Clinical trial NCT04814186
Conditions: Transthyretin Amyloid Cardiomyopathy
Keywords: Tafamidis
Sponsor: Pfizer
Start date: 2021-07-22; Completion date: 2023-10-16
Enrollment: 53 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a national, multi-center, single-arm study, open-label to patients with symptomatic Transthyretin amyloid cardiomyopathy (ATTR-CM) who are tafamidis naïve. This study is to obtain safety, descriptive efficacy, Pharmacokinetics (PK) and Pharmacodynamics (PD) data for tafamidis orally once daily.

Subject eligibility for participation in the study will receive tafamidis once daily or 12 months following the assessment as the screening and baseline, month 1, 3, 6, 9 and 12 visits (or Early Study Discontinuation).

Detailed description:

Arms: arm 1: treatment group with tafamidis
Interventions: intervention 1: Tafamidis
Intervention descriptions: intervention 1: 61 mg, once daily, oral administration, for 12 months.

Protocol documents:
Prot_000.pdf: 
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)

SAP_001.pdf: 
Protocol B3461077 (Tafamidis) Statistical Analysis Plan
Protocol B3461077
A STUDY TO CHARACTERIZE THE SAFETY AND EFFICACY OF TAFAMIDIS ONCE 
DAILY IN THE TREATMENT OF TRANSTHYRETIN AMYLOID CARDIOMYOPATHY IN 
CHINESE PARTICIPANTS
Statistical Analysis Plan 
(SAP)
Version:
2
Date:
07 Nov 2023
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Protocol B3461077 (Tafamidis) Statistical Analysis Plan
TABLE OF CONTENTS
LIST OF TABLES..................................................................................................................3
APPENDICES.......................................................................................................................3
1. VERSION HISTORY .........................................................................................................4
2. INTRODUCTION...............................................................................................................4
2.1. Modifications to the Analysis Plan Described in the Protocol.................................4
2.2. Study Objectives, Endpoints, and Estimands ........................................................4
2.3. Study Design.........................................................................................................5
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND CONVENTIONS ..........6
3.1. Primary Endpoint(s) ..............................................................................................6
3.2. Secondary Endpoint(s)..........................................................................................6
3.2.1. Efficacy Endpoint(s)..................................................................................6
3.2.2. Safety Endpoint(s) ....................................................................................6
3.2.3. Pharmacodynamics (PD) Endpoints..........................................................6
3.2.4. Quality of Life Endpoints ...........................................................................7
3.2.5. Pharmacokinetic (PK) Endpoints...............................................................7
3.3. Other Safety Endpoints .........................................................................................7
3.3.1. Laboratory Data ........................................................................................7
3.3.2. Electrocardiogram Data ............................................................................7
3.3.3. Echocardiograph Data ..............................................................................8
3.3.4. Vital Signs.................................................................................................8
3.3.5. Physical Examination................................................................................8
3.3.6. Body Mass Index (BMI) and modified Body Mass Index (mBMI)...............8
3.4. Other Endpoints (Efficacy Endpoints)....................................................................8
3.5. Baseline Variables ................................................................................................9
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS) .......................................................9
5. GENERAL METHODOLOGY AND CONVENTIONS.........................................................9
5.1. Hypotheses and Decision Rules............................................................................9
5.2. General Methods...................................................................................................9
5.2.1. Analyses for Continuous Endpoints...........................................................9
5.2.2. Analyses for Categorical Endpoints.........................................................10
5.3. Methods to Manage Missing Data.......................................................................10
6. ANALYSES AND SUMMARIES ......................................................................................10
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Protocol B3461077 (Tafamidis) Statistical Analysis Plan
6.1. Primary Endpoint(s) ............................................................................................10
6.1.1. Incidence of Treatment Emergent Adverse Events .................................10
6.2. Secondary Endpoint(s)........................................................................................10
6.2.1. Safety Summaries and Analyses Endpoint(s) .........................................11
6.2.2. PK Endpoint(s)........................................................................................11
6.3. Other Safety Summaries and Analyses Endpoints ..............................................11
6.3.1. Laboratory Data ......................................................................................11
6.3.2. Electrocardiograms.................................................................................11
6.3.3. Echocardiograph.....................................................................................11
6.3.4. Vital Signs...............................................................................................11
6.3.5. Physical Examination..............................................................................11
6.3.6. BMI and mBMI ........................................................................................12
6.4. Other Endpoints (Efficacy Endpoints)..................................................................12
6.5. Subset Analyses .................................................................................................12
6.6. Baseline and Other Summaries and Analyses ....................................................12
6.6.1. Baseline Summaries ...............................................................................12
6.6.2. Study Conduct and Participant Disposition..............................................12
6.6.3. Study Treatment Exposure .....................................................................12
6.6.4. Concomitant Medications and Nondrug Treatments................................13
6.7. Additional Analyses Depicting COVID-19 Pandemic Impact................................13
7. INTERIM ANALYSES......................................................................................................13
7.1. Introduction .........................................................................................................13
7.2. Interim Analyses and Summaries........................................................................13
LIST OF TABLES
Table 1.
Summary of Changes..............................................................................4
APPENDICES
Appendix 1. Data Derivation Details....................................................................................13
Appendix 1.1. Definition and Use of Visit Windows in Reporting .........................................13
Appendix 2. List of Abbreviations ........................................................................................14
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Protocol B3461077 (Tafamidis) Statistical Analysis Plan
1. VERSION HISTORY
Table 1.
Summary of Changes
Version/
Date
Associated 
Protocol 
Amendment
Rationale
Specific Changes
2
03 Nov 2023
1
26 Mar 2021
Per protocol 
amendment 1

