Acute Respiratory Illness Surveillance (ARIS) by Monitoring Voice and Illness Symptom Changes Using a Mobile Application in a Low-Interventional Decentralized Study.
Conditions: Healthy
Sponsor: Pfizer

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
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Title P a ge  
Ac ute Res pir at or y Ill ness S ur veill a nce ( A cRI S) b y  
M o nit ori n g V oice a n d Ill ness S y m pt o m C h a n ges usi n g a M o bile 
a p plic ati o n i n a L o w -I nter ve nti o n al Dece ntr ali ze d St u d y. 
 
C o m p o u n d N u m ber:  
N/ A  
C o m p o u n d N a me:  
N/ A  
U S I N D N u m ber:  
N/ A  
E u dr a C T N u m ber:  
N/ A  
Pr ot oc ol N u m ber:  
X 9 0 0 1 2 9 3  
P h ase:  
N/ A  
S h ort Title:  Ac ute Res pirat or y Ill ness S ur veilla nce ( A cRI S) wit h a M o bile A p plicati o n i n a L o w -
I nter ve nti o nal Dece ntralize d  St u d y . 
 
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 n ce 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 b e pr o m ptl y n otifie d.  
 
 
 

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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 a n d R ati o n ale f or C h a n ges  
A me n d me nt  # 1  
2 8 Se pte m ber 2 0 2 1  
Secti o n 1. 1. S y n o psis  O bjecti ves a n d 
E n d p oi nts , Secti o n 3 Rese arc h 
Q uesti o ns, O bjecti ves a n d E n d p oi nts.  
C h a n ge of Pri m ar y O bjecti ve  a n d 
Pri m ar y E n d p oi nt  (s): It reflects t he 
c ha n ge t o obtai n dat a t o c haracteri ze t he 
relati o ns hi p bet wee n  s y m pt o ms a n d v oice 
feat ur es f or partici pa nts wit h ac ute viral 
res pirat or y ill ness. T his d ata will be use d 
as t he basis t o  b uil d v oice a n d s y m pt o m 
al g orit h m(s) f or det ecti o n a n d m o nit ori n g 
of t hese ill ness es.  
I n c or p orate d c h a n ges t hr o u g h o ut t he 
pr ot oc ol  b o d y  t o reflect u p date . 
Rati o nale:  D ue t o c urre nt l o w attac k rat e 
of S A R S -C o V -2 see n i n t his st u d y t h us 
far, t he pri mar y o bjecti ve has bee n 
m o difie d a n d e x pa n d e d t o i ncl u de  S A R S -
C o V -2 , i nfl ue nza vir us , a n d R S V.  
C h a n ge of N u m ber of P artici p a nts : T he 
t otal sa m ple size u p date d fr o m 6 2 5 0 t o 
a p pr o xi matel y 8 7 0 0 t o reflect t he u p date d 
pri mar y o bjecti ve of t h e a me n d me nt, t he 
u p date d o verall esti mate of t he 
s y m pt o matic attac k rate f or t he 3 vir uses, 
a n d t he u p date d data attriti o n rate (as 
descri be d i n t he u p d ate d S a m ple S ize 
D eter mi nati o n  S ecti o n 9. 2 ). 
Secti o n 1. 1 S y n o psis St u d y C o h orts a n d 
D ur ati o n of St u d y P artici p ati o n, 
Secti o n 4. 1 O ver all Desi g n: Pr ot oc ol 
b o d y te xt u p date d  t o re m o ve t he ai m of 
e q ual distri b uti o n i n 4 gr o u ps 

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of  n = 2 5  eac h: ( Male > 6 0 y/ o; Male  6 0 
y/ o;  Fe male  > 5 0  y/ o;  Fe male  5 0  y/ o ). 
Rati o nale: I A res ults s h o w t hat 
recr uit me nt of s o me of t he a ge/ ge n der 
gr o u ps has bee n c halle n gi n g . M ore o ver, 
si nce t he 1 0 0 p ositi ve s y m pt o matic cases  
ca n n o w s pa n t h e 3  vir us es, we will n o 
l o n ger ai m f or a n y a ge a n d ge n der  
distri b uti o n .  
Secti o n  1. 3 . S che d ule of A cti vities  
C ha n ges refl ect ne w visit  date  wi n d o ws. 
Self -s wa b # 1 Da ys 2 + 6, Self -s wa b # 2 
s y m pto matic partici pa nts Da ys 2 + 4 0, 
Self -s wa b # 2 as y m pto matic partici pa nts  
Da ys 4 2 + 1 , E n d of St u d y Q uesti o n naire at 
Da y 4 2 + 4 da ys . S uc h c ha n ges are 
reflecte d i n t he Sc he ma s h o w n i n Secti o n 
1. 2 . 
Rati o nale: I n crease fl e xi bilit y a n d 
c o m plia nce wit h self -s wa b bi n g, i ncrease 
ti mi n g f or partici pa nt t o recei ve t est 
res ults a n d decreas e p ote ntial pr ot oc ol 
de viati o ns.  
Secti o n 5. 2. E xcl usi o n Criteri a  
C ha n ges reflect ne w e xcl usi o n cr iteria f or 
p artici pa nts 
w h o 
h a v e 
recei ve d a n y 
i n vesti gati o nal or lice ns e d  R S V vacci ne or 
pla n ni n g 
t o 
recei ve 
d uri n g 
st u d y 
partici pati o n.  
Partici pa nts 
w h o ha ve pre vi o usl y bee n 
e nr olle d i n t he st u d y ca n n ot be re -e nr olle d.  
R ati o nale: T o o pti mize e nr oll me nt of 
s y m pt o matic partici pa nts. 
Secti o n 5. 4.  Scree n F ail ures   

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C ha n ges refl ect t hat scree n fail ure d ata are 
c ollecte d a n d re p orte d t o t he cli nical 
data base . 
Rati o nale: Scree n fail ures are bei n g 
rec or de d i n t he cli nical d ata base. 
Secti o n 6. 1. 1  Perf or m a nce of Di a g n ostic 
St u d y I nter ve nti o ns . 
M o difie d te xt f or 
R T -P C R s a m ple testi n g. Ne w te xt re a ds 
as f oll o ws : T he R T -P C R  sa m ples will be 
use d o nl y f or scie ntific researc h. E ac h 
sa m ple will be la belle d wit h a c o de s o t hat 
t he la b orat or y 
p ers o n nel testi n g t he 
sa m ples will n ot k n o w t he partici p a nt ’s 
i de ntit y. 
Sa m ples 
t hat 
re mai n 
after 
perf or mi n g assa ys o utli n e d i n t he pr ot oc ol 
ma y be st ore d b y Pfizer. U nless a ti me 
li mitati o n is re q uire d b y l ocal re g ulati o ns 
or et hical re q uire me nts, t he sa m ples will be 
st ore d f or u p t o 1 5 years after t he e n d of t he 
st u d y a n d t he n destr o ye d. If all o we d b y t he 
I C D, st ore d sa m ples 
ma y be use d f or 
a d diti o nal testi n g t o better u n dersta n d t he 
i m m u ne res p o nses t o t he vacci n e(s) u n d er 
st u d y i n t his pr ot oc ol, t o i nf or m t he 
de vel o p me nt of ot her  pr o d ucts, a n d/ or f or 
vacci ne -rel ate d assa y 
w or k s u p p orti n g 
vacci ne pr o gra ms. 
N o testi n g of t he 
partici pa nt ’s 
g e netic 
material 
will 
be 
perf or me d.   
T he partici pa nt ma y re q u est t hat his or her 
sa m ples, if still i de ntifia ble, be destr o ye d at 
a n y ti me; h o we v er , a n y data alrea d y 
c ollecte d fr o m t h ose sa m ples will still be 
use d f or t his researc h. T he bi ol o gical 
sa m ples 
ma y 
be s hare d 
wit h 
ot her 
researc hers as l o n g as c o nfi de ntialit y is 
mai ntai ne d 
a n d 
n o 
testi n g 
of 
t he 
partici pa nt ’s ge netic mat erial is perf or me d. 
Rati o nal e: Sa m ples 
will be use d f or 
a d diti o nal testi n g t o better u n dersta n d t he 
i m m u ne res p o nses t o t he vacci n e(s) u n d er 
st u d y i n t his pr ot oc ol, t o i nf or m t he 
de vel o p me nt of ot her pr o d ucts, a n d/ or f or 

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
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vacci ne -rel ate d assa y 
w or k s u p p orti n g 
vacci ne pr o gra ms.  
 
Secti o n 8. 1. 1 Electr o nic Di ar y 
S y m pt o ms a n d V oice Assess m e nts  
C ha n ges refl ect t he ne w defi niti o n of 
fe ver i n t he El ectr o nic di ar y : 
•  N o ne: less t ha n 3 8. 0° C or 1 0 0. 4° F  
•  Mil d ( Gra de 1) ≥3 8. 0° C t o 3 8. 4° C or 
1 0 0. 4° F t o 1 0 1. 1° F  
•  M o derate ( Gra d e 2) > 3 8. 4° C t o 
3 8 . 9° C or 1 0 1. 2° F t o 1 0 2. 0° F  
•  Se vere ( Gra d e 3) > 3 8. 9° C t o 4 0. 0° C 
or 1 0 2. 1° F t o 1 0 4. 0° F  
•  Gra de 4 > 4 0. 0° C or > 1 0 4. 0° F  
•  Te m perat ur e n ot ta ke n.  
Rati o nale: C ha n ge fr o m s u bjecti ve 
defi niti o n of fe ver as “feeli n g fe veris h” t o 
a m ore o bjecti ve cli nical defi niti o n t o 
i m pr o ve t he data q ualit y . 
8. 1. 2  N as al S elf-s w a b A d de d w heezi n g as 
a ne w or i ncrease d s y m pt o m f or 
s wa b bi n g. 
Rati o nale:   W heezi n g  is a c o m m o n 
s y m pt o m f or R S V. 
9. 2. S a m ple S ize D eter mi n ati o n  U p date d 
t o reflect t he u p d ate d pri mar y o bjecti ve, 
 
 
 
 
 
 
 T he 
t otal sa m ple esti mate is u p date d 
P P D

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acc or di n gl y  (fr o m 6 2 5 0 t o 8 7 0 0 
partici pa nts) . 
Rati o nale: Si nce t he 1 0 0 p ositi ve 
s y m pt o matic cases n o w s pa n t he 3 
vir uses.  
 
1 0. 1. 3. Milest o nes U p d ate d milest o nes 
t o refl ect new ti meli nes.  
 
1 1. Refere nces Delete d refere nce  
5.  C or o na vir us Disease 2 0 1 9 ( C O VI D -1 9) 
| 2 0 2 0 I nt eri m Case Defi niti o n, A p pr o ve d 
A pril 5, 2 0 2 0. ( 2 0 2 0). C D C. G o v.  
 
Rati o nale: N o l o n ger a p plica ble.  
 
 
C h a n ges m a de t hr o u g h o ut t he 
d oc u me nt b o d y  
C ha n ge of st u d y a b bre viati o n fr o m A RI S 
t o Ac RI S. 
C orrecti o ns of t y p o gra p hical err ors a n d 
a d mi nistrati ve e dits were ma de  per clarit y 
a n d c o nsiste nc y.  
 
Ori gi nal pr ot oc ol  
1 9 Ja n uar y 2 0 2 1   
N/ A  
 
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.  
 
 

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T A B L E O F C O N T E N T S  
1. P R O T O C O L S U M M A R Y  ...................................................................................................1 1  
1. 1. S y n o psis  ..................................................................................................................1 1  
1. 2.  Sc he ma  ....................................................................................................................1 5  
1. 3. Sc he d ule of A cti vities  .............................................................................................1 6  
2. I N T R O D U C TI O N  ...............................................................................................................1 8  
2. 1. St u d y Rati o nale  .......................................................................................................1 8  
2. 2. Bac k gr o u n d  .............................................................................................................1 8  
2. 2. 1. Cli nical O v er vie w  .......................................................................................1 8  
2. 3. Be nefit/ Ris k Assess me nt  .........................................................................................1 8  
3. R E S E A R C H Q U E S TI O N S, O BJ E C TI V E S A N D E N D P OI N T S  .......................................1 9  
3. 1. Varia bles  ..................................................................................................................2 1  
4. S T U D Y D E SI G N .................................................................................................................2 3  
4. 1. O verall D esi g n  .........................................................................................................2 3  
4. 2. Scie ntific Rati o nale f or St u d y Desi g n  .....................................................................2 4  
4. 2. 1. Li mitati o ns of t he St u d y Desi g n a n d Met h o ds  ...........................................2 4  
4. 2. 2. Partici pa nt I n p ut I nt o Desi g n  ......................................................................2 4  
4. 3. J ustificati o n f or D os e  ..............................................................................................2 5  
4. 4. E n d of St u d y Defi niti o n  ..........................................................................................2 5  
5. S T U D Y P O P U L A TI O N  ......................................................................................................2 5  
5. 1. I n cl usi o n Criteria  .....................................................................................................2 5  
5. 2. E xcl u si o n Criteria ....................................................................................................2 5  
5. 3. Lifest yle C o nsi derati o ns  ..........................................................................................2 6  
5. 4. Scree n Fail ures  ........................................................................................................2 6  
5. 5. Criteria f or T e m p oraril y Dela yi n g E nr oll me nt . ......................................................2 7  
6. S T U D Y I N T E R V E N TI O N S  ...............................................................................................2 7  
6. 1. St u d y I nter v e nti o n(s)  ...............................................................................................2 7  
6. 1. 1. Perf or ma n ce of Di a g n ostic St u d y I nter v e nti o ns  .........................................2 7  
6. 1. 2. Me dical De vic es  .........................................................................................2 8  
6. 2. Pre parati o n/ Ha n dli n g/ St ora ge/ Acc o u nta bilit y  ........................................................2 8  
6. 2. 1. Pre parati o n a n d Dis pe nsi n g  ........................................................................2 8  
6. 3. Met h o ds t o Mi ni mize Bias  ......................................................................................2 8  
6. 3. 1. All ocati o n t o St u d y I nter ve nti o n  ................................................................2 8  

