) u ntil t he ne xt st u d y  visit of M o nt h 1 visit. At t he e n d of 
t he cli nic visit, t he partici pa nts will be re mi n de d t o ta ke t heir me dicati o n i n t he cli nic, rat her 
t ha n at h o me, o n t he da y of t he ne xt visit of M o nt h 1, as i n dicate d o n t he Partici pa nt Dail y 
D osi n g Diar y . 
O n t he da y  of t he M o nt h 1 st u d y visit, partici pa nts will N O T ta ke t heir st u d y me dicati o n at 
h o me pri or t o t he cli nic visit.  St u d y  me dicati o n o n t he da y of t he M o nt h 1 visit will be ta ke n 
i n t he cli nic w he n i nstr ucte d b y cli nic staff, i n or der t o acc uratel y a n d c o n ve nie ntl y ti me t he 
tafa mi dis c o nce ntrati o n bl o o d sa m ple, w hic h is t o be c ollecte d pre-d ose as well as 3 h o urs 
(± 1. 5 h o urs) after t he act ual ti me of d osi n g. T he act ual ti me of d osi n g will be rec or de d b y  t he 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 4 4
st u d y site pers o n nel. St u d y site pers o n nel will als o rec or d i n t he C R F t he ti me of d osi n g o n 
t he da y bef ore t he M o nt h 1 visit as re p orte d by t he partici pa nt .
D uri n g M o nt h 3 visit ( Tele p h o ne visit), s c he d ule t he ne xt a p p oi nt me nt a n d partici pa nt will be 
i nstr ucte d t o ta ke t heir me dicati o n at h o me pri or t o t he ne xt cli nic visit as i n dicate d o n t he 
Partici pa nt Dail y  D osi n g Diar y.  Visit sc he d uli n g a n d d osi n g ti me i nstr ucti o ns f or 
partici pa nts m ust c o nsi der t hat t he tafa mi dis c o nce ntrati o n sa m ple is t o be c ollecte d 7 h o urs 
( ± 2. 5 h o urs) after d osi n g. It s h o ul d be n ote d t hat t he partici pa nts are per mitte d t o ta ke t he 
me dicati o n pri or t o t he M o nt h 6 visit i n t he after n o o n or e ve ni n g o n t he da y  pri or t o M o nt h 6 
visit if necessar y  t o a d here t o t he P K sa m pli n g sc he d ule. Partici pa nts will be i nstr ucte d t o 
acc uratel y rec or d o n t he Partici pa nt Dail y  D osi n g Diar y t he act ual ti me at w hic h t he y t o o k 
t heir pri or 2 d oses of me dicati o n ta ke n at h o me pri or t o t he M o nt h 6 visit. T he partici pa nt
will be re mi n de d t o ret ur n t o t he cli nic wit h all dis pe nse d st u d y  me dicati o n. 
F or M o nt h 6 visit, it s h o ul d be n ote d t hat d osi n g s h o ul d t a ke place 7 h o urs ( ± 2. 5 h o urs) pri or 
t o t he ti mi n g of P K sa m ple.  O n t he da y pri or t o M o nt h 6 visit, partici pa nts are per mitte d t o 
ta ke t heir us ual A M d ose a n d t he n ta ke t he ne xt da y’s d ose i n t he after n o o n or e ve ni n g if 
necessar y  t o a d here t o t he P K sa m pli n g sc he d ule.  Partici pa nts will ta ke t heir sc he d ule d d ose 
at h o me pri or t o t he cli nic visit (eit her i n after n o o n or e ve ni n g of t he da y  pri or t o t his visit 
da y , or i n A M of t his visit da y) a n d rec or d t he act ual ti me of d osi n g o n t heir Partici pa nt
S u bject D ail y D osi n g Diar y.  St u d y site pers o n nel will rec or d i n t he C R F t he ti me of t he pri or 
2 d oses of me dicati o n ta ke n at h o me pri or t o t he M o nt h 6 visit as re p ort e d b y t he partici pa nt
o n t heir Partici pa nt Dail y D osi n g Diar y .  
D uri n g M o nt h 9 visit ( Tele p h o ne v isit), sc he d ule t he ne xt a p p oi nt me nt a n d partici pa nt will be 
i nstr ucte d t o ta ke t heir me dicati o n i n t he cli nic, rat her t ha n at h o me, o n t he da y  of t he  ne xt 
visit of M o nt h 1 2.  A Partici pa nt Dail y  D osi n g Diar y stati n g t he date a n d ti me of t he ne xt 
visit of M o nt h 1 2 will be iss ue d t o t he partici pa nt .  Partici pa nts will be i nstr ucte d t o 
acc uratel y rec or d o n t he Partici pa nt Dail y  D osi n g Diar y t he act ual ti me at w hic h t he y t o o k 
t heir d ose of me dicati o n at h o me o n t he da y bef ore t he M o nt h 1 2 visit orE n d of Treat me nt
visit .  T he partici pa nt will be re mi n de d t o ret ur n t o t he cli nic wit h all dis pe nse d st u d y  
me dicati o n. 
O n t he da y  of t he M o nt h 12 st u d y visit, partici pa nts will N O T ta ke t heir st u d y me dicati o n at 
h o me pri or t o t he M o nt h 1 2 cli nic visit.  St u d y me dicati o n o n t he da y of t he M o nt h 1 2 visit 
will be ta ke n i n t he cli nic i n or der t o acc uratel y  a n d c o n ve nie ntly ti me t he tafa mi dis 
c o nce ntrati o n bl o o d sa m ple, w hic h is t o be 1 h o ur ( ± 3 0 mi n utes) af ter t he act ual ti me of 
d osi n g. T he act ual ti me of d osi n g will be rec or de d b y t he st u d y site pers o n nel. St u d y  site 
pers o n nel will rec or d i n t he C R F t he ti me of d osi n g o n t he da y  bef ore t he M o nt h 12 visit as 
rec or de d by t he partici pa nt o n t heir Partici pa nt Dail y  D osi n g Diar y.
I n t he e ve nt t hat partici pa nts e x perie nce a d verse e ve nts t hat ma y be ass ociate d wit h t he 
t olera bilit y of treat me nt wit h tafa mi dis t hat ma y i m pact d osi n g a d here nce, t he y s h o ul d ret ur n 
t o t he cli nic wit h t heir me dicati o n.  If t he i n vesti gat or assesses t hat t he t olera bilit y iss ue is 
persiste nt a n d a ntici pate d t o i m pact d osi n g a d here nce a n d t hat t he partici pa nt ’s safety is n ot 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 4 5
c o m pr o mise d b y c o nti n ui n g treat me nt, t he site has t he o pti o n t o disc o nti n ue d osi n g f or t his 
partici pa nt a n d t o ter mi nate st u d y  partici pati o n.
6. 2. Pre p ar ati o n/ H a n dli n g/ St or a ge/ Acc o u nt a bilit y
T he i n vesti gat or or desi g nee m ust c o nfir m a p pr o priate te m perat ure c o n diti o ns ha ve 
bee n mai ntai ne d d uri n g tra nsit f or all st u d y i nter ve nti o ns recei ve d a n d a n y 
discre pa ncies are re p orte d a n d res ol ve d bef ore use of t he st u d y i nter ve nti o n, as 
a p plica ble f or te m perat ure -m o nit ore d s hi p me nts. 
O nl y  partici pa nts e nr olle d i n t he st u d y ma y recei ve st u d y i nter ve nti o n a n d o nl y 
a ut h orize d site staff ma y s u p pl y or a d mi nister st u d y i nter ve nti o n.  All st u d y 
i nter ve nti o ns m ust be st ore d i n a sec ure, e n vir o n me ntall y c o ntr olle d, a n d m o nit ore d 
( ma n ual or a ut o mate d rec or di n g) area i n acc or da nce wit h t he la bele d st ora ge 
c o n diti o ns wit h access li mite d t o t he i n vesti gat or a n d a ut h orize d site staff.  At a 
mi ni m u m, dail y  mi ni m u m a n d ma xi m u m te m perat ures f or all site st ora ge l ocati o ns 
m ust be d oc u me nte d a n d a vaila ble u p o n re q uest.  Data f or n o n w or ki n g da ys m ust 
i n dicate t he mi ni m u m a n d ma xi m u m te m perat ure si nce pre vi o usly d oc u me nte d f or all 
site st ora ge l ocati o ns up o n ret ur n t o b usi ness.
T he i n vesti gat or, i nstit uti o n, or t he hea d of t he me dical i nstit uti o n ( w here a p plica ble) 
is res p o nsi ble f or st u dy i nter ve nti o n acc o u nta bilit y, rec o nciliati o n, a n d rec or d 
mai nte na nce (ie, recei pt, rec o nciliati o n, a n d fi nal dis p ositi o n rec or ds).  All st u d y 
i nter ve nti o ns will be acc o u nte d f or usi n g a n i n vesti gati o nal pr o d uct acc o u nta bilit y 
f or m/rec or d.  At eac h sc he d ule d cli nic visits starti n g at M o nt h 1; partici pa nts will 
bri n g t heir st u d y me dicati o n wit h t he m t o t he site .  T he i n vesti gat or’s site m ust 
mai ntai n a de q uate rec or ds d oc u me nti n g t he recei pt, use, l oss, or ot her dis p ositi o n of 
t he dr u g s u p plies as o utli ne d i n t he m o nit ori n g pla n.
F urt her g ui da nce a n d i nf or mati o n f or t he fi nal dis p ositi o n of u n use d st u d y  
i nter ve nti o ns are pr o vi de d i n t he pac ka ge i nsert.
A n y  st ora ge c o n diti o ns state d i n t he S R S D will be s u perse de d by t he st ora ge 
c o n diti o ns state d o n t he pr o d uct la bel. 
St u d y  i nter ve nti o ns s h o ul d be st ore d i n t heir ori gi nal c o ntai ners a n d i n acc or da nce 
wit h t he la bels. 
Site staf f will i nstr uct partici pa nts o n t he pr o per st ora ge re q uire me nts f or ta ke-h o me 
st u d y i nter ve nti o n. 
A n y  e xc ursi o ns fr o m t he st u d y i nter ve nti o n la bel st ora ge c o n diti o ns s h o ul d be 
re p orte d t o Pfizer u p o n disc o ver y al o n g wit h a ny acti o ns ta ke n.  T he site s h o ul d 
acti vel y p urs ue o pti o ns f or ret ur ni n g t he st u d y i nter ve nti o n t o t he st ora ge c o n diti o ns 
descri be d i n t he la beli n g, as s o o n as p ossi ble.  O nce a n e xc ursi o n is i de ntifie d, t he 
st u d y i nter ve nti o n m ust be q uara nti ne d a n d n ot use d u ntil Pfizer pr o vi des per missi o n 
t o use t he st u d y i nter ve nti o n.  It will n ot be c o nsi dere d a pr ot oc ol de viati o n if Pfizer 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 4 6
a p pr o ves t he use of t he st u d y i nter ve nti o n after t he te m perat ure e xc ursi o n. Use of t he 
st u d y i nter ve nti o n pri or t o Pfizer a p pr o val will be c o nsi dere d a pr ot oc ol de viati o n. 
S pecific details re gar di n g t he defi niti o n of a n e xc ursi o n a n d i nf or mati o n t he site 
s h o ul d re p ort f or eac h e xc ursi o n will be pr o vi de d t o t he site i n t he pac ka ge i nsert.
T he s p o ns or or desi g nee will pr o vi de g ui da nce o n t he destr ucti o n of u n use d st u d y  
i nter ve nti o n (e g, at t he site).  If destr ucti o n is a ut h orize d t o ta ke place at t he 
i n vesti gat or site, t he i n vesti gat or m ust e ns ure t hat t he materials are destr oye d i n 
c o m plia nce wit h a p plica ble e n vir o n me ntal re g ulati o ns, i nstit uti o nal p olic y, a n d a n y 
special i nstr ucti o ns pr o vi de d b y Pfizer, a n d all destr ucti o n m ust be a de q uatel y 
d oc u me nte d.
6. 2. 1. Pre p ar ati o n a n d Dis pe nsi n g
See t he pac ka ge i nsert f or i nstr ucti o ns o n h o w t o pre pare t he i n vesti gati o nal pr o d uct f or 
a d mi nistrati o n.  In vesti gati o nal pr o d uct s h o ul d be pre pare d a n d dis pe nse d b y a n 
a p pr o priatel y q ualifie d a n d e x perie nce d me m ber of t he st u d y staff (e g, p h ysicia n, n urse, 
p h y sicia n’s assista nt, n urse practiti o ner, p har mac y assista nt/tec h nicia n, or p har macist) as 
all o we d b y l ocal, state, a n d i nstit uti o nal g ui da nce.
6. 3. Me as ures t o Mi ni mize Bi as: R a n d o miz ati o n a n d Bli n di n g
6. 3. 1. All oc ati o n t o I n vesti g ati o n al Pr o d uct
T his is a si n gle -ar m st u d y.  Partici pa nt eli gi bilit y f or partici pati o n i n t he st u d y will recei ve 
tafa mi dis 6 1 m g, t he a p pr o ve d d ose i n C hi na, o nce dail y for 1 2 m o nt hs f oll o wi n g t he 
assess me nts at t he scree ni n g a n d baseli ne visits.
T here is n o re q uire me nt of bli n di n g a n d ra n d o mizati o n.
6. 4. St u d y I nter ve nti o n C o m pli a nce
Partici pa nts will be i nstr ucte d t o ta ke t he me dicati o n o n a dail y basis.  T he y will als o be
i nstr ucte d t o bri n g all of t heir st u d y me dicati o n bac k t o t he st u d y site, i ncl u di n g use d a n d
u n use d st u d y  me dicati o n, at eac h sc he d ule d st u dy visit s o t hat t he t otal a m o u nt of dr u g ta ke n 
ca n be deter mi ne d a n d u n use d me dicati o n c ollecte d b y site pers o n nel. 
Partici pa nt c o m plia nce wit h i n vesti gati o nal pr o d uct will be assesse d at eac h visit.  
C o m plia nce will be assesse d b y  c o u nti n g ret ur ne d ca ps ules.  Partici pa nts will be c o nsi dere d
t o be a d here nt t o t he d osi n g re q uire me nts of t he st u d y if t he y ha ve ta ke n st u dy me dicati o n 
per da y  o n at least 8 0 % of t he da ys of st u dy partici pati o n.  De viati o n(s) fr o m t he prescri be d 
d osa ge re gi me n s h o ul d be rec or de d i n t he C R F.  Partici pa nts wit h less t ha n 8 0 % d osi n g 
a d here nce will be e xcl u de d fr o m t he per pr ot oc ol a nalys is set.
All d oses of i n vesti gati o nal pr o d uct will be a d mi nistere d b y t he a p pr o priatel y desi g nate d 
st u d y staff at t he i n vesti gat or site.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 4 7
6. 5. C o nc o mit a nt T her a p y
Me dicati o ns ta ke n wit hi n 2 8 da y s bef ore t he first d ose of trial me dicati o n will be d oc u me nte d 
as a pri or me d icati o n.  Me dicati o ns ta ke n after t he first d ose of trial me dicati o n will be 
d oc u me nte d as c o nc o mita nt me dicati o ns.
C o nc o mita nt Treat me nt is defi ne d as o n g oi n g or i nitiate d at a n y ti me o n or after baseli ne
( Da y 1) of t he st u d y t hr o u g h t he fi nal st u d y visit.  C o nc o mita nt treat me nts i ncl u de a ny
s u bsta nce i n geste d, i njecte d, a bs or be d, i n hale d, or ot her wise e nters t he b o d y f or a t hera pe utic
p ur p ose re gar dless of n u m ber of d oses ta ke n.  T his i ncl u des prescri pti o n a n d
o ver -t he-c o u nter me dici nes, vita mi ns, a n d her bal re me dies.
Partici pa nts ma y  use s u p ple me nts a n d me dicati o ns d uri n g t he c o urse of t he st u d y wit h t he
e xce pti o n of t h ose liste d i n pac ka ge i nsert.  Me dicati o n c o nsi dere d t o be sta n dar d of care are 
per mitte d b ut s h o ul d be rec or de d o n t he C R F. If a partici pa nt is offere d, i n acc or da nce wit h 
t he pre vaili n g l ocal g ui deli nes, a C O VI D-1 9 vacci ne, it s h o ul d be per mitte d. T his w o ul d be 
rec or de d as a c o nc o mita nt me dicati o n a n d sta n dar d A E c ollecti o n a n d re p orti n g pr ocesses 
w o ul d be f oll o we d.
Pr o hi bite d T hera pies: 
Use of n o n -ster oi dal a nti-i nfla m mat or y dr u gs ( N S AI Ds) ot her t ha n t h ose n ote d bel o w 
is pr o hi bite d.  S o me N S AI Ds, li ke difl u nisal, ca n bi n d t o t he t h yr o xi ne bi n di n g sites 
o n tra nst h y reti n. C hr o nic use ( greater t ha n 4 ti mes/ m o nt h) of N S AI Ds bef ore t he 
st u d y is pr o hi bite d e xce pt t he f oll o wi n g per mitte d N S AI Ds: acetyl salic ylic aci d, 
et o d olac, i b u pr ofe n, i n d o met haci n, ket o pr ofe n, na b u met o ne, na pr o xe n, ni mes uli de, 
pir o xica m, a n d s uli n dac. T o pical o p ht hal mic N S AI Ds a d mi nistere d w hile t he 
patie nt’s nasal p u nct u m is occl u de d are als o per mitte d.
Use of a n y i n vesti gati o nal dr u g or vacci ne d uri n g t he st u d y  is pr o hi bite d.
A d diti o nall y , t he use of difl u nisal, ta ur o urs o de o xyc h olate a n d d o x yc yc li ne or a n y 
ot her T T R sta bilizi n g a ge nt or e x peri me ntal i nter ve nti o ns f or tra nst hyreti n a m yl oi d 
car di o m y o pat h y wit hi n 3 0 da y s pri or t o t he st u d y e ntr y a n d/ or d uri n g st u d y 
partici pati o n is n ot per mitte d.
Di gitalis a n d calci u m c ha n nel bl oc kers (e g, vera pa mil, diltiaze m) are pr o hi bite d
c o nc o mita nt me dicati o ns beca use t he y bi n d t o am y l oi d fi brils a n d ma y lea d t o
i ncrease d t o xicit y.
Use of a n y d osa ge f or m of tafa mi dis bef ore t he st u d y is pr o hi bite d.
C o ntrai n dicate d t hera pies m ust be i n acc or da nce wit h i n vesti gati o nal dr u g pac ka ge i nsert.
H or m o nal c o ntrace pti ves t hat meet t he re q uire me nts of t his st u d y  are all o we d t o be use d i n 
partici pa nts w h o are w o me n of c hil d beari n g p ote ntial ( W O C B P) (see A p pe n di x 4 ).
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 4 8
Use of tra diti o nal C hi nese me dici ne s h o ul d o btai n t he per missi o n of i n vesti gat or.
6. 5. 1. Resc u e Me dici ne 
T here is n o resc ue t hera p y t o re verse t he a d verse e ve nts ( A Es) o bser ve d wit h tafa mi dis; 
sta n dar d me dical s u p p orti ve care m ust be pr o vi de d t o ma na ge t he A Es. 
6. 6. D ose M o dific ati o n 
N ot a p plica ble.
6. 7. I nter ve nti o n After t he E n d of t he St u d y
N o i nter ve nti o n will be pr o vi de d t o st u d y partici pa nts at t he e n d of t he st u d y. Partici pa nts 
s h o ul d refer t o r o uti ne cli nical care pr oce d ure wit h c o ns ulti n g fr o m cli nical p h ysicia ns after 
e n d of t he st u d y.
7. DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L
7. 1. Disc o nti n u ati o n of St u d y I nter ve nti o n
Partici pa nts wit h o ne or m ore of t he f oll o wi n g criteria i n t he st u d y  d urati o n will disc o nti n ue 
t he i n vesti gati o nal dr u g:
E x perie nce a d verse e ve nts t hat ma y  be ass ociate d wit h t he t olera bilit y of treat me nt wit h 
tafa mi dis, ot her safet y criteria(e g, A E, P K criteria), disease state criteria (e g, 
pr o gressi ve disease), etc.  T he site has t he o pti o n t o disc o nti n ue d osi n g f or t his 
p artici pa nt a n d t o ter mi nate t he partici pa nt 's st u dy partici pati o n.
N ote t hat disc o nti n uati o n of st u d y  i nter ve nti o n d oes n ot re prese nt wit h dra wal fr o m t he st u d y 
u nless t he patie nt re q uests wit h dra wal fr o m t he st u d y .  If st u d y i nter ve nti o n is defi niti vel y 
di sc o nti n ue d, t he partici pa nt will re mai n i n t he st u d y t o be e val uate d f or t he E n d of 
Treat me nt visit ( wit hi n 2 wee ks after t he E n d of Treat me nt date).  See t he S o A f or data t o be 
c ollecte d at t he ti me of disc o nti n uati o n of st u d y  i nterve nti o n a n d f oll o w -u p f or a n y  f urt her 
e val uati o ns t hat nee d t o be c o m plete d. I n t he e ve nt of early St u d y I nter ve nti o n 
Disc o nti n uati o n, t he site staff will f oll o w- u p o n t he partici pa nt’s vital stat us at M o nt h 1 2 
fr o m baseli ne ( or at Earl y St u d y Disc o nti n uati o n visit f or a partici pa nt w h o wit h dra ws 
c o nse nt f or a n y f urt her c o ntact).
I n t he e ve nt of disc o nti n uati o n of st u d y i nter ve nti o n, it m ust be d oc u me nte d o n t he 
a p pr o priate C R F/i n t he me dical rec or ds w het her t he partici pa nt is disc o nti n ui n g f urt her 
recei pt of st u d y  i nter ve nti o n or als o fr o m st u d y pr oce d ures, p osttreat me nt st u d y f oll o w- u p, 
a n d/ or f ut ure c ollecti o n of a d diti o nal i nf or mati o n.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 4 9
E C G C h a n ges 
A partici pa nt w h o meets eit her b ullete d criteri o n base d o n electr ocar di o gra m (E C G ) rea di n gs 
will be wit h d ra w n fr o m t he st u d y. 
Q Tc F > 5 0 0 msec.
C ha n ge fr o m baseli ne: Q Tc > 6 0 msec.
If a cli nicall y si g nifica nt fi n di n g is i de ntifie d (i ncl u di n g, b ut n ot li mite d t o, c ha n ges fr o m 
baseli ne i n Q Tc F after e nr oll me nt), t he i n vesti gat or or q ualifie d desi g nee will deter mi ne if 
t he partici pa nt ca n c o nti n ue i n t he st u d y a n d if a n y c ha n ge i n partici pa nt ma na ge me nt is 
nee de d.  T his re vie w of t he E C G pri nte d at t he ti me of c ollecti o n m ust be d oc u me nte d.  A n y  
ne w cli nicall y rele va nt fi n di n g s h o ul d be re p orte d as a n A E.
See t he S o A f or data t o be c ollecte d at t he ti me of i nter ve nti o n disc o nti n uati o n a n d f oll o w- u p 
a n d f or a n y f urt her e val uati o ns t hat nee d t o be c o m plete d.
7. 1. 1. Te m p or ar y Disc o nti n u ati o n 
N ot a p plica ble.
7. 1. 2. Rec h alle n ge
N ot a p plica ble.
7. 2. P artici p a nt Disc o nti n u ati o n/ Wit h dr a w al Fr o m t he St u d y 
A partici pa nt ma y  wit h dra w fr o m t he st u d y at a ny ti me at his/ her o w n re q uest.  Reas o ns f or 
disc o nti n uati o n fr o m t he st u d y  i ncl u de t he f oll o wi n g:

Ref use d f urt her f oll o w -u p;

L ost t o f oll o w - u p;

Deat h;