Update whole document per protocol 
amendment 1 changes

Update use the latest SAP template

Add in details about the endpoints 
definitions in section 3

Add in analyses details in Section 6, 
including COVID-19 analysis

Add in the analysis window for 
endpoints assessed less frequently in 
Appendix 1.1

Add in the Abbreviations in Appendix 2
1
23 Aug 2019
Original
28 Jun 2019
N/A
N/A
2. INTRODUCTION
This statistical analysis plan (SAP) provides the detailed methodology for summary and 
statistical analyses of the data collected in Study B3461077.
2.1. Modifications to the Analysis Plan Described in the Protocol
Protocol section 9.4.1.2 Electrocardiogram Analyses states categories for QTcF as change 
from baseline are: ≥30 msec increase, ≥60 msec increase.  A ≥75 msec increase category is 
added in Section 6.2.3.2 as deemed clinical important.
Protocol section 9.4.1.4 Other Safety Assessments states all clinical laboratory data will be 
summarized by frequency of events and mean changes from baseline.  This change from 
baseline summary will not be done as considered clinical meaningless.
Protocol section 9.4.1.4 Other Safety Assessments states all vital sign measurements will be 
displayed in listings by participant with changes from baseline values included.  This change 
from baseline values will not be listed as considered clinical meaningless.
Protocol section 9.4.2 states PD endpoints will also be analyzed by TTR genotype.  This 
subset analysis will only be done if sample sizes for both TTR wild-type and variant 
genotype subsets allowed.
2.2. Study Objectives, Endpoints, and Estimands
Type
Objective
Endpoint
Estimand
Safety
To characterize the safety 
profile of tafamidis once daily 
for the treatment of Chinese 
ATTR-CM patients in clinical 
practice
Incidence of 
treatment-
emergent adverse 
events.
Not 
applicable
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Protocol B3461077 (Tafamidis) Statistical Analysis Plan
Assessment of 
laboratory, ECG, 
Echocardiography, 
PE, Vital signs, 
BMI and mBMI at 
scheduled visits 
Efficacy
To characterize the 
descriptive efficacy of 
tafamidis once daily in 
Chinese ATTR-CM patients
Assessment of 6-
MWT, NT-pro BNP, 
cardiac troponin I, 
and NYHA at 
scheduled visits
Not 
applicable
Pharmacodynamics
To characterize tafamidis
pharmacodynamics (PD) in 
Chinese ATTR-CM patients
TTR stabilization 
and TTR 
concentration at 
baseline (pre 
dosing) on Day 1, 
at Months 1, 6, and 
12 (or End of 
Treatment (EOT))
Not 
applicable
Quality of Life
To characterize the impact 
on quality of life of tafamidis 
once daily for the treatment 
of Chinese ATTR-CM 
patients
Kansas City 
Cardiomyopathy 
Questionnaire 
overall summary 
scores, EQ-5D-5L 
index scores and 
EQ-5D VAS 
scores, 12-Item 
Short Form Survey 
(SF-12) scores, at 
Day 1, Months 6, 
12 (or EOT)
Not 
applicable
Pharmacokinetics
To characterize tafamidis 
pharmacokinetic (PK) in 
Chinese ATTR-CM patients
Plasma 
concentrations of 
tafamidis at Months 
1, 6, and 12 (or 
EOT)
Not 
applicable
2.3. Study Design
This is a post approval commitment study conducted in China.  It is a single-arm, open-label, 
multicenter study designed to obtain safety, efficacy, PK and PD data in ATTR-CM patients 
in China.  Patients will be evaluated for study eligibility during the screening period between 
Days -45 and Day -1.  At least 53 patients will be treated.  All enrolled patients will receive 
tafamidis free acid (called as tafamidis in the texts hereafter) 61 mg soft capsules orally, 
once daily for 12 months, starting on Day 1, with scheduled visits at Baseline/Day 1, Month 
1, 3, 6, 9 and 12.  For the purpose of this study, 1 month is defined as 30 days.
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Protocol B3461077 (Tafamidis) Statistical Analysis Plan
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND CONVENTIONS
3.1. Primary Endpoint(s)

Incidence of treatment-emergent adverse events
An adverse event is any untoward medical occurrence in a patient or clinical study 
participant, temporally associated with the use of study intervention, whether or not 
considered related to the study intervention.  All adverse events that start after the first 
dosing but before or on the last dose plus the lag time (28 days) will be flagged as treatment 
emergent adverse events.  Adverse events will be coded according to the Medical 
Dictionary for Regulatory Activities (MedDRA).
3.2. Secondary Endpoint(s)
Baseline for below endpoints is defined as the last measurement prior to dosing on Day 1 of 
the study.  Change from baseline value is calculated by subtracting the baseline value from 
follow up visit value.
3.2.1. Efficacy Endpoint(s)

Change from Baseline in the distance walked during 6 Minute Walk Test (6MWT)
6MWT is a kind of exercise test for patients with moderate to severe cardiopulmonary 
disease.  It measures the longest distance a patient can walk on a straight course in 6 
minutes.
6MWT will be conducted at baseline, Month 6 and 12.  

Change from Baseline in NT-proBNP concentration
Plasma amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is a guideline-
mandated biomarker in heart failure. Used as an inclusion criterion for therapeutic trials, 
NT-proBNP enriches trial populations and is a valid surrogate endpoint.  NT-proBNP 
offers prognostic information independent of standard clinical predictors and refines risk 
stratification.
Blood sample collection will be performed at baseline, Month 6 and 12 for evaluation of 
NT-proBNP.
3.2.2. Safety Endpoint(s)
Not applicable.
3.2.3. Pharmacodynamics (PD) Endpoints

TTR stabilization at Months 1, 6 and 12 (or EOT)
A responder in TTR stabilization is the participant who achieved TTR stabilization (ie, a 
participant who is TTR stabilized), defined as the patient whose percent stabilization 
≥32%. The stabilization cut-off threshold was based on statistical modeling results: 
percent stabilization falling above 95% CI in placebo-treated participants with ATTR-CM 
in Phase 3 Study B3461028 (32%) were determined to be “stabilized”.
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Protocol B3461077 (Tafamidis) Statistical Analysis Plan