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7. 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 F R O M S T U D Y  ......................2 9  
7. 1. Partici pa nt Disc o nti n uati o n/ Wit h dra wal Fr o m t he St u d y  .......................................2 9  
7. 1. 1. Wit h dra wal of C o nse nt  ...............................................................................2 9  
7. 2. L ost t o F oll o w -u p  ....................................................................................................2 9  
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  ...............................................................3 0  
8. 1. Efficac y Assess me nts  ..............................................................................................3 1  
8. 1. 1. Electr o nic Diar y S y m pt o ms a n d V oice Ass ess me nts:  ................................3 1  
8. 1. 2. Nasal Self -s w a b ..........................................................................................3 1  
8. 1. 3. Ot h er Electr o ni c diar y Acti vities  ................................................................3 3  
8. 1. 4.  Rater Q ualificati o ns  ....................................................................................3 3  
8. 1. 5. I m a gi n g Assess me nts ..................................................................................3 3  
8. 2. Safet y Assess me nts  .................................................................................................3 3  
8. 2. 1. Pr o t oc ol-Re q uire d Cli nical Safet y La b orat or y Assess me nts  ......................3 4  
8. 3. A d verse E v e nts a n d Seri o us A d verse E v e nts  ..........................................................3 4  
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  .......3 4  
8. 3. 1. 1. Re p orti n g S A Es t o Pfizer Safet y  ...............................................3 5  
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  ...................3 5  
8. 3. 2. Met h o d of Dete cti n g A Es a n d S A Es  ..........................................................3 5  
8. 3. 3. F oll o w -u p of A Es a n d S A Es  .......................................................................3 5  
8. 3. 4. Re g ulat or y Re p orti n g Re q uire me nts f or S A Es  ...........................................3 6  
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 E n vir o n me ntal 
E x p os ure  ..........................................................................................................3 6  
8. 3. 5. 1. E x p os ure D uri n g Pre g na nc y  ......................................................3 6  
8. 3. 5. 2. E x p os ure D uri n g Breastfee di n g  ................................................3 7  
8. 3. 5. 3. E n vir o n me ntal E x p os ure  ...........................................................3 8  
8. 3. 6. Car di o vasc ular a n d Deat h E ve nts  ...............................................................3 8  
8. 3. 7. Disease Relate d E ve nts a n d/ or Diseas e Relate d O utc o mes N ot 
Q ualif yi n g as A Es or S A Es ..............................................................................3 8  
8. 3. 8. A d verse E v e nts of S pecial  I nterest .............................................................3 8  
8. 3. 8. 1. Lac k of Efficac y  ........................................................................3 8  
8. 3. 9. Me dical De vic e Deficie nci es  ......................................................................3 8  
8. 3. 9. 1. Ti me Peri o d f or Detecti n g Me dical De vice Defici e ncies  .........3 8  
8. 3. 9. 2. Pr o m pt Re p orti n g of De vice Defi cie ncies t o S p o ns or  ..............3 8  

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8. 3. 9. 3. F oll o w -u p of Me dical De vice Defi cie ncies ...............................3 9  
8. 3. 9. 4. Re g ulat or y Re p orti n g Re q uire me nts f or De vice 
Deficie n cies  .......................................................................................3 9  
8. 4. Treat me nt of O v er d ose  ............................................................................................3 9  
8. 5. P har mac o ki netics  ....................................................................................................3 9  
8. 6. P har mac o d y na mics  ..................................................................................................3 9  
8. 7. Ge netics  ...................................................................................................................3 9  
8. 8. Bi o mar kers  ..............................................................................................................3 9  
8. 9. I m m u n o ge nicit y Ass ess me nts  .................................................................................3 9  
8. 1 0. Healt h Ec o n o mics  .................................................................................................3 9  
9. S T A TI S TI C A L C O N SI D E R A TI O N S  ................................................................................4 0  
9. 1. Statistical H y p ot heses  .............................................................................................4 0  
9. 2. S a m ple Size Deter mi nati o n  .....................................................................................4 0  
9. 3. Data Ma n a ge me nt  ...................................................................................................4 1  
9. 4. Case Re p ort F or ms/ Data C ollecti o n T o ols/ Electr o nic Data Rec or d  .......................4 1  
9. 5. Data A nal ysis  ..........................................................................................................4 1  
9. 6.  I nteri m A nal yses .....................................................................................................4 2  
9. 7. Data M o nit ori n g C o m mittee or Ot her I n de p e n de nt O versi g ht C o m mittee  .............4 2  
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  ..........................................................................................................4 3  
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  ...............4 3  
1 0. 1. 1.  Re g ulat or y  a n d Et hical C o nsi derati o ns  ....................................................4 3  
1 0. 1. 1. 1. Re p orti n g of Safet y Iss ues a n d Ser i o us Breac h es of t he 
Pr ot oc ol or I C H G C P  .........................................................................4 3  
1 0. 1. 2. Res p o nsi ble Parties  ...................................................................................4 4  
1 0. 1. 3. Milest o nes  .................................................................................................4 4  
1 0. 1. 4. Fi na nc ial Discl os ure .................................................................................4 4  
1 0. 1. 5. I nf or me d C o nse nt Pr ocess  ........................................................................4 4  
1 0. 1. 6. Data Pr otecti o n  .........................................................................................4 5  
1 0. 1. 7. Disse mi nati o n of Cli nical St u d y Data  ......................................................4 6  
1 0. 1. 8. Data Q ualit y Ass ura nce  ............................................................................4 7  
1 0. 1. 9. S o urce D oc u m e nts  ....................................................................................4 8  
1 0. 1. 1 0. St u d y a n d Site Start a n d Cl os ure  ............................................................4 8  

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1 0. 1. 1 1. P u blicati o n P olic y  ...................................................................................4 9  
1 0. 2. A p pe n di x 2: 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  ......................................................................5 1  
1 0. 2. 1. Defi niti o n of A E  .......................................................................................5 1  
1 0. 2. 2. Defi niti o n of S A E  .....................................................................................5 2  
1 0. 2. 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 .......................5 5  
1 0. 2. 4. Re p orti n g of S A Es  ....................................................................................5 8  
1 0. 3. A p pe n di x 3: Li ver Safet y: S u g geste d Acti o ns a n d F oll o w -u p Ass ess me nts  ........6 0  
1 0. 4. A p pe n di x 4: A b bre viati o ns  ...................................................................................6 2  
1 1. R E F E R E N C E S  ..................................................................................................................6 5  
 
 

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 1 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  Ac ute Res pir at or y Ill ness S ur veilla nce ( A cRI S) wit h M o bile A p plicati o n i n a L o w -
I nter ve nti o nal D ece ntr alize d St u d y. 
R ati o n ale : T he rati o nale f or c o n d ucti n g t he st u d y is t o better u n dersta n d if t here are v oice 
feat ur es t hat c orrelate wit h a c ute vir al  res pir at or y ill ness s y m pt o ms. Ver y little w or k has bee n 
p u blis he d usi n g v oice as a n o bjecti ve  ass ess me nt of t he stat us of res pirat or y ill nesses 1, 2. 
T o  better  u n derst a n d  if t here are v oice feat ures t hat c orrel ate wit h ac ut e viral  res pirat or y ill ness 
s y m pt o ms, Pfizer c o n d ucte d a n i n -cli nic a n d at -h o me e x pl orat or y st u d y d uri n g t he c ol d a n d 
fl u seas o n of 2 0 1 8. V oice a n d res pirat or y ill ness s y m pt o m data were  c ollecte d,  a n d 2 2 v oice 
feat ur es were i de ntifie d t hat differe d b et wee n sic k a nd well states  a n d c orres p o n de d t o self -
re p orte d s y m pt o m c ha n g es3. T he AcRI S m o bile a p p is a s oft ware -bas e d s yste m ( m o bile p h o ne 
a p p pl us cl o u d -base d tra nsfer a n d st ora ge) use d t o rec or d dail y partici pa nt re p orte d s y m pt o ms 
of ac ute vir al  res pirat or y tract ill ness as well as brief a u di o rec or di n gs (scri pte d s peec h a n d 
p h o ne mes) self -ca pt ur e d b y partici pa nts. T he Electr o nic diar y offers a n i n n o vati ve a p pr oac h 
t o detect a n d m o nit or s y m pt o ms of viral  res pirat or y tract ill nesses i n a n o ut of cli nic setti n g.  
T he p ur p ose  of t h e A cRI S st u d y is t o o btai n data t o c haracteri ze t he relati o ns hi p bet wee n 
s y m pt o ms a n d v oice feat ures f or R T -P C R c o nfir me d S A R S -C o V -2, i nfl ue nzavir us, or R S V 
p ositi ve partici pa nts  wit h ac ute viral res pirat or y ill ness . T his data will be use d as t he basis t o 
b uil d v oice a n d s y m pt o m al g orit h m(s) f or det ecti o n a n d m o nit ori n g of t hese ill nesses . T his 
w o ul d be nefit vacci ne de vel o p me nt acr oss se v eral ke y disease areas,  i ncl u di n g S A R S -C o V -
2 ,  i nfl ue nza vir us  a n d R S V .  
T he st u d y  als o m o dels  c o nce pts of m ore efficie nt “fle xi ble”  cli nical  trials i n v ol vi n g n ot o nl y 
v oice 
ca pt ure, b ut 
als o 
we b -bas e d 
p artici pa nt recr uit me nt, 
e n h a nce d 
partici pa nt 
e n ga ge me nt,  a n d re m ote sa m ple c ollecti o n t hat c o ul d ma ke f ut ure cli nical st u dies m or e 
efficie nt. T h e cli nical data o btai ne d i n t his o bser vati o nal st u d y c o ul d pr o vi de t he 
d oc u me ntati o n of t he te c h n ol o g y’s perf or ma n ce nee d e d t o e na ble its de pl o y me nt i n f ut ure 
i nter ve nti o nal st u dies. 
O bjecti ves a n d E n d p oi nts  
Pri m ar y O bjecti ve(s):  
Pri m ar y E n d p oi nt(s):  
● O btai n data t o c haract eri ze t he 
relati o ns hi p bet wee n s y m pt o ms a n d 
v oice feat ures f or partici pa nts wit h ac ute 
viral res pirat or y ill ness.  T his data will be 
use d as t he basis t o b uil d v oice a n d 
s y m pt o m al g orit h m(s) f or detecti o n a n d 
m o nit ori n g of t hese ill nesses.  
 
● C ha n ge i n  self-re p orte d s y m pt o m 
sc ores i n t he Electr o nic diar y fr o m well 
t o sic k i n s y m pt o matic partici pa nts wit h 
R T -P C R c o nfir me d S A R S -C o V -2, 
i nfl ue nza vir us, or  R S V . 
● C ha n ge i n v oice feat ures s uc h as pitc h, 
jitter, har m o nicit y, e ntr o p y, flat ness, 
s hi m mer fr o m t he v oice c ollecti o n as 
ca pt ure d b y t he Electr o ni c diar y fr o m 

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 1 2   
well t o sic k i n s y m pt o matic partici pa nts 
wit h R T -P C R c o nfir me d S A R S -C o V -2, 
i nfl ue nza vir us, or R S V.  
 
Sec o n d ar y O bjecti ve(s):  
Sec o n d ar y E n d p oi nt(s):  
•  Assess c o m plia nce of t he partici pa nts 
usi n g t he  Electr o nic diar y t o c ollect 
data.  
•  Perce nta ge of t otal da ys of s y m pt o ms 
e ntere d i n t he Electr o nic diar y.  
•  Perce nta ge of t otal da ys of v oice 
rec or di n gs e nt ere d i n t he Electr o nic 
diar y.  
 
•  Test t he q ualit y of t he rec or di n g fr o m 
t he Electr o nic diar y t o c ollect data t hat is 
usa ble f or i nter pretati o n.   
•  Perce nta ge of rec or di n gs wit h si g nal t o 
n oise rati o  ≥ 2 0  d B t hat ha ve d urati o n  ≥ 
3  sec f or p h o n e me a n d ≥ 1 0 sec f or 
rea di n g tas ks.  
 
•  Deter mi ne rates of p ositi vit y f or S A R S -
C o V -2/ i nfl ue nza vir us / R S V i nfecti o n.  
•  Perce nta ge of partici pa nts wit h S A R S -
C o V -2; a n d/ or i nfl ue nza vir us ; a n d/ or 
R S V R T -P C R base d p ositi vit y i n self -
s wa bs.  
 
•  E val uate t he feasi bilit y of o btai ni n g  self-
s wa bs. 
•  Perce nta ge  of partici pa nts a d mi nisteri n g 
t he self-s wa b at self-s w a b # 1  a n d self-
s wa b # 2.    
•  Perce nta ge of partici pa nts re p orti n g 
s y m pt o ms i n t he Electr o nic diar y, w h o 
ha ve a self -s wa b c ollecte d at or ar o u n d 
s y m pt o m o nset.  
•  Perce nta ge of self -s wa bs wit h vali d 
( p ositi ve or ne gati ve) or i n vali d ( n o n- 
re porta ble d ue t o tec h nical or self -
c ollecti o n fail ures) res ults.  
 

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 1 3   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
S afet y O bjecti v e(s):  
S afet y E n d p oi nt(s):  
● T o descri be t he s afet y pr ofile of self -
a d mi nistere d nasal s w a bs f or S A R S -
C o V -2/ i nfl ue nza vir us / R S V R T-
P C R test a m o n g partici pa nts.  
● I n ci de nce a n d se v erit y of a d verse 
e ve nts ( A Es)/researc h  rel ate d i nj uries 
( R RIs) a m o n g all e nr olle d partici pa nts. 
C CI