St u d y  ter mi nated b y  s p o ns or;
Partici pa nts s h o ul d be q uesti o ne d re gar di n g t heir reas o n f or wit h dra wal.  T he partici pa nt will 
be per ma ne ntl y  disc o nti n ue d b ot h fr o m t he i n vesti gati o nal pr o d uct a n d fr o m t he st u d y at t hat 
ti me.If a partici pa nt wit h dra ws fr o m t he st u dy, he/s he ma y  re q uest destr ucti o n of a n y 
re mai ni n g sa m ples ta ke n a n d n ot teste d,  a n d t he i n vesti gat or m ust d oc u me nt a n y s uc h 
re q uests i n t he site st u d y rec or ds a n d n otif y t he s p o ns or acc or di n gl y.
If t he partici pa nt wit h dra ws fr o m t he st u d y a n d als o wit h dra ws c o nsent (see Secti o n 7. 2. 1 ) 
f or discl os ure of f ut ure i nf or mati o n, n o f urt her e val uati o ns s h o ul d be perf or me d a n d n o 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 5 0
a d diti o nal data s h o ul d be c ollecte d.  T he s p o ns or ma y  retai n a n d c o nti n ue t o use a n y data 
c ollecte d bef ore s uc h wit h dra wal of c o nse nt.
Lac k of c o m pleti o n of all or a n y of t he wit h dra wal/earl y ter mi nati o n pr oce d ures will n ot be 
vie we d as pr ot oc ol de viati o ns s o l o n g as t he partici pa nt’s safet y was preser ve d.
7. 2. 1.
Wit h dr a w al of C o nse nt 
Partici pa nts w h o re q uest t o disc o nti n ue recei pt of st u d y  treat me nt will re mai n i n t he st u d y 
a n d m ust c o nti n ue t o be f oll o we d f or pr ot oc ol -s pecifie d f oll o w- u p pr oce d ures.  T he o nly 
e xce pti o n t o t his is w he n a partici pa nt s pecificall y wit h dra ws c o nse nt f or a n y f urt her c o ntact 
wit h hi m or her or pers o ns pre vi o usl y a ut h orize d b y t he partici pa nt t o pr o vi de t his 
i nf or mati o n.  Partici pa nts s h o ul d n otif y t he i n vesti gat or i n writi n g of t he decisi o n t o 
wit h dra w c o nse nt fr o m f ut ure f oll o w- u p, w he ne ver p ossi ble.  T he wit h dra wal of c o nse nt 
s h o ul d be e x plai ne d i n detail i n t he me dical rec or ds b y  t he i n vesti gat or, as t o w het her t he 
wit h dra wal is o nl y  fr o m f urt her recei pt of st u d y i nter ve nti o n or als o fr o m st u d y pr oce d ures 
a n d/ or p osttreat me nt st u d y f oll o w-u p, a n d e ntere d o n t he a p pr o priate C R F pa ge. I n t he e ve nt 
t hat vital stat us ( w het her t he partici pa nt is ali ve or dea d) is bei n g meas ure d, p u blicl y 
a vaila ble i nf or mati o n s h o ul d be use d t o deter mi ne vital stat us o nl y  as a p pr o priatel y directe d 
i n acc or da nce wit h l ocal la w.
7. 3. L ost t o F oll o w -u p 
A partici p a 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 
sc he d ule d visits a n d is u na ble t o be c o ntacte d by t he st u d y  site.
T he f oll o wi n g acti o ns m ust be ta ke n if a partici pa nt fails t o ret ur n t o t he cli nic f or a re q uire d 
st u d y visit:
T he site m ust atte m pt t o c o ntact t he partici pa nt a n d resc he d ule t he misse d visit as s o o n as 
p ossi ble a n d c o u nsel t he partici pa nt o n t he i m p orta nce of mai ntai ni n g t he assi g ne d 
visit sc he d ule a n d ascertai n w het her or n ot t he partici pa nt wis hes t o a n d/ o r s h o ul d 
c o nti n ue i n t he st u d y;
Bef ore a partici pa nt is dee me d l ost t o f oll o w- u p, t he i n vesti gat or or desi g nee m ust ma ke 
e ver y eff ort t o re gai n c o ntact wit h t he partici pa nt ( w here p ossi ble, 3 tele p h o ne calls 
a n d, if necessar y, a certifie d letter t o t he partici pa nt’s last k n o w n maili n g a d dress or 
l ocal e q ui vale nt met h o ds).  T hese c o ntact atte m pts s h o ul d be d oc u me nte d i n t he 
partici pa nt’s me dical rec or d;
S h o ul d t he partici pa nt c o nti n ue t o be u nreac ha ble, he/s he will be c o nsi dere d t o ha ve 
wit h dra w n fr o m t he st u d y . 
Disc o nti n uati o n of s pecific sites or of t he st u d y  as a w h ole is ha n dle d as part of A p pe n di x 1 .
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 5 1
8. S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S
T he i n vesti gat or ( or a n a p pr o priate dele gate at t he i n vesti gat or site) m ust o btai n a si g ne d a n d 
date d I C D bef ore perf or mi n g a n y st u d y- s pecific pr oce d ures.  
St u d y  pr oce d ures a n d t heir ti mi n g are s u m marize d i n t he S o A .  Pr ot oc ol wai vers or 
e xe m pti o ns are n ot all o we d.
W here m ulti ple pr oce d ures are sc he d ule d at t he sa me n o mi nal ti me p oi nt(s) relati ve t o 
d osi n g, t he f oll o wi n g c hr o n ol o g y  of e ve nts is s u g geste d:
1. E C G
2. Vitals: Bl o o d press ure/ p ulse rate
3. Bl o o d sa m ple c ollecti o n
4. Bl o o d s peci me ns f or plas ma c o nce ntrati o ns of tafa mi dis, T T R sta bilizati o n, a n d T T R 
c o nce ntrati o ns s h o ul d be o btai ne d wit hi n t he s pecifie d ti me wi n d o ws if a p plica ble.
I m me diate safet y c o ncer ns s h o ul d be disc usse d wit h t he s p o ns or i m me diatel y u p o n 
occ urre nce or a ware ness t o deter mi ne if t he partici pa nt s h o ul d c o nti n ue or disc o nti n ue 
i n vesti gati o nal pr o d uct.
A d here nce t o t he st u d y desi g n re q uire me nts, i ncl u di n g t h ose s pecifie d i n t he S o A , is esse ntial 
a n d re q uire d f or st u d y c o n d uct.
All scree ni n g e val uati o ns m ust be c o m plete d a n d re vie we d t o c o nfir m t hat p ote ntial 
partici pa nts meet all eli gi bilit y  criteria.  T he i n vesti gat or will mai ntai n a scree ni n g l o g t o 
rec or d details of all partici pa nts scree ne d a n d t o c o nfir m eli gi bilit y or rec or d reas o ns f or 
scree ni n g fail ure, as a p plica ble.
Pr oce d ures c o n d ucte d as part of t he partici pa nt’s r o uti ne cli nical ma na ge me nt (e g, bl o o d 
c o u nt) a n d o btai ne d bef ore si g ni n g of t he I C D ma y be utilize d f or scree ni n g or baseli ne 
p ur p oses pr o vi de d t he pr oce d ures met t he pr ot oc ol -s pecifie d criteria a n d were perf or me d 
wit hi n t he ti me fra me def i ne d i n t he S o A .
E ver y  eff ort s h o ul d be ma de t o e ns ure t hat pr ot oc ol-re q uire d tests a n d pr oce d ures are 
c o m plete d as descri be d.  H o we ver, it is a ntici pate d t hat fr o m ti me t o ti me t here ma y  be 
circ u msta nces o utsi de t he c o ntr ol of t he i n vesti gat or t hat ma y  ma ke it u nfeasi ble t o perf or m 
t he test.  In t hese cases, t he i n vesti gat or m ust ta ke all ste ps necessar y  t o e ns ure t he safety a n d 
well - bei n g of t he partici pa nt.  W he n a pr ot oc ol-re q uire d test ca n n ot be perf or me d, t he 
i n vesti gat or will doc u me nt t he reas o n f or t he misse d test a n d a n y c orrecti ve a n d pre ve nti ve 
acti o ns t hat he or s he has ta ke n t o e ns ure t hat re q uire d pr ocesses are a d here d t o as s o o n as 
p ossi ble.  T he st u d y  tea m m ust be i nf or me d of t hese i nci de nts i n a ti mel y ma n ner.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 5 2
A d diti o n all y, visits s h o ul d be c o m plete d as cl ose t o t he sc he d ule d ti mefra me as p ossi ble b ut 
n ot t o e xcee d 1 wee k of t he tar get date f or eac h sc he d ule d visit. T he d urati o n of t his st u d y  is 
1 2 m o nt hs.  F oll o w - u p visit dates s h o ul d be base d o n t he date of t he Baseli ne visit, n ot t he 
date of t he pre vi o us f oll o w -u p visit e xce pt t he p ost- treat me nt f oll o w- u p.
F or sa m ples bei n g c ollecte d a n d s hi p pe d, detaile d c ollecti o n, pr ocessi n g, st ora ge, a n d 
s hi p me nt i nstr ucti o ns a n d c o ntact i nf or mati o n will be pr o vi de d t o the i n vesti gat or site pri or 
t o i nitiati o n of t he st u d y.
T he t otal pla n ne d per pr ot oc ol bl o o d sa m pli n g v ol u me f or i n di vi d ual partici pa nts i n t his 
st u d y is a p pr o xi matel y 2 8 0 m L , i ncl u di n g p ote ntial ad diti o nal bl o o d sa m ples ta ke n f or safet y 
assess me nts at ti me s s pecifie d by i n vesti gat or. A d diti o nal bl o o d sa m ples ma y be ta ke n f or 
safety assess me nts w he n re q uire d f or ma na ge me nt of a d verse e ve nts, pr o vi de d t he t otal 
v ol u me ta ke n d uri n g t he st u d y  d oes n ot e xcee d 5 5 0 m L  d uri n g a ny peri o d of 5 6 c o nsec uti ve 
da y s.I n e xce pti o nal circ u msta nces, s uc h as me dical e mer ge ncies, t his v ol u me ma y  be 
e xcee de d a n d will n ot c o nstit ute a pr ot oc ol de viati o n i n s uc h circ u msta nces. 
8. 1. Effic ac y Assess me nts
6 - Mi n ute W al k Test ( 6-M W T)
A 6 -M W T will be c o n d ucte d at ti me p oi nts i n t he S o A .  T he test will be c o n d ucte d i n 
acc or da nce wit h g ui deli nes esta blis he d b y t he A merica n T h oracic S ociet y. 
Ne w Y or k He art Ass oci ati o n Cl assific ati o n
Partici pa nts will be e val uate d usi n g t he Ne w Y or k Heart Ass ociati o n ( N Y H A) classifi cati o n 
at ti me p oi nts i n t he S o A . F or N Y H A classificati o ns refer t o A p pe n di x 8 . 
8. 2. S afet y Assess me nts
Pla n ne d ti me p oi nts f or all safet y  assess me nts are pr o vi de d i n t he S o A .  U nsc he d ule d cli nical 
la b orat or y meas ure me nts ma y be o btai ne d at a n y ti me d uri n g t he st u dy t o assess a n y 
percei ve d safet y  c o ncer ns.
8. 2. 1. P h ysic al E x a mi n ati o ns
A f ull p h y sical e xa mi nati o n s h o ul d i ncl u de all of t he f oll o wi n g assess me nt.
Hei g ht a n d wei g ht will als o be meas ure d a n d rec or de d.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 5 3
Ge neral a p peara nce
Hea d a n d nec k
E y es
Ears
S ki n
N ose
T hr oat
Ge nit o uri nar y
Ne ur ol o gical
Car di o vasc ular
A b d o me n
M usc ul os keletal
Res pirat or y
A brief p h ys ical e xa mi nati o n will i ncl u de, at a mi ni m u m, assess me nts of t he s ki n, l u n gs, 
car di o vasc ular s ys te m, a n d a b d o me n (li ver a n d s plee n) a n d are t o be perf or me d at all ot her 
st u d y visits.
Wei g ht will als o be meas ure d a n d rec or de d.
I n vesti gat ors s h o ul d pa y s pecial atte nti o n t o cli nical si g ns relate d t o pre vi o us seri o us 
ill nesses. 
8. 2. 2. Vit al Si g ns
Vital si g ns will be rec or de d at eac h st u d y  visit.
Vital si g ns will be meas ure d wit h t he partici pa nt i n a se mis u pi ne p ositi o n after at least 
5 m i n utes of rest a n d will i ncl u de b o d y te m perat ure, s yst olic a n d diast olic bl o o d press ure, 
a n d p ulse rate a n d res pirat or y  rate.  T hree rea di n gs of bl o o d press ure a n d p ulse rate will be 
ta ke n.  T he first rea di n g s h o ul d be rejecte d.  T he sec o n d a n d t hir d rea din gs s h o ul d be 
a vera ge d t o gi ve t he meas ure me nt t o be rec or de d i n t he C R F.
8. 2. 3. Electr oc ar di o gr a ms
1 2 -Lea d E C Gs s h o ul d be c ollecte d at ti mes s pecifie d i n t he S o A usi n g a n E C G mac hi ne t hat 
a ut o maticall y calc ulates t he heart rate a n d meas ures P R i nter val ( P R), Q T i nter val ( Q T), a n d 
c orrecte d Q T ( Q Tc) i nter vals a n d Q R S c o m ple x ( Q R S).  All sc he d ule d E C Gs s h o ul d be 
perf or me d bef ore bl o o d press ure or p ulse meas ure me nts or bl o o d c ollecti o n, F or E C G 
rec or di n gs, t he partici pa nts will re mai n s u pi ne f or a b o ut 5 mi n utes bef ore rec or di n g t he E C G. 
If a p ost d ose Q Tc F i nter val re mai ns ≥6 0 msec fr o m t he baseli ne a n d is > 4 5 0 msec; or b) a n 
a bs ol ute Q Tc F val ue is ≥5 0 0 msec f or a n y sc he d ule d E C G f or greater t ha n 4 h o urs ( or 
s o o ner, at t he discreti o n of t he i n vesti gat or), or Q Tc i nter vals get pr o gressi vel y l o n ger, t he 
partici pa nt s h o ul d u n der g o c o nti n u o us E C G m o nit ori n g.   A car di ol o gist s h o ul d be c o ns ulte d 
if Q Tc i nter vals d o n ot ret ur n t o less t ha n t he criteri o n liste d a b o ve after 8 h o urs of 
m o nit ori n g ( or s o o ner, at t he discreti o n of t he i n vesti gat or). 
E C G data will be s u b mitte d t o a site la b orat or y f or meas ure me nt.  The fi nal E C G re p ort fr o m 
t he ce ntral la b orat or y s h o ul d be mai ntai ne d i n t he partici pa nt’s s o urce d oc u me ntati o n a n d be 
t he fi nal i nter pretati o n of t he E C G rec or di n g.  A n y cli nicall y si g nifica nt c ha n ges fr o m t he 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 5 4
baseli ne/ Da y  1 E C G ma y p ote ntiall y be A Es (A p pe n di x 7 ) a n d s h o ul d be e val uate d f urt her, 
as cli nicall y warra nte d.  
I n s o me cases, it ma y be a p pr o priate t o re peat a b n or mal E C Gs t o r ule o ut i m pr o per lea d 
place me nt as c o ntri b uti n g t o t he E C G a b n or malit y.  It is i m p orta nt t hat lea ds be place d i n t he 
sa me p ositi o ns eac h ti me i n or der t o ac hie ve precise E C G rec or di n gs.  If a mac hi ne-rea d Q Tc 
val ue is pr ol o n ge d, as defi ne d a b o ve, re peat meas ure me nts ma y n ot be necessar y if a 
q ualifie d me dical pr o vi der’s i nter pretati o n deter mi nes t hat t he Q Tc F val ues are i n t he 
acce pta ble ra n ge.
E C G val ues of p ote ntial cli nical c o ncer n are liste d i n A p pe n di x 7 .
8. 2. 4. Ec h oc ar di o gr a ms
Ec h ocar di o gra p h y ( 2 D D o p pler) will be perf or me d f or all partici pa nts at ti mes s pecifie d i n 
t he S o A .  T he assess me nt of e n d-diast olic i nter ve ntric ular se ptal t hic k ness f or st u d y e ntr y 
will be base d o n t he ec h ocar di o gra m perf or me d at t he Scree ni n g visit as i nter prete d b y t he 
i n de pe n de nt ce ntral la b orat or y.  If t he Scree ni n g ec h ocar di o gra p hic rec or di n g is n ot clear 
e n o u g h t o acc uratel y deter mi ne t he e n d -diast olic i nter ve ntric ular se ptal wall t hic k ness, it 
m ust be re peate d.  Eac h ec h ocar di o gra m will be rec or de d a n d re vie we d l ocall y by t he cli nical 
site, a n d t he cli nical si g nifica nce of ec h ocar di o gra m fi n di n gs will be assesse d b y t he 
I n vesti gat or.  Eac h ec h ocar di o gra m will als o be se nt t o a n i n de pe n de nt ce ntral la b orat or y t hat 
will c o n d uct a ce ntralize d re vie w of t he res ults.  T he ce ntral rea di n g of t he Scree ni n g 
ec h ocar di o gra m m ust be c o m plete d pri or t o partici pa nt ra n d o mizati o n at t he Baseli ne visit.
T he f oll o wi n g para meters will be i ncl u de d i n t he assess me nt:
E n d -diast olic i nter ve ntric ular se ptal wall t hic k ness ( m m).
Left ve ntricle p osteri or wall t hic k ness ( m m).
Left ve ntric ular ejecti o n fracti o n ( %).
Left ve ntric ular str o ke v ol u me ( m L ).
Fracti o nal s h orte ni n g ( %).
Left atrial dia meter, a nteri or -p osteri or ( m m).
Left ve ntric ular e n d s ys t olic dia meter ( m m).
Left ve ntric ular e n d s ys t olic v ol u me ( m L).
Left ve ntric ular e n d-diast olic dia meter ( m m).
Left ve ntric ular e n d -diast olic v ol u me ( m L ).
Left ve ntric ular mass ( g).
T he rati o of pea k vel ocit y bl o o d fl o w fr o m gra vit y i n earl y diast ole (t he E wa ve) t o pea k 
vel ocit y  fl o w i n late diast ole ca use d by atrial c o ntracti o n (t he A wa ve) (E/ A ).  
8. 2. 5. Cli nic al S afet y L a b or at or y Assess me nts
See A p pe n di x 2 f or t he list of cli nical safety la b orat or y tests t o be perf or me d a n d t he S o A f or 
t he ti mi n g a n d fre q ue nc y. All pr ot oc ol -re q uire d la b orat or y assess me nts, as defi ne d i n 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 5 5
A p pe n di x 2 , m ust be c o n d ucte d i n acc or da nce wit h t he la b orat or y ma n ual a n d t he S o A .
U nsc he d ule d cli nical la b orat or y  meas ure me nts ma y be o btai ne d at a n y ti me d uri n g t he st u d y 
t o assess a ny percei ve d safet y iss ues.
T he i n vesti gat or m ust re vie w t he la b orat or y  re p ort, d oc u me nt t his re vie w, a n d rec or d a ny 
cli nicall y rele va nt c ha n ges occ urri n g d uri n g t he st u d y i n t he A E secti o n of t he C R F.  
Cli nicall y  si g nifica nt a b n or mal la b orat or y fi n di n gs are t h ose w hic h are n ot ass ociate d wit h 
t he u n derlyi n g disease, u nless j u d ge d b y t he i n vesti gat or t o be m ore se vere t ha n e x pecte d f or 
t he partici pa nt's c o n diti o n.
All la b orat or y  tests wit h val ues c o nsi dere d cli nicall y si g nifica ntly a b n or mal d uri n g 
partici pati o n i n t he st u d y  or wit hi n 2 8 da y s after t he last d ose of st u d y i nter ve nti o n s h o ul d be 
re peate d u ntil t he val ues ret ur n t o n or mal or baseli ne or are n o l o n ger c o nsi dere d cli nicall y 
si g nifica nt by t he i n vesti gat or or me dical m o nit or.
If la b orat or y val ues fr o m n o n-pr ot oc ol -s pecifie d la b orat or y assess me nts perf or me d at t he 
i nstit uti o n’s l ocal la b orat or y re q uire a c ha n ge i n partici pa nt ma na ge me nt or are c o nsi dere d 
cli nicall y si g nifica nt by t he i n vesti gat or (e g, S A E or A E or d ose m o dificati o n), t he n t he 
res ults m ust be rec or de d i n t he C R F.
8. 2. 6. B o d y M ass I n de x/ M o difie d B o d y M ass I n de x .
Tra nst h y reti n, i n t he m o n o meric f or m, ca n e nter car diac a n d ne ural tiss ues.  As part of t he
p ol y ne ur o pat h y , T T R ca n ca use se vere gastr oi ntestinal pr o ble ms res ulti n g i n wasti n g.  A
mea ns of deter mi ni n g if t here is gastr oi ntesti nal i n v ol ve me nt i n partici pa nts is t o calc ulate 
t he m o difie d B o d y Mass I n de x ( m B MI). B o d y Mass I n de x ( B MI) is calc ulate d as wei g ht
( k g)/[ hei g ht ( meters)].  T he m B MI is calc ulate d b y  m ulti pl yi n g B MI by ser u m al b u mi n
c o nce ntrati o n ( g/ L).
8. 2. 7. H os pit aliz ati o n Deter mi n ati o n
Sites will deter mi ne at eac h visit w het her t he partici pa nt has bee n h os pitalize d (i ncl u di n g t he
reas o n f or h os pitalizati o n). 
H os pitalizati o n is defi ne d as a n o n -electi ve a d missi o n t o a n ac ute care setti n g f or me dical 
t hera py t hat res ults i n at least a 2 4 -h o ur sta y  ( or a date c ha n ge if t he ti me of 
a d missi o n/ disc har ge is n ot a vaila ble).  Car di o vasc ular -relate d h os pitalizati o n i ncl u des
h os pitalizati o ns wit h a dis c har ge dia g n osis t hat i ncl u des a car di o vasc ular reas o n f or
h os pitalizati o n.
H os pitalizati o n d oes n ot i ncl u de a d missi o n t o t he f oll o wi n g:
Re ha bilitati o n facilities.
H os pice facilities.
Res pite care (e g, care gi ver relief).
S kille d n ursi n g facilities.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 5 6
N ursi n g h o mes.
R o uti ne e mer ge nc y  r o o m a d missi o ns (less t ha n 2 4 h o urs).
Sa me -d a y  s ur geries (as o ut patie nt/sa me-d a y /a m b ulat or y pr oce d ures).
8. 2. 8. Pre g n a nc y Testi n g 
Pre g na nc y  tests s h o ul d be ser u m tests, b ut m ust ha ve a se nsiti vit y  of at least 2 5 mI U/ m L.  
Pre g na nc y  tests will be perf or me d i n W O C B P at t he ti mes liste d i n t he S o A .  A ne gati ve 
pre g na nc y  test res ult will be re q uire d pri or t he partici pa nt’s recei vi n g t he tafa mi dis.  
Pre g na nc y  tests will als o be d o ne w he ne ver 1 me nstr ual c ycle is misse d d uri n g t he acti ve 
treat me nt peri o d ( or w he n p ote ntial pre g na nc y is ot her wise s us pecte d) a n d at t he e n d of t he 
st u d y.  Pre g na nc y tests ma y als o be re peate d if re q ueste d b y i nstit uti o nal re vie w b oar ds 
(IR Bs)/et hics c o m mittees ( E Cs) or if re q uire d b y  l ocal re gulati o ns.  
8. 3. A d verse E ve nts a n d Seri o us A d verse E ve nts
T he defi niti o ns of a n A E a n d a n S A E ca n be f o u n d i n A p pe n di x 3 .
A Es will be re p orte d b y t he partici pa nt ( or, w he n a p pr o priate, b y a care gi ver, s urr o gate, or 
t he partici pa nt's le gall y a ut h orize d re prese ntati ve).
T he i n vesti gat or a n d a n y q ualifie d desi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g, a n d 
rec or di n g e ve nts t hat meet t he defi niti o n of a n A E or S A E a n d re mai n res p o nsi ble t o p urs ue 
a n d o btai n a de q uate i nf or mati o n b ot h t o deter mi ne t he o utc o me a n d t o assess w het her t he 
e ve nt meets t he criteria f or classificati o n as a n S A E or ca use d t he partici pa nt t o disc o nti n ue 
t he st u d y i nter ve nti o n (see Secti o n 7. 1 ). 
Eac h partici pa nt le gall y a ut h orize d re prese ntati ve will be q uesti o ne d a b o ut t he occ urre nce of 
A Es i n a n o nlea di n g ma n ner.
I n a d diti o n, t he i n vesti gat or ma y be re q ueste d b y Pfizer Safety t o o btai n s pecific f oll o w - u p 
i nf or mati o n i n a n e x pe dite d fas hi o n.
8. 3. 1. Ti me Peri o d a n d Fre q ue nc y f or C ollecti n g A E a n d S A E I nf or m ati o n
T he ti me peri o d f or acti vel y  eliciti n g a n d c ollecti n g A Es a n d S A Es (“acti ve c ollecti o n 
peri o d”) f or eac h partici pa nt be gi ns fr o m t he ti me t he partici pa nt pr o vi des i nf or me d c o nse nt, 
w hic h is o btai ne d be f ore t he partici pa nt’s partici pati o n i n t he st u d y (ie, bef ore u n der g oi n g 
a n y st u d y-relate d pr oce d ure a n d/ or recei vi n g st u d y i nter ve nti o n), t hr o u g h a n d i ncl u di n g a 
mi ni m u m of 2 8 cale n dar da y s, e xce pt as i n dicate d bel o w after t he last a d mi nistrati o n of t he 
st u d y i nter ve nti o n.
F oll o w u p b y  t he i n vesti gat or c o nti n ues t hr o u g h o ut a n d after t he acti ve c ollecti o n peri o d a n d 
u ntil t he A E or S A E or its se q uelae res ol ve or sta bilize at a le vel acce pta ble t o t he 
i n vesti gat or a n d Pfizer c o nc urs wit h t hat assess me nt.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 5 7
F or partici pa nts w h o are scree n fail ures, t he acti ve c ollecti o n peri o d e n ds w he n scree n fail ure 
stat us is deter mi ne d.
If t he partici pa nt wit h dra ws fr o m t he st u d y a n d als o wit h dra ws c o nse nt f or t he c ollecti o n of 
f ut ure i nf or mati o n, t he acti ve c ollecti o n peri o d e n ds w he n c o nse nt is wit h dra w n.
If a partici pa nt defi niti vel y disc o nti n ues or te m p oraril y disc o nti n ues st u d y i nter ve nti o n 
beca use of a n A E or S A E, t he A E or S A E m ust be rec or de d o n t he C R F a n d t he S A E 
re p orte d usi n g t he C T S A E Re p ort F or m.
I n vesti gat ors are n ot o bli gate d t o acti vely see k A Es or S A Es after t he partici pa nt has 
c o ncl u de d st u d y partici pati o n .  H o we ver, if t he i n vesti gat or lear ns of a ny S A E, i ncl u di n g a 
deat h, at a n y ti me after a partici pa nt has c o m plete d t he st u d y, a n d he/s he c o nsi ders t he e ve nt 
t o be reas o na bl y relate d t o t he st u d y i nter ve nti o n, t he i n vesti gat or m ust pr o m ptl y re p ort t he 
S A E t o Pfizer usi n g t he C T S A E Re p ort F or m.
8. 3. 1. 1. Re p orti n g S A Es t o Pfizer S afet y
All S A Es occ urri n g i n a partici pa nt d uri n g t he acti ve c ollecti o n peri o d as descri be d i n 
Secti o n 8. 3. 1 are re p orte d t o Pfizer Safet y o n t he C T S A E Re p ort F or m im me diatel y  u p o n 
a ware ness a n d u n der n o circ u msta nce s h o ul d t his e xcee d 2 4 h o urs, as i n dicate d i n 
A p pe n di x 3 .  T he i n vesti gat or will s u b mit a n y u p date d S A E data t o t he s p o ns or wit hi n 
2 4 h o urs of it bei n g a vaila ble.
8. 3. 1. 2. Rec or di n g N o nseri o us A Es a n d S A Es o n t he C R F
All n o nseri o us A Es a n d S A Es occ urri n g i n a partici pa nt d uri n g t he acti ve c ollecti o n peri o d, 
w hic h b e gi ns after o btai ni n g i nf or me d c o nse nt as descri be d i n Secti o n 8. 3. 1 , will be rec or de d 
o n t he A E secti o n of t he C R F.  
T he i n vesti gat or is t o rec or d o n t he C R F all directl y  o bser ve d a n d all s p o nta ne o usl y re p orte d 
A Es a n d S A Es re p orte d b y  t he partici pa nt.
8. 3. 2. Met h o d of Detecti n g A Es a n d S A Es
T he met h o d of rec or di n g, e val uati n g, a n d assessi n g ca usalit y  of A Es a n d S A Es a n d t he 
pr oce d ures f or c o m pleti n g a n d tra ns mitti n g S A E re p orts are pr o vi de d i n A p pe n di x 3 .
Care will be ta ke n n ot t o i ntr o d uce bias w he n detecti n g A Es a n d/ or S A Es.  O pe n -e n de d a n d 
n o nlea di n g ver bal q uesti o ni n g of t he partici pa nt is t he preferre d met h o d t o i n q uire a b o ut 
A E occ urre nces.
8. 3. 3. F oll o w - u p of A Es a n d S A Es
After t he i ni tial A E/ S A E re p ort, t he i n vesti gat or is re q uire d t o pr oacti vely f oll o w eac h 
partici pa nt at s u bse q ue nt visits/c o ntacts.  F or eac h e ve nt, t he i n vesti gat or m ust p urs ue a n d 
o btai n a de q uate i nf or mati o n u ntil res ol uti o n, sta bilizati o n, t he e ve nt is ot her wise e x p lai ne d, 
or t he partici pa nt is l ost t o f oll o w- u p (as defi ne d i n Secti o n 7. 3 ).
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 5 8
I n ge neral, f oll o w-u p i nf or mati o n will i n cl u de a descri pti o n of t he e ve nt i n s ufficie nt detail t o 
all o w f or a c o m plete me dical assess me nt of t he case a n d i n de pe n de nt deter mi nati o n of 
p ossi ble ca usalit y .  A ny i nf or mati o n rele va nt t o t he e ve nt, s uc h as c o nc o mita nt me dicati o ns 
a n d ill nesses, m ust be pr o vi de d.  I n t he case of a partici pa nt deat h, a s u m mar y of a vaila ble 
a ut o ps y fi n di n gs m ust be s u b mitte d as s o o n as p ossi ble t o Pfizer Safet y. 
F urt her i nf or mati o n o n f oll o w -u p pr oce d ures is gi ve n i n A p pe n di x 3 .
8. 3. 4. Re g ul at or y Re p orti n g Re q uire me nts f or S A Es
Pr o m pt n otificati o n b y  t he i n vesti gat or t o t he s p o ns or of a n S A E is esse ntial s o t hat le gal 
o bli gati o ns a n d et hical res p o nsi bilities t o war ds t he safet y of partici pa nts a n d t he safet y of a 
st u d y i nter ve nti o n u n der cli nical i n vesti gati o n are met.
T he s p o ns or has a le gal res p o nsi bilit y  t o n otif y b ot h t he l ocal re g ulat or y a ut h orit y a n d ot her 
re g ulat or y a ge ncies a b o ut t he safety of a st u d y i nter ve nti o n u n der cli nical i n vesti gati o n.  T he 
s p o ns or will c o m pl y wit h c o u ntr y-s pecific re g ulat or y re q uire me nts relati n g t o safety 
re p orti n g t o t he re g ulat or y a ut h ority, I RBs/ E Cs, a n d i n vesti gat ors.
I n vesti gat or safet y re p orts m ust be pre pare d f or S U S A Rs acc or di n g t o l ocal re g ulat or y 
re q uire me nts a n d s p o ns or p olic y a n d f or war de d t o in vesti gat ors as necessar y.
A n i n vesti gat or w h o recei ves S U S A Rs or ot her s pecific safet y i nf or mati o n (e g, s u m mar y or 
listi n g of S A Es) fr o m t he s p o ns or will re vie w a n d t he n file it al o n g wit h t he S R S D(s) f or t he 
st u d y a n d will n otif y t he I R B/ E C, if a p pr o priate acc or di n g t o l ocal re q uire me nts.
8. 3. 5. E x p os ure D uri n g Pre g n a nc y or Bre astfee di n g, a n d Occ u p ati o n al E x p os ure
E x p os ure t o t he st u d y  i nter ve nti o n u n der st u d y d uri n g pre g na nc y or breastfee di n g a n d 
occ u pati o nal e x p os ure are re p orta ble t o Pfizer Safet y  wit hi n 2 4 ho urs of i n vesti gat or 
a ware ness.
8. 3. 5. 1. E x p os ure D uri n g Pre g n a nc y
A n E D P occ urs if:

A fe male partici pa nt is f o u n d t o be pre g na nt w hile recei vi n g or after disc o nti n ui n g 
st u d y i nter ve nti o n.

A male partici pa nt w h o is recei vi n g or has disc o nti n ue d st u d y  i nter ve nti o n ex p oses a 
fe male part ner pri or t o or ar o u n d t he ti me of c o nce pti o n.

A fe male is f o u n d t o be pre g na nt w hile bei n g e x p ose d or ha vi n g bee n e x p ose d t o 
st u d y i nter ve nti o n d ue t o e n vir o n me ntal e x p os ure.  Bel o w are e xa m ples of 
e n vir o n me ntal e x p os ure d uri n g pre g na nc y :

A fe male fa mil y  me m ber or healt hcare pr o vi der re p orts t hat s he is pre g na nt 
after ha vi n g bee n e x p ose d t o t he st u d y  i nter ve nti o n b y i n gesti o n.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 5 9

A male fa mil y me m ber or healt hcare pr o vi der w h o has bee n e x p ose d t o t he 
st u d y i nter ve nti o n by i n gesti o n t he n e x p oses his fe male part ner pri or t o or 
ar o u n d t he ti me of c o nce pti o n.
T he i n vesti gat or m ust re p ort E D P t o Pfizer Safet y wit hi n 2 4 h o urs of t he i n vesti gat or’s 
a ware ness, irres pecti ve of w het her a n S A E has occ urre d.  T he i nitial i nf or mati o n s u b mitte d 
s ho ul d i ncl u de t he a ntici pate d date of deli ver y  (see bel o w f or i nf or mati o n relate d t o 
ter mi nati o n of pre g na nc y).

If E D P occ urs i n a partici pa nt or a partici pa nt’s part ner, t he i n vesti gat or m ust re p ort 
t his i nf or mati o n t o Pfizer Safet y o n t he C T S A E Re p ort F or m a n d a n E D P 
S u p ple me ntal F or m, re gar dless of w het her a n S A E has occ urre d.  Details of t he 
pre g na nc y  will be c ollecte d after t he start of st u d y i nter ve nti o n a n d u ntil 2 8 cale n dar
da y s after last a d mi nistrati o n of t he st u d y i nter ve nti o n.

If E D P occ urs i n the setti n g of e n vir o n me ntal e x p os ure, t he i n vesti gat or m ust re p ort 
i nf or mati o n t o Pfizer Safet y usi n g t he C T S A E Re p ort F or m a n d E D P S u p ple me ntal 
F or m.  Si nce t he e x p os ure i nf or mati o n d oes n ot pertai n t o t he partici pa nt e nr olle d i n 
t he st u d y, t he i nf or matio n is n ot rec or de d o n a C R F; h o we ver, a c o p y of t he 
c o m plete d C T S A E Re p ort F or m is mai ntai ne d i n t he i n vesti gat or site file.
F oll o w u p is c o n d ucte d t o o btai n ge neral i nf or mati o n o n t he pre g na nc y  a n d its o utc o me f or 
all E D P re p orts wit h a n u n k n o w n o utc o me.  T he i n vesti gat or will f oll o w t he pre g na nc y  u ntil 
c o m pleti o n ( or u ntil pre g na nc y  ter mi nati o n) a n d n otif y Pfizer Safety of t he o utc o me as a 
f oll o w u p t o t he i nitial E D P S u p ple me ntal F or m.  I n t he case of a li ve birt h, t he str uct ural 
i nte grity of t he ne o nat e ca n be assesse d at t he ti me of birt h.  I n t he e ve nt of a ter mi nati o n, t he 
reas o n(s) f or ter mi nati o n s h o ul d be s pecifie d a n d, if cli nicall y p ossi ble, t he str uct ural 
i nte grity of t he ter mi nate d fet us s h o ul d be assesse d b y gr oss vis ual i ns pecti o n ( u nless 
pr e pr oce d ure test fi n di n gs are c o ncl usi ve f or a c o n ge nital a n o mal y a n d t he fi n di n gs are 
re p orte d).
A b n or mal pre g na nc y  o utc o mes are c o nsi dere d S A Es.  If t he o utc o me of t he pre g na nc y meets 
t he criteria f or a n S A E (ie, ect o pic pre g na nc y, s p o nta ne o us a b orti o n, i ntra uteri ne fetal 
de mise, ne o natal deat h, or c o n ge nital a n o mal y i n a li ve -b or n ba b y, a ter mi nate d fet us, a n 
i ntra uteri ne fetal de mise, or a ne o natal deat h), t he i n vesti gat or s h o ul d f oll o w t he pr oce d ures 
f or re p orti n g S A Es.  A d diti o nal i nf or mati o n a b o ut preg na nc y  o utc o mes t hat are re p orte d t o 
Pfizer Safet y  as S A Es f oll o ws:

S p o nta ne o us a b orti o n i ncl u di n g miscarria ge a n d misse d a b orti o n;

Ne o natal deat hs t hat occ ur wit hi n 1 m o nt h of birt h s h o ul d be re p orte d, wit h o ut re gar d 
t o ca usalit y, as S A Es.  I n a d diti o n, infa nt deat hs after 1 m o nt h s h o ul d be re p orte d as 
S A Es w he n t he i n vesti gat or assesses t he i nfa nt deat h as relate d or p ossi bl y  relate d t o 
e x p os ure t o t he st u d y i nter ve nti o n.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 6 0
A d diti o nal i nf or mati o n re gar di n g t he E D P ma y  be re q ueste d b y t he s p o ns or.  F urt her foll o w 
u p of birt h o utc o mes will be ha n dle d o n a case b y case basis (e g, f oll o w u p o n preter m 
i nfa nts t o i de ntif y de vel o p me ntal dela ys).  I n t he case of pater nal e x p os ure, t he i n vesti gat or 
will pr o vi de t he partici pa nt wit h t he Pre g na nt Part ner Release of I n f or mati o n F or m t o deli ver 
t o his part ner.  T he i n vesti gat or m ust d oc u me nt i n t he s o urce d oc u me nts t hat t he partici pa nt 
was gi ve n t he Pre g na nt Part ner Release of I nf or mati o n F or m t o pr o vi de t o his part ner.
T he Tafa mi dis E n ha nce d S ur veilla nce Pre g na nc y  O utc omes ( T E S P O) pr o gra m f oll o ws t he 
pr o gress a n d o utc o me of re p orte d pre g na ncies i n w o me n e x p ose d t o tafa mi dis.  Tafa mi dis 
e x p os ure d uri n g pre g na nc y will be re p orte d t o T E S P O pr o gra m.
8. 3. 5. 2. E x p os ure D uri n g Bre astfee di n g
A n e x p os ure d uri n g breastfee di n g occ urs if:

A fe male partici pa nt is f o u n d t o be breastfee di n g w hile recei vi n g or after 
disc o nti n ui n g st u d y  i nter ve nti o n.

A fe male is f o u n d t o be breastfee di n g w hile bei n g e x p ose d or ha vi n g bee n e x p ose d t o 
st u d y i nter ve nti o n (ie, e n vir o n me ntal e x p os ure).  A n e xa m ple of e n vir o n me ntal 
e x p os ure d uri n g breastfee di n g is a fe male fa mil y  me m ber or healt hcare pr o vi der w h o 
re p orts t hat s he is breastfee di n g after ha vi n g bee n e x p ose d t o t he st u d y i nter ve nti o n 
b y  i n halati o n or s ki n c o ntact.
T he i n vesti gat or m ust re p ort e x p os ure d uri n g breastfee di n g t o Pfizer Safet y  wit hi n 2 4 h o urs 
of t he i n vesti gat or’s a ware ness, irres pecti ve of w het her a n S A E has occ urre d.  T he 
i nf or mati o n m ust be re p orte d usi n g t he C T S A E Re p ort F or m.  W he n e x p os ure d uri n g 
breastfee di n g occ urs i n t he setti n g of e n v ir o n me ntal e x p os ure, t he e x p os ure i nf or mati o n d oes 
n ot pertai n t o t he partici pa nt e nr olle d i n t he st u d y, s o t he i nf or mati o n is n ot rec or de d o n a 
C R F.  H o we ver, a c o p y of t he c o m plete d C T S A E Re p ort F or m is mai ntai ne d i n t he 
i n vesti gat or site file.
A n e x p os ure d uri n g breastfee di n g re p ort is n ot create d w he n a Pfizer dr u g s pecificall y 
a p pr o ve d f or use i n breastfee di n g w o me n (e g, vita mi ns) is a d mi nistere d i n acc or d wit h 
a ut h orize d use.  H o we ver, if t he i nfa nt e x perie nces a n S A E ass ociate d wit h s uc h a dr u g, t he
S A E is re p orte d t o get her wit h t he e x p os ure d uri n g breastfee di n g.
8. 3. 5. 3. Occ u p ati o n al E x p os ure
A n occ u pati o nal e x p os ure occ urs w he n a pers o n recei ves u n pla n ne d direct c o ntact wit h t he 
st u d y i nter ve nti o n, w hic h ma y or ma y n ot lea d t o t he occ urre nce of a n A E.  S uc h pers o ns 
ma y  i ncl u de healt hcare pr o vi ders, fa mily me m bers, a n d ot her r oles t hat are i n v ol ve d i n t he 
trial partici pa nt’s care.
T he i n vesti gat or m ust re p ort occ u pati o nal e x p os ure t o Pfizer Safet y wit hi n 2 4 h o urs of t he 
i n vesti gat or’s a ware ness, re gar dless of w het her t here is a n ass ociate d S A E.  T he i nf or mati o n 
m ust be re p orte d usi n g t he C T S A E Re p ort F or m.  Si nce t he i nf or mati o n d oes n ot pertai n t o a 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 6 1
partici pa nt e nr olle d i n t he st u d y, t he i nf or mati o n is n ot rec or de d o n a C R F; h o we ver, a c o p y  
of t he c o m plete d C T S A E Re p ort F or m is mai ntai ne d i n t he i n vesti gat or site file.
8. 3. 6. C ar di o v asc ul ar a n d De at h E ve nts
N ot a p plica ble. Car di o vasc ular a n d deat h e ve nts will be c ollecte d as A E/ S A E e ve n t h o u g h 
t hese e ve nts are ma nifestati o ns of t he e n d sta ge of T T R-C M.
8. 3. 7. Dise ase -Rel a te d E ve nts a n d/ or Dise ase-Rel ate d O utc o mes N ot Q u alif yi n g as A Es 
or S A Es
N ot a p plica ble.
8. 3. 8. A d verse E ve nts of S peci al I nterest
N ot a p plica ble.
8. 3. 8. 1. L ac k of Effic ac y
Lac k of efficac y  i n a n a p pr o ve d i n dicati o n s h o ul d be re p orte d as a n S A E t o Pfizer Safet y.
8. 3. 9. Me dic al De vice Deficie ncies
N ot a p plica ble. 
8. 3. 9. 1. Ti me Peri o d f or Detecti n g Me dic al De vice Deficie ncies 
N ot a p plica ble. 
8. 3. 9. 2. F oll o w u p of Me dic al De vice Deficie ncies
N ot a p plica ble. 
8. 3. 9. 3. Pr o m pt Re p orti n g of De vice Deficie ncies t o S p o ns or
N ot a p plica ble. 
8. 3. 9. 4. Re g ul at or y Re p orti n g Re q uire me nts f or De vice Deficie ncies
N ot a p plica ble. 
8. 3. 1 0. Me dic ati o n Err ors
Me dicati o n err ors ma y  res ult fr o m t he a d mi nistrati o n or c o ns u m pti o n of t he st u d y 
i nter ve nti o n b y t he wr o n g partici pa nt, or at t he wr o n g ti me, or at t he wr o n g d osa ge stre n gt h.
E x p os ures t o t he st u d y  i nter ve nti o n u n der st u d y ma y occ ur i n cli nical trial setti n gs, s uc h as 
me dicati o n err ors.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 6 2
S afet y E ve nt
Rec or de d o n t he C R F
Re p orte d o n t he C T S A E Re p ort 
F or m t o Pfizer S afet y Wit hi n 2 4 
H o urs of A w are ness
Me dicati o n err ors 
All (re gar dless of w het her 
ass ociate d wit h a n A E)
O nl y  if ass ociate d wit h a n S A E
Me dicati o n err ors i ncl u de:

Me dicati o n err ors i n v ol vi n g partici pa nt e x p os ure t o t he st u d y i nter ve nti o n;