TTR concentration at baseline (pre dosing) on Day 1, at Months 1, 6 and 12 (or EOT)
Refer to the separate Bioanalytical Plan as Appendix of Bioanalytical Report for calculation 
of TTR concentration and percent stabilization.
3.2.4. Quality of Life Endpoints
All quality of life endpoints will be assessed at baseline, Month 6 and 12 (or EOT)

Change from baseline in the Kansas City Cardiomyopathy Questionnaire Overall 
Summary scores (KCCQ-OS)
Changes from baseline in the KCCQ domain scores (Physical Limitation, Symptom 
Stability, Symptom Frequency, Symptom Burden, Total Symptom, Self-efficacy, Social 
Limitation, and Quality of Life) and Clinical Summary Score are also included as 
endpoints.
Total Symptom Score is calculated as the mean of Symptom Frequency and Symptom 
Burden Scores.  Clinical Summary Score is calculated as the mean of Physical 
Limitation Symptom Frequency and Symptom Burden Scores.  Overall Summary Score 
is calculated as the mean of Physical Limitation, Symptom Frequency, Symptom 
Burden, Quality of Life, and Social Limitation Scores.

Change from baseline in Short-Form Survey 12 (SF-12, version 2, Acute) score
The 12-item Short Form Scale scores are summed into 2 scales: physical component 
summary score (PCS) and mental component summary score (MCS).  In addition, 8 
sub-scale scores are also included as endpoints: physical function (PF), role physical 
(RP), role emotional (RE), mental health (MH), bodily pain (BP), general health (GH), 
vitality (VT), and social function (SF).  Higher scores indicate better quality of life.

Change from baseline in EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) index score and 
visual analog scale (VAS) scores
3.2.5. Pharmacokinetic (PK) Endpoints

Plasma concentrations of tafamidis at Month 1, 6 and 12
3.3. Other Safety Endpoints
3.3.1. Laboratory Data

Incidence of laboratory abnormalities
Laboratory assessments include hematology, serum chemistry, urinalysis, coagulation and 
RBP tests performed at screening or baseline, Month 1, 6 and 12.
3.3.2. Electrocardiogram Data

Change from baseline in ECG measurements and incidence of electrocardiogram (ECG) 
abnormalities
12 lead ECG will be measured during screening, baseline, Month 1, 6 and 12. ECG 
parameters include heart rate, PR interval, QT interval, QTcF interval and QRS interval. 
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Protocol B3461077 (Tafamidis) Statistical Analysis Plan
3.3.3. Echocardiograph Data

Change from baseline in Echocardiography measurements and incidence of clinically 
significant changes in Echocardiography from baseline
Echocardiography parameters include end-diastolic interventricular septal wall thickness 
(mm), left ventricle posterior wall thickness (mm), left ventricular ejection fraction (%), left 
ventricular stroke volume (mL), fractional shortening (%), left atrial diameter, anterior-
posterior (mm), left ventricular end systolic diameter (mm), left ventricular end systolic 
volume (mL), left ventricular end-diastolic diameter (mm), left ventricular end-diastolic 
volume (mL), left ventricular mass (g), and the ratio of peak velocity blood flow from gravity 
in early diastole (the E wave) to peak velocity flow in late diastole caused by atrial 
contraction (the A wave) (E/A).
Echocardiography will be measured at screening, Month 6 and 12.
3.3.4. Vital Signs

Incidence of vital sign abnormalities
Vital sign measures include systolic blood pressure, diastolic blood pressure, pulse rate, 
respiratory rate, and body temperature.  Vital signs will be measured at screening, baseline, 
Month 1, 6 and 12. 
3.3.5. Physical Examination