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 1 4   
O ver all De si g n 
T his is a l o w -i nter ve nti o nal, o bser vati o nal st u d y wit h pla n ne d e nr oll me nt of a p pr o xi matel y 
8 7 0 0  partici pa nts  1 8 years of a ge or ol d er.  
Partici pa nts will rec or d ac ute viral  res pirat or y ill n ess s y m pt o ms a n d v oice data dail y f or  u p t o 
a ma xi m u m of 8  wee ks i n b ot h t he well state a n d, s h o ul d t he y bec o m e ill,  t he sic k state, 
utilizi n g t he electr o nic diar y o n t heir m o bile a p plicati o n.   O nce e nr olle d, t he partici pa nt will 
start recor di n g s y m pt o ms a n d v oic e i n t he electr o ni c diar y, wit h dail y ti me c o m mit me nt t o t his 
p orti o n of t he st u d y  e x pecte d t o be 2 -4 mi n utes. T w o nasal s elf -s wa b c oll ecti o n kits will be 
or dere d f or deli ver y t o t h e partici pa nt o nce t he y are e nr olle d i n t he st u d y. T he partici pa nt will 
be as ke d t o self -s wa b w h e n t he test kit arri ves (s wa b # 1). T he kit, i ncl u di n g t he s peci me n, will 
be ret ur n e d t o t he ce ntr al la b f or R T -P C R S A R S -C o V 2/ i nfl ue nza vir us / R S V R T-P C R testi n g.  
T he  partici pa nt  is e x pect e d t o c o m plete 3 p h o ne mes a n d 5 li nes of rea di n g eac h d a y, i n a d diti o n 
t o sc ore t he s elf-re p orte d s y m pt o ms i n t he Electr o nic diar y. If p artici pa nts bec o me si c k  (self-
re p ort) wit h n e w or i ncrease d  s y m pt o ms of res pir at or y ill ness, t he y will be  as ke d t o s elf -s w a b 
(s wa b # 2) a n d ret ur n t h e sa m ple f or ce ntral S A R S-C o V -2/ i nfl ue nza vir us / R S V R T-P C R 
testi n g. If t h e partici pa nt d oes n ot de vel o p a n y n e w or i ncrease d s y m pt o ms bet wee n s w a b # 1 
a n d e n d of Wee k 6 , t he y will o btai n a self-s wa b (s wa b # 2) at D a y 4 2 . 
If t he partici pa nt tests p ositi ve f or a n y of t he t hree vir uses at s wa b # 1 or s wa b # 2, t he y will 
c o nti n ue t he st u d y u ntil e n d of w ee k 8 . If t he y test ne gati ve f or a n y of  t he t hree vir uses at s wa b 
# 1 a n d s wa b # 2, t he y will e xit t he st u d y at a p pr o xi matel y t he e n d of wee k 6 . Res ults of t he RT -
P C R testi n g will be s hare d wit h partici pa nts.  
De m o gra p hic, me dical hist or y, a n d s m o ki n g stat us data  will be c ollecte d. At t he e n d of t h e 
st u d y, v oice a n d s y m pt o m traject ories will be a n al yze d t o u n dersta n d t he i nfecti o us res pir at or y 
disease tr aject or y.  A nal ysis of s y m pt o m a n d v oice c ha n ges will be e xa mi ne d base d o n S A R S -
C o V -2/ i nfl ue nza vir us / R S V test res ults. T he st u d y desi g n p urel y c o nte m plates ca pt ure of 
s y m pt o ms a n d v oici n g b y a researc h partici pa nt.  It d oes n ot i n v ol ve i n a n y res pect t he 
assess me nt, e xa mi nati o n, dia g n osis, pr o g n osticati o n or treat me nt of a n y st u d y partici pa nt.  
N u m ber of P artici p a nts  
 
Pla n ne d e nr oll me nt of a p pr o xi matel y 8 7 0 0 partici pa nts 1 8 years of a ge or ol der i n or der t o 
c ollect a t otal of N =  1 0 0 partici pa nts wit h ( 1) R T -P C R c o nfir me d ne gati ve S A R S -C o V -2,  
i nfl ue nza vir us or R S V  R T -P C R (s wa b # 1) a n d ( 2) R T -P C R  c o nfir me d p ositi ve S A R S -C o V -
2 ,  i nfl ue nza vir us a n d R S V, (s wa b # 2) s y m pt o matic c o m pleters.  
St u d y C o h orts a n d D ur ati o n of St u d y P artici p ati o n  
T he st u d y has 8, 7 0 0 p artici pa nts t o e nr oll t o c ollect N = 1 0 0 . It is a ntici pat e d t o reassess st u d y 
feasi bilit y a n d e nr oll me nt re q uire m e nts o nce we h a ve a nal yze d i nfecti o n rate a n d c o m plia nce 
data fr o m t he first 1, 0 0 0 c o m pleters . Eac h s u bject will be re q uire d t o sta y i n t he st u d y f or 6 
wee ks . If t he partici pa nt tests p ositi ve f or a n y of t h e t hree vir us es at s w a b # 1 or s wa b # 2, t he y 
will c o nti n ue t he st u d y u ntil t he e n d of Wee k 8 . 
 

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 1 5   
D at a M o nit ori n g C o m mittee  or Ot her I n de pe n de nt O versi g ht C o m mittee: N o  
St atistic al Met h o d  
We wil l be assessi n g cha n ge s o ver ti me i n self -re p orte d s y m pt o m sc ores i n t he electr o nic diar y 
fr o m well t o sic k i n s y m pt o matic partici pa nts wit h R T -P C R c o nfir m e d S A R S -C o V -2,  
i nfl ue nza vir us, or  R S V . N o nli near m o dels, s uc h as e x p o ne ntial or si g m oi d m o dels, will be 
utilize d t o e x pl ore disease pr o gressi o n fr o m well t o sic k a n d assess earl y detecti o n. Mea n 
esti mates, c o nfi de nce i nter vals, a n d si g nifica n ce t ests of c ha n ges ( or m o del para meters) will 
be pr o vi de d. A d diti o nal m o dels ma y als o be c o nsi dere d a s a p pr o priate, a n d t he m o dels' 
g o o d ness of fit will be assesse d usi n g A kai ke/ Ba y esia n i nf or mati o n criteria ( AI C/ BI C).  
C orrelati o n bet wee n c h a n ges i n s y m pt o ms a n d v oice feat ur es will be assesse d b y Pears o n or 
S pear ma n ra n k or der c orrelati o ns.  
1. 2.  Sc he m a
S elf-S w a b # 2 ne w or 
i ncre ase d s y m pt o ms O R  
D a y 4 2 + 1 if n o 
s y m pt o ms  
Recr uit me nt  
( D a y -7 t o -1) 
Pre - 
Scree ni n g  
( D a y -7 t o -1) 
E O S  
(D a y 4 2 + 4 ) 
e C o nse nt 
( D a y 1)  
Scree ni n g  
( D a y 1) 
D ail y V oice & 
S y m pt o m 
C ollecti o n  ( D a y 1 
u p t o 5 6 ) 
E nr olle d  
E n d of St u d y 
Q uesti o n n aire  
(D a y 4 2 + 4  or 5 6 )  
Self -S w a b # 1  ( D a y 2+ 6)  
E O S  
( D a y 5 6) 
S w a b kits se nt  ( qt y 2) 
D o w nl oa d 
Electr o nic Di ar y  
P ositi ve test  S A R S -C o V -
2/ i nfl ue nz a/ R S V 
Ne g ati ve test S A R S -
C o V -2/ i nfl ue nz a/ R S V  
Scree ni n g / E nr oll me nt Peri o d   
( D a y -7 t o -1) 
St u d y P a rtici p ati o n ( D a y 1 + 1  t o D a y 4 2 + 4 o r D a y 5 6 ) 

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 1 6   
1. 3.  Sc he d ule of Acti vities  
T he S o A ta ble pr o vi des a n o ver vie w of t h e 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 d etaile d i nf or mati o n o n eac h pr oce d ure a n d assess m e nt r e 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 h e 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 u ct e va l uati o ns or 
assess me nts re q uir e d t o pr otect t he well -b ei n g of t he partici pa nt.  
Visit I de ntifier  
Scree ni n g  
 
 
 
( Da y 1) 
E nr oll me n
t 
 
 
 
( Da y 1 + 1 
da y)  
Self -s w a b 
# 1  
 
 
 
( Da y 2 + 6  
da ys)  
Self -s w a b # 2 
S y m pt o m ati
c 
p artici p a nts  
 
( Da y 2  + 4 0  
da ys ) 
Self -s w a b # 2 
As y m pt o m ati
c 
p artici p a nts  
 
( Da y 4 2  + 1  
da ys ) 
E xte n de d electr o nic 
di ar y  
O nl y f or vir us p ositi ve 
partici pa nts f 
 
( Da y 4 2  t o 5 6 ) 
 
I nf or me d c o ns e nt 
X  
 
 
 
 
 
I n cl usi o n a n d e xcl usi o n criteria 
X  
 
 
 
 
 
Access Electr o nic diar y  
 
X  
 
 
 
 
De m o gra p h y  
 
X  
 
 
 
 
E nr oll me nt Q uesti o n nair e 
(i ncl u des self-re p orte d m e dical 
hist or y)  
 
X  
 
 
 
 
Dail y s y m pt o m a n d v oice e ntr y 
o n t he Electr o nic diar y  
 
X  
→  
→  
→  
→  
O btai n S A R S -C o V -
2/ i nfl ue nzavir us /R S V  nasal 
self-s wa b 
 
 
X a 
X b 
X c 
 
E nter date a n d ti me of self -
s wa b w he n c o m plete d i n 
Electr o nic diar y  
 
 
X  
X  
X  
 

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 1 7   
Visit I de ntifier  
Scree ni n g  
 
 
 
( Da y 1) 
E nr oll me n
t 
 
 
 
( Da y 1 + 1 
da y)  
Self -s w a b 
# 1  
 
 
 
( Da y 2 + 6  
da ys)  
Self -s w a b # 2 
S y m pt o m ati
c 
p artici p a nts  
 
( Da y 2  + 4 0  
da ys ) 
Self -s w a b # 2 
As y m pt o m ati
c 
p artici p a nts  
 
( Da y 4 2  + 1  
da ys ) 
E xte n de d electr o nic 
di ar y  
O nl y f or vir us p ositi ve 
partici pa nts f 
 
( Da y 4 2  t o 5 6 ) 
 
C o nfir m n o A E’s 1 2 h o urs after 
self-s wa b; e nt er date a n d ti me 
i n Electr o nic diar y 
 
 
X  
 
X  
 
E n d of St u d y Q uesti o n naire  
 
 
 
 
X d 
X e 
C ollect A Es a n d R RIs as 
a p pr o priate  
X  
X  
→ 
→ 
→ 
→ 
a. 
Partici p a nt is re q uire d t o perf or m self -s wa b # 1 as s o o n as p ossi ble o nce t h e y recei v e t h e c ollecti o n kit. 
b . 
Partici p a nt is re q uire d t o perf or m self -s wa b # 2 if t h e y de vel o p ne w or i n crease d s y m pt o ms. 
c. 
Partici p a nt is re q uire d t o pe rf or m self-s wa b # 2 if t h e y ha ve re mai n e d as y m pt o matic at da y 4 2 + 1 . 
d . 
Partici p a nt is re q uire d t o rec or d E n d of St u d y Q uesti o n naire at Da y 4 2 + 4  da ys (f or partici p a nts w h o ha ve teste d ne gati ve  or i n vali d f or b ot h self -s wa b # 1 a n d # 2).  
e. 
Partici p a nt is re q uire d t o rec or d E n d of St u d y Q uesti o n naire at Da y 5 6 (f or partici p a nts w h o ha ve ha d a p ositi ve res ult f or eit her self-s wa b # 1 or # 2) 
f. 
Partici p a nt is dee me d p ositi ve f or vir us if bi ol o gical sa m ple is deter mi n e d t o c o ntai n S A R S -C o V -2 a n d/ or i nfl u e nza vir us  a n d/ or R S V vir uses as detecte d b y 
 R T -
P C R test.  
 
Please n ote f or t h e ta ble w he n t h e t w o n u m bers f or a da y  are se parate d b y a “ +”, w hat i t mea n s is t hat t h e s wa b ma y be ta ken  as s o o n as t h e first n u m ber of t he t w o a n d as late 
as t h e s u m of t h e first a n d sec o n d of t h e n u m bers . 
 
 
C CI

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 1 8   
2.  I N T R O D U C TI O N 
T he rece nt C O VI D -1 9 pa n de mic has pr o ve n t o be c halle n gi n g  t o c o ntr ol d ue t o  li mite d 
accessi bilit y t o testi n g, a pr ol o n ge d as y m pt o matic p hase  i n i nfecte d carriers, a n d n o n-s pecific 
s y m pt o ms. T he g oal of  t his st u d y is t o c haracterize t he relati o ns hi p of v oi c e a n d s y m pt o ms  f or 
partici pa nts wit h ac ute viral res pir at or y ill nesses , i ncl u di n g S A R S -C o V -2 , i nfl ue nza vir us a n d 
R S V . T his data will be use d as t he b asis t o b uil d v oice a n d s y m pt o m al g orit h m(s) f or det ecti o n 
a n d m o nit ori n g of t hese ill nesses . T his will he l p vacci ne de vel o p me nt acr oss ke y disease areas 
i ncl u di n g S A R S -C o V -2, i nfl ue nza vir us a n d R S V . 
Res pirat or y  p h ysi ol o g y is a n area  wit h m ultifari o us diseases ra n gi n g i n m or bi dit y a n d 
m ortalit y. Ofte n patie nts prese nt wit h n o n -s p ecifi c s y m pt o ms s uc h as c o u g h or s h ort ness of  
breat h  ma ki n g it diffic ult t o o bjecti vel y dia g n ose , pr o g n osticate , a n d differe ntiat e fr o m 
i nfecti o us vs n o ni nfecti o us eti ol o g y .  
 
2. 1.  St u d y R ati o n ale  
T he p ur p ose of t he A cRI S st u d y is t o  c h aracteri ze t he relati o ns hi p of s y m pt o ms a n d v oice 
feat ur es f or partici pa nts wit h ac ute viral res pir at or y ill ness  as t he y pr o gress fr o m well t o sic k  
states. T his data will be use d as t h e basis t o b uil d v oice a n d s y m pt o m al g orit h m(s) f or detecti o n 
a n d m o ni t ori n g of t hes e ill nesses. This  w o ul d be n efit vacci ne de vel o p me nt acr oss se veral ke y 
disease areas,  i ncl u di n g S A R S -C o V -2, i nfl ue nza vir us a n d R S V .  
T he st u d y  als o m o dels  c o nce pts of m ore effici e nt “fle xi ble” trials i n v ol vi n g n ot o nl y v oice 
ca pt ure b ut als o  we b -base d partici pa nt recr uit me nt, e n ha nce d partici pa nt e n ga ge me nt,  a n d 
re m ote sa m ple c ollecti o n t hat c o ul d ma ke f ut ure cli nical st u dies m ore effi cie nt. T he cli nical 
data o btai ne d i n t his o bser vati o nal st u d y c o ul d pr o vi de t he d oc u me ntati o n of t he tec h n ol o g y’s 
perf or ma n ce n ee de d t o e na ble its de pl o y me nt i n f ut ure i nter ve nti o nal st u dies.  
2. 2.  B ac k gr o u n d  
2. 2. 1.  Cli nic al O ver vie w  
T he rati o nal e f or c o n d ucti n g t he st u d y is t o better u n dersta n d if t here are v oice feat ures t h at 
c orrel ate wit h a c ute res pirat or y ill ness s y m pt o ms . Ver y little w or k has bee n p u blis he d usi n g 
v oice 
as 
a n 
o bj ecti ve  assess me nt 
of 
t he 
stat us 
of 
res pirat or y 
ill ne ss1 ,2. 
T o  better  u n derst a n d  if t here are v oice feat ures t hat c orrelate wit h  ac ute res pirat or y ill ness 
s y m pt o ms, Pfizer c o n d ucte d a n i n -cli nic a n d at -h o me e x pl orat or y st u d y d uri n g t he c ol d a n d 
fl u seas o n of 2 0 1 8. V oice a n d res pirat or y ill ness s y m pt o m data w ere c ollecte d,  a n d 2 2 v oice 
feat ur es were i de ntifie d t hat differe d b et wee n sic k a n d well states a n d c orres p o n de d t o self -
re p orte d s y m pt o m c ha n g es3. T he AcRI S m o bile a p p is a s oft war e-bas e d s yste m ( m o bile p h o ne 
a p p pl us cl o u d -base d tra nsfer a n d st ora ge) use d t o rec or d dail y partici pa nt re p orte d s y m pt o ms 
of ac ute res pir at or y tract ill ness as well as brief a u di o rec or di n gs (scri pte d s peec h a n d 
p h o ne mes) self -ca pt ure d b y partici pa nts. T h e electr o nic diar y offers a n i n n o vati ve a p pr oac h t o 
detect a n d m o nit or s y m pt o ms of res pirat or y tract ill ness i n a n  o ut of cli nic setti n g.  
2. 3.  Be nefit/ Ris k Assess m e nt  
•  We d o n ot a ntici p ate a n y o b vi o us ris ks fr o m p artici pati n g i n t his st u d y. T he nasal s wa b 
dia g n ostic pr oce d ure is st a n dar d of care, h o we v er, t here is t he p ossi bilit y of disc o mf ort 
wit h t his pr oce d ure.  