P ote ntial me dicati o n err ors or uses o utsi de of w hat is f oresee n i n t he pr o t oc ol t hat d o 
or d o n ot i n v ol ve t he st u d y  partici pa nt.
S uc h me dicati o n err ors occ urri n g t o a st u d y partici pa nt are t o be ca pt ure d o n t he me dicati o n 
err or pa ge of t he C R F, w hic h is a s pecific versi o n of t he A E pa ge.
I n t he e ve nt of a me dicati o n d osi n g err or, t he s p o ns or s h o ul d be n otifie d wit hi n 2 4 h o urs.
W het her or n ot t he me dicati o n err or is acc o m pa nie d b y  a n A E, as deter mi ne d b y t he 
i n vesti gat or, t he me dicati o n err or is rec or de d o n t he me dicati o n err or pa ge of t he C R F a n d, if 
a p plica ble, a n y ass ociate d A E(s), seri o us a n d n o nseri o us, are rec or de d o n a n A E pa ge of t he 
C R F.
Me dicati o n err ors s h o ul d be re p orte d t o Pfizer Safet y wit hi n 2 4 h o urs o n a C T S A E Re p ort 
F or m o nl y w he n ass oci ate d wit h a n S A E.
8. 4. Tre at me nt of O ver d ose
F or t his st u d y , a n y d ose of tafa mi dis greater t h a n dail y d ose of st u d y i nter ve nti o n wit hi n a 
2 4 -h o ur ti me peri o d will be c o nsi dere d a n o ver d ose.
S p o ns or d oes n ot rec o m me n d s pecific treat me nt f or a n o ver d ose a n d ma y be use d i n case of 
d o ver d ose .
I n t he e ve nt of a n o ver d ose, t he i n vesti gat or/treati n g p hys icia n s h o ul d:
C o ntact t he me dical m o nit or wit hi n 2 4 h o urs .
Cl osel y  m o nit or t he partici pa nt f or a ny A Es/ S A Es a n d la b orat or y  a b n or malities f or at 
least 5 half -li ves or 2 8 cale n dar da ys after t he o ver d ose of tafa mi dis. Cl osel y m o nit or 
t he partici pa nt f or a ny A Es/ S A Es.
D oc u me nt t he q ua ntit y o f t he e xcess d ose as well as t he d urati o n of t he o ver d ose i n 
t he C R F.
O ver d ose is re p orta ble t o Safet y o nl y w he n ass oci ate d wit h a n S A E .
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 6 3
O btai n a bl o o d sa m ple f or P K a nal ys is wit hi n 1 4 da y s fr o m t he date of t he last d ose 
of st u d y  i nter ve nti o n if re q ueste d by t he me dical m o nit or ( deter mi ne d o n a 
case b yc ase basis).
Decisi o ns re gar di n g d ose i nterr u pti o ns or m o dificati o ns will be ma de b y t he i n vesti gat or i n 
c o ns ultati o n wit h t he me dical m o nit or ba se d o n t he cli nical e val uati o n of t he partici pa nt.
8. 5. P h ar m ac o ki netics 
Bl o o d sa m ples of a p pr o xi matel y  3 m L , t o pr o vi de a n a p pr o xi matel y 1 m L plas ma, will be 
c ollecte d i nt o a p pr o priatel y la bele d t u bes c o ntai ni n g di p otassi u m et hyl e ne dia mi netetraacetic 
aci d ( K 2 E D T A) f or meas ure me nt of plas ma c o nce ntrati o ns of tafa mi dis as s pecifie d i n t he 
S o A .  Instr ucti o ns f or t he c ollecti o n a n d ha n dli n g of bi ol o gical sa m ples will be pr o vi de d i n 
t he la b orat or y ma n ual.  T he act ual date a n d ti me ( 2 4-h o ur cl oc k ti me) of eac h sa m ple will be 
rec or de d.  
Sa m ples will be use d t o e val uate t he P K of tafa mi dis .  Sa m ples c ollecte d f or a nalys es of 
tafa mi dis plas ma c o nce ntrati o n ma y  als o be use d t o e val uate safety or efficac y as pects 
relate d t o c o ncer ns arisi n g d uri n g or after t he st u d y , f or meta b olite i de ntificati o n a n d/ or 
e val uati o n of t he bi oa nal ytical met h o d.
Ge netic a nal ys es will n ot be perf or me d o n t hese plas ma sa m ples u nless c o nse nt f or t his was 
i ncl u de d i n t he i nf or me d c o nse nt.  Partici pa nt c o nfi de ntialit y will be mai ntai ne d.
Sa m ples c ollecte d f or meas ure me nt of plas ma c o nce ntrati o ns of tafa mi dis will be a nal yz e d 
usi n g a vali date d a nal yt ical met h o d i n c o m plia nce wit h a p plica ble sta n dar d o perati n g 
pr oce d ures ( S O Ps).
T he P K sa m ples m ust be pr ocesse d a n d s hi p pe d as i n dicate d i n t he i nstr ucti o ns pr o vi de d t o 
t he i n vesti gat or site t o mai ntai n sa m ple i nte grit y. A n y  de viati o ns fr o m t he P K sa m ple 
ha n dli n g pr oce d ure (e g, sa m ple c ollecti o n a n d pr ocessi n g ste ps, i nteri m st ora ge or s hi p pi n g 
c o n diti o ns), i ncl u di n g a n y acti o ns ta ke n, m ust be d oc u me nte d a n d re p orte d t o t he s p o ns or.  
O n a case -b y -case basis, t he s p o ns or ma y ma ke a deter mi nati o n as t o w het her sa m ple 
i nte grity has bee n c o m pr o mise d .
A n y  c ha n ges i n t he ti mi n g or a d diti o n of ti me p oi nts f or a ny pla n ne d st u d y assess me nts m ust 
be d oc u me nte d a n d a p pr o ve d b y  t he rele va nt st u d y tea m me m ber a n d t he n arc hi ve d i n t he 
s p o ns or a n d site st u d y files, b ut will n ot c o nstit ute a pr ot oc ol a me n d me nt.  T he IR B/ E C will 
be i nf or me d of a n y safet y iss ues t hat re q uire alterati o n of t he safety m o nit ori n g sc he me or 
a me n d me nt of t he I C D.
8. 6. P h ar m ac o d y n a mics
P har mac o d y na mic ( P D) para meters will be e val uate d i n t his st u d y.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 6 4
T T R St a biliz ati o n a n d T T R C o nce ntr ati o n Me as ure me nts
O ne ( 1) di p otassi u m et h yle ne dia mi netetraacetic aci d ( K 2 E D T A) bl o o d sa m ple of 
a p pr o xi mate 1 0 m L  (wit h e xce pti o n of a n a d diti o nal a p pr o xi mate 1 0 m L  of t he pre-d ose 
bl o o d sa m ple o nl y  o n Da y 1 f or met h o d de vel o p me nt a n d vali dati o n) will be c ollecte d as 
s pecifie d i n t he S o A f or meas ure me nt of T T R sta bilizati o n a n d T T R c o nce ntrati o n.  T he 
act ual date a n d ti me ( 2 4-h o ur cl oc k ti me) of eac h sa m ple will be rec or de d. S a m ples will be 
a nal yz e d usi n g vali date d a nal yt ical met h o ds i n c o m plia nce wit h Pfizer sta n dar d o perati n g 
pr oce d ures.   Detaile d i nstr ucti o ns f or collecti o n, st ora ge, la beli n g, a n d s hi p me nt of all 
sa m ples are pr o vi de d i n a se parate st u d y  la b orat or y ma n ual.
As part of u n dersta n di n g t he P D of t he st u d y  i nter ve nti o n, sa m ples ma y be use d f or 
e val uati o n of t he bi oa nal ytical met h o d.  T hese data will n ot be i ncl u de d i n t he Cli nical St u d y 
Re p ort ( C S R). 
T he P D sa m ples m ust be pr ocesse d a n d s hi p pe d as i n dicate d i n t he i nstr ucti o ns pr o vi de d t o 
t he i n vesti gat or site t o mai ntai n sa m ple i nte grit y.  A n y de viati o ns fr o m t he P D sa m ple 
ha n dli n g pr oce d ure (e g, sa m ple c ollecti o n a n d pr ocessi n g ste ps, i nteri m st ora ge, or s hi p pi n g 
c o n diti o ns), i ncl u di n g a n y acti o ns ta ke n, m ust be d oc u me nte d a n d re p orte d t o t he s p o ns or.  
O n a case -b y -case basis, t he s p o ns or ma y  ma ke a deter mi nati o n as t o w het her sa m ple 
i nte grity has bee n c o m pr o mise d.
8. 7. Ge netics
G e netics i nf or mati o n will be c ollecte d i n t he st u d y . 
8. 7. 1. S pecifie d Ge netics
B l o o d sa m ples of a p pr o xi matel y 3 ml will be c ollecte d f or meas ure me nt of g e n ot y pi n g f or 
m utati o n of T T R ge ne at scree ni n g peri o d f or eac h partici pa nt.
8. 7. 2. B a n ke d Bi os peci me ns f or Ge netics
N ot a p plica ble .
8. 8. Bi o m ar kers
Bi o mar kers are n ot e val uate d i n t his st u d y .
8. 8. 1. S pecifie d Ge ne E x pressi o n ( R N A) Rese arc h 
S pecifie d ge ne e x pressi o n ri b o n ucleic aci d ( R N A) researc h is n ot i ncl u de d i n t his st u d y.
8. 8. 2. S pecifie d Pr otei n Rese arc h 
S pecifie d pr otei n researc h is n ot i ncl u de d i n t his st u d y .
8. 8. 3. S pecifie d Met a b ol o mic Rese arc h 
S pecifie d meta b ol o mic researc h is n ot i ncl u de d i n t his st u d y .
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 6 5
8. 9. He alt h Ec o n o mics
H ealt h Ec o n o mics para meters will be e val uate d i n t his st u d y  as Patie nt Re p orte d O utc o me s:
Sites will be pr o vi de d wit h a n a p pr o ve d tra nslate d versi o n of eac h pa per -base d q uesti o n naire 
t hat will be re q uire d f or use i n t he st u d y.
K a ns as Cit y C ar di o m y o p at h y Q uesti o n n aire
T he Ka nsas Cit y Car di o m y o pat h y Q uesti o n naire ( K C C Q) ( Secti o n 1 0. 9. 1 ) ( Gree n 2 0 0 0)8 is a 
2 3 -ite m s u bject-c o m plete d q uesti o n naire t hat assesses healt h stat us a n d healt h -relate d q ualit y 
of life i n partici pa nts wit h heart fail ure.  Ite ms assess t he a bilit y  t o perf or m acti vities of dail y 
li vi n g, fre q ue nc y a n d se verit y of s ym pt o ms, t he i m pact of t hese s y m pt o ms, a n d healt h -
relate d q ualit y of life.  Res p o nse o pti o ns var y b y q uesti o n.  Sc ori n g yiel ds sc ores f or 6 
d o mai ns ( P h y sical li mitati o n, S ym pt o m sta bilit y , S ym pt o ms, Self -efficac y, S ocial li mitati o n, 
a n d Q ualit y of life), d o mai n s u m mar y sc ores ( F u ncti o nal s u m mar y a n d Cli nical s u m mar y), as 
well as a n O verall S u m mar y  sc ore.  D o mai n sc ores are tra nsf or me d t o a 0 t o 1 0 0 ra n ge; 
hi g her sc ores i n dicate better healt h stat us.  It ta kes a p pr o xi matel y  4-6 mi n utes f or a 
partici pa nt t o c o m plete t he K C C Q.  Partici pa nts will c o m plete t he K C C Q at t he ti mes liste d 
i n t he Sc he d ule of Acti vities .  In eac h i nsta nce of a d mi nistrati o n, t he K C C Q s h o ul d be 
c o m plete d b y partici pa nts bef ore c o m pleti n g t he E Q - 5 D-5 L ( Secti o n 1 0. 9. 2 ) a n d S F- 1 2 
(Secti o n 1 0. 9. 3 ).  T he K C C Q ca n be f o u n d i n Secti o n 1 0. 9. 1
E ur o Q o L 5 Di me nsi o ns 5 Le vels (E Q - 5 D- 5 L)
T he E Q - 5 D-5 L  ( 5 le vels versi o n) is a brief, self-a d mi nistere d ge neric healt h stat us i nstr u me nt 
t hat ta kes a b o ut 5 mi n utes t o c o m plete.9  T he i nstr u me nt c o nsists of 2 parts.  I n t he first part, 
res p o n de nts are as ke d t o rate t heir c urre nt healt h state o n 5 di me nsi o ns ( m o bilit y , self-care, 
us ual acti vities, pai n or disc o mf ort, a n d a n xiet y  or de pressi o n) wit h eac h di me nsi o n ha vi n g 3 
le vels of f u ncti o n ( 1 = n o pr o ble m, 2 =s o me pr o ble m, a n d 3 =e xtre me pr o ble m).  T he sec o n d 
part is a partici pa nt ’s self-rati n g of c urre nt healt h state o n a Vis ual A nal o g Scale ( E Q-5 D 
V A S) wit h e n d p oi nts la be le d ‘ best i ma gi na ble healt h state’ (sc ore of 1 0 0) a n d ‘ w orst 
i ma gi na ble healt h state’ (sc ore of 0).  T he sc ores fr o m t he 5 di me nsi o ns ma y  be use d t o 
calc ulate a si n gle i n de x val ue, als o k n o w n as a utilit y  sc ore.  Partici pa nts will c o m plete t he 
E Q - 5 D-5 L ( Secti o n 1 0. 9. 2 ) at t he ti mes liste d i n t he Sc he d ule of Acti vities .
Partici pa nts s h o ul d c o m plete t he E Q- 5 D-5 L  after t he K C C Q (Secti o n 1 0. 9. 1 ).  T he 
E Q - 5 D-5 L  ca n be f o u n d i n (Secti o n 1 0. 9. 2 ).
1 2 - ite m s h ort f or m he alt h s ur ve y ( S F-1 2)
A patie nt’s o verall q ualit y of life, as meas ure d b y t he 1 2-Ite m S h ort F or m S ur ve y ( S F-1 2), 
will be assesse d at t he ti mes liste d i n t he S o A .  T his q uesti o n naire s h o ul d be c o m plete d by 
t he patie nt after t he K C C Q a n d E Q- 5 D-5 L , a n d pri or t o ot her re q uire d visit assess me nts.  
S F- 1 2 is de vel o pe d as a s h orter alter nati ve t o t he S F- 3 6 f or use i n lar ge -scale st u dies, a n d its 
relia bilit y a n d vali dit y ha ve bee n d oc u me nte d.  It is a n i nstr u me nt wit h differe nt wei g hts f or 
sc ori n g p hys ical a n d me ntal healt h, a n d meas ures healt h-relate d q ualit y of life wit h 1 2 ite ms 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 6 6
cate g orize d i n ei g ht areas: p h ys ical f u ncti o ni n g, r ole p h ysical, b o dil y pai n, ge neral healt h, 
vitalit y , s ocial f u ncti o ni n g, r ole e m oti o nal, a n d me ntal healt h.
A sa m ple of t he S F -1 2 is pr o vi de d i n Secti o n 1 0. 9. 3 .
8. 1 0. Bi o ps y D oc u me nt ati o n of A m yl oi d
I n t he e ve nt t hat t here is n o d oc u me ntati o n of pri or bi o ps y or ra di o n ucli de b o ne sci nti gra p hy 
( 9 9 m Tc-P Y P) a n d de m o nstrati o n of T T R a m yl oi d de p ositi o n b y eit her mass s pectr o metr y , 
i m m u n o hist oc he mistr y or sci nti gra p h y, car diac or n o n-car diac tiss ue will be bi o psie d a n d 
teste d b y t he i n vesti gati o nal site as per t he site’s sta n dar d of care a n d e val uate d wit h C o n g o 
re d stai n or ot her a nalys is ca n be utilize d t o c o nfir m t he de p osit of a m yl oi d.  Stai ne d tiss ue 
will be vie we d u n der p olarize d li g ht use d t o de m o nstrate a m yl oi d c haracteristic ‘a p ple -gree n’ 
birefri n ge nce.  F or partici pa nts wit h o ut i de ntificati o n of a T T R varia nt a n d de m o nstrati o n of 
a m yl oi d de p ositi o n w h o ma y ha ve a dia g n osis of wil d -t ype A T T R -C M, a nal y sis will be 
perf or me d t o c o nfir m t he prec urs or pr otei n basis f or a m yl oi d de p ositi o n, b y eit her: mass 
s pectr o metr y or i m m u n o hist oc he mistr y.
F or p ur p oses of t his st u d y, a n e xisti n g bi o ps y  res ult will be c o nsi dere d vali d if it is 
d oc u me nte d i n writi n g a n d t he bi o ps y  was perf or me d wit hi n 5 years of st u d y e nr oll me nt.  If 
t he bi o ps y is n ot vali d, it will be re peate d as a scree ni n g pr oce d ure at t he i n vesti gati o nal site.
9. S T A TI S TI C A L C O N SI D E R A TI O N S
Detaile d met h o d ol o g y  f or s u m mar y a n d statistical a nalys es of t he data c ollecte d i n t his st u d y  
is o utli ne d here a n d f urt her detaile d i n a statistical a nalys is pla n ( S A P), w hic h will be 
mai ntai ne d b y  t he s p o ns or.  T he S A P ma y m o dif y w hat is o utli ne d i n t he pr ot oc ol w here 
a p pr o priate; h o we ver, a n y maj or m o dificati o ns of t he pri mar y e n d p oi nt defi niti o ns or t heir 
a nal ys es will als o be reflecte d i n a pr ot oc ol a me n d me nt.
9. 1. Esti m a n ds a n d St atistic al H y p ot heses
T his is a n esti mati o n st u d y wit h n o statistical h y p ot hesis t o test.
9. 2. S a m ple Size Deter mi n ati o n
In or der t o attai n a n 8 0 % pr o ba bilit y  of o bser vi n g at least 1 partici pa nt ha vi n g a n e ve nt f or 
T E A E s wit h i nci de nce rate of 3 %, at least 5 3 partici pa nts nee d t o be treate d.
9. 3. P o p ul ati o ns f or A n al ysis
F or p ur p oses of a nal y sis, t he f oll o wi n g p o p ulati o ns are defi ne d:
P o p ul ati o n
Descri pti o n
E nr olle d 
All partici pa nts w h o si g n t he I C D
Efficac y
All partici pa nts w h o ta ke at least 1 d ose of tafa mi dis
Safet y
All partici pa nts w h o ta ke at least 1 d ose of tafa mi dis
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 6 7
P o p ul ati o n
Descri pti o n
P har mac o ki netic ( P K)
All partici pa nts w h o ha ve at least 1 q ua ntifia ble plas ma 
tafa mi dis c o nce ntrati o n
P har mac o d y na mic ( P D)
All partici pa nts w h o ha ve at least 1 data of t he T T R 
sta bilizati o n
9. 4. St atistic al A n al yses
T he S A P will be de vel o pe d a n d fi nalize d bef ore data base l oc k a n d will descri be t he 
partici pa nt p o p ulati o ns t o be i ncl u de d i n t he a nal y ses, a n d pr oce d ures f or acc o u nti n g f or 
missi n g, u n use d, a n d s p uri o us data.  T his secti o n is a s u m mar y  of t he pla n ne d statistical 
a nal ys es of t he pri mar y a n d sec o n dar y e n d p oi nts.
U nles s ot her wise state d, descri pti ve a nal yses will be d o ne f or o verall a n d b y N Y H A b aseli ne 
classificati o n.  Baseli ne f or a n y e n d p oi nts is defi ne d as t he last meas ure me nt pri or t o d osi n g 
o n D a y 1 of t he st u d y.   C ha n ge fr o m baseli ne val ue is calc ulate d b y  s u btracti n g t he baseli ne 
val ue fr o m eac h f oll o w u p visit val ue.
9. 4. 1. S afet y A n al yses
All safet y a nal ys es will be perf or me d o n t he safet y p o p ulati o n.   
9. 4. 1. 1. Tre at me nt E mer ge nt A d verse E ve nt
All a d verse e ve nts t hat start after t he first d osi n g b ut bef ore t he last d ose pl us t he la g ti me are 
treat me nt e mer ge nt a d verse e ve nts.  A d verse e ve nts will be c o de d acc or di n g t o t he Me dical 
Dicti o nar y  f or Re g ulat or y Acti vities ( Me d D R A) .
T he i nci de nce of treat me nt-e mer ge nt a d verse e ve nts will be ta b ulate d b y  s yste m or ga n class.  
T h e i nci de nce of treat me nt -e mer ge nt a d verse e ve nts will be dis pla y e d b y s e verit y a n d
attri b uti o n.  In a d diti o n, t he i nci de nce of seri o us a d verse e ve nts a n d a d verse e ve nts t hat ca use 
wit h dra wal will be ta b ulate d.  All a d verse e ve nts will be liste d.
9. 4. 1. 2. Electr oc ar di o gr a m A n al yses
Ce ntrall y  o ver-rea d E C G varia bles will be s u m marize d b y mea n c ha n ge fr o m baseli ne t o 
eac h meas ure me nt ti me f or heart rate, P R i nter val, Q R S wi dt h, Q T i nter val, a n d Q Tc F 
( Fri dericia’s c orrecti o n) val ues. 
A d diti o nall y , t he i nci de nce of cate g orical i ncreases i n Q Tc i nter vals will be pr o vi de d. 
Cate g ories f or Q Tc F are ≥4 5 0 msec, ≥4 8 0 msec, a n d ≥5 0 0 msec.  Cate g ories f or Q Tc F as 
c ha n ge fr o m baseli ne are: ≥3 0 msec i ncrease, ≥6 0 msec i ncrease.  Q Tc F is c o nsi dere d t he 
pri mar y  Q Tc val ue as t his c orrecti o n is a ntici pate d t o be m ore a p pr o priate. 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 6 8
9. 4. 1. 3. B o d y M ass I n de x/ M o difie d B o d y M ass I n de x
B MI a n d m B MI val ues at eac h visit a n d c ha n ge fr o m baseli ne will be prese nte d i n s u m mar y
ta bles a n d data listi n gs.  Descri pti ve statistics will be pr o vi de d by visit.
9. 4. 1. 4. Ot h er S afet y Assess me nts
All cli nical la b orat or y data will be s u bjecte d t o cli nical re vie w a n d s u m marize d b y  fre q ue nc y 
of e ve nts a n d mea n c ha n ges fr o m baseli ne.
All vital si g n meas ure me nts will be dis pla y e d i n listi n gs b y partici pa nt f or eac h sa m ple
c ollecti on date a n d ti me wit h c ha n ges fr o m baseli ne val ues i ncl u de d .
9. 4. 2. P h ar m ac o d y n a mics A n al yses: T T R C o nce ntr ati o n a n d T T R St a biliz ati o n
T he T T R c o nce ntrati o n a n d perce nt T T R sta bilizati o n will be deter mi ne d.--Declari n g a 
partici pa nt t o ha ve bee n “sta biliz e d” is defi ne d as perce nt sta bilizati o n is e q ual t o or m ore 
t ha n 3 2 %. 
All p har mac o d y na mic a nal yses will be perf or me d o n t he P D p o p ulati o n .  T T R c o nce ntrati o n 
a n d perce nt sta bilizati o n will be s u m marize d descri pti vel y as c o nti n u o us meas ures, b y visit,
f or o verall, b y T T R ge n ot ype, a n d b y  N Y H A baseli ne classificati o n.
T he pr o p orti o n of 
partici pa nts w h o ac hie ve T T R sta bilizati o n (ie, w h o has bee n sta bilize d) a n d its 9 5 % 
c o nfi de nce i nter val will be calc ulate d a n d s u m marize d, as cate g orical meas ure, at eac h p ost -
baseli ne ti me p oi nt , f or o verall, by T T R ge n ot y pe, a n d b y N Y H A baseli ne classificati o n .
9. 4. 3. A n al yses f or Effic ac y E n d p oi nts
All efficac y  a nal yses will be perf or me d o n t he efficac y p o p ulati o n.  F or b ot h baseli ne a n d 
c ha n ge fr o m baseli ne efficac y  meas ures , descri pti ve statistics will be pr o vi de d f or eac h ti me 
p oi nt.   
9. 4. 3. 1. N T -Pr o B N P
Plas ma a mi n o -ter mi nal pr o- B-t ype natri uretic pe pti de ( N T -pr o B N P) is a g ui deli ne -ma n date d 
bi o mar ker i n heart fail ure. Use d as a n i ncl usi o n criteri o n f or t hera pe utic trials, N T- pr o B N P 
e nric hes trial p o p ulati o ns a n d is a vali d s urr o gate e n d p oi nt.  N T -pr o B N P offers pr o g n ostic 
i nf or mati o n i n de pe n de nt of sta n dar d cli nical pre dict ors a n d refi nes ris k stratificati o n. 
9. 4. 3. 2. T nI
Car diac tr o p o ni n T (c T n T) a n d car diac tr o p o ni n I (c T nI) were rec o g nize d as mar kers of 
m y ocar dial da ma ge, Tr o p o ni n T or tr o p o ni n I  or b ot h ma y be c hr o nicall y ele vate d i n car diac 
a m yl oi d osis.  Car diac tr o p o ni n I is t h o u g ht t o be m ore acc urate i n assess me nt of m yocar dial 
da ma ge.  I n t he a p pr o priate cli nical c o nte xt of a t hic ke ne d ve ntricle a n d heart fail ure, a n 
ele vate d tr o p o ni n val ue ( o utsi de of a n ac ute c or o nar y  sy n dr o me) s h o ul d tri g ger s us pici o n f or 
car diac a m yl oi d osis.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 6 9
9. 4. 3. 3. 6 Mi n ute W al k
Si x -mi n ute wal ki n g test is a ki n d of e xercise test f or patie nts wit h m o derate t o se vere 
car di o p ul m o nar y  disease.  T he 6- M W T meas ures t he l o n gest dista nce a patie nt ca n wal k o n a 
strai g ht c o urse i n 6 mi n utes. 
9. 4. 3. 4. Ne w Y or k He art Ass oci ati o n Cl assific ati o n 
T he Ne w Y or k Heart Ass ociati o n f u ncti o nal classificati o n ( N Y H A class) is use d t o descri be 
t he f u ncti o nal ca pacit y of a d ults wit h c o n ge nital heart disease t o descri be t he se verity of 
s ym pt o ms a n d e xercise i nt olera nce.   A n i ncrease or decrease i n N Y H A classificati o n relati ve 
t o baseli ne will be s u m marize d usi n g a s hift ta ble at eac h ti me p oi nt p ost-base li ne.
9. 4. 4. Q u alit y of Life A n al yses
Q ualit y of life a nal ys es will be perf or me d o n t he efficac y p o p ulati o n.  B ot h baseli ne a n d 
c ha n ge fr o m baseli ne meas ures will be s u m marize d descri pti vel y b y visit.
9. 4. 4. 1. K a ns as Cit y C ar di o m y o p at h y Q uesti o n n aire O ver all Sc ore
T he K C C Q o verall sc ore assess t he a bilit y t o perf or m acti vities of dail y li vi n g, fre q ue nc y a n d 
se verity of s y m pt o ms, t he i m pact of t hese sy m pt o ms, a n d healt h -relate d q ualit y of life. 
Res p o nse o pti o ns var y  b y q uesti o n.  C ha n ge fr o m baseli ne i n Ka nsas Cit y Car di o m y o pat h y 
Q uesti o n naire: ( K C C Q) d o mai n sc ores ( P h ys ical li mitati o n, S ym pt o m sta bilit y , Sy m pt o ms, 
Self -efficac y, S ocial li mitati o n, a n d Q ualit y  of life) a n d d o mai n s u m mar y sc ores ( F u ncti o nal
s u m mar y a n d Cli nical s u m mary) will be e val uate d.
9. 4. 4. 2. E Q- 5 D- 5 L
T he E Q - 5 D-5 L  esse ntiall y c o nsists of 2 pa ges: t he E Q- 5 D descri pti ve sys te m a n d t he E Q 
vis ual a nal o g ue scale ( E Q V A S).
T he descri pti ve s ys te m c o m prises 5 di me nsi o ns: m o bilit y, self-care, us ual acti vities, 
pai n/ disc o mf ort a n d a n xiet y/ de pressi o n.  Eac h di me nsi o n has 5 le vels: n o pr o ble ms, sli g ht 
pr o ble ms, m o derate pr o ble ms, se vere pr o ble ms a n d e xtre me pr o ble ms.  T he patie nt is as ke d 
t o i n dicate his/ her healt h state b y tic ki n g t he b o x ne xt t o t he m ost a p pr o priate state me nt i n 
eac h of t he 5 di me nsi o ns.  T his decisi o n res ults i n a 1 -di git n u m ber t hat e x presses t he le vel 
selecte d f or t hat di me nsi o n.  T he di gits f or t he 5 di me nsi o ns ca n be c o m bi ne d i nt o a 5-di git 
n u m ber t hat descri bes t he patie nt’s healt h state.   T he E Q -5 D utilit y  sc ores were calc ulate d 
base d o n t he a vaila ble C hi nese val ue set f or t he E Q- 5 D-5 L i nstr u me nt.  T he sc ore ra n ges 
fr o m -0. 3 9 1 t o 1, w here 1 re prese nts f ull healt h, 0 re prese nts deat h, a n d a sc ore less t ha n 
0 re prese nts a healt h stat us w orse t ha n deat h.T he E Q V A S rec or ds t he patie nt’s self- rate d 
he alt h o n a vertical vis ual a nal o g ue scale, w here t he e n d p oi nts are la belle d ‘ T he best healt h 
y o u ca n i ma gi ne’ a n d ‘ T he w orst healt h y o u ca n i ma gi ne’.  T he V A S sc ores ca n be use d as a 
q ua ntitati ve meas ure of o verall self-rate d healt h stat us t hat ra n ge d fr o m 0 ( w orst healt h) t o 
1 0 0 ( best healt h).
C ha n ge fr o m baseli ne i n  E Q - 5 D-5 L : t he E Q- 5 D-5 L  sc ores a n d E Q V A S sc ores will be 
e val uate d.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 7 0
9. 4. 4. 3. 1 2 -Ite m S h ort F or m S ur ve y ( S F- 1 2)
T he 1 2 -ite m S h ort F or m Scale sc ores are esti mate d f or 4 of t he healt h c o nce pts ( p h ysical 
f uncti o n ( P F), r ole p h y sical ( R P), r ole e m oti o nal ( R E) , a n d me ntal healt h ( M H) usi n g t w o 
ite ms eac h, w hereas t he re mai ni n g 4 ( b o dily pai n ( B P), ge neral healt h ( G H), vitalit y  ( V T), 
s ocial f u ncti o n ( S F) are re prese nte d by a si n gle ite m.  T he ra w sc ores of eac h ite m are c o de d, 
wei g hte d, a n d s u m me d i nt o 2 scales: p h y sical c o m p o ne nt s u m mar y sc ore ( P C S) a n d me ntal 
c o m p o ne nt s u m mar y sc ore ( M C S).  Hi g her sc ores i n dicate better q ualit y of life.  C ha n ge 
fr o m baseli ne i n  1 2 Ite m-S ur ve y  F or m ( S F-1 2) Sc ore: t he P h y sical C o m p o ne nt 
S u m mar y ( P C S), t he Me ntal C o m p o ne nt S u m mar y ( M C S) a n d o verall sc ores ( P h ysical 