Incidence of clinical abnormality in physical examination
Full physical examination includes general appearance, head and neck, eyes, ears, skin, 
nose, throat, genitourinary, neurological, cardiovascular, abdomen, musculoskeletal, and 
respiratory and assessed at screening.  Brief physical examination includes skin, lungs, 
cardiovascular, and abdomen.  It will be assessed at baseline, Month 1, 6 and 12.
3.3.6. Body Mass Index (BMI) and modified Body Mass Index (mBMI)

Change from baseline in BMI and mBMI
BMI is calculated as Weight (kg) / Height (m) ^2.  mBMI is calculated by multiplying BMI 
(kg/m2) by serum albumin level (g/L).
Height will be measured at screening.  Weight will be measured at screening, baseline, 
Month 1, 6 and 12.
3.4. Other Endpoints (Efficacy Endpoints)

Change from Baseline in cardiac troponin I
Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) were recognized as markers of 
myocardial damage, Troponin T or troponin I or both may be chronically elevated in 
cardiac amyloidosis.  Cardiac troponin I is thought to be more accurate in assessment of 
myocardial damage.  In the appropriate clinical context of a thickened ventricle and heart 
failure, an elevated troponin value (outside of an acute coronary syndrome) should 
trigger suspicion for cardiac amyloidosis.
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Protocol B3461077 (Tafamidis) Statistical Analysis Plan
Blood sample collection will be performed at baseline, Month 6 and 12 for evaluation of 
cardiac troponin I.

Change from Baseline in New York Heart Association (NYHA) classification
The NYHA functional classification is used to describe the functional capacity of adults 
with congenital heart disease to describe the severity of symptoms and exercise 
intolerance.
NYHA functional classification will be assessed at screening, baseline, Month 6 and 12.
3.5. Baseline Variables