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 1 9   
T he be nefits of t his st u d y i ncl u de de vel o p me nt of easil y accessi ble t o ols t hat ca n be utilize d t o 
d etect a n d m o nit or  res pir at or y ill nesses. 
3.  R E S E A R C H Q U E S TI O N S, O B J E C TI V E S A N D E N D P OI N T S  
O bjecti ves  
E n d p oi nts  
Pri m ar y O bjecti ve(s):  
Pri m ar y E n d p oi nt(s):  
● O btai n data t o c haract eri ze t he 
relati o ns hi p bet wee n s y m pt o ms a n d 
v oice feat ures f or partici pa nts wit h ac ute 
viral res pirat or y ill ness. T his data will be 
use d as t he basis t o b uil d v oice a n d 
s y m pt o m al g orit h m(s) f or detecti o n a n d 
m o nit ori n g of t hese ill nes ses. 
 
 
● C ha n ge i n self -re p orte d s y m pt o m 
sc ores i n t he Electr o nic diar y fr o m well 
t o sic k i n s y m pt o matic partici pa nts wit h 
R T -P C R c o nfir me d S A R S -C o V -2, 
i nfl ue nza vir us, or  R S V.  
● C ha n ge i n v oice feat ures s uc h as pitc h, 
jitter, har m o nicit y, e ntr o p y, flat ness, 
s hi m mer fr o m t he v oice c ollecti o n as 
ca pt ure d b y t he Electr o ni c diar y fr o m 
well t o sic k i n s y m pt o matic partici pa nts 
wit h R T -P C R c o nfir me d S A R S -C o V -2, 
i nfl ue nza vir us, or R S V.  
 
Sec o n d ar y O bjecti ve(s):  
Sec o n d ar y E n d p oi nt(s):  
•  Assess c o m plia nce of t he partici pa nts 
usi n g t he  Electr o nic diar y t o c ollect 
data.  
•  Perce nta ge of t otal da ys of s y m pt o ms 
e ntere d i n t he Electr o nic diar y.  
•  Perce nta ge of t otal da ys of v oice 
rec or di n gs e nt ere d i n t he Electr o nic 
diar y.  
 
•  Test t he q ualit y of t he rec or di n g fr o m 
t he Electr o nic diar y t o c ollect data t hat is 
usa ble f or i nter pretati o n.   
•  Perce nta ge of rec or di n gs wit h si g nal t o 
n oise rati o  ≥ 2 0  d B t hat ha ve d urati o n  ≥ 
3  sec f or p h o n e me a n d ≥ 1 0 sec f or 
rea di n g tas ks.  
 
•  Deter mi ne rates of p ositi vit y f or S A R S -
C o V -2/ i nfl ue nza vir us / R S V i nfecti o n.  
•  Perce nta ge of partici pa nts wit h S A R S -
C o V -2; a n d/ or i nfl ue nza vir us ; a n d/ or 
R S V R T -P C R base d p ositi vit y i n self -
s wa bs.  
 
•  E val uate t he feasi bilit y of o btai ni n g  self-
s wa bs. 
•  Perce nta ge  of partici pa nts a d mi nisteri n g 
t he self-s wa b at self-s w a b # 1  a n d self-
s wa b # 2.    

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 2 0   
•  Perce nta ge of partici pa nts re p orti n g 
s y m pt o ms i n t he Electr o nic diar y, w h o 
ha ve a self -s wa b c ollecte d at or ar o u n d 
s y m pt o m o nset.  
•  Perce nta ge of self -s wa bs wit h vali d 
( p ositi ve or ne gati ve) or i n vali d ( n o n- 
re porta ble d ue t o tec h nical or self -
c ollecti o n fail ures) res ults.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
S afet y O bjecti v e(s):  
S afet y E n d p oi nt(s):  
C CI

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 2 1   
● T o descri be t he s afet y pr ofile of self -
a d mi nistere d nasal s w a bs f or S A R S -
C o V -2/ i nfl ue nza vir us / R S V R T-P C R 
a m o n g partici pa nts.  
● I n ci de nce a n d se v erit y of a d verse 
e ve nts ( A Es)/researc h  rel ate d i nj uries 
( R RIs) a m o n g all e nr olle d partici pa nts. 
 
3. 1.  V ari a bles   
V ari a ble  
R ole  
D at a s o urce(s)  
O per ati o n al 
defi niti o n  
De m o gra p hics  
Baseli ne 
c haracteristic  
Electr o nic diar y  
Self -re p ort e d 
q uesti o n naire  
E nr oll me nt Q uesti o n nair e  
(i ncl u des self-re p orte d 
me dical  hist or y)  
Baseli ne 
c haracteristic  
Electr o nic diar y  
Self -re p ort e d 
q uesti o n naire  
Self -s wa b 1 test r es ult 
stat us at st u d y be gi n ni n g 
Baseli ne 
c haracteristic  
C o va nce  
Dia g n ostic test  
C ha n ge i n self -re p orte d 
s y m pt o m sc ores i n t he 
Electr o nic diar y fr o m well 
t o sic k, i n s y m pt o matic 
partici pa nts wit h R T -P C R  
c o nfir me d S A R S -C o V -2, 
i nfl ue nza vir us, or  R S V   
Pri mar y 
o utc o me 
e n d p oi nt  
Electr o nic diar y  
 
Details pr o vi de d i n 
t he S A P 
C ha n ge i n 
v oice  feat ures s uc h as 
pitc h, jitter, har m o nicit y, 
e ntr o p y, flat ness,  s hi m mer 
fr o m t he v oice c ollecti o n i n 
t he Electr o nic diar y fr om 
well t o sic k i n s y m pt o matic 
partici pa nts wit h R T -P C R 
c o nfir me d S A R S -C o V -2, 
i nfl ue nza vir us, or  R S V  
Pri mar y 
o utc o me 
e n d p oi nt  
Electr o nic diar y  
 
Details pr o vi de d i n 
t he S A P 
Perce nta g e of t otal da ys of 
s y m pt o ms e ntere d i n t he 
Electr o nic diar y  
Sec o n dar y 
o utc o me 
e n d p oi nt  
Electr o nic diar y  
Details pr o vi de d i n 
t he S A P 
Perce nta g e of t otal da ys of 
v oice rec or di n gs e ntere d i n 
t he Electr o nic diar y 
Sec o n dar y 
o utc o me 
e n d p oi nt  
Electr o nic  diar y  
Details pr o vi de d i n 
t he S A P 
Perce nta g e of rec or di n gs 
wit h si g nal t o n oise rati o  ≥ 
2 0  d B t hat ha ve d urati o n  ≥ 
3  sec f or p h o n e me a n d ≥ 1 0 
sec f or rea di n g tas ks 
Sec o n dar y 
o utc o me 
e n d p oi nt  
Electr o nic diar y  
Details pr o vi de d i n 
t he S A P 

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 2 2   
V ari a ble  
R ole  
D at a s o urce(s)  
O per ati o n al 
defi niti o n  
Perce nta g e of partici pa nts 
wit h S A R S -C o V -2 a n d/ or 
i nfl ue nza vir us  a n d/ or R S V  
R T -P C R base d p ositi vit y i n 
self-s wa bs  
Sec o n dar y 
o utc o me 
e n d p oi nt  
C o va nce  
Details pr o vi de d i n 
t he S A P 
Perce nta g e  of partici pa nts 
a d mi nisteri n g t he self-
s wa b at self-
s wa b # 1  a n d self-s wa b # 2  
Sec o n dar y 
o utc o me 
e n d p oi nt  
Electr o nic diar y  
Details pr o vi de d i n 
t he S A P 
Perce nta g e of partici pa nts 
re p orti n g s y m pt o ms i n t he 
Electr o nic diar y, w h o ha ve 
a self-s w a b c ollect e d at or 
ar o u n d s y m pt o m o nset  
Sec o n dar y 
o utc o me 
e n d p oi nt  
Electr o nic diar y  
Details pr o vi de d i n 
t he S A P 
Perce nta g e of self -s wa bs 
wit h vali d ( p ositi ve or 
ne gati ve) or i n v ali d ( n o n - 
re p orta ble d u e t o tec h nic al 
fail ures) res ults 
Sec o n dar y 
o utc o me 
e n d p oi nt  
C o va nce  
Details pr o vi de d i n 
t he S A P 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C CI

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 2 3   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I n ci de nce a n d se v erit y of 
a d verse e ve nts 
( A Es)/res earc h rel ate d 
i nj uries ( R RIs) a m o n g all 
e nr olle d partici pa nts  
Safet y o utc o me 
e n d p oi nt  
C R F  
Details pr o vi de d i n 
t he S A P 
Deat h details  
Safet y o utc o me 
e n d p oi nt  
C R F  
Details pr o vi de d i n 
t he S A P 
 
4.  S T U D Y D E SI G N  
4. 1.  O ver all Desi g n  
T his is a l o w -i nter ve nti o nal, o bser vati o nal st u d y wit h pla n ne d e nr oll me nt of a p pr o xi matel y 
8 7 0 0  partici pa nts 1 8 y ears of a g e or ol der i n or der t o c ollect a t otal N = 1 0 0 partici pa nts wit h 
( 1) R T -P C R c o nfir me d ne gati ve S A R S -C o V -2,  i nfl ue nza vir us a n d R S V (s wa b # 1) a n d ( 2) 
R T -P C R  c o nfir me d p ositi ve S A R S -C o V -2 ,  i nfl ue nza vir us a n d R S V (s wa b # 2 or a n y 
s u bse q ue nt s wa b) s y m pt o matic c o m pleters.  
Eac h s u bject will be re q uire d t o sta y i n t he st u d y f or 6 wee ks. If t he partici pa nt tests p ositi ve 
f or a n y of t he t hree vir us es at s wa b # 1 or s wa b # 2, t he y will c o nti n ue t he st u d y u ntil t he e n d of 
Wee k 8.  
Partici pa nts will rec or d ac ute res pir at or y ill ness  s y m pt o ms a n d v oice data dail y f or u p t o a 
ma xi m u m of 8  wee ks i n b ot h t he w ell state a n d, s h o ul d t he y bec o me ill,  t he sic k state, utilizi n g 
t he Electr o nic diar y o n t heir M o bile a p plicati o n.  O nce e nr olle d, t he partici pa nt will start 
rec or di n g s y m pt o ms a n d v oice i n t he Electr o nic diar y, wit h dail y ti me c o m mit me nt t o t his 
C CI

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 2 4   
p orti o n of t he st u d y  e x pecte d t o be 2 -4 mi n utes. T w o nasa l s elf-s wa b c oll ecti o n kits will be 
or dere d f or deli ver y t o t h e partici pa nt o nce t he y are e nr olle d i n t he st u d y. T he partici pa nt will 
be as ke d t o self -s wa b w h e n t he test kit arri ves (s wa b # 1). T he kit, i ncl u di n g t he s peci me n, will 
be ret ur n e d t o t he ce ntra l la b f or R T-P C R S A R S -C o V 2/ i nfl ue nza vir us / R S V R T-P C R testi n g.  
T he  partici pa nt  is e x pect e d t o c o m plete 3 p h o ne m es a n d 5 li nes of rea di n g eac h d a y, i n a d diti o n 
t o sc ore t he s elf-re p orte d s y m pt o ms i n t he Electr o nic diar y. If p artici pa nts bec o me si c k  (self-
re p ort) wit h ne w or i ncrease d  s y m pt o ms of res pirat or y ill ness , t he y will be  as ke d t o self -s wa b 
(s wa b # 2) a n d ret ur n t h e sa m ple f or ce ntral S A R S-C o V -2/ i nfl ue nza vir us / R S V R T-P C R 
testi n g. If t h e partici pa nt d oes n ot de vel o p a n y n e w or i ncrease d s y m pt o ms bet wee n s w a b # 1 
a n d e n d of Wee k 6 , t he y will o btai n a self-s wa b (s wa b # 2) at D a y 4 2 . 
If t he partici pa nt tests p ositi ve f or a n y of t he t hree vir uses at s wa b # 1 or s wa b # 2, t he y will 
c o nti n ue t he st u d y u ntil e n d of wee k 8 . If t he y test ne gati ve f or t he t hree vir uses at s wa b # 1 
a n d s wa b # 2, t he y will e xit t he st u d y at a p pr o xi matel y t he e n d of wee k 6  w he n t he test res ults 
are ret ur ne d. T h e r es ults of t he R T -P C R testi n g will be s hare d wit h partici p a nts.  
De m o gra p hic, me dical h ist or y, a n d s m o ki n g stat us data will be c ollecte d. At t he e n d of t h e 
st u d y, v oice a n d s y m pt o m traject ories will be a nal yze d t o u n d ersta n d t he S A R S -C o V -
2 /i nfl ue nza vir us / R S V res pirat or y diseas e traj ect ories.  A nal ysis of c ha n g es i n s y m pt o ms a n d 
v oice c haracteristics will be stratifie d b y S A R S -C o V -2/ i nfl ue nza vir us / R S V test res ults. T he 
st u d y desi g n p urel y c o nt e m plates ca pt ure of s y m pt o ms a n d v oici n g b y a researc h s u bject. It 
d oes n ot i n v ol ve i n a n y res pect t he assess me nt, e xa mi nati o n, dia g n osis, pr o g n osticat i o n or 
treat me nt of a n y st u d y partici pa nt. 
4. 2.  Scie ntific R ati o n ale f or St u d y Desi g n  
T his is a l o w -i nter ve nti o nal st u d y desi g n l o o ki n g at c ollecti n g  v oice a n d res pirat or y s y m pt o ms  
data i n partici pa nts  w h o bec o me i nfect e d wit h S A R S -C o V -2 /i nfl ue nza vir us / R S V. T he 
rati o nale be hi n d t he desi g n is t o c haracterize t he relati o ns hi p bet wee n s y m pt o ms a n d v oice 
feat ur es f or partici pa nts wit h ac ute viral res pir at or y ill nesses as t he y pr o gress fr o m well t o sic k 
states. T his data will be use d as t h e basis t o b uil d v oice a n d s y m pt o m al g orit h m(s) f or detecti o n 
a n d 
m o nit ori n g of t hese ill nesses. F urt her m ore,  t he st u d y is c o m pletel y re m ote a n d 
dece ntr alize d all o wi n g fl e xi bilit y a n d less b ur de n t o partici pa nts.  
4. 2. 1.  Li mit ati o ns of t he St u d y Desi g n a n d Met h o ds  
O ne li mitati o n of t his s t u d y’s met h o ds is its de pe n de nce o n partici pa nts’ rec or di n g v oice a n d 
s y m pt o ms i n t heir Electr o nic diar y a n d c ollecti n g nasal self-s w a bs if t he y d e vel o p a n y ne w or 
i ncreas e d s y m pt o ms. Dail y re mi n ders t o t he partici pa nt via t he Electr o nic diar y will als o ser ve 
t o rei nf orce a n d re mi n d partici pa nts of t he nee d t o c o m plete t he tas ks. Dat a e ntr y will be cl osel y 
m o nit ore d, st u d y pers o n nel will f oll o w u p wit h t he partici pa nts if n o nc o m plia nce is n ote d 
des pite iss ua nce of a ut o mate d re mi n ders.  As  t his st u d y is n ot pr o visi o ni n g de vices , an ot her  
li mitati o n w o ul d be if t he partici pa nt fails t o c o n nect t heir de vice t o t he cl o u d. 
4. 2. 2.  P artici p a nt I n p ut I nt o Desi g n  
N ot A p plica ble  