C o m p o ne nt S u m mar y  a n d Me ntal C o m p o ne nt S u m mar y) will be e val uate d.
9. 4. 5. P h ar m ac o ki netic D at a
Pre -d ose a n d p ost -d ose plas ma c o nce ntrati o ns of tafa mi dis at sc he d ule d visit wi ll be 
s u m marize d descri pti vel y.
9. 5. I nteri m A n al yses
N o f or mal i nteri m a nal ys is will be c o n d ucte d f or t his st u d y. As t his is a n 
o pe nla bel/ -s p o ns or-o pe n st u d y , t he s p o ns or ma y c o n d uct u n bli n de d re vie ws of t he data 
d uri n g t he c o urse of t he st u d y  f or t he p ur p ose of safet y assess me nt, facilitati n g 
d oseescalati o n - decisi o ns, facilitati n g P K/ P D m o deli n g, a n d/ or s u p p orti n g cli nical 
de vel o p me nt.
9. 5. 1. D at a M o nit ori n g C o m mittee 
T his st u d y  will n ot use a data m o nit ori n g c o m mittee ( D M C). 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 7 1
1 0. S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L C O N SI D E R A TI O N S
1 0. 1. A p pe n di x 1: 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. 1. 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  will 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 nter nati o nal C o u ncil f or Har m o nisati o n (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, i ncl u di n g a p plica ble pri vac y  la ws.
T he pr ot oc ol, pr ot oc ol a me n d me nts, I C D, i n vesti gat or’s br oc h ure (I B), a n d ot her rele va nt 
d oc u me nts (e g, a d vertise me nts) m ust be re vie we d a n d a p pr o ve d b y  t he s p o ns or a n d 
s u bmitte d t o a n I R B/ E C b y  t he i n vesti gat or a n d re vie we d a n d a p pr o ve d by t he I R B/ E C 
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/ E C 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 ges necessa r 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 i n vesti gat 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/ E C a n n uall y or m ore 
fre q ue ntly i n acc or da nce wit h t he re q uire me nts, p olicie s, a n d pr oce d ures esta blis he d 
b y  t he I R B/ E C;
N otif y i n g t he I R B/ E C of S A Es or ot her si g nifica nt safety fi n di n gs as re q uire d b y I RB/ E C 
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 o de of Fe deral Re g ulati o ns ( C F R), I CH g ui deli nes, t he I R B/ E C, 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), a n d all ot her a p plica ble l ocal 
re g ulati o ns.
1 0. 1. 1. 1. Re p orti n g of S afet y Iss ues a n d Seri o us Bre ac hes of t he Pr ot oc ol or I C H G C P
I n t he e ve nt of a ny pr o hi biti o n or restricti o n i m p ose d (ie, cli nical h ol d) b y  a n a p plica ble 
re g ulat or y a ut h ority i n a n y area of t he w orl d, or if t he i n vesti gat or is a ware of a n y ne w 
i nf or mati o n t hat 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 t he st u d y 
i nter ve nti o n, Pfizer s h o ul d be i nf or me d i m me diatel y. 
I n a d diti o n, t he i n vesti gat or will i nf or m Pfizer i m me diatel y of a n y ur ge nt safety meas ures 
ta ke n by t he i n vesti gat or t o pr otect t he st u d y partici pa nts a gai nst a n y i m me diate hazar d, a n d 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 7 2
of a n y seri o us breac hes of t his pr ot oc ol or of I C H G C P t hat t he i n vesti gat or bec o mes a ware 
of.
1 0. 1. 2. Fi n a nci al Discl os ure
I n vesti gat ors a n d s u bi n vesti gat ors will pr o vi de t he s p o ns or wit h s ufficie nt, acc urate fi na ncial 
i nf or mati o n as re q ueste d t o all o w t he s p o ns or t o s u b mit c o m plete a n d acc urate fi na ncial 
certificati o n or discl os ure state me nts t o t he a p pr o priate re g ulat or y  a ut h orities.  In vesti gat ors 
are res p o nsi ble f or pr o vi di n g i nf or mati o n o n fi na ncial i nterests d uri n g t he c o urse of t he st u d y 
a n d f or 1 ye ar after c o m pleti o n of t he st u d y .
1 0. 1. 3. I nf or me d C o nse nt Pr ocess
T he i n vesti gat 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 his/ her 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 d y.
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, I C H g ui deli nes, Healt h I ns ura nce 
P orta bilit y  a n d Acco u nta bilit y  Act ( HI P A A) re q uire me nts, w here a p plica ble, a n d t he I R B/ E C 
or st u d y  ce nter.
T he i n vesti gat or m ust e ns ure t hat eac h st u d y  partici pa nt or his/her le gall y a ut h orize d 
re prese ntati ve is f ull y i nf or me d a b o ut t he nat ure a n d o bjecti ves of t he st u d y, t he s hari n g of 
data relate d t o t he st u d y , a n d p ossi ble ris ks ass ociate d wit h partici pati o n, i ncl u di n g t he ris ks 
ass ociate d wit h t he pr ocessi n g of t he partici pa nt’s pers o nal data. 
T he partici pa 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 p o 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.
T he partici pa nt m ust be i nf or me d t hat his/ her me dical rec or ds ma y  be e xa mi ne d b y Cli nical 
Q ualit y  Ass ura nce 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 RB/ E C me m bers, a n d b y i ns pect ors fr o m re g ulat or y a ut h orities.
T he i n vesti gat or f urt her m ust e ns ure t hat eac h st u d y partici pa nt or his /her le gall y  a ut h orize d 
re prese ntati ve is f ull y i nf or me d a b o ut his or her ri g ht t o access a n d c orrect his or her pers o nal 
data a n d t o wit h dra w c o nse nt f or t he pr ocessi n g of his or her pers o nal data.
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 D.
Partici pa nts m ust be rec o nse nte d t o t he m ost c urre nt versi o n of t he I C D(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 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 7 3
A c o p y of t he I C D(s) m ust be pr o vi de d t o t he partici pa nt or t he partici pa nt’s le gall y 
a ut h orize d re prese ntati ve.
A partici pa nt w h o is rescree ne d is n ot re q uire d t o si g n a n ot her I C D if t he rescree ni n g d oes 
n ot e xcee d 4 5 d a y s fr o m t he pre vi o us I C D si g nat ure date.
If t he e x pl orat or y researc h will be c o n d ucte d, t he I C D will c o ntai n a se parate secti o n t hat 
a d dresses t he use of re mai ni n g ma n dat or y  sa m ples f or o pti o nal e x pl orat or y researc h.  T he 
i n vesti gat or or a ut h orize d desi g nee will e x plai n t o eac h partici pa nt t he o bjecti ves of t he 
e x pl orat or y researc h.  Partici pa nts will be t ol d t hat t he y are free t o ref use t o partici pate a n d 
ma y  wit h dra w t heir c o nse nt at a n y ti me a n d f or a n y reas o n d uri n g t he st ora ge peri o d.  A 
se parate sig nat ure will be re q uire d t o d oc u me nt a partici pa nt's a gree me nt t o all o w a n y  
re mai ni n g s peci me ns t o be use d f or e x pl orat or y researc h.  Partici pa nts w h o decli ne t o 
partici pate i n t his o pti o nal researc h will n ot pr o vi de t his se parate si g nat ure.
1 0. 1. 4. D at a Pr otecti 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 partici pa nt data.
Partici pa nts’ 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 f or m a n d 
will be pass w or d pr otecte d 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 disast er.  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, partici pa nts will be assi g ne d a si n gle, partici pa nt -s pecific n u merical c o de.  
A n y  partici pa nt rec or ds or data sets t hat are tra nsferre d t o t he s p o ns or will c o ntai n t he 
n u merical c o de; part ici pa nt na mes will n ot be tra nsferre d.  All ot her i de ntifia ble data 
tra nsferre d t o t he s p o ns or will be i de ntifie d b y t his si n gle, partici pa nt-s pecific c o de.  T he 
st u d y site will mai ntai n a c o nfi de ntial list of partici pa nts w h o partici pate d i n t he st u d y, 
lin ki n g eac h partici pa nt’s n u merical c o de t o his or her act ual i de ntit y.  I n case of data 
tra nsfer, t he s p o ns or will pr otect t he c o nfi de ntialit y of partici pa 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.
1 0. 1. 5. Disse mi n ati o n of Cli nic al St u d y D at a
Pfizer f ulfills its c o m mit me nt t o p u blicl y  discl ose cli nical st u d y res ults t hr o u g h p osti n g t he 
res ults of st u dies o n w w w.cli nicaltrials. g o v ( Cli nical Trials. g o v), t he E ur o pea n Cli nical Trials 
Data base ( E u dra C T), a n d/ or w w w. pfize r.c o m, a n d ot her p u blic re gistries i n acc or da nce wit h 
a p plica ble l ocal la ws/re g ulati o ns.  I n a d diti o n, Pfizer re p orts st u d y  res ults o utsi de of t he 
re q uire me nts of l ocal la ws/re g ulati o ns p urs ua nt t o its sta n dar d o perati n g pr oce d ures ( S O Ps).
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 7 4
I n all cases, stu d y  res ults are re p orte d by Pfizer i n a n o bjecti ve, acc urate, bala nce d, a n d 
c o m plete ma n ner a n d are re p orte d re gar dless of t he o utc o me of t he st u d y or t he c o u ntr y i n 
w hic h t he st u d y  was c o n d ucte d.
w w w.cli nicaltrials. g o v
Pfizer p osts cli nical trial U S Basic Res ults o n w w w.cli nicaltrials. g o v f or Pfizer -s p o ns ore d 
i nter ve nti o nal st u dies (c o n d ucte d i n patie nts) t hat e val uate t he safety a n d/ or efficac y of a 
pr o d uct, re gar dless of t he ge o gra p hical l ocati o n i n w hic h t he st u d y is c o n d ucte d.  U S Basic 
Res ults are ge n erall y s u b mitte d f or p osti n g wit hi n 1 year of t he pri mar y c o m pleti o n date 
( P C D) f or st u dies i n a d ult p o p ulati o ns or wit hi n 6 m o nt hs of t he P C D f or st u dies i n pe diatric 
p o p ulati o ns.
P C D is defi ne d as t he date t hat t he fi nal partici pa nt was e xa mi ne d or recei ve d a n i nter ve nti o n 
f or t he p ur p oses of fi nal c ollecti o n of data f or t he pri mar y o utc o me, w het her t he cli nical 
st u d y c o ncl u de d acc or di n g t o t he pres pecifie d pr ot oc ol or was ter mi nate d.
E u dra C T
Pfizer p osts E ur o pea n U ni o n ( E U) Basic Res ults o n E u dra C T f or a ll Pfizer-s p o ns ore d 
i nter ve nti o nal st u dies t hat are i n sc o pe of E U re q uire me nts.  E U Basic Res ults are s u b mitte d 
f or p osti n g wit hi n 1 year of t he P C D f or st u dies i n a d ult p o p ulati o ns or wit hi n 6 m o nt hs of 
t he P C D f or st u dies i n pe diatric p o p ulati o ns.
w w w. p fizer.c o m
Pfizer p osts p u blic discl os ure s y n o pses ( C S R s y n o pses i n w hic h a n y data t hat c o ul d be use d 
t o i de ntif y i n di vi d ual partici pa nts ha ve bee n re m o ve d) o n w w w. pfizer.c o m f or 
Pfizer -s p o ns ore d i nter ve nti o nal st u dies at t he sa me ti me t he U S Basic Res ults d oc u me nt is 
p oste d t o w w w.cli nicaltrials. g o v.
D oc u me nts wit hi n mar keti n g a ut h orizati o n pac ka ges/s u b missi o ns
Pfizer c o m plies wit h t he E ur o pea n U ni o n P olic y  0 0 7 0, t he pr oacti ve p u blicati o n of cli nical 
data t o t he E ur o pea n Me dici nes A ge nc y  ( E M A) we bsite.  Clinical data, u n der P hase 1 of t his 
p olic y , i ncl u des cli nical o ver vie ws, cli nical s u m maries, C S Rs, a n d a p pe n dices c o ntai ni n g t he 
pr ot oc ol a n d pr ot oc ol a me n d me nts, sa m ple C R Fs, a n d statistical met h o ds.  Cli nical data, 
u n der P hase 2 of t his p olic y , i ncl u des t he p u blis hi n g of i n di vi d ual partici pa nt data.  P olic y  
0 0 7 0 a p plies t o ne w mar keti n g a ut h orizati o n a p plicati o ns s u b mitte d via t he ce ntralize d 
pr oce d ure si nce 0 1 Ja n uar y 2 0 1 5 a n d a p plicati o ns f or li ne e xte nsi o ns a n d f or ne w i n dicati o ns 
s u b mitte d via t he ce ntralize d pr oce d ure si nce 0 1 J ul y 2 0 1 5.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 7 5
Data S hari n g
Pfizer pr o vi des researc hers sec ure access t o patie nt- le vel data or f ull C S Rs f or t he p ur p oses 
of “ b o na -fi de scie ntific researc h” t hat c o ntri b ute t o t he scie ntific u n dersta n di n g of t he 
disease, tar get, or c o m p o u n d class.  Pfizer will ma ke a vaila ble data fr o m t hese trials 2 4 
m o nt hs after st u d y  c o m pleti o n.  Patie nt-le vel data will be a n o n ymize d i n acc or da nce wit h 
a p plica ble pri vac y la ws a n d re g ulati o ns.  C S Rs will ha ve pers o nally i de ntifia ble i nf or mati o n 
re dacte d.
Data re q uests are c o nsi dere d fr o m q ualifie d researc hers wit h t he a p pr o priate c o m pete ncies t o 
perf or m t he pr o p ose d a nal yses.  Researc h tea ms m ust i ncl u de a bi ostatisticia n.  Data will n ot 
be pr o vi de d t o a p plica nts wit h si g nifica nt c o nflicts of i nterest, i ncl u di n g i n di vi d uals 
re q uesti n g access f or c o m mercial/c o m petiti ve or le gal p ur p oses.
1 0. 1. 6. 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 o n pri nte d or electr o nic 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 i n vesti gat or is 
res p o nsi ble f or verif yi n g t hat data e ntries are acc urate a n d c orrect b y p h ysicall y or 
electr o nicall y si g ni n g t he C R F.
T he i n vesti gat 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.
T he i n vesti gat or m ust e ns ure t hat t he C R Fs are sec urel y st ore d at t he st u d y site i n e ncr y pte d 
electr o nic f or m a n d are pass w or d pr otecte d 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 m ust per mit st u d y -relate d m o nit ori n g, a u dits, I R B/ E C re vie w, a n d 
re g ulat or 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.  T his 
verificati o n ma y  als o occ ur after st u d y c o m pleti o n.  It is i m p orta nt t hat t he i n vesti gat or(s) 
a n d t heir rele va nt pers o n nel are a vaila ble d uri n g t he m o nit ori n g visits a n d p ossi ble a u dits or 
i ns pecti o ns a n d t hat s ufficie nt ti me is de v ote d t o t he pr ocess.
M o nit ori n g details descri bi n g strate g y  (e g, ris k-base d i nitiati ves i n o perati o ns a n d q ualit y  
s uc h as ris k ma na ge me nt a n d miti gati o n strate gies a n d a nalyt ical ris k-base d m o nit ori n g), 
met h o ds, res p o nsi bilities, a n d re q uire me nts, i ncl u di n g ha n dli n g of n o nc o m plia nce iss ues a n d 
m o nit ori n g tec h ni q ues (ce ntral, re m ote, or o n -site m o nit ori n g), are pr o vi de d i n t he 
m o nit ori n g pla n.
T he s p o ns or or desi g nee is res p o nsi ble f or t he data ma na ge me nt of t his st u d y , i ncl u di n g 
q ualit y  c hec ki n g of t he data.
St u d y  m o nit ors will perf or m o n g oi n g s o urce data verificati o n t o 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; t hat t he safet y a n d ri g hts of partici pa nts are bei n g pr otecte d; a n d t hat t he st u d y  is 
bei n g c o n d ucte d i n acc or da nce wit h t he c urre ntl y  a p pr o ve d pr ot oc ol a n d a n y ot her st u d y 
a gree me nts, IC H G C P, a n d all a p plica ble re g ulat or y re q uire me nts.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 7 6
Rec or ds a n d d oc u me nts, i ncl u di n g si g ne d I C Ds, 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 i n vesti gat or f or 1 5 ye ars 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.  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 as l o n g as t he y are 
mai ntai ne d.
W he n partici pa nt data are t o be delete d, t he i n vesti gat or will e ns ure t hat all c o pies of s uc h 
data are pr o m ptl y  a n d irre v oca bly delete d fr o m all s yste ms.
T he i n vesti gat or(s) will n otif y  t he s p o ns or or its a ge nts i m me diatel y of a n y re g ulat or y 
i ns pecti o n n otificati o n i n relati o n t o t he st u d y.  F urt her m ore, t he i n vesti gat or will c o o perate 
wit h t he s p o ns or or its a ge nts t o pre pare t he i n vesti gat or site f or t he i ns pecti o n a n d will all o w 
t he s p o ns or or its a ge nt, w he ne ver feasi ble, t o be prese nt d uri n g t he i ns pecti o n.  T he 
i n vesti gat or site a n d i n vesti gat or will pr o m ptl y res ol ve a n y discre pa ncies t hat are i de ntifie d 
bet wee n t he st u d y data a n d t he partici pa nt's me dical rec or ds.  T he i n vesti gat or will pr o m ptl y  
pr o vi de c o pies of t he i ns pecti o n fi n di n gs t o t he s p o ns or or its a ge nt.  Bef ore res p o nse 
s u b missi o n t o t he re g ulat or y a ut h orities, t he i n vesti gat or will pr o vi de t he s p o ns or or its 
a ge nts wit h a n o p p ort u nit y t o re vie w a n d c o m me nt o n res p o nses t o a ny s uc h fi n di n gs.
1 0. 1. 7. 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 grity of t he data c ollecte d.  S o urce d oc u me nts are file d at t he i n vesti gat or site.
Data re p orte d o n t he C R F or e ntere d i n t he electr o nic C R F (e C R F) t hat are tra nscri be d fr o m 
s o urce d oc u me nts m ust be c o nsiste nt wit h t he s o urce d oc u me nts or t he discre pa ncies m ust be 
e x plai ne d.  T he i n vesti gat or ma y nee d t o re q uest pre vi o us me dical rec or ds or tra nsfer 
rec or ds, de pe n di n g o n t he st u d y.  Als o, c urre nt me dical rec or ds m ust be a vaila ble.
Defi niti o n of w hat c o nstit utes s o urce data ca n be f o u n d i n t he h os pital's partici pa nt c hart or 
HI S s y ste m.
1 0. 1. 8. St u d y a n d Site Cl os ure
T he s p o ns or desi g nee reser ves t he ri g ht t o cl ose t he st u d y site or ter mi nate t he st u d y at a n y 
ti me f or a ny reas o n at t he s ole discreti o n of t he s p o ns or.  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 all re q uire d d oc u me nts a n d st u d y 
s u p plies ha ve bee n c ollecte d a n d a stu d y -site cl os ure visit has bee n perf or me d.
T he i n vesti gat or ma y  i nitiate st u d y-site cl os ure at a n y ti me u p o n n otificati o n t o t he C o ntract 
Researc h Or ga nizati o n ( C R O) if re q ueste d t o d o s o b y  t he res p o nsi ble I R B/ E C or if s uc h 
ter mi nati o n is re q uire d t o pr otect t he healt h of st u d y partici pa nts.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 7 7
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 ma y i ncl u de b ut are n ot li mite d 
t o:
Fail ure of t he i n vesti gat 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/ E C 
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 recr uit me nt of partici pa nts b y  t he i n vesti gat or;
Disc o nti n uati o n of f urt her i n vesti gati o nal pr o d uct de vel o p me nt.
St u d y  ter mi nati o n is als o pr o vi de d f or i n t he cli nical st u d y a gree me nt.  If t here is a n y c onflict 
bet wee n t he c o ntract a n d t his pr ot oc ol, t he c o ntract will c o ntr ol as t o ter mi nati o n ri g hts.
1 0. 1. 9. P u blic ati o n P olic y
T he res ults of t his st u d y  ma y be p u blis he d or prese nte d at scie ntific meeti n gs by t he 
i n vesti gat or after p u blicati o n of t he o verall st u d y res ults or 1 year after e n d of t he st u d y ( or 
st u d y ter mi nati o n), w hic he ver c o mes first. 
T he i n vesti gat or a grees t o refer t o t he pri mar y  p u blicati o n i n a n y s u bse q ue nt p u blicati o ns 
s uc h as sec o n dar y ma n uscri pts, a n d s u b mits all ma n uscri pts or a bstracts t o the s p o ns or 
3 0 da y s bef ore s u b missi o n.  T his all o ws t he s p o ns or t o pr otect pr o prietar y i nf or mati o n a n d t o 
pr o vi de c o m me nts a n d t he i n vesti gat or will, o n re q uest, re m o ve a n y pre vi o usl y  u n discl ose d 
c o nfi de ntial i nf or mati o n bef ore discl os ure, e xce pt f or a n y st u d y - or Pfizer 
i nter ve nti o n-relate d i nf or mati o n necessar y f or t he a p pr o priate scie ntific prese ntati o n or 
u n dersta n di n g of t he st u d y  res ults.
F or all p u blicati o ns relati n g t o t he st u d y, t he i n vesti gat or will c o m pl y wit h rec o g nize d et hical 
sta n dar ds c o ncer nin g p u blicati o ns a n d a ut h ors hi p, i ncl u di n g t h ose esta blis he d b y  t he 
I nter nati o nal C o m mittee of Me dical J o ur nal E dit ors.
T he s p o ns or will c o m pl y  wit h t he re q uire me nts f or p u blicati o n of t he o verall st u d y res ults 
c o veri n g all i n vesti gat or sites.  I n acc or da nc e wit h sta n dar d e dit orial a n d et hical practice, t he 
s p o ns or will s u p p ort p u blicati o n of m ultice nter st u dies o nl y i n t heir e ntiret y a n d n ot as 
i n di vi d ual site data.  In t his case, a c o or di nati n g i n vesti gat or will be desi g nate d b y  m ut ual 
a gree me nt.
A ut h ors hi p of p u blicati o ns f or t he o verall st u d y  res ults will be deter mi ne d b y m ut ual 
a gree me nt 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. 
If p u blicati o n is a d dresse d i n t he cli nical st u d y a gree me nt, t he p u blicati on p olic y  set o ut i n 
t his secti o n will n ot a p pl y.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 7 8
1 0. 1. 1 0. S p o ns or’s Q u alifie d Me dic al Pers o n nel
T he c o ntact i nf or mati o n f or t he s p o ns or's a p pr o priatel y q ualifie d me dical pers o n nel f or t he 
st u d y is d oc u me nte d i n t he st u d y c o ntact list l ocate d i n t he st u d y p ortal. 
T o facilitate access t o a p pr o priatel y q ualifie d me dical pers o n nel o n st u d y- relate d me dical 
q uesti o ns or pr o ble ms, partici pa nts are pr o vi de d wit h a c o ntact car d.  T he c o ntact car d 
c o ntai ns, at a mi ni m u m, pr ot oc ol a n d st u d y  i nter ve nti o n i de ntifiers, partici pa nt n u m bers, 
c o ntact i nf or mati o n f or t he i n vesti gat or site, a n d c o ntact details f or a c o ntact ce nter i n t he 
e ve nt t hat t he i n vesti gat or site staff ca n n ot be reac he d t o pr o vi de a d vice o n a me dical 
q uesti o n or pr o ble m ori gi nati n g fr o m a n ot her healt hcare pr of essi o nal n ot i n v ol ve d i n t he 
partici pa nt’s partici pati o n i n t he st u d y .  T he c o ntact n u m ber ca n als o be use d b y i n vesti gat or 
staff if t he y are see ki n g a d vice o n me dical q uesti o ns or pr o ble ms; h o we ver, it s h o ul d be use d 
o nl y  i n t he e ve nt t hat t he esta blis he d c o m m u nicati o n pat h wa ys bet wee n t he i n vesti gat or site 
a n d t he st u d y tea m are n ot a vaila ble.  It is t heref ore i nte n de d t o a u g me nt, b ut n ot re place, t he 
esta blis he d c o m m u nicati o n pat h wa y s bet wee n t he i n vesti gat or site a n d t he st u d y tea m f or 
a d vice o n me dical q uesti o ns or pr o ble ms t hat ma y arise d uri n g t he st u d y .  T he c o ntact 
n u m ber is n ot i nte n de d f or use b y t he partici pa nt directl y, a n d if a partici pa nt calls t hat 
n u m ber, he or s he will be directe d bac k t o t he i n vesti gat or site.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 7 9
1 0. 2 . A p pe n di x 2: Cli nic al L a b or at or y Tests
T he f oll o wi n g safet y la b orat or y  tests will be perf or me d at ti mes defi ne d i n t he S o A secti o n of 
t his pr ot oc ol.  A d diti o nal la b orat or y res ults ma y be re p orte d o n t hese sa m ples as a res ult of 
t he met h o d of a nal ys is or t he t ype of a nal yz er use d b y t he cli nical la b orat or y; or as deri ve d 
fr o m calc ulate d val ues.  T hese a d diti o nal tests w o ul d n ot re q uire a d diti o nal c ollecti o n of 
bl o o d.  U nsc he d ule d cli nical la b orat or y  meas ure me nts ma y be o btai ne d at a n y ti me d uri n g 
t he st u d y t o assess a n y percei ve d safet y c o ncer ns.
T a ble 1 .
Pr ot oc ol -Re q uire d S afet y L a b or at or y Assess me nts
H e m at ol o g y
C he mistr y
Di pstic k Uri n al ysis
Ot her
W hite bl o o d cell c o u nt
H e m o gl o bi n 
Re d bl o o d cell c o u nt
Ne utr o p hils
L y m p h oc ytes
H e m at ocrit 
Mea n c or p usc ular 
v ol u me
M o n oc ytes
Mea n c or p usc ular 
he m o gl o bi n 
E osi n o p hils
Mea n c or p usc ular 
he m o gl o bi n 
c o nce ntrati o n
Bas o p hils
Platelets
S o di u m I n or ga nic 
P h os p h or us
As partate 
a mi n otra nsferase ( A S T)
P otassi u m 
Gl uc ose
Ga m ma gl uta m y l 
tra nsferase
C hl ori de 
T otal bilir u bi n
C h olester ol
T otal pr otei n
Uric aci d
Bl o o d Urea Nitr o ge n 
Al b u mi n T h yr oi d -
sti m ulati n g h or m o ne
Creati ni ne 
Gl o b uli n
T otal t h yr o xi ne ( T 4)
Calci u m 
Ala ni ne 
a mi n otra nsferase ( A L T)
Free T 4
Reti n ol bi n di n g pr otei n
Al kali ne P h os p hatase
p H 
Bl o o d (free H b)
Ket o nes 
Gl uc ose 
Bilir u bi n
Pr otei n 
Nitrite
S pecific gra vit y
Ur o bili n o ge n
N T -pr o B N P
T n I
I nter nati o nal n or malize d rati o 
(I N R) 
Pr ot hr o m bi n ti me ( P T)
Acti vate d partial 
t hr o m b o plasti n ti me ( A P T T)
Fi bri n o ge n ( FI B)
He patitis B s urface a nti ge n
He patitis C a nti b o d y
H u ma n i m m u n o deficie nc y
vir us a nti b o d y
S y p hilis a nti b o d y (a nti-T P)
I n vesti gat ors m ust d oc u me nt t heir re vie w of eac h la b orat or y safety re p ort.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 8 0
1 0. 3. A p pe n di x 3: A d verse E ve nts: Defi niti o ns a n d Pr oce d ures f or Rec or di n g, 
E v a l u ati n g, F oll o w-u p, a n d Re p orti n g
1 0. 3. 1. Defi niti o n of A E
A E Defi niti o n