Demographic characteristics

Basic disease diagnosis

Medical history

Serology
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)
Participant Analysis 
Set
Description
Enrolled 
All participants who sign the ICD
Safety
All enrolled participants who take at least 1 dose of
tafamidis free acid 61 mg soft capsule
Efficacy
The same as the above safety analysis set
Pharmacokinetic (PK)
All safety population who have at least 1 quantifiable 
plasma tafamidis concentration
Pharmacodynamic (PD)
All safety population who have at least 1 TTR 
concentration/stabilization value
5. GENERAL METHODOLOGY AND CONVENTIONS
5.1. Hypotheses and Decision Rules
This is an estimation study with no statistical hypothesis nor decision rules.
5.2. General Methods
5.2.1. Analyses for Continuous Endpoints
The data for all continuous endpoints will be summarized by time point in tables containing 
descriptive statistics (N, mean, standard deviation, standard error of the mean, minimum, 1st, 
2nd (median) and 3rd quartiles and maximum) for baseline and change from baseline for 
those endpoints measured at baseline.  
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Protocol B3461077 (Tafamidis) Statistical Analysis Plan
For analyses of PK continuous endpoint of tafamidis concentration, PD continuous 
endpoints of TTR concentration and percent stabilization (as well as TTR tetramer 
concentration and FOI used to calculate percent stabilization), percent coefficient of 
variation (CV%) was used in descriptive statistics instead of standard error of the mean.
5.2.2. Analyses for Categorical Endpoints
The data for categorical endpoints (including binary) will be summarized by contingency 
tables that show the counts/frequency and percentage in the various categories at each time
point.  For some categorical endpoints, such as the presence or severity of adverse events, 
contingency or frequency tables will consider the data over the entire duration of the study 
and will not be constructed at each time point.  
The 2-sided 90% confidence interval for the proportion estimate will be calculated with 
Clopper-Pearson exact method.
5.3. Methods to Manage Missing Data
For safety data, missing dates and severity of adverse events will be imputed following 
Pfizer Reporting Standards.  No imputation will be done for missing vital signs, ECG, 
Echocardiography, laboratory and physical examination measurements.
For the KCCQ-OS, SF-12 and EQ-5D-5L instruments, rules suggested by the developers of 
these will be followed in calculating scores when individual question/items may be missing.  
If these rules are not enough for calculating a score, then the endpoint will be considered to 
have a missing value.  Missing values in any of the endpoints will not be imputed when 
summarizing these endpoints using descriptive statistics.
No imputation will be done for 6-MWT, NT-proBNP, tafamidis concentration, TTR 
stabilization and TTR concentration. Values <LLOQ will be imputed as ½ LLOQ.
6. ANALYSES AND SUMMARIES
All efficacy and safety analyses will base on safety population.  The analysis for PD 
endpoints (TTR stabilization and TTR concentration) will base on PD population.  PK 
analysis will base on PK population.  Refer to Section 4 for population definition.
6.1. Primary Endpoint(s)
6.1.1. Incidence of Treatment Emergent Adverse Events
TEAEs will be summarized according to Pfizer Reporting Standards.  The summary tables of 
TEAE and TEAE by System Organ Class (SOC) will be provided.  The incidence and 
severity of TEAE will be presented by SOC and MeDRA Preferred Term (PT).  Incidence of 