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 2 5   
4. 3.  J ustific ati o n f or D ose  
N ot a p plica ble  
4. 4.  E n d of St u d y Defi niti o n  
A partici p a nt is c o nsi dere d t o  h a ve c o m plete d t h e st u d y if h e/s he h as c o m plete d all p h ases of 
t he st u d y, i ncl u di n g t he last sc he d ule d pr o ce d ure s h o w n i n t he S o A . 
T he e n d of t he st u d y is d efi ne d as t h e date of t he last sc he d ule d pr oce d ure s h o w n i n t he S o A  
f or t he last partici p a nt i n t he trial gl o ball y. 
T he partici p a nt is re q uir e d t o c o m plete t h e E n d of St u d y Q uesti o n naire as 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 oll e d.  T he f oll o wi n g 
eli gi bilit y criteria are d esi g ne d t o select partici p a 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 priat e.   
Pr os pecti ve a p pr o val of pr ot oc ol d e 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 x e m pti o ns, is n ot per mitte d.  
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:  
1.  Male or fe m al e partici pa nts ≥1 8 years of a ge ( or t he  state’s mi ni m u m specific a ge of 
c o nse nt if > 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 acteristi cs:  
2.  Partici pa nts w h o are willi n g a n d a ble t o c o m pl y wit h dail y s y m pt o m a n d v oice 
assess me nts  o n t he electr o nic diar y a p plicati o n  a n d ot her st u d y pr oce d ures, i ncl u di n g 
self-c ollecti o n of n asal s wa bs.  
3.  E x pecte d t o be a vaila ble f or t he d urati o n of t h e st u d y.  
I nf or me d C o nse nt: 
4.  Ca pa ble of gi vi n g si g ne d i nf or me d c o nse nt as d es cri be d i n A p pe n di x 1 . 
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:  

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 2 6   
1.  Partici pa nts w h o self -re p ort a n y me dical c o n diti o n, recreati o nal s u bsta n ce use, or 
me dicati o n use w hic h w o ul d pre ve nt t he m fr o m c o m pleti n g st u d y tas ks or i m pair t he 
pr o vi di n g of i nf or me d c o nse nt , or i n t he i n vesti gat or’s j u d g me nt, ma ke t he partici pa nt 
i na p pr o priate f or t he st u d y.  
Pri or/ C o nc o mit a nt T her a p y:   
2.  Partici pa nts w h o ha ve b ee n v acci nate d wit h C O VI D -1 9 vacci ne  or are pla n ni n g t o get  
vacci nat e d d uri n g st u d y partici pati o n.  
Partici pa nts ca n c o nti n ue t o use all ot her pres cri pti o n or n o n -pres cri pti o n me dicati o ns . 
Pri or/ C o nc urre nt Cli nic al St u d y E x perie nce:  
3.  Pr evi o us vacci nati o n wit h a n y lice nse d or i n vesti gati o nal R S V vacci ne or are pla n ni n g 
t o get vacci nate d d uri n g st u d y partici pati o n.  
4.  Pre vi o us a d mi nistrati o n wit h a n i n vesti gati o nal dr u g wit hi n 3 0  da ys of e nr oll me nt ( or 
as deter mi ne d b y t he l oc al re q uire me nt) or pla n ni n g t o partici pate i n a n i nter ve nti o nal 
trial d uri n g st u d y c o n d uct. 
Di a g n ostic Assess m e nts:  
5.   S cree ni n g dia g n ostic ass ess me nts are  n ot  re q uire d f or eli gi bilit y p ur p oses.  
Ot her E xcl usi o ns:  
6.  I n v esti gat or site staff or Pfizer e m pl o yees directl y i n v ol ve d i n t he c o n d uct of t he st u d y, 
site staff ot her wise s u per vise d b y t he i n vesti gat or i ncl u di n g ve n d ors, a n d t heir 
res pecti ve fa mil y me m bers. 
7.  Partici pa nts w h o us e a m o bile de vice t hat d o es n ot meet t he mi ni m u m re q uire me nts of 
t he Electr o nic diar y. 
8.  Part ici pa nts w h o ha ve pre vi o usl y bee n e nr olle d i n t he st u d y ca n n ot be re-e nr olle d. 
5. 3.  Lifest yle C o nsi der ati o ns  
N o restricti o ns are re q uir e d d uri n g t he c o urse of st u d y partici pati o n.  
5. 4.  Scree n F ail ures  
Scree n fail ures are defi n e d as partici pa nts w h o c o nse nt t o parti ci pate i n t he cli nical st u d y b ut 
are n ot s u bse q u e ntl y e nr olle d i n t he st u d y .   
Scree n fail ure dat a are c ollecte d a n d re p orte d t o t h e cli nical data b ase . 
I n di vi d uals w h o d o n ot meet t he criteri a f or p arti ci pati o n i n t his st u d y (scree n fail ure) ma y  b e 
rescreene d.   

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 2 7   
5. 5.  Criteri a f or Te m p or aril y Del a yi n g E nr oll me nt . 
T he f oll o wi n g c o n diti o ns ma y all o w a partici pa nt t o be e nr olle d o nce t he c o n diti o ns re n deri n g 
t he partici pa nt i neli gi ble ha ve res ol v e d a n d t he partici pa nt bec o mes eli gi ble: 
•  Ac q uire a n a p pr o priate m o bile de vice  
•  Bec o me eli gi ble base d o n a ge  
•  N o l o n ger self-re p orti n g me dical c o n diti o ns pre ve nti n g fr o m e nr oll me nt .  
6.  S T U D Y I N T E R V E N TI O N S  
I n t his st u d y, t here are n o t hera p e utic st u d y i nter ve nti o ns, h o we ver t he st u d y d oes i n v ol ve 
pr ot oc ol -re q uir e d dia g n ostic or 
m o nit ori n g pr oce d ures (st u d y i nter ve nti o ns) t hat are 
c o nsi dere d t o be l o w ris k or b ur de n t o t he st u d y partici pa nt; s pecificall y:  
•  Nas al S wa b T esti n g  
•  Electr o nic Diar y V oice  a n d S y m pt o ms  E ntr y . 
6. 1.  St u d y I nter ve nti o n(s)  
6. 1. 1.  Perf or m a nce of Di a g n ostic St u d y I nter ve nti o ns  
Partici pa nts will be re q uire d t o a d mi nister t w o n as al s wa b tests f or cli nical dia g n ostic p ur p oses  
d uri n g t he d urati o n of t he st u d y.  
T w o nasal s wa b sa m ples will be self -c ollecte d b y t he s u bject at h o me usi n g a nas al s wa b t hat 
is st ore d i n U T M me dia . T he first s wa b c ollecti o n is re q uire d as s o o n as t he partici pa nt recei ves 
t he kits. T he sec o n d s wa b c ollecti o n is re q uire d eit her if t he s u bject self-re p orts ne w or 
i ncreas e d s y m pt o ms or at e n d of wee k 6  if t he y ha ve re mai ne d as y m pt o matic 
T he R T -P C R  sa m ples will be use d o nl y f or scie ntific res earc h. E ac h s a m ple will be la belle d 
wit h a c o de s o t hat t he la b orat or y pers o n nel testi n g t he sa m ples will n ot k n o w t he partici pa nt ’s 
i de ntit y. Sa m ples t hat re mai n after perf or mi n g assa ys o utli ne d i n t he pr ot oc ol ma y be st or e d 
b y Pfizer. U nless a ti me li mitati o n is re q uire d b y l ocal re g ulati o ns or et hical re q uire me nts, t he 
sa m ples will be st ore d f or u p t o 1 5 years after t he e n d of t he st u d y a n d t he n destr o ye d. If 
all o we d b y t he I C D, st ore d sa m ples ma y be use d f or a d diti o nal testi n g t o bett er u n dersta n d t he 
i m m u ne res p o nses t o t he vacci ne(s) u n d er st u d y i n t his pr ot oc ol, t o i nf or m t he de vel o p me nt of 
ot her pr o d ucts, a n d/ or f or vacci ne -relate d assa y w or k s u p p orti n g vacci ne pr o gra ms. N o testi n g 
of t he partici pa nt ’s g e netic material will be perf or me d.  
T he partici pa nt ma y re q uest t hat his or her sa m ples, if still i de ntifia ble, be destr o ye d at a n y 
ti me; h o wever, a n y data alrea d y c ollecte d fr o m t h ose sa m ples will still be use d f or t his 
researc h. T he bi ol o gical sa m ples 
ma y be s h are d 
wit h ot h er researc hers as l o n g as 
c o nfi de ntialit y is mai ntai ne d a n d n o testi n g of t he partici pa nt ’s ge n etic mat erial is perf or me d. 
 

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 2 8   
T he partici pa nt will be n otifie d of  t heir res ults f or s wa b # 1 a n d # 2 . If t he y were t o ha ve a n y 
q uesti o ns after recei vi n g t heir res ults, a c o ntact n u m ber will be ma de a vaila ble t o t he m s o t he y 
ca n c o nta ct t he i n vesti gat or or desi g nate d st u d y me m ber t o a ns wer a n y q uesti o ns t hat t he 
partici pa nt mi g ht ha ve.   
Electr o nic Diar y V oice a n d S y m pt o ms E ntr y : 
Partici pa nts will perf or m t heir v oice a n d s y m pt o m tas ks o nce a da y. I nstr ucti o ns a n d trai ni n g 
i n t he Electr o nic diar y will g ui de t he partici pa nts o n h o w a n d w hen t o c o m plete t hese tas ks. 
T he partici pa nt will be e x pecte d t o rec or d t heir dail y v oice a n d s y m pt o ms u ntil t he y fi nis h t he 
partici pati o n i n t he st u d y.  
6. 1. 2.  Me dic al De vic es  
N ot A p plica bl e  
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  
I nstr u cti o ns f or t he c ollecti o n, ha n dli n g, st ora g e, a n d s hi p me nt of bi ol o gical sa m ples will b e 
pr o vi de d i n t he h o me c ollecti o n kit pr o vi de d b y t he s p o ns or.  Sa m ples will be a nal yze d usi n g 
t he e mer g e nc y us e a ut h orize d ( E U A)
 S A R S-C o V -2/ Fl u/ R S V m ulti ple x 
res pirat or y R T-P C R assa y f or detecti o n of t he prese nce or a bse n ce of S A R S -C o V 2 / i nfl ue nza 
vir us  A a n d B/ R S V i nfecti o n. T he assa y will be vali date d at a C LI A accre dite d ce ntral 
la b orat or y. Sa m ples m ust be c ollecte d a n d s hi p pe d as i n dicate d t o mai ntai n sa m ple i nte grit y.  
A n y de viati o n fr o m t he h a n di n g i nstr ucti o ns s h o ul d be re p ort e d t o t he s p o ns or.  
6. 2. 1.   Pre p ar ati o n a n d Dis pe nsi n g  
•  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 n al c o ntai ners.  
•  Site staff 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. 
•  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 d y i nter ve nti o n acc o u nt a bilit y, rec o nciliati o n, a n d rec or d 
mai nte na nce  of  all st u d y i nter ve nti o ns t o be acc o u nte d f or usi n g a st u d y i nter ve nti o n 
acc o u nta bilit y f or m/rec or d.  All st u d y i nter ve nti o n  t hat is ta ke n h o m e b y t he p artici pa nt, 
b ot h use d a n d u n use d, m ust be ret ur ne d t o t he i n vesti gat or or desi g nee  b y t he 
partici pa nt.  Ret ur ne d st u d y i nter ve nti o n m ust n ot be re-dis pe ns e d t o t he partici pa nts.  
6. 3.  Met h o ds t o Mi ni mize Bi as  
6. 3. 1.  All oc ati o n t o St u d y I nter ve nti o n  
All e nr olle d partici pa nts will be assi g ne d t o t h e sa me st u d y ar m.   T his is  a l o w i nter ve nti o nal 
st u d y all partici pa nts will recei ve t he sa me e mer ge nc y use a ut h orize d ( E U A) 
 
 S A R S -C o V -2/ Fl u/ R S V m ulti ple x res pirat or y R T -P C R assa y . 
  