A n A E is a n y u nt o war d me dical occ urre nce i n a patie nt or cli nical st u d y 
partici pa nt, te m p orall y ass ociate d wit h t he use of st u d y i nter ve nti o n, w het her or n ot 
c o nsi dere d relate d t o t he st u d y i nter ve nti o n.

N O T E: A n A E ca n t heref ore be a n y u nfa v ora ble a n d u ni nte n de d si g n (i ncl u di n g a n 
a b n or mal la b orat or y fi n di n g), sy m pt o m, or disease ( ne w or e xacer bate d) 
te m p orall y ass ociate d wit h t he use of st u d y i nter ve nti o n.
E ve nts Meeti n g
t he A E Defi niti o n

A n y  a b n or mal la b orat or y test res ults ( he mat ol o g y, cli nical c he mistr y, or uri nal ysis) 
or ot her safet y assess me nts (e g, E C G, ra di ol o gical sca ns, vital si g n meas ure me nts), 
i ncl u di n g t h ose t hat w orse n fr o m baseli ne, c o nsi dere d cli nically si g nifica nt i n t he 
me dical a n d scie ntific j u d g me nt of t he i n vesti gat or. A n y a b n or mal la b orat or y test 
res ults t hat meet a ny of t he c o n diti o ns bel o w m ust be rec or de d as a n A E:

Is ass ociate d wit h acc o m pa n yi n g sy m pt o ms.

Re q uires a d diti o nal dia g n ostic testi n g or me dical/s ur gical i nter ve nti o n.

Lea ds t o a c ha n ge i n st u d y  d osi n g ( o utsi de of a n y pr ot oc ols pecifie d d ose 
a dj ust me nts) or disc o nti n uati o n fr o m t he st u d y , si g nifica nt a d diti o nal 
c o nc o mita nt dr u g treat me nt, or ot her t hera p y.

E xacer bati o n of a c hr o nic or i nter mitte nt pree xisti n g c o n diti o n i ncl u di n g eit her a n 
i ncrease i n fre q ue nc y a n d/ or i nte nsit y of t he c o n diti o n.

Ne w c o n diti o ns detecte d or dia g n ose d after st u d y i nter ve nti o n a d mi nistrati o n e ve n 
t h o u g h it ma y ha ve bee n prese nt bef ore t he start of t he st u d y.

Si g ns, s y m pt o ms, or t h e cli nical se q uelae of a s us pecte d dr u g dr u g i nteracti o n.

Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d o ver d ose of eit her st u d y 
i nter ve nti o n or a c o nc o mita nt me dicati o n.  O ver d ose per se will n ot be re p orte d as 
a n A E/ S A E u nless it is a n i nte nti o nal o ver d ose ta ke n wit h p ossi ble 
s uici dal/self- har mi n g i nte nt.  S uc h o ver d oses s h o ul d be re p orte d re gar dless of 
se q uelae.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 8 1
T he si g ns, s y m pt o ms, a n d/ or cli nical se q uelae res ulti n g fr o m lac k of efficac y  will be 
re p orte d as a n A E or S A E if t he y f ulfill t he defi niti o n of a n A E or S A E a n d meet t he 
re q uire me nts as per Secti o n 8. 3. 8. 1 . Als o, “lac k of efficac y ” or “fail ure of e x pecte d 
p har mac ol o gical acti o n” c o nstit utes a n A E or S A E.
E ve nts N O T Meeti n g t he A E Defi niti o n
A n y  cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n gs or ot her a b n or mal safety 
assess me nts w hic h are ass ociate d wit h t he u n derl yi n g disease, u nless j u d ge d b y  t he 
i n vesti gat or t o be m ore se vere t ha n e x pecte d f or t he partici pa nt’s c o n diti o n.
T he disease/ dis or d er bei n g st u die d or e x pecte d pr o gressi o n, si g ns, or s y m pt o ms of t he 
disease/ dis or der bei n g st u die d, u nless m ore se vere t ha n e x pecte d f or t he partici pa nt’s 
c o n diti o n.
Me dical or s ur gical pr oce d ure (e g, e n d osc o p y, a p pe n dect o m y): t he c o n diti o n t hat lea ds t o 
the pr oce d ure is t he A E.
Sit uati o ns i n w hic h a n u nt o war d me dical occ urre nce di d n ot occ ur (s ocial a n d/ or 
c o n ve nie nce a d missi o n t o a h os pital).
A ntici pate d da y -t o-d a y  fl uct uati o ns of pree xisti n g disease(s) or c o n diti o n(s) prese nt or 
detecte d at t he start of t he st u d y t hat d o n ot w orse n.
1 0. 3. 2. Defi niti o n of S A E
If a n e ve nt is n ot a n A E per defi niti o n a b o ve, t he n it ca n n ot be a n S A E e ve n if seri o us 
c o n diti o ns are met (e g, h os pitalizati o n f or si g ns/s y m pt o ms of t he disease u n der st u d y , deat h 
d ue t o pr o gressi o n of disease).
A n S A E is defi ne d as a n y u nt o w ar d me dic al occ urre nce t h at, at a n y d ose:
a.
Res ults i n de at h
b.
Is life-t hre ate ni n g
T he ter m “life -t hreate ni n g” i n t he defi niti o n of “seri o us” refers t o a n e ve nt i n w hic h t he 
partici pa nt was at ris k of deat h at t he ti me of t he e ve nt.  I t d oes n ot refer t o a n e ve nt t hat 
h y p ot heticall y  mi g ht ha ve ca use d deat h if it were m ore se vere.
c.
Re q uires i n p atie nt h os pit aliz ati o n or pr ol o n g ati o n of e xisti n g h os pit aliz ati o n
I n ge neral, h os pitalizati o n si g nifies t hat t he partici pa nt has bee n detai ne d ( us uall y  
i n v ol vi n g at least a n o ver ni g ht sta y) at t he h os pital or e mer ge nc y war d f or o bser vati o n 
a n d/ or treat me nt t hat w o ul d n ot ha ve bee n a p pr o priate i n t he p h ys icia n’s office or 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 8 2
o ut patie nt setti n g.  C o m plicati o ns t hat occ ur d uri n g h os pital izati o n are A Es.  If a 
c o m plicati o n pr ol o n gs h os pitalizati o n or f ulfills a n y ot her seri o us criteria, t he e ve nt is 
seri o us.  W he n i n d o u bt as t o w het her “ h os pitalizati o n” occ urre d or was necessar y, t he A E 
s h o ul d be c o nsi dere d seri o us.
H os pitalizati o n f or el ecti ve treat me nt of a pree xisti n g c o n diti o n t hat di d n ot w orse n fr o m 
baseli ne is n ot c o nsi dere d a n A E.
d.
Res ults i n persiste nt dis a bilit y/i nc a p acit y

T he ter m disa bilit y mea ns a s u bsta ntial disr u pti o n of a pers o n’s a bilit y  t o c o n d uct 
n or mal life f u ncti o ns.

T his defi niti o n is n ot i nte n de d t o i ncl u de e x perie nces of relati vel y mi n or me dical 
si g nifica nce s uc h as u nc o m plicate d hea dac he, na usea, v o miti n g, diarr hea, 
i nfl ue nza, a n d acci de ntal tra u ma (e g, s prai ne d a n kle) w hic h ma y i nterfere wit h or 
pre ve nt e ver y d a y  life f u ncti o ns b ut d o n ot c o nstit ute a s u bsta ntial disr u pti o n.
e.
Is a c o n ge nit al a n o m al y/ birt h defect
f.
Ot her sit u ati o ns:

Me dical or scie ntific j u d g me nt s h o ul d be e xercise d i n deci di n g w het her S A E 
re p orti n g is a p pr o priate i n ot her sit uati o ns s uc h as i m p orta nt me dical e ve nts t hat 
ma y  n ot be i m me diately l ife-t hreate ni n g or res ult i n deat h or h os pitalizati o n b ut 
ma y  je o par dize t he partici pa nt or ma y re q uire me dical or s ur gical i nter ve nti o n t o 
pre ve nt o ne of t he ot her o utc o mes liste d i n t he a b o ve defi niti o n.  T hese e ve nts 
s h o ul d us uall y be c o nsi dere d seri o us.

E xa m ples of s uc h e ve nts i ncl u de i n vasi ve or mali g na nt ca ncers, i nte nsi ve treat me nt 
i n a n e mer ge nc y r o o m or at h o me f or aller gic br o nc h os pas m, bl o o d d yscrasias or 
c o n v ulsi o ns t hat d o n ot res ult i n h os pitalizati o n, or de vel o p me nt of dr u g 
de pe n de nc y  or dr u g a b use.

S us pecte d tra ns missi o n via a Pfizer pr o d uct of a n i nfecti o us a ge nt, pat h o ge nic or 
n o n -pat h o ge nic, is c o nsi dere d seri o us.  T he e ve nt ma y  be s us pecte d fr o m cli nical 
s ym pt o ms or la b orat or y  fi n di n gs i n dicati n g a n i nfecti o n i n a patie nt e x p ose d t o a 
Pfizer pr o d uct.  T he ter ms “s us pecte d tra ns missi o n” a n d  “tra ns missi o n” are 
c o nsi dere d s y n o n y m o us.  T hese cases are c o nsi dere d u ne x pecte d a n d ha n dle d as 
seri o us e x pe dite d cases b y p har mac o vi gila nce pers o n nel.  S uc h cases are als o 
c o nsi dere d f or re p orti n g as pr o d uct defects, if a p pr o priate.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 8 3
1 0. 3. 3. Rec or di n g/ Re p orti n g a n d F oll o w -u p of A Es a n d/ or S A Es
A E a n d S A E Rec or di n g/ Re p orti n g
T he ta ble bel o w s u m marizes t he re q uire me nts f or rec or di n g a d verse e ve nts o n t he C R F 
a n d f or re p orti n g seri o us a d verse e ve nts o n t he C T S A E Re p ort F or m t o Pfizer Safet y.  
T hese re q uire me nts are deli neate d f or 3 t y pes of e ve nts: ( 1) S A Es; ( 2) n o nseri o us a d verse 
e ve nts ( A Es); a n d ( 3) e x p os ure t o t he st u d y  i nter ve nti o n u n der st u d y d uri n g pre gna nc y  or 
breastfee di n g, a n d occ u pati o nal e x p os ure. 
It s h o ul d be n ote d t hat t he C T S A E Re p ort F or m f or re p orti n g of S A E i nf or mati o n is n ot 
t he sa me as t he A E pa ge of t he C R F.  W he n t he sa me data are c ollecte d, t he f or ms m ust be 
c o m plete d i n a c o nsiste nt ma n ner.  A Es s h o ul d be rec or de d usi n g c o ncise me dical 
ter mi n ol o g y a n d t he sa me A E ter m s h o ul d be use d o n b ot h t he C R F a n d t he C T S A E 
Re p ort F or m f or re p orti n g of S A E i nf or mati o n.
S afet y E ve nt
Rec or de d o n t he C R F
Re p orte d o n t he C T S A E 
Re p ort F or m t o Pfizer
S afet y Wit hi n 2 4 H o urs of 
A w are ness
S A E
All
All
N o nseri o us A E
All
N o ne
E x p os ure t o t he st u d y  
i nter ve nti o n u n der st u dy 
d uri n g pre g na nc y  or 
breastfee di n g, a n d 
occ u pati o nal e x p os ure
All A Es/ S A Es ass ociate d 
wit h e x p os ure d uri n g 
pre g na nc y  or breastfee di n g
Occ u pati o nal e x p os ure is 
n ot rec or de d.
All (a n d E D P s u p ple me ntal 
f or m f or E D P)  
N ote:  I ncl u de all S A Es 
ass ociate d wit h e x p os ure 
d uri n g pre g na nc y  or 
breastfee di n g. I ncl u de all 
A Es/ S A Es ass ociate d wit h 
occ u pati o nal e x p os ure.

W he n a n A E/ S A E occ urs, it is t he res p o nsi bilit y of t he i n vesti gat or t o re vie w all 
d oc u me ntati o n (e g, h os pital pr o gress n otes, la b orat or y  re p orts, a n d dia g n ostic 
re p orts) relate d t o t he e ve nt.

T he i n vesti gat or will t he n rec or d all rele va nt A E/ S A E i nf or mati o n i n t he C R F.

It is n ot acce pta ble f or t he i n vesti gat or t o se n d p h ot oc o pies of t he partici pa nt’s 
me dical rec or ds t o Pfizer Safet y  i n lie u of c o m pleti o n of t he C T S A E Re p ort 
F or m/ A E/ S A E C R F pa ge.

T here ma y  be i nsta nces w he n c o pies of me dical rec or ds f or certai n cases are 
re q ueste d by P fizer Safet y.  I n t his case, all partici pa nt i de ntifiers, wit h t he 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 8 4
e xce pti o n of t he partici pa nt n u m ber, will be re dacte d o n t he c o pies of t he me dical 
rec or ds bef ore s u b missi o n t o Pfizer Safet y.

T he i n vesti gat or will atte m pt t o esta blis h a dia g n osis of t he e ve nt base d o n si g ns, 
s ym pt o ms, a n d/ or ot her cli nical i nf or mati o n.  W he ne ver p ossi ble, t he dia g n osis 
( n ot t he i n di vi d ual si g ns/s ym pt o ms) will be d oc u me nte d as t he A E/ S A E.
Assess me nt of I nte nsit y
T he i n vesti gat or will ma ke a n assess me nt of i nte nsit y f or eac h A E a n d S A E re p orte d 
d uri n g t he st u d y a n d assi g n it t o 1 of t he f oll o wi n g cate g ories: 

Mil d: A n e ve nt t hat is easil y  t olerate d b y t he partici pa nt, ca usi n g mi ni mal 
disc o mf ort a n d n ot i nterferi n g wit h e ver y d a y  acti vities.

M o derate: A n e ve nt t hat ca uses s ufficie nt disc o mf ort a n d i nterferes wit h n or mal 
e ver yd a y  acti vities.

Se vere: A n e ve nt t hat pre ve nts n or mal e ver y d a y  acti vities.  A n A E t hat is assesse d 
as se vere s h o ul d n ot be c o nf use d wit h a n S A E. Se vere is a cate g or y  utilize d f or 
rati n g t he i nte nsity of a n e ve nt; a n d b ot h A Es a n d S A Es ca n be assesse d as se vere.
A n e ve nt is defi ne d as “seri o us” w he n it meets at least 1 of t he pre defi ne d o utc o mes as 
descri be d i n t he defi niti o n of a n S A E, N O T w he n it is rate d as se vere.
Assess me nt of C a us alit y

T he i n vesti gat or is o bli gate d t o assess t he relati o ns hi p bet wee n i n vesti gati o nal 
pr o d uct a n d eac h occ urre nce of eac h A E/ S A E.

A “reas o na ble p ossi bilit y” of a relati o ns hi p c o n ve ys t hat t here are facts, e vi de nce, 
a n d/ or ar g u me nts t o s u g gest a ca usal relati o ns hi p, rat her t ha n a relati o ns hi p ca n n ot 
be r ule d o ut.

T he i n vesti gat or will use cli nical j u d g me nt t o deter mi ne t he relati o ns hi p.

Alter nati ve ca uses, s uc h as u n derl yi n g disease(s), c o nc o mita nt t hera p y, a n d ot her 
ris k fact ors, as well as t he te m p oral relati o ns hi p of t he e ve nt t o st u d y i nter ve nti o n
a d mi nistrati o n will be c o nsi dere d a n d i n vesti gate d.

T he i n vesti gat or will als o c o ns ult t he I B a n d/ or pr o d uct i nf or mati o n, f or mar kete d 
pr o d ucts, i n his/ her asse ss me nt.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 8 5

F or eac h A E/ S A E, t he i n vesti gat or m ust d oc u me nt i n t he me dical n otes t hat he/s he 
has re vie we d t he A E/ S A E a n d has pr o vi de d a n assess me nt of ca usalit y .

T here ma y  be sit uati o ns i n w hic h a n S A E has occ urre d a n d t he i n vesti gat or has 
mi ni mal i nf or mati o n t o i ncl u de i n t he i nitial re p ort t o t he s p o ns or.  H o we ver, it is 
ver y i m p ort a nt t h at t he i n vesti g at or al w a ys m a ke a n assess me nt of c a us alit y 
f or e ver y e ve nt bef ore t he i niti al tr a ns missi o n of t he S A E d at a t o t he s p o ns or.

T he i n vesti gat or ma y  c ha n ge his/ her o pi ni o n of ca usalit y  i n li g ht of f oll o w- u p 
i nf or mati o n a n d se n d a n S A E f oll o w-u p re p ort wit h t he u p date d ca usalit y  
assess me nt.

T he ca usalit y  assess me nt is o ne of t he criteria use d w he n deter mi ni n g re g ulat or y 
re p orti n g re q uire me nts.

If t he i n vesti gat or d oes n ot k n o w w het her or n ot t he st u d y i nter ve nti o n ca use d t he 
e ve nt, t he n t he e ve nt will be ha n dle d as “relate d t o st u d y  i nter ve nti o n” f or re p orti n g 
p ur p oses, as defi ne d b y t he s p o ns or.  I n a d diti o n, if t he i n vesti gat or deter mi nes t hat 
a n S A E is ass ociate d wit h st u d y pr oce d ures, t he i n vesti gat or m ust rec or d t his 
ca usal relati o ns hi p i n t he s o urce d oc u me nts a n d C R F, a n d re p ort s uc h a n 
assess me nt i n t he de dicate d secti o n of t he C T S A E Re p ort F or m a n d i n acc or da nce 
wit h t he S A E re p orti n g re q uire me nts.
F oll o w -u p of A Es a n d S A Es

T he i n vesti gat or is o bli gate d t o perf or m or arra n ge f or t he c o n d uct of s u p ple me ntal 
meas ure me nts a n d/ or e val uati o ns as me dicall y  i n dicate d or as re q ueste d b y t he 
s p o ns or t o el uci date t he nat ure a n d/ or ca usality of t he A E or S A E as f ull y a s 
p ossi ble.  T his ma y  i ncl u de a d diti o nal la b orat or y tests or i n vesti gati o ns, 
hist o pat h ol o gical e xa mi nati o ns, or c o ns ultati o n wit h ot her healt hcare pr ofessi o nals.

If a partici pa nt dies d uri n g partici pati o n i n t he st u d y or d uri n g a rec o g nize d 
f oll o w-u p peri o d, t he i n vesti gat or will pr o vi de Pfizer Safet y wit h a c o p y of a n y 
p ost m orte m fi n di n gs i ncl u di n g hist o pat h ol o g y .  

Ne w or u p date d i nf or mati o n will be rec or de d i n t he ori gi nall y  c o m plete d C R F.

T he i n vesti gat or will s u b mit a n y  u p date d S A E data t o t he s p o ns or wit hi n 2 4 h o urs 
of recei pt of t he i nf or mati o n.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 8 6
1 0. 3. 4. Re p orti n g of S A Es
S A E Re p orti n g t o Pfizer S afet y vi a a n Electr o nic D at a C ollecti o n T o ol

T he pri mar y  mec ha nis m f or re p orti n g a n S A E t o Pfizer Safet y will be t he 
electr o nic data c ollecti o n t o ol.

If t he electr o nic s ys te m is u na vaila ble, t he n t he site will use t he pa per S A E data 
c ollecti o n t o ol (see ne xt secti o n) i n or der t o re p ort t he e ve nt wit hi n 2 4 h o urs.

T he site will e nter t he S A E data i nt o t he electr o nic s y ste m as s o o n as t he data 
bec o me a vaila ble.

After t he st u d y is c o m plete d at a gi ve n site, t he electr o nic data c ollecti o n t o ol will 
be ta ke n off -li ne t o pre ve nt t he e ntr y of ne w data or c ha n ges t o e xisti n g data.

If a site recei ves a re p ort of a ne w S A E fr o m a st u d y partici pa nt or recei ves u p date d 
dat a o n a pre vi o usl y re p orte d S A E after t he electr o nic data c ollecti o n t o ol has bee n 
ta ke n off-li ne, t he n t he site ca n re p ort t his i nf or mati o n o n a pa per S A E f or m (see 
ne xt secti o n) or t o Pfizer Safet y  b y tele p h o ne.
S A E Re p orti n g t o Pfizer S afet y vi a C T S A E Re p ort F or m

Facsi mile tra ns missi o n of t he C T S A E Re p ort F or m is t he preferre d met h o d t o 
tra ns mit t his i nf or mati o n t o Pfizer Safet y.

I n circ u msta nces w he n t he facsi mile is n ot w or ki n g, n otificati o n by tele p h o ne is 
acce pta ble wit h a c o p y of t he C T S A E Re p o rt F or m se nt b y o ver ni g ht mail or 
c o urier ser vice.

I nitial n otificati o n via tele p h o ne d oes n ot re place t he nee d f or t he i n vesti gat or t o 
c o m plete a n d si g n t he C T S A E Re p ort F or m pa ges wit hi n t he desi g nate d re p orti n g 
ti me fra mes.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 8 7
1 0. 4. A p pe n di x 4: C o ntr ace pti ve G ui d a nce a n d C ollecti o n of Pre g n a nc y I nf or m ati o n
1 0. 4. 1. M ale P artici p a nt Re pr o d ucti ve I ncl usi o n Criteri a
Male partici pa nts are eli gi ble t o partici pate if t he y  a gree t o t he f oll o wi n g re q uire me nts d uri n g 
t he i nter ve nti o n peri o d a n d f or at least 2 8 d a y s after t he last d ose of st u d y i nter ve nti o n, w hic h
c orres p o n ds t o t he ti me nee de d t o eli mi nate st u d y i nter ve nti o n:

Refrai n fr o m d o nati n g s per m.
P L U S eit her :

Be a bsti ne nt fr o m heter ose x ual i nterc o urse wit h a fe male of c hil d beari n g p ote ntial as 
t heir preferre d a n d us ual lifest y le (a bsti ne nt o n a l o n g-ter m a n d persiste nt basis) a n d 
a gree t o re mai n a bsti ne nt. 
O R

M ust a gree t o use a male c o n d o m w he n e n ga gi n g i n a n y  acti vit y t hat all o ws f or 
passa ge of ejac ulate t o a n ot her pers o n.