serious adverse events and TEAEs that cause withdrawal will be summarized.  All adverse 
events will be listed. 
6.2. Secondary Endpoint(s)
For the efficacy endpoints in Section 3.2.1, PD endpoints in Section 3.2.3 and quality of life
endpoints in Section 3.2.4, the analysis method described in Section 5.2.1 and Section 5.2.2
will be followed, i.e. the basic summary statistics will be calculated by analysis visit.  The 
estimates over time will be plotted graphically.  The individual values will be listed.
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Protocol B3461077 (Tafamidis) Statistical Analysis Plan
6.2.1. Safety Summaries and Analyses Endpoint(s)
Not applicable.
6.2.2. PK Endpoint(s)
Plasma concentrations of tafamidis will be summarized graphically and with descriptive
statistics (N, number of participants with observations above lower limit of quantification
[NALQ], arithmetic mean, standard deviation, CV%, median, and minimum and maximum) 
by visit and nominal time. Due to the sparse nature of the pharmacokinetic sampling 
scheme, a population approach may be used for pharmacokinetic data analysis. Nonlinear 
mixed-effect modeling may be performed to characterize the pharmacokinetics of tafamidis. 
If appropriate, these pharmacokinetic data may be used for exposure-response analyses.  
These analyses results, if conducted, will not be included in CSR but will bereportedly 
separately.
6.3. Other Safety Summaries and Analyses Endpoints
6.3.1. Laboratory Data
The incidence of laboratory abnormalities observed at any time during the study will be 
tabulated following Pfizer Reporting Standards. Summary statistics for changes from 
baseline in RBP will be provided by visit.
6.3.2. Electrocardiograms
Centrally over-read ECG variables will be summarized by mean change from baseline to
each measurement time for heart rate, PR interval, QRS interval, QT interval and QTcF 
(Fridericia correction) intervals. Additionally, the incidence of categorical increases in QTc 
intervals will be provided. Categories for QTcF are ≥450 msec, ≥480 msec, and ≥500 msec. 
Categories for QTcF as change from baseline are ≥30 msec increase, ≥60 msec increase 
and ≥75 msec increase. QTcF is considered the primary QTc value as this correction is 
more appropriate.  In addition, the number (%) of subjects with normal, abnormal not 
clinically significant, abnormal clinically significant and unevaluable will also be summarized 
at each visit.
6.3.3. Echocardiograph
The number (%) of subjects with normal, abnormal not clinically significant, abnormal
clinically significant and unevaluable will be summarized at each visit. The number (%) of
subjects with no baseline/screening, no significant change and significant change compared
with baseline will be summarized at each visit.  Summary statistics for change from baseline 
values will also be provided by visit.
6.3.4. Vital Signs
Participants with abnormalities will be summarized by each vital sign parameter.  Individual
values for actual value will be listed.
6.3.5. Physical Examination
The number and percent of patients with clinical findings at each visit will be summarized
following Pfizer Reporting Standards.
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Protocol B3461077 (Tafamidis) Statistical Analysis Plan
6.3.6. BMI and mBMI
BMI and mBMI values at each visit and change from baseline will be presented in summary
tables and data listings.  Descriptive statistics will be provided by visit.
6.4. Other Endpoints (Efficacy Endpoints)