C CI
C CI

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 2 9   
7.  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 F R O M S T U D Y  
7. 1.  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 n y 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 h er f oll o w -u p;  
•  L ost t o f oll o w -u p;  
•  Deat h;  
•  St u d y ter mi nate d b y s p o ns or;  
If a p artici pa nt wit h dra ws fr o m t he st u d y, he/s he ma y re q uest destr u cti 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 p artici 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 discl os ure of f ut ure 
i nf or mati o n (see Secti o n 7. 1. 1 ), n o f urt her e val uati o ns s h oul d be perf or me d,  a n d n o a d diti o nal 
data s h o ul d b e c ollecte d.  T he s p o ns or ma y retai n a n d c o nti n ue t o us e a n y data c ollect e 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 h e pr ot o c ol -re q uir e d wit h dra wal/earl y ter mi nati o n 
pr oce d ure s will n ot be vi e we d as pr ot oc ol d e viati o ns s o l o n g as t he p artici pa nt’s safet y was 
preser ve d.  
7. 1. 1.  Wit h dr a w al of C o nse nt  
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 d ecisi o n t o wit h dra w c o ns e nt f or 
f ut ure f oll o w-u p, w he ne v er p ossi ble.  T he w it 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 site st u d y rec or ds b y t he i n vesti gat or, as t o w het her t he wit h dr a wal was fr o m st u d y 
pr oce d ures a n d/ or st u d y f oll o w -u p, a n d t his i nf or mati o n s h o ul d be 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 v aila ble i nf or mati o n s h o ul d be use d t o deter mi ne vit al stat us o nl y i n a 
ma n ner t hat is i n acc or da nce wit h l ocal la w.  
7. 2.  L ost t o F oll o w -u p  
A partici pa nt will be c o nsi dere d l ost t o f oll o w -u p if he or s h e fails t o ret ur n t he 2 s wa bs after 
a p pr o xi matel y at t he e n d of wee k 6 . T h e f oll o wi n g acti o ns m ust be ta ke n:  
•  T he i n vesti gat or or d esi g nate d st u d y me m b er will atte m pt t o c o ntact t he partici pa nt t o 
as k t he p artici pa nt t o ret ur n t he u n us e d s w a bs. S h o ul d t he partici pa nt be u nreac h a ble 
or n ot res p o n d t o c o nta ct, 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.  
•  If t he partici pa nt ca n n ot be c o ntact e d or ref uses t o ret ur n t he s w a bs, a re p ort will be 
file d i n t he C S R t o acc o u nt f or t he u nret ur n e d s wa bs  

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 3 0   
A partici pa nt will be c o nsi dere d l ost t o f oll o w -u p if he or s h e re p eate dl y fails t o c o m pl y wit h 
st u d y acti vities or is u na ble t o be c o ntacte d b y 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 part ici pa nt fails t o c o m plete electr o nic diar y e ntries 
f or 3 c o nsec uti ve da ys: 
•  T he site m ust atte m pt t o c o ntact t he partici pa nt a n d ascert ai n w het her or n ot t he 
partici pa nt wis hes t o a n d/ or 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 o ll o w u p, t he i n vesti gat or or desi g n ee m ust ma ke e v er y eff ort t o 
re gai n c o ntact wit h t he p artici pa nt ( w here p ossi bl e, 3 tele p h o ne calls a n d, if 
necessar y, a certifie d lett er 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 h ese  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 site st u d y 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.  
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 pri ate 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 p erf or mi n g a n y pr ot oc ol -re q uir e d pr oce d ure.   
Pr ot oc ol -re q uire d 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.  
Safet y iss ues relate d t o pr ot oc ol -re q uir e d pr oce d ures s h o ul d b e 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 w het her t he partici pa nt s h o ul d 
c o nti n ue or disc o nti n ue fr o m t he st u d y.  
A d here n ce t o t h e st u d y d esi g n re q uir e me nts, i ncl u di n g t h ose s pecifie d i n t h e S o A , is esse ntial 
a n d re q uir e 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 h e 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. 
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 oced ures (st u d y 
i nter ve nti o ns) are c o m plete d as descri be d.  H o we ver, it is a ntici pate d t hat 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 i nfeasi ble t o perf or m t he 
test.  I n t hese cases, t he i n vesti gat or m ust ta ke all steps necessar y t o e ns ure t he safet y 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 m e d, t he 
i n vesti gat or will d oc 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 v e nti ve 
acti o ns t hat he or s h e has ta ke n t o e ns u re t hat re q uire d pr ocesses are a d h ere 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.  

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 3 1   
F or s a m ples bei n g c ollect e d a n d s hi p pe d, detaile d c ollecti o n, pr ocessi n g, st or a ge, a n d s hi p me nt 
i nstr ucti o ns a n d c o nta ct i nf or mati o n will be pr o vi de d t o t he i n vesti gat or site pri or t o i nitiati o n 
of t he st u d y.  
8. 1.  Effic ac y Assess m e nts  
8. 1. 1.  Electr o nic Di ar y S y m pt o ms a n d V oice A ssess me nts: 
P artici pa nts will perf or m t heir v oice a n d s y m pt o m tas ks o nce a da y. I nstr ucti o ns a n d trai ni n g 
i n t he Electr o nic diar y will g ui de t he partici pa nts o n h o w a n d w he n t o c o m plete t hese tas ks. 
T he partici pa nt will be e x pecte d t o rec or d t heir dail y v oice a n d s y m pt o ms u ntil t he y fi nis h t he 
partici pati o n i n t he st u d y.  
T he f oll o wi n g v oice a n d s y m pt o m assess me nts will be e ntere d dail y b y t h e partici pa nt i n t he 
Electr o nic diar y:  
D ail y S y m pt o ms : Fe ver, c o u g h,  s h ort ness of breat h or diffic ult y breat hi n g , fati g ue, nasal 
co n gesti o n, r u n n y n ose, s ore t hr oat, l oss of taste or s mell, c hills, m uscle pai n, diarr hea, 
v o miti n g, hea dac he, n a usea, ri g ors , w heezi n g. I n a d diti o n, t he partici pa nt will rate eac h of 
t he s y m pt o ms fr o m N o ne, Ver y Mil d, Mil d, M o derate, Se vere. T he d efi niti ons of t he 
s y m pt o ms a n d rati n g se verit y are pr o vi de d i n t he Electr o nic diar y. F or fe v er , t he defi niti o n 
bel o w  will be f oll o we d:   
o  N o ne: less t ha n 3 8. 0° C or 1 0 0. 4° F  
o  Mil d ( Gra de 1) ≥3 8. 0° C t o 3 8. 4° C or 1 0 0. 4° F t o 1 0 1. 1° F  
o  M o derate ( Gra d e 2) > 3 8. 4° C t o 3 8. 9° C or 1 0 1. 2° F t o 1 0 2. 0° F  
o  Se vere ( Gra d e 3) > 3 8. 9° C t o 4 0. 0° C or 1 0 2. 1° F t o 1 0 4. 0° F  
o  Gra de 4 > 4 0. 0° C or > 1 0 4. 0° F  
o  Te m perat ur e n ot ta ke n.  
 
D ail y V oice Assess m e nts:  2 p h o ne m es: ‘eee ’ a n d ‘ m m m’ f or 4 sec o n ds ( mi ni m u m 3 sec o n ds), 
1 p h o ne me: “ah h ” s ustai ne d (as l o n g as p ossi ble)  a n d a 5 -se nte nce rea di n g passa ge: “ W he n 
t he s u nli g ht stri kes rai n dr o ps i n t he air, t he y act as a pris m a n d f or m a rai n b o w. T he rai n b o w 
is a di visi o n of w hite li g ht i nt o ma n y bea utif ul c ol ors. T hese ta ke t he s ha pe of a l o n g r o u n d 
arc h, wit h its pat h hi g h a b o ve, a n d its t w o e n ds a p pare ntl y be y o n d t he h oriz o n. T here is, 
acc or di n g t o le g e n d, a b oili n g p ot of g ol d at o ne e n d. Pe o ple l o o k, b ut n o o ne e ver fi n ds it. 
W he n a ma n l o o ks f or s o met hi n g be y o n d his reac h, his frie n ds sa y he is l o o ki n g f or t he p ot of 
g ol d at t he e n d of t he rai n b o w”.  
8. 1. 2.  N as al Self -s w a b  
Partici pa nts will nee d t o c o m plete t w o nasal self -s wa bs. 

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 3 2   
C ollecti o n of Self -s w a b # 1 
Partici pa nts will nee d t o per f or m Self-s w a b # 1 as s o o n as p ossi ble, o nce t he y recei ve t he 
h o me c ollecti o n kit.  
T he c ollecti o n of Self -s w a b # 2 mi g ht occ ur at 2  differe nt p oi nts i n t he st u dy:  
a)  If partici pa nt de v el o ps n e w or i ncrease d s y m pt o ms, t he partici pa nt will perf or m 
Self -s wa b # 2 (after Self -s wa b # 1 a n d b ef ore d a y 4 2 ). Self-s wa b # 2 Criteria: A n 
ill ness i n v ol vi n g a n y 1 or m ore of t he f oll o wi n g s y m pt o ms will tri g ger self-s wa b 
c ollecti o n:  
•  Ne w or i ncreas e d fe v er  
•  Ne w or i ncreas e d c o u g h   
•  Ne w or i ncreas e d s h ort ness of breat h or diffic ult y  breat hi n g.  
•  Ne w or i ncreas e d fati g ue  
•  Ne w or i ncreas e d nasal c o n gesti o n  
•  Ne w or i ncreas e d r u n n y n ose  
•  Ne w or i ncreas e d s ore t hr oat  
•  Ne w or i ncreas e d l oss of taste or s mell  
•  Ne w or i ncreas e d c hills  
•  Ne w or i ncreas e d ri g ors  
•  Ne w or i ncreas e d m uscle pai n  
•  Ne w or i ncreas e d diarr hea  
•  Ne w or i ncreas e d v o miti n g  
•  Ne w or i ncreas e d hea d ac he  
•  Ne w or i ncreas e d na usea  
•  Ne w or i ncre as e d w heezi n g  
 
b)  If partici p a nt d oes n ot de vel o p a n y ne w or i ncreas e d s y m pt o ms, t he partici pa nt will 
be as ke d t o self-s wa b at da y 4 2 . 
Detaile d i nstr ucti o ns o n c ollecti o n, pr ocessi n g, st ora ge, a n d s hi p me nt f or t he nasal self -s wa b 
a n d c o ntact i nf or mati o n will be pr o vi de d t o t he partici pa nt.  
De pe n di n g o n t he res ults of t he self -s w a b, t he f oll o wi n g res ults will deter mi ne t he e n d of st u d y 
f or t he p artici p a nt ( p ositive a n d ne g ative refer t o all vir uses teste d): 
a)  All ne gati ve or i n v ali d res ults fr o m self -s w a b # 1 a n d # 2, t he p artici pa nt will st o p 
t he st u d y at a p pr o xi matel y t he e n d of wee k 6 . 
b)  A n y p ositi ve self -s wa bs # 1 or # 2, t he partici pa nt will c o nti n ue t he st u d y u ntil e n d 
of Wee k 8 . 
c)  If b ot h s elf-s w a bs are i n vali d t he p artici pa nt will e xit t he st u d y at a p pr o xi matel y 
t he e n d of Wee k 6 . 

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
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Pa ge 3 3   
d)  If o ne self-s wa b is ne gati ve a n d a n ot her is i n vali d, t he partici pa nt will e xit t he st u d y 
at a p pr o xi matel y t he e n d of Wee k 6 . 
8. 1. 3.  Ot her Electr o nic di ar y Acti vities  
T he f oll o wi n g acti vities are t o be c o m plete d b y t h e partici pa nt o n t he Electr o nic diar y.  
•  Pre scree ni n g q uesti o n naire 
•  C o nse nt  
•  I n cl usi o n/e xcl usi o n criteria 
•  E nr oll me nt  
•  De m o gra p hics  
•  E nter date a n d ti me self -s wa b # 1 a n d # 2 perf or m e d. 
•  C o nfir m n o healt h e ve nts occ urre d wit hi n 1 2 hrs f oll o wi n g self -s wa b # 1 a n d # 2. 
•  E nr oll me nt a n d e n d of st u d y q uesti o n naires  
T he Electr o nic di ar y will ha ve t he f oll o wi n g A E re mi n ders after a s w a b f or t he partici pa nts:  
•  Re p ort a n y healt h e ve nts occ urri n g 1 2 hrs f oll o wi n g self -s wa b # 1 a n d # 2. 
I nstr u cti o ns a n d re mi n ders o n w he n a n d h o w t o re p ort a n y healt h e ve nts will be 
gi ve n t o t he partici pa nt, as well as a c o ntact tele p h o ne n u m ber.  
T he Electr o nic di ar y will ha ve t he f oll o wi n g dail y re mi n ders f or t he partici pa nts:  
•  Re mi n d partici pa nt t o c olle ct s wa b if ne w or i ncrease d s y m pt o ms occ ur.   
•  Re mi n d t he partici pa nt t o call 9 1 1 if a n y me dical e mer ge nc y.  
•  Re mi n d t he partici pa nt t o c o m plete dail y s y m pt o m a n d v oice e ntries o n Electr o nic 
diar y.  
8. 1. 4.  R ater Q u alific ati o ns  
N ot A p plica ble  
8. 1. 5.  I m a gi n g Assess me nts  
N ot A p plica ble  
8. 2.  S afet y Assess me nts  
U nsc he d ule d cli nical la b orat or y meas ure me nts or ot her safet y ass ess me nts ma y be o btai n e 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 s afet y iss ues.  

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 3 4   
8. 2. 1.  Pr ot oc ol -R e q uire d Cli nic al S afet y L a b or at or y Assess m e nts  
Pr ot oc ol -re q uire d cli nical safet y la b orat or y assess me nts will n ot be perf or me d i n t his st u d y.  
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, S A E a n d res earc h relate d inj ur y ( R RI) ca n be f o u n d i n A p pe n di x 2 . 
T he i n vesti gat or is re q uire d t o assess w het h er a n y A E ma y be relat e d t o partici pati o n i n t he 
st u d y. All A Es (i.e., s eri o us a n d n o n -s eri o us, i ncl u di n g t h ose attri b ute d t o a pr otoc ol -re q uire d 
pr oce d ure i de ntifie d as R RI) are c ollect e d i n t he cli nical st u d y data base. S h o ul d a partici pa nt, 
i n t he i n vesti gat or’s o pi ni o n, s uffer a me dicall y i m p orta nt researc h relat e d i nj ur y ca use d b y 
t heir partici pati o n i n t he st u d y, t he desi g nate d Pfizer cli nicia n or me dical m o nit or m ust be 
n otifie d i m me diatel y b y tele p h o ne or e mail.  
A Es ma y arise fr o m s y m pt o ms or ot her c o m plai nts re p orte d t o t he I n vesti gat or 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 g ate, or t he p artici pa nt's le g all y 
a ut h orize d re prese ntati ve) or t he y ma y arise fr o m cli nical fi n di n gs of t h e I n vesti gat or or ot her 
H C Ps (cli nical si g ns, test res ults, etc.).  
T he i n vesti gat or a n d a n y q ualifie d d esi 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 that me et 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 uat e 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 v e nt 
meets t he criteria f or cl assificati 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 6. 1 ). 
D uri n g t he acti ve c ollecti o n peri o d f or safet y e ve nts (see Secti o n 8. 3. 1 ), eac h partici pa nt will 
be q uesti o ne d a b o ut t he o cc 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 Safet y t o o btai n s pecific f oll o w-u p 
inf or mati o n i n a n e x pe dit e d fas hi o n.  
8. 3. 1.  Ti m e 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  
Pr oce d ure -O bser v ati o n Ti m e T a ble:  
Pr oce d ure  
Mi ni m u m O bser vati o n Ti me f or 
Secti o n  8. 3. 1.  
Nasal self -s wa b c ollecti o n 
U p -t o 1 2 H o urs  f oll o wi n g s wa b 
 
T he ti me peri o d f or acti v el 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 p artici pa nt b e gi ns at t he ti me t h at t he n asal  self-s w a b #1 a n d # 2 are p erf or me d a n d 
e n ds 1 2 h o urs  after t hat pr oce d ure/i nter ve nti o n has c o m plete d.  
T he i n vesti gat or is re q uire d t o p erf or m a p pr o priate f oll o w -u p of eac h a d v erse e v e nt 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/ S A E or its se q uelae res ol ve or sta bilize 
at a le vel a cce pt a 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.  