I n a d diti o n t o male c o n do m use, a hi g hl y effecti ve met h o d of c o ntrace pti o n ma y be 
c o nsi dere d i n W O C B P part ners of male partici pa nts (refer t o t he list of hi g hl y  
effecti ve met h o ds bel o w i n Secti o n 1 0. 4. 4 ).
1 0. 4. 2. Fe m ale P artici p a nt Re pr o d ucti ve I ncl usi o n Criteri a
A fe male partici pa nt is eli gi ble t o partici pate if s he is n ot pre g na nt or breastfee di n g, a n d at 
least 1 of t he f oll o wi n g c o n diti o ns a p plies:

Is n ot a W O C B P (see defi niti o ns bel o w i n Secti o n 1 0. 4. 3 ).
O R

Is a W O C B P a n d usi n g a c o ntrace pti ve met h o d t hat is hi g hl y effecti ve ( wit h a fail ure 
rate of < 1 % per year), as descri be d bel o w, d uri n g t he i nter ve nti o n peri o d a n d f or at 
least 2 8 d a y s after t he last d ose of st u d y i nter ve nti o n, w hic h c orres p o n ds t o t he ti me 
nee de d t o eli mi nate a n y re pr o d ucti ve safety ris k of t he st u d y i nter ve nti o n .  T he 
i n vesti gat or s h o ul d e val uate t he effecti ve ness of t he c o ntrace pti ve met h o d i n 
relati o ns hi p t o t he first d ose of st u d y i nter ve nti o n.
T he i n vesti gat or is res p o nsi ble f or re vie w of me dical hist or y , menstr ual hist or y , a n d rece nt 
se x ual acti vit y t o decrease t he ris k f or i ncl usi o n of a w o ma n wit h a n early u n detecte d 
pre g na nc y . 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 8 8
1 0. 4. 3. W o m a n of C hil d be ari n g P ote nti al ( W O C B P)
A w o ma n is c o nsi dere d fertile f oll o wi n g me narc he a n d u ntil bec o mi n g p ost me n o pa usal 
u nless per ma ne ntl y sterile (see bel o w).
If fertilit y is u nclear (e g, a me n orr hea i n a d olesce nts or at hletes) a n d a me nstr ual c ycle ca n n ot 
be c o nfir me d bef ore t he first d ose of st u d y i nter ve nti o n, a d diti o nal e val uati o n s h o ul d be 
c o nsi dere d.
W o me n i n t he f oll o wi n g cate g ories are n ot c o nsi dere d W O C B P:
1.
Pre me n o pa usal fe male wit h 1 of t he f oll o wi n g:

D oc u me nte d h ys terect o m y;

D oc u me nte d bilateral sal pi n gect o m y ;

D oc u me nte d bilateral o o p h orect o m y.
F or i n di vi d uals wit h per ma ne nt i nfertilit y  d ue t o a n alter nate me dical ca use ot her t ha n 
t he a b o ve, (e g, m ulleria n a ge nesis, a n dr o ge n i nse nsiti vit y), i n vesti gat or discreti o n 
s h o ul d be a p plie d t o deter mi ni n g st u d y e ntr y.
N ote: D oc u me ntati o n f or a n y of t he a b o ve cate g ories ca n c o me fr o m t he site 
pers o n nel’s re v ie w of t he partici pa nt’s me dical rec or ds, me dical e xa mi nati o n, or 
me dical hist or y  i nter vie w.  T he met h o d of d oc u me ntati o n s h o ul d be rec or de d i n t he 
partici pa nt’s me dical rec or d f or t he st u d y.
2.
P ost me n o pa usal fe male:

A p ost me n o pa usal state is defi ne d as a ge 6 0 y ears or ol der or n o me nses f or 
1 2 m o nt hs wit h o ut a n alter nati ve me dical ca use. 

A hi g h f ollicle -sti m ulati n g h or m o ne ( F S H) le vel i n t he p ost me n o pa usal ra n ge 
ma y  be use d t o c o nfir m a p ost me n o pa usal state i n w o me n n ot usi n g h or m o nal 
c o ntrace pti o n or h or m o ne re place me nt t hera p y ( H R T). 

Fe males o n H R T a n d w h ose me n o pa usal stat us is i n d o u bt will be re q uire d t o 
use o ne of t he n o nestr o ge n h or m o nal hi g hl y effecti ve c o ntrace pti o n met h o ds 
if t he y wis h t o c o nti n ue t heir H R T d uri n g t he st u d y.  Ot her wise, t he y m ust 
disc o nti n ue H R T t o all o w c o nfir mati o n of p ost me n o pa usal stat us bef ore st u d y  
e nr oll me nt.
1 0. 4. 4. C o ntr ace pti o n Met h o ds
I m pla nta ble pr o gest o ge n-o nl y  h or m o ne c o ntrace pti o n ass ociate d wit h i n hi biti o n of 
o v ulati o n.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 8 9
I ntra uteri ne de vice (I U D).
I ntra uteri ne h or m o ne-releasi n g sys te m (I U S).
Bilateral t u bal occl usi o n.
Vasect o mize d part ner:

Vasect o mize d part ner is a hi g hl y effecti ve c o ntrace pti ve met h o d pr o vi de d t hat t he 
part ner is t he s ole se x ual part ner of t he w o ma n of c hil d beari n g p ote ntial a n d t he 
a bse nce of s per m ha s bee n c o nfir me d.  If n ot, a n a d diti o nal hi g hl y effecti ve 
met h o d of c o ntrace pti o n s h o ul d be use d.  T he s per mat o ge nesis c y cle is 
a p pr o xi matel y 9 0 da ys.
C o m bi ne d (estr o ge n - a n d pr o gest o ge n -c o ntai ni n g) h or m o nal c o ntrace pti o n ass ociate d 
wit h i n hi biti o n of o v ul ati o n:

oral;

i ntra va gi nal;

tra ns der mal;

i njecta ble.
Pr o gest o ge n -o nl y h or m o ne c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n:

Oral;

I njecta ble.
Se x ual a bsti ne nce:

Se x ual a bsti ne nce is c o nsi dere d a hi g hl y effecti ve met h o d o nl y  if defi ne d as 
refrai ni n g fr o m heter ose x ual i nterc o urse d uri n g t he e ntire peri o d of ris k ass ociate d 
wit h t he st u d y i nter ve nti o n.  T he relia bilit y of se x ual a bsti ne nce nee ds t o be 
e val uate d i n relati o n t o t he d urati o n of t he st u d y a n d t he preferre d a n d us ual 
lifest yle of t he partici pa nt.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 9 0
1 0. 5. A p pe n di x 5: Ge netics
Use/ A n al ysis of D N A
Ge netic variati o n ma y  i m pact a partici pa nt’s res p o nse t o st u d y i nter ve nti o n, s usce pti bilit y 
t o, a n d se verity a n d pr o gressi o n of disease.  T heref ore, w here l ocal re g ulati o ns a n d 
I RBs/ E Cs all o w, a bl o o d sa m ple will be c ollecte d f or de o x yri b o n ucleic aci d ( D N A )
a nal ys is.
T he res ults of ge netic a nal y ses ma y be re p orte d i n t he Cli nical St u d y Re p ort ( C S R) or i n 
a se parate st u d y s u m mar y, or ma y be use d f or i nter nal decisi o n ma ki n g wit h o ut bei n g 
i ncl u de d i n a st u d y re p ort.
T he s p o ns or will st ore t he D N A sa m ples i n a sec ure st ora ge s pace wit h a de q uate 
meas ures t o pr otect c o nfi de ntialit y . 
T he sa m ples will be retai ne d as i n dicate d:

Sa m ples f or s pecifie d ge netic a nal ys is (see Sect i o n 8. 7. 1 ) will n ot be st ore d 
be y o n d t he c o m pleti o n of t his st u d y  (e g, C S R fi nalizati o n)].
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 9 1
1 0. 6. A p pe n di x 6: Li ver S afet y: S u g geste d Acti o n s a n d F oll o w- u p Assess me nts 
P ote nti al C ases of Dr u g -I n d uce d Li ver I nj ur y
H u ma ns e x p ose d t o a dr u g w h o s h o w n o si g n of li ver i nj ur y  (as deter mi ne d b y ele vati o ns i n 
tra nsa mi nases) are ter me d “t olerat ors,” w hile t h ose w h o s h o w tra nsie nt li ver i nj ur y, b ut a da pt 
are ter me d “a da pt ors.”  I n s o me partici pa nts, tra nsa mi nase ele vati o ns are a har bi n ger of a 
m ore seri o us p ote ntial o utc o me.  T hese partici pa nts fail t o a da pt a n d t heref ore are 
"s usce pti ble" t o pr o gressi ve a n d seri o us li ver i nj ur y, c o m m o nl y referre d t o as dr u g -i n d uce d 
li ver i nj ur y ( DI LI).  Partici pa nts w h o e x perie nce a tra nsa mi nase ele vati o n a b o ve 3 ti mes t he 
u p per li mit of n or mal ( × U L N) s h o ul d be m o nit ore d m ore fre q ue ntl y t o deter mi ne if t he y  are 
a n “a da pt or” or are “s usce pti ble.”
I n t he maj orit y of DI LI cases, ele vati o ns i n as partate a mi n otra nsferase ( A S T) a n d/ or ala ni ne 
a mi n otra nsferase ( A L T) prece de t otal bilir u bi n ( T Bili) ele vati o ns ( > 2 × U L N) b y  se veral 
da y s or wee ks.  T he i ncrease i n T Bili t ypicall y occ urs w hile A S T/ A L T is/are still ele vate d 
a b o ve 3 × U L N (ie, A S T/ A L T a n d T Bili val ues will be ele vate d wit hi n t he sa me la b orat or y  
sa m ple).  I n rare i nsta nces, b y t he ti me T Bili ele vati o ns are detecte d, A S T/ A LT val ues mi g ht 
ha ve decrease d.  T his occ urre nce is still re gar de d as a p ote ntial DI LI.  T heref ore , a b n or mal 
ele vati o ns i n eit her A S T O R A L T i n a d diti o n t o T Bili t hat meet t he criteria o utli ne d bel o w 
are c o nsi dere d p ote ntial DI LI (assesse d per H y ’s la w criteria) cases a n d s h o ul d al wa ys be 
c o nsi dere d i m p orta nt me dical e ve nts, e ve n bef ore all ot her p ossi ble ca uses of li ver i nj ur y  
ha ve bee n e xcl u de d.
T he t hres h ol d of la b orat or y  a b n or malities f or a p ote ntial DI LI case de pe n ds o n t he 
partici pa nt’s i n di vi d ual baseli ne val ues a n d u n derl yi n g c o n diti o ns.  Partici pa nts w h o prese nt 
wit h t he f oll o wi n g la b orat or y  a bn or malities s h o ul d be e val uate d f urt her as p ote ntial DI LI 
( Hy’s la w) cases t o defi niti vel y  deter mi ne t he eti ol o g y of t he a b n or mal la b orat or y val ues:

Partici pa nts wit h A S T/ A L T a n d T Bili baseli ne val ues wit hi n t he n or mal ra n ge w h o 
s u bse q ue ntl y prese nt wit h AS T O R A L T val ues > 3 × U L N A N D a T Bili val ue 
> 2 × U L N wit h n o e vi de nce of he m ol ys is a n d a n al kali ne p h os p hatase val ue 
< 2 × U L N or n ot a vaila ble.

F or partici pa nts wit h baseli ne A S T O R A L T O R T Bili val ues a b o ve t he U L N, t he 
f oll o wi n g t hres h ol d val ues are use d i n t he defi niti o n me nti o ne d a b o ve, as nee de d, 
de pe n di n g o n w hic h val ues are a b o ve t he U L N at baseli ne:

Pree xisti n g A S T or A L T baseli ne val ues a b o ve t he n or mal ra n ge: A S T or A L T 
val ues > 2 ti mes t he baseli ne val ues A N D > 3 × U L N; or > 8 × U L N ( w hic he ver is 
s maller).

Pree xisti n g val ues of T Bili a b o ve t he n or mal ra n ge: T Bili le vel i ncrease d fr o m 
baseli ne val ue b y a n a m o u nt of at least 1 × U L N o r if t he val ue reac hes 
> 3 × U L N ( w hic he ver is s malle r).
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 9 2
Rises i n A S T/ A L T a n d T Bili se parate d b y m ore t ha n a fe w wee ks s h o ul d be assesse d 
i n di vi d uall y base d o n cli nical j u d g me nt; a n y case w here u ncertai nt y re mai ns as t o w het her it 
re prese nts a p ote ntial H y’s la w case s h o ul d be re vie we d wit h t he s p o ns or.  
T h e partici pa nt s h o ul d ret ur n t o t he i n vesti gat or site a n d be e val uate d as s o o n as p ossi ble, 
prefera bl y wit hi n 4 8 h o urs fr o m a ware ness of t he a b n or mal res ults.  T his e val uati o n s h o ul d 
i ncl u de la b orat or y tests, detaile d hist or y, a n d p h ysical assess me nt.  
I n a d diti o n t o re peati n g meas ure me nts of A S T a n d A L T a n d T Bili f or s us pecte d cases of 
H y ’s la w, a d diti o nal la b orat or y tests s h o ul d i ncl u de al b u mi n, creati ne ki nase ( C K), direct a n d 
i n direct bilir u bi n, ga m ma-gl uta m yl  tra nsferase ( G G T), pr ot hr o m bi n ti me ( P T)/i nter nati o nal 
n or malize d rati o (I N R), t otal bile aci ds, a n d al kali ne p h os p hatase.  C o nsi derati o n s h o ul d als o 
be gi ve n t o dra wi n g a se parate t u be of cl otte d bl o o d a n d a n a ntic oa g ulate d t u be of bl o o d f or 
f urt her testi n g, as nee de d, f or f urt her c o nte m p ora ne o us a nal ys es at t he ti me of t he rec o g nize d 
i nitial a b n or malities t o deter mi ne eti ol o g y.  A detaile d hist or y, i ncl u di n g rele va nt 
i nf or mati o n, s uc h as re vie w of et ha n ol, aceta mi n o p he n (eit her b y itself or as a c of or m ulate d 
pr o d uct i n prescri pti o n or o ver -t he-c o unter me dicati o ns) , recreati o nal dr u g, s u p ple me nt 
( her bal) use a n d c o ns u m pti o n, fa mil y hist or y, se x ual hist or y, tra vel hist or y, hist or y of c o ntact 
wit h a ja u n dice d pers o n, s ur ger y , bl o o d tra nsf usi o n, hist or y of li ver or aller gic disease, a n d 
p ote ntial occ u p ati o nal e x p os ure t o c he micals, s h o ul d be c ollecte d.  F urt her testi n g f or ac ute 
he patitis A, B, C, D, a n d E i nfecti o n a n d li ver i ma gi n g (e g, biliar y  tract) a n d c ollecti o n of 
ser u m sa m ple f or aceta mi n o p he n dr u g a n d/ or pr otei n a d d uct le vels ma y be warra nte d. 
All cases de m o nstrate d o n re peat testi n g as meeti n g t he la b orat or y  criteria of A S T/ A LT a n d 
T Bili ele vati o n defi ne d a b o ve s h o ul d be c o nsi dere d p ote ntial DI LI ( H y ’s la w) cases if n o 
ot her reas o n f or t he li ver f u ncti o n test ( L F T) a b n or malities has y et bee n fo u n d.  S uc h 
p ote nti al DI LI ( H y’s l a w) c ases are t o be re p orte d as S A Es, irres pecti ve of a v ail a bilit y 
of all t he res ults of t he i n vesti g ati o ns perf or me d t o deter mi ne eti ol o g y of t he L F T 
a b n or m alities.
A p ote ntial DI LI ( H y ’s la w) case bec o mes a c o nfir me d case o nly after all res ults of 
reas o na ble i n vesti gati o ns ha ve bee n recei ve d a n d ha ve e xcl u de d a n alter nati ve eti ol o g y.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 9 3
1 0. 7. A p pe n di x 7: E C G Fi n di n gs of P ote nti al Cli nic al C o ncer n
E C G Fi n di n gs T h at M a y
Q u alif y as A d verse E ve nts ( A Es)

Mar ke d si n us bra d y car dia (rate < 4 0 b p m) lasti n g mi n utes.

Ne w P R i nter val pr ol o n gati o n > 2 8 0 msec.

Ne w pr ol o n gati o n of Q Tc F t o > 4 8 0 msec (a bs ol ute) or b y 6 0 msec fr o m baseli ne.

Ne w -o nset atrial fl utter or fi brillati o n, wit h c o ntr olle d ve ntric ular res p o nse rate: ie, 
rate < 1 2 0 b p m.

Ne w -o nset t y pe I sec o n d-de gree ( We nc ke bac h) Atri o ve ntric ular (A V ) bl oc k of 
> 3 0 sec o n ds’ d urati o n.

Fre q ue nt pre mat ure ve ntric ular c o m ple xes ( P V Cs), tri plets, or s h ort i nter vals 
( < 3 0 sec o n ds) of c o nsec uti ve ve ntric ular c o m ple xes.
E C G Fi n di n gs T h at M a y
Q u ali f y as Seri o us A d verse E ve nts ( S A Es)

Q Tc F pr ol o n gati o n > 5 0 0 msec.

Ne w S T - T c ha n ges s u g gesti ve of m y ocar dial isc he mia.

Ne w - o nset left b u n dle bra nc h bl oc k ( Q R S > 1 2 0 msec).

Ne w -o nset ri g ht b u n dle bra nc h bl oc k ( Q R S > 1 2 0 msec).

S y m pt o matic bra d y car dia. 

As y st ole:

I n a wa ke, sy m pt o m -free patie nts i n si n us r h yt h m, wit h d oc u me nte d peri o ds of 
as yst ole 3. 0 sec o n ds or a n y  esca pe rate < 4 0 b p m, or wit h a n esca pe r h yt h m 
t hat is bel o w t he A V n o de; 

I n a wa ke, sy m pt o m -free patie nts wit h atrial fi brillati o n a n d bra dyc ar dia wit h 
1 or m ore pa uses of at least 5 sec o n ds or l o n ger; 

Atrial fl utter or fi brillati o n, wit h ra pi d ve ntric ular res p o nse rate:
ra pi d = rate 
> 1 2 0 b p m.

S ustai ne d s u pra ve ntric ular tac h yc ar dia (rate > 1 2 0 b p m) (“s ustai ne d” = s h ort 
d urati o n wit h rele va nt s y m pt o ms or lasti n g > 1 mi n ute).
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 9 4

Ve ntric ular r h yt h ms > 3 0 sec o n ds’ d urati o n, i ncl u di n g i di o ve ntric ular r h y t h m (rate 
< 4 0 b p m), accelerate d i di o ve ntric ular r h yt h m ( 4 0 < x < 1 0 0), a n d 
m o n o m or p hic/ p ol y m or p hic
ve ntric ular tac h yc ar dia > 1 0 0 b p m (s uc h as t orsa des de 
p oi ntes).

T yp e II sec o n d-de gree ( M o bitz II) A V bl oc k.

C o m plete (t hir d- de gree) heart bl oc k.
E C G Fi n di n gs T h at Q u alif y as Seri o us A d verse E ve nts

C ha n ge i n patter n s u g gesti ve of ne w m y ocar dial i nfarcti o n. 

S ustai ne d ve ntric ular tac h y arr h yt h mias ( > 3 0 sec o n ds’ d urati o n).

Sec o n d - or t hir d -de gree A V bl oc k re q uiri n g pace ma ker place me nt.

As y st olic pa uses re q uiri n g pace ma ker place me nt.

Atrial fl utter or fi brillati o n wit h ra pi d ve ntric ular res p o nse re q uiri n g car di o versi o n.

Ve ntric ular fi brillati o n/fl utter.

At t he discreti o n of t he i n vesti gat or, a n y arr h yt h mia classifie d as a n a d verse 
e x perie nce.
T he e n u merate d list of maj or e ve nts of p ote ntial cli nical c o ncer n are rec o m me n de d as “alerts” or 
n otificati o ns fr o m t he c ore E C G la b orat or y t o t he i n vesti gat or a n d Pfizer st u d y tea m, a n d n ot t o be 
c o nsi dere d as all i ncl usi ve of w hat t o be re p orte d as A Es/ S A Es.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 9 5
1 0. 8. A p pe ni d x 8: Ne w Y or k He art Ass oci ati o n Cl assific ati o n
Ne w Y or k Heart Ass ociati o n ( N Y H A) Classificati o n:
Class I
Patie nts wit h car diac disease b ut wit h o ut res ulti n g li mitati o ns of p h ysical acti vit y.  Or di nar y
p h y sical acti vit y d oes n ot ca use u n d ue fati g ue, pal pitati o n, d ys p nea, or a n gi nal pai n.
Class II
Patie nts wit h car diac disease res ulti n g i n sli g ht li mitati o n of p h y sical acti vit y.  T he y are
c o mf orta ble at rest. Ordi nar y  p h ysical acti vit y res ults i n fati g ue, pal pitati o n, d ys p nea, or
a n gi nal pai n.
Class III
Patie nts wit h car diac disease res ulti n g i n mar ke d li mitati o n of p h y sical acti vit y.  T he y are
c o mf orta ble at rest.  Less t ha n or di nar y  p h ysical acti vit y ca uses fati gue, pal pitati o n, d y s p nea,
or a n gi nal pai n.
Class I V
Patie nts wit h car diac disease res ulti n g i n i na bilit y  t o carr y o n a n y p h ysical acti vit y wit h o ut
disc o mf ort.  S y m pt o ms of car diac i ns ufficie nc y  or of t he a n gi nal sy n dr o me ma y be prese nt
e ve n at rest.  If a n y p h ys ical acti vit y is u n derta ke n, disc o mf ort is i ncrease d.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 9 6
1 0. 9. A p pe n di x 9: He alt h Ec o n o mics
1 0. 9. 1. T he K a ns as Cit y C ar di o m y o p at h y Q uesti o n n aire O ver all Sc ore
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)
C O P Y RI G H T E D M A T E RI A L

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 9 7
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)
C O P Y RI G H T E D M A T E RI A L

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 9 8
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)
C O P Y RI G H T E D M A T E RI A L

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 9 9
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)
C O P Y RI G H T E D M A T E RI A L

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 0 0
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)
C O P Y RI G H T E D M A T E RI A L

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 0 1
1 0. 9. 2. E ur o Q o L 5 Di me nsi o ns 5 Le vels ( E Q- 5 D- 5 L)
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)
C O P Y RI G H T E D M A T E RI A L

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 0 2
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)
C O P Y RI G H T E D M A T E RI A L

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 0 3
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)
C O P Y RI G H T E D M A T E RI A L
C O P Y RI G H T E D M A T E RI A L

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 0 4
1 0. 9. 3. 1 2- Ite m S h ort F or m S ur ve y ( S F-1 2) 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)
C O P Y RI G H T E D M A T E RI A L

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 0 5
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)
C O P Y RI G H T E D M A T E RI A L

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 0 6
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)
C O P Y RI G H T E D M A T E RI A L

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 0 7
1 0. 1 0. A p pe n di x 1 0 : Alter n ati ve Me as ures D uri n g P u blic E mer ge ncies
T he alter nati ve st u d y meas ures descri be d i n t his secti o n are t o be f oll o we d d uri n g p u blic 
e mer ge ncies, i ncl u di n g t he C O VI D -1 9 pa n de mic. T his a p pe n di x a p plies f or t he d urati o n of 
t he C O VI D-1 9 pa n de mic gl o ball y a n d will bec o me effecti ve f or ot her p u blic e mer ge ncies 
o nl y  u p o n writte n n otificati o n fr o m Pfizer. 
Use of t hese alter nati ve st u d y  meas ures are e x pecte d t o cease u p o n t he ret ur n of b usi ness as 
us ual circ u msta nces (i ncl u di n g t he lifti n g of a n y q uara nti nes a n d tra vel ba ns/a d vis ories). 
I n vesti gat ors s h o ul d c o nti n ue t o f oll o w t he pr ot oc ol a n d data e ntr y ti meli nes.  A n y de viati o ns 
t o t he pr ot oc ol d ue t o p u blic e mer ge ncies, i ncl u di n g t he C O VI D- 1 9，s h o ul d be d oc u me nte d 
a n d rec or de d as de viati o ns as re q ueste d b y Healt h A ut h orities. W he n t he sit uati o n per mits, 
e g, q uara nti nes or tra vel ba ns/a d vis ories cease d, i t is e x pecte d t hat partici pa nts g o will ret ur n 
t o t heir ori gi nal st u d y sites t o c o m plete a n i n-cli nic visit i n dicate d i n Sc he d ule of Acti vities 
(S o A ) f or t he nearest missi n g visit (es peciall y t he visit of M o nt h 1 2 or E n d of Treat me nt ), 
e ve n if t he date is o ut of t he sc he d ule d visit wi n d o w a n d s o me of t he st u d y meas ures ha ve 
alrea d y bee n perf or me d at a n alter nati ve facilit y. 
1 0. 1 0. 1. Eli gi bilit y
W hile S A R S -C o V 2 testi n g is n ot ma n date d f or t his st u d y , l ocal cli nical practice sta n dar ds f or 
testi n g s h o ul d be f oll o we d. A patie nt s h o ul d be e xcl u de d if he/s he has a p ositi ve test res ult 
f or S A R S-C o V 2 i nfecti o n, is k n o w n t o ha ve as y m pt o matic i nfecti o n, or is s us pecte d of 
ha vi n g S A R S - C o V 2. Patie nts wit h acti ve i nfecti o ns are e xcl u de d fro m st u d y  partici pati o n as 
per E xcl usi o n Criteri a 1 ( me dic al c o n diti o ns) . W he n t he i nfecti o n res ol ves, t he patie nt 
s h o ul d n ot be c o nsi dere d f or re-scree ni n g. I n di vi d uals w h o has si g ne d t he I C D f or 
partici pati o n i n t his st u d y  a n d are o ut of t he scree ni n g wi nd o w d ue t o assess me nt of t he 
eli gi bilit y d ue t o p u blic e mer ge ncies, i ncl u di n g C O VI D - 1 9, ca n be rescree ne d. All t he 
scree ni n g, rescree ni n g a n d baseli ne pr oce d ures s h o ul d be d o ne at t he st u dy sites, acc or di n g t o 
S o A.
1 0. 1 0. 2. Tele he alt h Visits
I n t he e ve nt t hat i n- cli nic st u d y visits ca n n ot be c o n d ucte d, e ver y  eff ort s h o ul d be ma de t o 
f oll o w u p o n t he safet y of st u d y partici pa nts at sc he d ule d visits per t he Sc he d ule of 
Acti vities or u nsc he d ule d visits. Tele healt h visits ma y be use d t o c o nti n ue t o assess 
partici pa nt s afet y a n d c ollect data p oi nts. Tele healt h i ncl u des t he e xc ha n ge of healt hcare 
i nf or mati o n a n d ser vices via telec o m m u nicati o n tec h n ol o gies (e g, a u di o, vi de o, vi de o-
c o nfere nci n g s oft ware) re m otel y, all o wi n g t he partici pa nt a n d t he i n vesti gat or t o 
c o m m u nicate o n as pects of cli nical care, i ncl u di n g me dical a d vice, re mi n ders, e d ucati o n, a n d 
safety m o nit ori n g. T he f oll o wi n g assess me nts m ust be perf or me d d uri n g a tele healt h visit:
 

Re vie w a n d rec or d st u d y i nter ve nti o n(s), i ncl u di n g c o m plia nce a n d misse d d oses.