Change from Baseline in cardiac troponin I
The analysis method described in Section 5.2.1 will be followed, i.e. the basic summary 
statistics will be calculated by analysis visit.  The estimates over time will be plotted 
graphically.

Change from Baseline in New York Heart Association (NYHA) classification
An increase or decrease in NYHA classification relative to baseline will be summarized 
using a shift table at each time point post-baseline.
6.5. Subset Analyses
All efficacy, safety, quality of life, and PD endpoints (including TTR concentration, percent 
stabilization [as PD continuous measures], the proportion of participants who achieve TTR 
stabilization [ie, who has been stabilized, also called responder in TTR stabilization] and its 
95% confidence interval [as PD categorical measure]) analyses will be repeated by NYHA 
baseline classification (I/II or III+).  PD endpoints analyses will be repeated by TTR genotype 
(wild-type or variant), if the sample sizes for both subsets allowed.
6.6. Baseline and Other Summaries and Analyses
6.6.1. Baseline Summaries
Baseline variables will be summarized descriptively.  Continuous variables will follow 
methods in Section 5.2.1.  Categorical variables will follow methods in Section 5.2.2.  
Medical history will be listed by participant.
6.6.2. Study Conduct and Participant Disposition
The end of treatment subject disposition will be shown. Frequency/counts will be provided 
for subject discontinuation(s) and completion.
6.6.3. Study Treatment Exposure
The duration of treatment will be calculated as: data of the last dose – date of the first dose 
+ 1.  Any missed doses/off drug period will be ignored in the duration calculation.  The 
treatment exposure will be defined as the number of days that participant took the study 
drug (gaps not counted).  Both will be summarized in following categories (days): 1, 2-30 (≤1 
month), 31-90 (1-3 months), 91-180 (3-6 months), 181-270 (6-9 months), ≥271 (9-12 
months).
Since study treatment should be taken once daily, study drug compliance will be calculated 
for each patient as: treatment exposure / treatment duration × 100.  Compliance will be 
listed as both a continuous and categorical (<80%, ≥80%) endpoint.
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Protocol B3461077 (Tafamidis) Statistical Analysis Plan
6.6.4. Concomitant Medications and Nondrug Treatments
Concomitant medication usage by medication type will be tabulated using the WHO-Drug 
dictionary and listed following Pfizer Data Standard.  Nondrug treatment will be listed as 
well.
6.7. Additional Analyses Depicting COVID-19 Pandemic Impact
In order to report the impact of COVID-19 on clinical trial populations and study data, the
following listings and summaries will be produced:

Listing of subjects with alternative facility or telehealth visits due to COVID-19 
pandemic

A separate summary table solely for subject discontinuations from investigational
product and withdrawal from study related to COVID-19 pandemic, if any, will be
provided

Protocol deviations related to COVID-19 pandemic will be summarized and listed
separately. Both important and non-important PDs related to COVID-19 pandemic
will be reported