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
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If t he partici pa nt wit h dra ws fr o m t h e 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 dr a w n. 
If a participa 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 NI S A E Re p ort f or m.  
Si nce t here is n o pr o d uct u n der st u d y, t here is n o p ost -st u dy acti ve re p orti n g peri o d f or t he 
S A Es t o be c o m m u nicate d t o Pfizer Safet y.   
S y m pt o ms of res pirat or y ill ness will be c ollecte d fr o m t he ti me of c o nse nti n g t o t he cli nical 
researc h t hr o u g h t h e e n d of t he st u d y dail y t hr o u g h t he Electr o nic di ar y. T his i nf ormati o n will 
n ot be re p orte d o n a n A E C R F  u nless t hat t he y occ ur wit hi n t he 1 2 hrs f oll o wi n g s wa b.   
8. 3. 1. 1.  Re p orti n g S A Es t o Pfiz er 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 p eri o d (see Secti o n 8. 3. 1 ) are 
re p orte d t o Pfizer Safet y o n t he NI S A E Re p ort f or m  im me diatel y u p o n a ware ness, as i n dicate d 
i n A p pe n di x 2 ; u n der n o circ u msta nce s h o ul d t he ti me bet wee n a ware n ess a n d re p orti n g of t he 
S A E  e xcee d 2 4 h o urs . T he i n vesti gat or will als o 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.  
Re p orta ble S A Es i ncl u de e ve nts relate d t o a n a p pr o ve d  Pf izer pr o d uct ta ke n b y t he partici pa nt 
u n der r o uti ne care, d uri n g t he ti me t he y are partici pati n g i n t he st u d y, s h o ul d s uc h e ve nts c o me 
t o t he atte nti o n of t he I n v esti gat or (i ncl u di n g a n o ver d ose or a me dicati o n err or t hat le d t o t he 
S A E). Refer t o  A p p e n di x 2  f or t he defi niti o n of a n o ver d ose or m e dicati o n err or. 
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 a p plica ble S A Es a n d n o nseri o us A Es, as descri be d i n A p pe n di x 2 , t hat are directl y 
o bser ve d a n d/ or s p o nta n e o usl y re p orte d b y t he partici pa nt  d uri n g t he acti v e c ollecti o n peri o d 
( descri be d i n Secti o n 8. 3. 1 ) will be rec or de d o n t h e A E pa ge of t he C R F.  
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 2 . 
Care will be ta ke n n ot t o i ntr o d uce bias w he n d et ecti 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 p a 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  
Afte r t h e i nitial A E/ S A E re p ort, t he i n vesti gat or is re q uir e d t o pr oacti vel y 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 he r wise e x plai ne d, or 
t he partici pa nt is l ost t o f oll o w-u p (as defi n e d i n Secti o n 7. 2 ). 

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
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I n g e neral, f oll o w-u p i nf or mati o n will i ncl u de a d escri pti o n of t he e v e nt i n s ufficie nt detail t o 
all o w f or a c o m plete m e dical assess me nt of t he cas e a n d i n de pe n de nt det er mi nati o n of p oss i ble 
ca usalit y.  A n y 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 cas e of a p artici pa nt deat h, a s u m mar y of a vaila bl e 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 u rt 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 2 . 
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 p artici 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 l e 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 g e ncies a b o ut 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.  T he 
s p o ns or will c o m pl y wit h c o u ntr y -s p ecific re g ul at or y re q uir e me nts relati n g t o safet y re p orti n g 
t o t he re g ulat or y a ut h orit y, I R Bs/ E Cs, a n d i n vesti gat ors. 
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 E n vir o n m e nt al E x p os ure  
T he re q uire me nts f or re p orti n g pre g na nc y or breastfee di n g a n d e n vir o n me ntal e x p os ure a p pl y 
t hr o u g h o ut t he e ntire acti ve c ollecti o n peri o d a n d are o utli ne d bel o w; w he n s uc h re p orts are 
re q uire d per prot oc ol, t he re p ort m ust be tra ns mitte d t o Pfizer Safet y wit hi n 2 4 h o 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 p artici pa nt is f o u n d t o be pre g na nt w hile ta ki n g a n y Pfizer pr o d uct u n der 
r o uti ne care, at a n y ti me d uri n g t he st u d y peri o d (e. g., a c o n c o mita nt me dicati o n t hat is 
n ot re q uire d b y t he st u d y pr ot oc ol); or,  
•  A male partici pa nt uses a n y Pfizer pr o d uct u n der r o uti ne care d uri n g t he st u d y peri o d 
(i.e., a c o nc o mita nt me dicati o n t hat is n ot re q uire d b y t he st u d y prot oc ol) a n d his 
part ner s u bse q u e ntl y bec o mes pre g na nt.  
T he i n vesti gat or m ust re p ort t he 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, w h et her or n ot 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 h o ul d i ncl u de t he a ntici p ate d deli ver y date of t he 
ba b y (see b el 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).  
•  A n E D P re p ort is n ot re q uire d if t he Pfizer pr o d uct ta ke n u n der r o uti ne care is 
s pecificall y a p pr o ve d f or use i n pre g na nt w o me n (e. g., vita mi ns) a n d is a d mi nis tere d 
i n acc or d wit h a ut h orize d use. H o we v er, if t h e 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 m ust be re p orte d al o n g wit h t he E D P.  

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 3 7   
T he I n vesti gat or m ust re p ort t he E D P t o Pfizer S afet y o n t he NI S A E Re p ort F or m a n d t he 
E D P S u p ple me ntal F or m . Rele va nt details of t he e x p os ure a n d t he pre g na nc y will be c ollecte d 
fr o m t he ti me i nf or me d c o nse nt was pr o vi de d u ntil fi nal st u d y f oll o w-u p.  If t here is a n S A E 
ass ociate d wit h t he E D P , t he n t he S A E is re p orte d t o Pfizer Safet y usi n g t he NI S A E Re p ort 
F or m.  
F oll o w -u p m ust be c o n d u cte d t o o btai n ge neral i nf or mati o n o n t he pre g n a nc y a n d its o utc o m e 
f or all E D P re p orts.  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 Safet y 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.  F or a li ve birt h, i nf or m ati o n re gar di n g t he str uct ural i nte grit y of t he 
ne o nate at t he ti me of birt h s h o ul d be pr o vi de d.  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 pr o vi de d a n d i nf or m ati o n re gar di n g t he str uct ural i nte grit y of t he 
ter mi nate d fet us s h o ul d be i ncl u de d i n t he re p ort (if a vaila bl e; n ot re q uir e d if pre-pr oce d ure 
test fi n di n gs were c o ncl usi ve f or a c on ge nital a n o mal y a n d t h ose fi n di n gs are pr o vi d e d i n t he 
re p ort). 
A b n or mal pre g na n c 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 n c y meets 
t he criteria f or a n S A E (i.e., ect o pic pre g na n c y, s p o nta ne o us a b orti o n, i ntra uteri ne fetal de mise, 
ne o n atal deat h, or c o n ge nital a n o mal y), t he n 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 pre g na nc y o ut c o mes t hat m ust be re p orte d t o Pfizer Safet y as S A Es i ncl u de:  
•  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, i nfa nt d eat 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 ma y be relate d t o e x p os ure  t o t he 
Pfizer pr o d uct us e d u n der r o uti ne care d uri n g t he st u d y  
A d diti o nal i nf or mati o n re gar di n g t he E D P ma y b e re q u este d b y t he s p o ns or.  F urt her f oll o w  
u p of birt h o ut c 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 
ma y b e re q u este d t o i de ntif y de vel o p me ntal dela ys).  I n t he case of p ater 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 nf or m ati 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 doc u me nts t hat t he 
partici pa nt was gi ve n t h e Pre g na nt Part ner Rel eas e of I nf or mati o n F or m.  
8. 3. 5. 2.  E x p os ure D uri n g Bre astfee di n g  
•  A n E D B occ urs if fe m ale partici pa nt is f o u n d t o be breastf ee di n g w hile ta ki n g a n y 
Pfizer pr o d uct u n der r o uti ne care, at a n y ti me d uri n g t he st u d y p eri o d (e. g., a 
c o nc o mita nt me dicati o n t hat is n ot re q uire d b y t he st u d y pr ot oc ol).  
•  A n E D B re p ort is n ot re q uire d w he n a Pfizer pr o d uct 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 oriz e d use.  
H o we ver, if t he i nfa nt e x perie nces a n S A E ass oci ate d wit h s u c h a dr u g, t h e S A E m ust 
be re p ort e d al o n g wit h t he E D B.  

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
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T he i n vesti gat or m ust re p ort a n E D B t o Pfizer S afet y wit hi n 2 4 h o urs of t he i n vesti gat or’s 
a ware ness, w h et her or n ot a n S A E has occ urre d.   
•  T he i n vesti gat or m ust re p ort E D B t o Pfizer Safet y usi n g t he NI S A E Re p ort f or m.  
•  If t he E D B is ass o ciate d wit h a S A E, t he n t he S A E m ust be re p ort e d usi n g t he sa me 
NI S A E Re p ort f or m . 
8. 3. 5. 3.  E n vir o n me nt al E x p os ure  
N ot A p plica ble. E n vir o n me ntal or occ u pati o nal e x p os ure is n ot re p orta ble i n t his st u d y si nce 
t here is n o Pfizer pr o d uct u n der st u d y. 
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  
8. 3. 7.  Dise ase  Rel at e 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 p lica 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 is t he fail ure of e x pecte d p har mac ol o gic acti o n or t hera pe utic be nefit. I n t his 
st u d y, lac k of effic ac y is re p orta ble t o Pfizer Safet y f or a n a p pr o ve d Pfizer pr o d uct use d b y t he 
partici pa nt u n der r o uti ne care, if t he I n vesti gat or is ma de a ware.  
Lac k of effi cac y s h o ul d be re p orte d as a n S A E t o Pfizer Safet y if t he lac k of effi cac y i n v ol ves 
a v acci ne, a c o ntr ace ptive or a pr o d uct t hat is use d i n t he tre at me nt of life -t hre ate ni n g dise ases 
or c o n diti o ns (e. g., a nti -i nfectives) (excl u di n g HI V a n d c a ncer). 
F or Pfizer pr o d ucts t hat are n ot c o vere d i n para gra p h a b o ve, lac k of efficac y  is re p orta ble t o 
Pfizer Safet y o nl y if ass ociate d wit h a n S A E . 
8. 3. 9.  Me dic al De vic e Defi cie ncies  
N ot a p plica bl e  
8. 3. 9. 1.  Ti m e Peri o d f or Detecti n g Me dic al De vice Defi cie ncies  
N ot a p plica ble  
8. 3. 9. 2.  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  

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8. 3. 9. 3.  F oll o w -u p of Me dic al De vice Deficie ncies  
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 Defici e ncies  
N ot a p plica ble  
8. 4.  Tre at me nt of O ver d ose  
N ot A p plica ble.  
8. 5.  P h ar m ac o ki netics  
P har mac o ki netic para met ers are n ot e val uat e d i n t his st u d y.   
8. 6.  P h ar m ac o d y n a mics  
P har mac o d y na mic p ara m eters are n ot e val u ate d i n t his st u d y.  
8. 7.  Ge netics  
N ot A p plica ble  
8. 8.  Bi o m ar kers  
T w o nasal s wa b s a m ples will be self -c ollect e d b y t he s u bject at h o me usi n g a nasal s wa b t h at 
is st ore d i n U T M me dia . T he first s wa b c ollecti o n is re q uire d as s o o n as t he partici pa nt 
recei v es t he kits. T he sec o n d s wa b c ollecti o n is re q uire d eit her if t he s ubj ect self -re p orts n e w 
or i ncrease d s y m pt o ms or at e n d of wee k 6  if t he y ha ve re m ai ne d as y m pt o matic. I nstr u cti o ns 
f or t he c ollecti o n, ha n dli n g, st ora ge, a n d s hi p me nt of bi ol o gical sa m ples will be pr o vi de d i n 
t he h o me c ollecti o n kit pr o vi de d b y t he s p o ns or.   
Partici pa nt is dee me d p ositi ve f or vir us if bi ol o gical sa m ple is deter mi ne d t o c o ntai n S A R S -
C o V -2 a n d/ or i nfl ue nza vir us  a n d/ or R S V vir uses as detecte d b y 
 R T -P C R test.  
T he partici p a nt will be n otifie d of  t heir res ults. If t he y were t o ha v e a n y q uesti o ns after 
recei vi n g t heir res ults, a c o ntact n u m ber will be m a de a vaila ble t o t he m s o t he y ca n c o ntact t h e 
i n vesti gat or or desi g nate d st u d y me m ber t o a ns wer a n y q uesti o ns t hat t he partici pa nt mi g ht 
ha ve.   
8. 9.  I m mu n o ge nicit y Assess me nts  
I m m u n o ge nicit y ass ess me nts will n ot be perf or me d i n t his st u d y. 
8. 1 0.  He alt h Ec o n o mics  
Healt h ec o n o mics/ me dic al res o ur ce utilizati o n a n d healt h ec o n o mics  p ara meters are n ot 
e val uate d i n t his st u d y.  
C CI

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
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9.  S T A TI S TI C A L C O N SI D E R A TI O N S  
9. 1.  St atistic al H y p ot heses  
T his is a n e x pl orat or y st u d y  pri maril y  i nte n de d t o c ollect data t o c h aracterize t he relati o ns hi p 
bet wee n s y m pt o ms a n d v oice feat ures f or partici p a nts wit h ac ut e viral res pirat or y ill ness. T he 
data will be use d t o q ua ntif y  c ha n ges fr o m well t o si c k usi n g v oice a n d self -re p orte d s y m pt o ms 
c ollecte d wit h a n Electr o nic diar y  i n s y m pt o matic S A R S -C o V -2/ i nfl ue nza vir us / R S V p ositi ve 
partici pa nts . T he h y p ot h eses t hat v oice a n d s elf-re p orte d s y m pt o ms will c han ge  wit h ac ute 
viral  res pirat or y ill ness will be teste d.  T his data will be use d as t he basis t o b uil d v oice a n d 
s y m pt o m al g orit h m(s) f or detecti o n a n d m o nit ori n g of t hese ill nesses.  
9. 2.  S a m ple Size Deter mi n ati o n  
T he sa m ple size deter mi nati o n is base d o n t he pri mar y st u d y o bjecti v e, w hic h is t o o btai n data 
t o c haracteriz e t he relati o ns hi p bet wee n s y m pt o ms a n d v oice feat ur es f or ac ute viral res pir at or y 
ill ness f or R T -P C R c o nfir me d S A R S -C o V -2 , i nfl ue nza vir us , or R S V  p ositi ve  partici pa nts  as 
t he y pr o gress  fr o m well t o sic k states.  
F or t his e x pl orat or y st u d y, it is pla n ne d t o o btai n a t otal of 1 0 0 c o m pleters w h o are R T -P C R 
c o nfir me d ne g ati ve t o S A R S -C o V -2,  i nfl ue nza vir us a n d R S V  R T -P C R ( at s wa b # 1), a n d 
S A R S -C o V -2 ,  i nfl ue nza or R S V  R T -P C R c o nfir me d p ositi ve ( at s w a b # 2) re p orti n g ne w or 
i ncreas e d s y m pt o ms. 
 
 
 it is esti mated  t hat a p pr o xi matel y 5 5 0 0 partici pa nts 
(8 7 0 0 i n t otal i ncl u di n g partici pa nts t hat h a ve bee n e nr olle d pri or t o pr ot o c ol a me n d me nt  # 1 ) 
will be nee de d t o be e nr olle d i n t he st u d y.  
 