Re vie w a n d rec or d a n y   A Es a n d S A Es si nce t he last c o ntact. Refer t o Secti o n 8. 3 .

Re vie w a n d rec or d a n y ne w c o nc o mita nt me dicati o ns or c ha n ges i n c o nc o mita nt 
me dicati o ns si nce t he last c o ntact.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 0 8

Re vie w a n d rec or d c o ntrace pti ve met h o d a n d res ults of pre g na nc y testi n g. C o nfir m 
t hat t he partici pa nt is a d heri n g t o t he c o ntrace pti o n met h o d(s) re q uire d i n t he 
pr ot oc ol. Refer t o Secti o n s 1 0. 4 a n d 1 0. 1 0. 3. 1 of t his a p pe n di x re gar di n g pre g na nc y 
tests.
St u d y  partici pa nts m ust be re mi n de d t o pr o m ptl y n otif y site staff a b o ut a ny c ha n ge i n t heir 
healt h stat us.
1 0. 1 0. 3. Alter n ati ve F acilities f or S afet y Assess me nts
Safet y  assess me nt, i ncl u di n g c o m plete p h ys ical e xa mi nati o n ( P E)/a b bre viate d P E, vital 
si g ns, la b orat or y tests, i ma gi n g, a n d E C Gs ca n be perf or me d at a l ocal alter nati ve facilit y if 
t he i n vesti gat or c o nsi dere d it as necessar y a n d t he st u d y partici pa nt is u na ble t o visit t he 
st u d y site, w here all o wa ble b y la w or l ocal g ui da nce. T he s pecific alter nati ve facilit y f or eac h 
partici pa nt s h o ul d be rec o m me n de d b y  t he i n vesti gat or w h o has alrea d y ha d a n ali g n me nt 
wit h t he s p o ns or i n a case b y  case basis. 
All t he res ults of safet y assess me nts perf or me d at a l ocal alter nati ve facilit y s h o ul d be well 
d oc u me nte d a n d pr o vi de d t o t he site staff as i n dicate d i n S ecti o ns 1 0. 1 0. 3. 1 , 1 0. 1 0. 3. 2 a n d 
1 0. 1 0. 3. 3 bel o w .
1 0. 1 0. 3. 1. L a b or at or y Testi n g
If a st u dy partici pa nt is u na ble t o visit t he site f or pr ot oc ol -s pecifie d safet y la b orat or y 
e val uati o ns, testi n g m a y  be c o n d ucte d at a l ocal la b orat or y  if per mitte d b y l ocal 
re g ulati ons. T he l ocal la b orat or y  ma y be a sta n dal o ne i nstit uti o n or wit hi n a h os pital. T he 
f oll o wi n g safety la b orat or y e val uati o ns ma y be perf or me d at a l ocal la b orat or y:  
T a ble 2 .
Pr ot oc ol -Re q uire d S afet y L a b or at or y Assess me nts per mitte d at a l oc al 
l a b or at or y
H e m at ol o g y
C he mistr y
Di pstic k Uri n al ysis
Ot her
W hite bl o o d cell c o u nt
H e m o gl o bi n 
Re d bl o o d cell c o u nt
Ne utr o p hils
L y m p h oc ytes
H e m at ocrit 
Mea n c or p usc ular 
v ol u me
M o n oc ytes
Mea n c or p usc ular 
he m o gl o bi n E osi n o p hils
Mea n c or p usc ular 
he m o gl o bi n 
c o nce ntrati o n
Bas o p hils
Platelets
S o di u m I n or ga nic 
P h os p h or us
As partate 
a mi n otra nsferase ( A S T)
P otassi u m 
Gl uc ose
Ga m ma gl uta m yl 
tra nsferase
C hl ori de 
T otal bilir u bi n
C h olester ol
T otal pr otei n
Uric aci d
Bl o o d Urea Nitr o ge n 
Al b u mi n 
T h yr oi d -sti m ulati n g 
h or m o ne
Creati ni ne 
p H 
Bl o o d (free H b)
Ket o nes 
Gl uc ose 
Bilir u bi n
Pr otei n 
Nitrite
S pecific gra vit y
Ur o bili n o ge n
N T -pr o B N P
T n I
I nter nati o nal n or malize d 
rati o (I N R) 
Pr ot hr o m bi n ti me ( P T)
Acti vate d partial 
t hr o m b o plasti n ti me ( A P T T)
Fi bri n o ge n ( FI B)
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 0 9
T a ble 2 .
Pr ot oc ol -Re q uire d S afet y L a b or at or y Assess me nts per mitte d at a l oc al 
l a b or at or y
H e m at ol o g y
C he mistr y
Di pstic k Uri n al ysis
Ot her
Gl o b uli n
T otal t h yr o xi ne ( T 4)
Calci u m 
Ala ni ne a mi n otra nsferase 
( A L T)
Free T 4
Reti n ol bi n di n g pr otei n
Al kali ne P h os p hatase
It is e x pecte d t hat all partici pa nt s s h o ul d ha ve pr ot oc ol-s pecifie d safety la b orat or y  tests 
perf or me d per pr ot oc ol S o A .
If a l ocal la b orat or y is use d, q ualifie d st u d y site pers o n nel m ust or der, recei ve, a n d re vie w 
res ults. Site staff m ust c ollect t he l ocal la b orat or y refere nce ra n ges a n d 
certificati o ns/accre ditati o ns f or fili n g at t he site. La b orat or y  test res ults are t o be pr o vi de d t o 
t he site staff as s o o n as p ossi ble. T he l ocal la b orat or y  re p orts s h o ul d be file d i n t he 
partici pa nt’s s o urce d oc u me nts/ me dical rec or ds. Rele va nt data fr o m t he l ocal la b orat or y  
re p ort s h o ul d be rec or de d o n t he C R F. 
If a partici pa nt re q uiri n g pre g na nc y testi n g ca n n ot visit a l ocal la b orat or y f or pre g na nc y 
testi n g, a h o me uri ne pre g na nc y testin g kit wit h a se nsiti vit y  of at least 2 5 m I U/ m L ma y be 
use d b y  t he partici pa nt t o perf or m t he test at h o me, if c o m plia nt wit h l ocal re g ulat or y 
re q uire me nts. T he pre g na nc y test o utc o me s h o ul d be d oc u me nte d i n t he partici pa nt’s s o urce 
d oc u me nts/ me dical rec or ds a n d rele va nt data rec or de d o n t he C R F. C o nfir m t hat t he 
partici pa nt is a d heri n g t o t he c o ntrace pti o n met h o d(s) re q uire d i n t he pr ot oc ol. 
1 0. 1 0. 3. 2. I m a gi n g
If t he partici pa nt is u na ble t o visit t he st u d y site f or Ec h ocar di o gra p h y, t he partici pa nt ma y 
visit a n alter nati ve facilit y  t o ha ve t he Ec h ocar di o gra p h y perf or me d. Q ualifie d st u d y site 
pers o n nel m ust or der, recei ve, a n d re vie w res ults. 
1 0. 1 0. 3. 3. Electr oc ar di o gr a ms
If t he partici pa nt is u na ble t o visit t he st u d y site f or E C Gs, t he partici pa nt ma y visit a n 
alter nati ve facilit y t o ha ve t he E C Gs perf or me d. Q ualifie d st u d y site pers o n nel m ust or der, 
recei ve, a n d re vie w res ults. 
1 0. 1 0. 4. St u d y I nter ve nti o n
If t he safety of a tr ial partici pa nt is at ris k beca use t he y ca n n ot c o m plete re q uire d e val uati o ns 
or a d here t o critical miti gati o n ste ps, t he n disc o nti n ui n g t hat partici pa nt fr o m st u d y  
i nter ve nti o n m ust be c o nsi dere d.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 1 0
Tafa mi dis m a y be s hi p pe d b y  c o urier t o st u d y partici pa nts if per mitte d b y l ocal re g ulati o ns 
a n d i n acc or da nce wit h st ora ge a n d tra ns p ortati o n re q uire me nts f or t he tafa mi dis. Pfizer d oes 
n ot per mit t he s hi p me nt of tafa mi dis b y mail. T he trac ki n g rec or d of s hi p me nts a n d t he c hai n 
of c ust o d y  of tafa mi dis m ust be ke p t i n t he partici pa nt’s s o urce d oc u me nts/ me dical rec or ds.
T he st u d y dr u g s h o ul d o nl y be per mitte d t o be s hi p pe d t o t he partici pa nts after t he 
assess me nts b y t he i n vesti gat ors. A n d t he dis pe nse d i n vesti gati o nal pr o d uct b ottle s h o ul d be 
c ollecte d at t he ne xt o nsite visit.
1 0. 1 0. 5. H o me He alt h Visits
A h o me healt h care ser vice will n ot be utilize d i n t his st u d y.
1 0. 1 0. 6. A d verse E ve nts a n d Seri o us A d verse E ve nts
If a partici pa nt has C O VI D-1 9 d uri n g t he st u d y , t his s h o ul d be re p orte d as a n a d verse e ve nt 
( A E) or seri o us a d verse e ve nts ( S A E) a n d a p pr o priate me dical i nter ve nti o n pr o vi de d. St u d y  
treat me nt s h o ul d c o nti n ue u nless t he i n vesti gat or/treati n g p hys icia n is c o ncer ne d a b o ut t he 
safety of t he partici pa nt, i n w hic h case te m p orar y or per ma ne nt disc o nti n uati o n ma y be 
re q uire d. 
It is rec o m me n de d t hat t he i n vesti gat or disc uss te m p orar y or per ma ne nt disc o nti n uati o n of 
st u d y i nter ve nti o n wit h t he st u d y me dical m o nit or. 
1 0. 1 0. 7. Effic ac y Assess me nts
Efficac y  assess me nt, i ncl u di n g 6 -M W T, N T -pr o B N P, Tr o p ni n I  ca n be perf or me d at a l ocal 
alter nati ve facilit y if t he i n vesti gat or c o nsi dere d it as necessar y a n d t he st u d y partici pa nt is 
u na ble t o visit t he st u d y  site, w here all o wa ble by l a w or l ocal g ui da nce. T he st u d y 
i n vesti gat or ca n gi ve i nstr ucti o ns t o t he healt h care pr o vi der at a l ocal alter nati ve facility t o 
kee p t he c o nsiste nc y  of t he assess me nt. T he res ults of t hese assess me nts perf or me d at a l ocal 
alter nati ve facilit y s h o ul d be well d oc u me nte d a n d pr o vi de d t o t he site i n vesti gat ors.   
F or patie nt re p ort o utc o mes, i ncl u di n g Ka nsas Cit y Car di o m y o pat h y Q uesti o n naire o verall 
s u m mar y sc ores, E Q- 5 D-5 L  i n de x sc ores a n d E Q-5 D V A S sc ores, 1 2 -Ite m S h ort F or m 
S ur ve y  ( S F- 1 2) sc ores, pa per scales will be maile d t o t he partici pa nt at t he c orres p o n di n g 
visit wi n d o w, if t he st u d y partici pa nt is u na ble t o visit t he st u d y site. T he res ults will be 
re p orte d by t he partici pa nt i n t he sc he d ule d visit wi n d o w a n d maile d bac k t o t he i n vesti gat or 
i n a ti mel y ma n ner.
F or T T R sta bilizati o n a n d T T R c o nce ntrati o n assa y, plas ma c o nce ntrati o ns of tafa mi dis, 
bl o o d sa m ple will n ot be c ollecte d at t he alter nati ve facilit y d ue t o t he c o m ple xit y  of sa m ple 
ma na ge me nt.
1 0. 1 0. 8. I n de pe n de nt O versi g ht C o m mittees
T his st u d y  will n ot use a n In de pe n de nt O versi g ht C o m mittee. 
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 1 1
1 0. 1 1. A p pe n di x 1 1: A b bre vi ati o ns
T he f oll o wi n g is a list of a b bre via ti o ns t hat ma y be use d i n t he pr ot oc ol
A b bre vi ati o n
Ter m
6 -M W T 
6 -mi n utes wal k  test
9 9 mTc -P Y P
9 9 m Tc p y r o p h os p hate
A E
A d verse e ve nt
A L
Li g ht c hai n a m y l oi d osis
A L T
Ala ni ne a mi n otra nsferase
A nti -H C V
he patitis C a nti b o d y
A nti -HI V
H u ma n i m m u n o deficie nc y vir us a nti b o d y
A nti -T P
S y p hilis a nti b o d y
A S T
As partate a mi n otra nsferase
A T T R -C M
Tra nst h y reti n a myl oi d car di o m y o pat h y
A T T R -P N
Tra nst h yreti n A m yl oi d P ol y ne ur o pat h y
A U C
Area u n der t he c ur ve
A U C i nf
Area u n der t he c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o i nfi nit y
A U C ta u
Area u n der t he c o nce ntrati o n -ti me c ur ve o ver t he d osi n g i nter val 
ta u
A V
Atri o ve ntric ular
B A
Bi oa vaila bilit y
B B S
Bi os peci me n Ba n ki n g S yste m
B E
Bi oe q ui vale nce
B MI
B o d y Mass I n de x
B P
B o d y pai n
b p m
Beats per mi n ute
B U N
Bl o o d urea nitr o ge n
C F R
C o de of Fe deral Re g ulati o ns
CI
C o nfi de nce i nter val
CI O M S
C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical Scie nces
C K
Creati ne ki nase
C ma x
Ma xi m u m o bser ve d dr u g c o nce ntrati o n
C ma x,ss
Ma xi m u m dr u g c o nce ntrati o n at stea d y state
C mi n,ss
Mi ni m u m dr u g c o nce ntrati o n at stea d y state
C M C
C he mistr y , Ma n ufact uri n g, a n d C o ntr ols
C O 2
Car b o n di o xi de ( bicar b o nate)
C O N S O R T
C o ns oli date d Sta n dar ds of Re p orti n g Trials
C R F
Case re p ort f or m
C R O
C o ntract Researc h Or ga nizati o n
C R U
Cli nical researc h u nit
C S R
Cli nical St u d y  Re p ort
C T
Cli nical trial
c T N T
Car diac tr o p o ni n T
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 1 2
A b bre vi ati o n
Ter m
c T NI
Car diac tr o p o ni n I
C V
C ar di o vasc ular
D C T
Data c ollecti o n t o ol
D DI
D r u g-dr u g i nteracti o n
DI LI
Dr u g -i n d uce d li ver i nj ur y
D M C
Data m o nit ori n g c o m mittee
D N A
De o x yri b o n ucleic aci d
D R E
Disease -relate d e ve nt
D U
Dis pe nsa ble u nit
E/ A
R ati o of pea k vel ocit y bl o o d fl o w fr o m gra vit y i n earl y diast ole 
(t he E wa ve) t o pea k vel ocit y fl o w i n late diast ole ca use d by at rial 
c o ntracti o n (t he A wa ve).
E C
Et hics c o m mittee
E C G
Electr ocar di o gra m
e C R F
electr o nic case re p ort f or m
E -D M C
e xter nal data m o nit ori n g c o m mittee 
E D P
e x p os ure d uri n g pre g na nc y
E D R
e xte m p ora ne o us dis pe nsi n g rec or d
E M A
E ur o pea n Me dici nes A ge nc y
E O T
E n d of Treat me nt
E Q -5 D V A S
E ur o Q o L 5 Di me nsi o ns vis ual a nal o g ue scale
E Q -5 D -5 L
E ur o Q o L 5 Di me nsi o ns 5 L e vels
E U
E ur o pea n U ni o n
E u dra C T
E ur o pea n Cli nical Trials Data base
F OI
F racti o n of i nitial tetra mer c o nce ntrati o n
F S H
F ollicle -sti m ulati n g h or m o ne
G C P
G o o d Cli nical Practice
G G T
G a m ma-gl uta m yl  tra nsferase
G H
G e neral healt h
H Bs A g 
He patitis B s urface a nti ge n
HI P A A
Healt h I ns ura nce P orta bilit y  a n d Acc o u nta bilit y Act
HI V
H u ma n i m m u n o deficie nc y vir us
H R T
H or m o ne re place me nt t hera p y
I B
I n vesti gat or’s br oc h ure
I C D
I nf or me d c o nse nt d oc u me nt
I C H
I nter nati o nal C o u ncil f or Har m o nisati o n
I D
I de ntificati o n
I M P
I n vesti gati o nal me dici nal pr o d uct
I ND
I n vesti gati o nal ne w dr u g 
I N R
I nter nati o nal n or malize d rati o
I P ma n ual
I n vesti gati o nal pr o d uct ma n ual
I RB
I nstit uti o nal re vie w b oar d
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 1 3
A b bre vi ati o n
Ter m
I R C
I nter nal re vie w c o m mittee
I UD
I ntra uteri ne de vice
I U S
I ntra uteri ne h or m o ne-releasi n g sys te m
I W R
I nteracti ve We b-base d res p o nse
K 2 E D T A
Di p otassi u m et h y le ne dia mi netetraacetic aci d 
K C C Q
Ka nsas Cit y  Car di o m yo pat h y  Q uesti o n naire 
L B B B
Left b u n dle bra nc h bl oc k
L F T
Li ver f u ncti o n test
L T E
L o n g -ter m e xte nsi o n
M A T E
M ulti dr u g a n d t o xi n e xtr usi o n tra ns p orter
m B MI
M o difie d B o d y Mass I n de x
M C S
Me ntal c o m p o ne nt s u m mar y  sc ore 
Me d D R A
Me dical Dicti o nar y  f or Re g ulat or y Acti vities 
M H
M e ntal healt h
M H L W
Mi nistr y  of Healt h, La b or a n d Welfare
M R
M olar rati o
msec
Millisec o n d
N/ A
N ot a p plica ble
N A b
Ne utralizi n g a nti b o dies
NI M P
N o ni n vesti gati o nal me dici nal pr o d uct
N S AI D
N o n -ster oi d a nti-i nfla m mat or y dr u gs
N T -pr o B N P
N Ter mi nal pr o h or m o ne B t y pe Natri uretic Pe pti de
N Y H A
Ne w Year Heart Ass ociati o n
O A T
Or ga nic a ni o n tra ns p orter
O A T P
Or ga nic a ni o n -tra ns p orti n g p oly pe pti de tra ns p orters
O C T
Or ga nic cati o n tra ns p orter
P C D
Pri mar y  c o m pleti o n date
P C S
P h y sical c o m p o ne nt s u m mar y
P D
P har mac o d y na mics(s)
P F
P h y sical f u ncti o n
PI
Pri nci pal I n vesti gat or
P K
P har mac o ki netic(s)
P R
P R i nter val
P T
Pr ot hr o m bi n ti me
P V C
Pre mat ure ve ntric ular c o m ple x
Q D
O nce dail y
Q R S
Q R S co m ple x
Q T
Q T i nter val
Q Tc
C orrecte d Q T
Q Tc F
C orrecte d Q T ( Fri dericia met h o d)
q ual
Q ualitati ve
R E
R ole e m oti o nal
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 1 4
A b bre vi ati o n
Ter m
R N A
Ri b o n ucleic aci d
R P
R ole p h y sical
S A E
Seri o us a d verse e ve nt
S A P
Statistical a nal y sis pla n
S F
S ocial f u ncti o n
S F -1 2
1 2 -s h ort ite m s ur ve y f or m
S o A
Sc he d ule of acti vities
S O P
Sta n dar d o perati n g pr oce d ure
S R S D
Si n gle refere nce safet y d oc u me nt
S U S A R
S us pecte d u ne x pecte d seri o us a d verse reacti o n
T Bili
T otal bilir u bi n
T E A E
Treat me nt -e mer ge nt a d verse e ve nts
T E S P O
Tafa mi dis E n ha nce d S ur veilla nce Pre g na nc y  O utc o mes
T H A O S
Tra nst h y reti n-Ass ociate d A m y l oi d osis O utc o mes S ur ve y
T nI
Tr o p o ni n I
T R A C S
Tra nst h yreti n A m yl oi d Car diac St u d y 
T T R 
Tra nst h y reti n
U G T
U D P gl uc ur o n os y ltra nsferase
U L N
U p per li mit of n or mal
U S
U nite d States
V T
V italit y
W O C B P
W o me n of c hil d beari n g p ote ntial
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)

Tafa mi dis
Pr ot oc ol B 3 4 6 1 0 7 7
Pr ot oc ol A me n d m e nt 1 , 2 6
M arc h 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nic al Pr ot oc ol Te m pl ate P h ase 1 2 3 4 (1 5 Ma y 2 0 2 0 )
Pa ge 1 1 5
1 1. R E F E R E N C E S
1.
Wei H T, Z he n J, Li u Q. Cli nical c haracteristics of 1 3 patie nts wit h car diac a m y l oi d osis. 
Jili n me dici ne( C hi nese). 2 0 1 2: 3 3( 1 3): 2 7 5 0- 2 7 5 1.
2.
H ua n g Y Q, Z ha n J X, Wei X B, et al. Cli nical c haracteristics of 4 2 patie nts wit h car diac 
a m yl oi d osis. C hi n J Inter n Me d 2 0 1 4; 5 3( 7): 5 4 6 -9.
3.
Z he n g F S, Qi X W, Ka n g N N. A case re p ort o n car diac a m yl oi d osis b y  heart bi o ps y. 
C hi n J R he u mat ol 2 0 0 3; 7( 8): 5 2 0.
4.
Wa n g ZJ, S u Y G. O ne case re p ort o n car diac a m yl oi d osis. C hi n J Diffic C o m pl Cas
2 0 0 4; 3( 1): 4 7.
5.  
Q u F X, A n Y, L u C H, et al. O ne case re p ort o n car diac a m yl oi d osis wit h literat ure 
re vie w. C hi n J E vi d Base d Car di o vasc Me d 2 0 1 7; 9( 4): 4 8 8- 9.
6.
S h u Y W, L ia o Y H, Wa n g X, et al. Case re p ort o n car diac a myl oi d osis wit h literat ure 
re vie w. J Cli n Car di ol ( C hi na) 2 0 0 5; 2 1( 7): 4 4 7 - 8.
7.
Fa n g J P, W u W, C he n W, et al. O ne case re p ort o n tra nst h y reti n a myl oi d 
car di o m y o pat h y. C hi n J Car di ol 2 0 1 4; 4 2( 9): 7 8 4 - 5.
8.
Gree n C P, P orter C B, Bres na ha n D R, et al. De vel o p me nt a n d e val uati o n of t he 
Ka nsas Cit y  Car di o m yo pat h y Q uesti o n naire: a ne w healt h stat us meas ure f or heart 
fail ure. J A m C oll Car di ol o g y 2 0 0 0; 3 5: 1 2 4 5- 1 2 5 5.
9.
Her d ma n M, G u de x C, Ll o y d A, Ja nsse n M, Ki n d P, Par ki n D, B o nsel G, Ba dia X, 
De vel o p me nt a n d preli mi nar y testi n g of t he ne w fi ve -le vel versi o n of E Q-5 D ( E Q - 5 D-
5 L ). Q ual Life Res 2 0 1 1 Dec; 2 0( 1 0): 1 7 2 7- 1 7 3 6.
0 9 0 1 7 7 e 1 9 6 c 1 c 2 6 d\ A p pr o v e d\ A p pr o v e d O n: 1 3- A pr- 2 0 2 1 0 3: 1 2 ( G M T)