COVID-19 related AEs, if any, will be reported separately
7. INTERIM ANALYSES
No interim analysis will be conducted for this study. As this is an open-label study, the 
sponsor may conduct unblinded reviews of the data during the course of the study for the 
purpose of safety assessment, facilitating PK/PD modeling, and/or supporting clinical 
development.
7.1. Introduction
Not applicable.
7.2. Interim Analyses and Summaries
Not applicable.
Appendix 1. Data Derivation Details
Appendix 1.1. Definition and Use of Visit Windows in Reporting
To maximize the use of all available data, the analysis visit windows are expanded.  For 
endpoints with post-baseline assessments at Month 1, 6 and 12 (except PK endpoints), the 
analysis windows are defined in below table.  The study day will be calculated as: date of 
assessment/collection – date of the first dose + 1.  If two or more visits/observations fall into 
the same window, the visit / observation closest to the target day should be used in the 
analyses.  If there is a tie, the later visit should be used.  Note: for ECG and 
Echocardiogram, the central laboratory reading data takes priority.  For NT-proBNP, TNI and 
RBP, only the central laboratory reading data are included in analysis.
Visit Label
Target Day
Definition [Day 
Window] - Lower
Definition [Day 
Window] - Upper
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Protocol B3461077 (Tafamidis) Statistical Analysis Plan
Baseline
1
Day 1 = date of first dose of study treatment taken in the study
Prior to first dose of study treatment taken in the study
Month 1
31
16
105
Month 6
181
106
270
Month 12
361
≥271 (Note: Set upper at Day 375 for PD endpoints)
For endpoints with post-baseline assessments only at Month 6 and 12, the analysis visit 
windows are defined as below.
Visit Label
Target Day
Definition [Day 
Window] - Lower
Definition [Day 
Window] - Upper
Baseline
1
Day 1 = date of first dose of study treatment taken in the study
Prior to first dose of study treatment taken in the study
Month 6
181
91
270
Month 12
361
≥271
For PK, tafamidis concentrations will be measured at Month 1 pre-dose and 3 hours (±1.5 
hours) post-dose; Month 6, 7 hours (± 2.5 hours) post-dose; Month 12, 1 hour (± 30 
minutes) post-dose.  The PK sampling windows are defined in below table.  The sampling 
time window will be calculated as: time of sample collection – time of dosing of most recent 
study treatment.
Visit Label
Planned Time Post 
Dose (hours)
Definition [Time 
Window] – Lower 
(hours)
Definition [Time 
Window] – Upper 
(hours)
Month 1 
0 (Pre-dose)
Prior to dosing of study treatment on the 
sample collection day
Month 1 
3 
1.5
4.5
Month 6 
7 
4.5
9.5
Month 12
1
0.5
1.5
Appendix 2. List of Abbreviations
Abbreviation
Term
6-MWT 
6-minutes walk  test
AE
Adverse event
ATTR-CM
Transthyretin amyloid cardiomyopathy
ATTR-PN
Transthyretin Amyloid Polyneuropathy
BMI
Body Mass Index
BP
Body pain
CI
Confidence interval
cTNT
Cardiac troponin T
cTNI
Cardiac troponin I
CV
Coefficient of variation
E/A
Ratio of peak velocity blood flow from gravity in early diastole (the 
E wave) to peak velocity flow in late diastole caused by atrial 
contraction (the A wave).
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Protocol B3461077 (Tafamidis) Statistical Analysis Plan
Abbreviation
Term
ECG
Electrocardiogram
EOT
End of Treatment
EQ-5D VAS
EuroQoL 5 Dimensions visual analogue scale
EQ-5D-5L
EuroQoL 5 Dimensions 5 Levels
FOI
Fraction of initial tetramer concentration
KCCQ
Kansas City Cardiomyopathy Questionnaire 
mBMI
Modified Body Mass Index
MCS
Mental component summary score 
MH
Mental health
NT-proBNP
N Terminal prohormone B type Natriuretic Peptide
NYHA
New Year Heart Association
PCS
Physical component summary
PD
Pharmacodynamics(s)
PK
Pharmacokinetic(s)
PR
PR interval
QD
Once daily
QRS
QRS complex
QT
QT interval
QTc
Corrected QT
QTcF
Corrected QT (Fridericia method)
RE
Role emotional
RP
Role physical
SAE
Serious adverse event
SAP
Statistical analysis plan
SF
Social function
SF-12
12-short item survey form
TEAE
Treatment-emergent adverse events
TnI
Troponin I
TTR 
Transthyretin
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