A reass ess me nt of  st u d y feasi bilit y a n d e nr oll me nt re q uire me nts is a ntici pate d, i ncl u di n g t he 
re q uire d s a m ple size, aft er i nfecti o n rates a n d c o m plia nce data fr o m t he first 1 0 0 0 c o m pleters 
a nal yze d. 
T he c ase defi niti o n t hat will be use d t o defi ne cas es f or t h e pri mar y o bjecti ve of t he st u d y will 
be as f oll o w s: 
Ne gati ve R T -P C R at s wa b # 1 a n d P ositi ve R T -P C R  at s wa b # 2 w h o de vel o p 1  or m ore  ne w or 
i ncreas e d s y m pt o ms fr o m baseli ne fr o m t he f oll o wi n g list:  
F e ver, c hills, ri g ors, m yal gia, hea dac he, fati g ue, s ore t hr oat, r hi n orr hea, c o n gesti o n, v o miti n g, 
na usea, diarr hea,  ne w olfact or y a n d taste dis or der(s) , c o u g h, w heezi n g, s h ort ness of breat h, or 
diffic ult y breat hi n g . 
De pe n di n g o n t he distri b uti o n of t he 3  vir uses, t his sa m ple size ma y be a de q uate t o b uil d  
ge neral al g orit h m(s) f or earl y dete cti o n of u p per res pirat or y ill nesses.  T his sa m ple size will 
all o w i de ntificati o n of a n y a d diti o nal data re q uir e d t o fi nalize t his al go rit h m(s). 
 
P P D

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
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P FI Z E R C O N FI D E N TI A L  
 
Pa ge 4 1   
9. 3.  D at a M a n a ge me nt  
T he s p o ns or or desi g ne e is res p o nsi ble f or t he d ata 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 d ata.  
9. 4.  C ase Re p ort F or ms/ D at a C ollecti o n T o ols/ Electr o nic D at a Rec or d  
As use d i n t his pr ot oc ol, t he ter m C R F  s h o ul d be u n derst o o d t o refer t o a n electr o ni c data 
rec or d. 
A C R F  is re q uire d a n d s h o ul d be c o m plete d f or eac h i ncl u de d partici p a nt.  T he c o m plete d 
ori gi nal C R Fs are t he s ole pr o pert y of Pfizer a n d s h o ul d n ot be ma de a vaila ble i n a n y f or m t o 
t hir d parties, e xce pt f or a ut h orize d re pres e ntati ves of Pfizer or a p pr o priate re g ulat or y 
a ut h orities, wit h o ut writte n per missi o n fr o m Pfizer.  T he i n vesti gat or s hall e ns ure t hat t he 
C R Fs  are sec urel y st or e d at t he st u d y site i n e ncr y pte d electr o nic a n d/ or p a per  f or m a n d will 
be pass w or d pr otecte d or sec ure d i n a l oc ke d r o o m  t o pre ve nt access b y u na ut h orize d t hir d 
parties.  
T he i n vesti gat or has ulti mate res p o nsi bilit y f or t he c ollecti o n a n d re p orti n g of all cli nical, 
safet y, a n d la b orat or y data e ntere d o n t he C R Fs a n d a n y ot her data c ollecti o n f or ms (s o urce 
d oc u me nts) a n d e ns uri n g t hat t he y are acc urate, a ut he ntic/ ori gi nal, attri b uta ble, c o m plete, 
c o nsiste nt, le gi ble, ti mel y (c o nte m p ora n e o us), e n d uri n g, a n d a vaila ble w he n re q uir e d.  T he 
C R Fs m ust be si g ne d b y t he i n vesti gat or or b y a n a ut h orize d staff me m b er t o attest t hat t he 
data c o ntai ne d o n t he C R Fs are tr u e.  A n y c orrecti o ns t o e ntries ma de i n t he C R Fs or s o urce 
d oc u me nts m ust be date d, i nitiale d, a n d e x plai ne d (if necessar y) a n d s h o ul d n ot o bsc ure t he 
ori gi nal e ntr y.  
In  t his st u d y t he s o urce d oc u me nts are t he site st u d y rec or ds. In s o me cases , t hese mi g ht be  t he 
h os pital or t he p h ysicia n's c hart.  I n t hese cas es, data c ollecte d o n t he C R Fs m ust matc h t he 
s o urce.  
I n s o me cas es, t he C R F will ser ve as t he s o urce d oc u me nt.  I n t hese cases, a d oc u me nt s h o ul d 
be a vaila ble at t he i n vesti gat or site a n d at Pfizer t hat cl earl y i de ntifies t h os e data t hat will be 
rec or de d o n t he C R F, a n d f or w hic h t he C R F will sta n d as t he s o urce d oc u me nt.   
9. 5.  D at a A n al ysis  
T he pri mar y o bje cti ve of t he st u d y is t o o btai n data t o c haracterize t he relati o ns hi p of 
s y m pt o ms a n d v oice feat ures f or s y m pt o matic R T -P C R c o nfir me d p ositi ve partici pa nts  wit h 
S A R S -C o V -2, i nfl ue nza vir us  a n d/ or R S V as t he y pr o gress fr o m w ell t o sic k states . T he data 
will be  use d as t he bas is t o b uil d v oice a n d s y m pt o m al g orit h m(s) f or detecti o n a n d 
m o nit ori n g of t hese ill nesses. De pe n di n g o n t he act ual c ollecte d data, a p pr o priate al g orit h ms 
a n d statistical m o dels will be e x pl ore d.  
 
Baseli ne well -state c h aracteristics (s uc h as d ail y variati o n a n d c o nfi d e nce li mits) a n d c ha n ge 
o ver ti me i n self -re p orte d s y m pt o m sc ores i n t he Electr o nic diar y fr o m well t o sic k i n 
s y m pt o matic R T -P C R c o nfir me d S A R S -C o V -2,  i nfl ue nza vir us, or R S V p ositi ve partici pa nts 
will be e val uate d d escri pti vel y a n d gra p hicall y as a p pr o pri ate. N o nli near m o dels, s uc h as 

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
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e x p o ne ntial or si g m oi d m o dels, will be utilize d t o e x pl ore disease pr o gressi o n fr o m well t o 
sic k a n d assess earl y dete cti o n. Mea n esti mates, c o nfi de nce i nter vals, a n d si g nifica nce t ests of 
c ha n ges ( or m o del para meters ) will be pr o vi de d. A d diti o nal m o dels ma y als o be c o nsi dere d as 
a p pr o priate, a n d t h e 
m o dels' g o o d ness of fit will be assesse d usi n g A kai ke/ Ba yesia n 
i nf or mati o n criteria ( AI C/ BI C). 
T he v oic e c ollecti o n i n t he Electr o nic diar y fr o m well t o sic k i n s y m pt o mati c R T -P C R 
c o nfir me d S A R S -C o V -2, i nfl ue nza vir us, or  R S V p ositi ve partici pa nts will be first a nal yze d 
b y e xtracti n g sta n dar d ac o ustic feat ur es s uc h as pitc h, jitter, har m o nicit y, e ntr o p y, flat ness, 
s hi m mer, usi n g esta blis he d r o uti nes. Ot her v oice feat ures 
m a y als o be c o nsi dere d as 
a p pr o priate. Si milar a nal yses a n d m o deli n g c o nsi derati o ns as f or s y m pt o m sc ores will b e 
c o n d ucte d f or t he e xtract e d ac o ustic feat ures.  Dist a nce metri cs base d o n all or m ost si g nifica nt 
ac o ustic feat ures will als o be e x pl ore d t o e v al uate c ha n ges o ver ti me fr o m well t o sic k.  
C orrelati o n bet wee n c h a n ges i n s y m pt o ms a n d v oice feat ur es will be assesse d b y Pears o n or 
S pear ma n ra n k or der c orrelati o ns.   
A nal ys es f or i n di vi d ual vir us p o p ulati o ns as well as p o ole d a nal yses acr oss t he t hree v ir uses 
will  be assesse d if dee me d feasi ble.  
Detaile d met h o d ol o g y f or s u m mar y a n d statistical a nal yses of dat a c ollecte d i n t his st u d y will 
be d oc u me nte d i n a statistical a nal ysis pla n ( S A P), w hic h will be date d, file d a n d mai ntai ne d 
b y t he s p o ns or.  T he S A P ma y m o dif y t he pla ns o utli ne d i n t he pr ot oc ol; a n y maj or 
m o dificati o ns of pri mar y e n d p oi nt defi niti o ns or t heir a nal yses w o ul d be refl ecte d i n a pr ot oc ol 
a me n d me nt.  
9. 6.  I nteri m A n al yses 
T he o verall attac k rate , attac k rate b y ge o gra p h y, attriti o n rate, Ele ctr o nic diar y a n d self -
s wa b # 1 a n d # 2 c o m plia nce, S A R S-C O V -2/ i nfl ue nza vir us / R S V p ositi ve rate at self-s wa b # 1, 
rate of s y m pt o matic partici pa nts at e nr oll me nt, a n d A Es/ R RIs will be m o nit ore d o n a n o n g oi n g 
basis i n t he st u d y. If a n i nteri m a nal ysis is perf or me d, t he st u d y will c o nti n ue w hilst t he a nal ysis 
is bei n g c o n d ucte d. T he a nal ysis details will be pr o vi de d i n t he S A P or i n a n i nteri m a nal ysis 
S A P.  
9. 7.  D at a M o nit ori n g C o m mittee or Ot her I n de pe n de nt O versi g ht 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.  

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 4 3   
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 n ce 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 n ci 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 CI O M S I nter nati o nal Et hical G ui deli nes;  
•  A p plica ble I C H 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, S R S D(s), a n d ot her rel e 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 b mitte 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 b y t he I R B/ E C bef ore t he st u d y is i ni tiate 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 d e t o t he st u d y desi g n, e xce pt f or c h a n ges necessar y t o eli mi nate a n i m me diate 
hazar d t o st u d y partici pa nts.  
T he 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 u all y or m ore 
fre q ue ntl y i n acc or da nce wit h t he re q uir e me nts, p olicies, a n d pr oce d ures esta blis he d 
b y t he I R B/ E C;  
•  N otif yi n g t he I R B/ E C of S A Es or ot her si g nifica nt safet y f i n di n gs as re q uire d b y 
I R B/ 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 F R, I C H 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 r e 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 n y pr o hi biti o n or restricti o n i m p ose d (i.e., cli nical h ol d) b y a n a p plica ble 
re g ulat or y a ut h orit y 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 h e e v al 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 g at or will i nf or m Pfizer i m me diatel y of a n y ur ge nt safet y measures 
ta ke n b y t he i n v esti gat or t o pr otect t he st u d y partici pa nts a gai nst a n y i m m e diate hazar d, a n d 
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.  

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 4 4   
1 0. 1. 2.  Res p o nsi ble P arties  
Pri nci p al I n vesti g at or(s) of t he Pr ot oc ol  
N a me, de gree(s)  
J o b Title  
Affili ati o n  
A d dress  
Dr. 
 
 
 
 
 
 
 
 L A 
 
 
1 0. 1. 3.  Milest o nes  
Milest o ne  
Pl a n ne d d ate  
Start of data c ollecti o n  
1 2 A pril  2 0 2 1  
E n d of data c ollecti o n   
1 1 A pril 2 0 2 2  
I nteri m re p ort 1 
O nce t he first 1 0 0 0 partici pa nts ha ve 
c o m plete d t he st u d y.  
Fi nal st u d y re p ort  
1 1  Marc h  2 0 2 3  
1 0. 1. 4.  Fi n a nci al Discl os ure  
N ot A p plica ble  
1 0. 1. 5.  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 pl ai n t he nat ure of t he st u d y t o t he partici pa nt 
a n d a ns wer all q uesti o ns re gar di n g t he st u d y.  T he partici pa nt s h o ul d be gi ve n s ufficie nt ti me 
a n d o p p ort u nit y t o as k q uesti o ns a n d t o deci de w h et her or n ot t o partici p ate i n t he trial. 
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 will be re q uire d 
t o si g n a state me nt of i nf or me d c o ns e nt t hat m eets 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 n es, HI P A A re q uir e me nts, w here a p plica ble, a n d t h e 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 p arti ci pa nt is f ull y i nf or me d a b o ut t he nat ur e 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 oci ate 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 d ata 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 p a nt.  
P P D
P P D
P P D
P P D
P P D
P P D

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 4 5   
T he partici pa nt m ust be i nf or me d t hat his/ her me dical a n d site st u d y rec or ds ma y be e x a 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 R B/ E C me m bers, a n d b y i ns pect ors fr o m re g ul at 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 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 site st u d y 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 h e partici p a 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 bt ai 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 v ersi 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.  
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 . 
U nless pr o hi bite d b y l oc al re q uir e me nts or I R B/ E C decisi o n, 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 sa m ples f or o pti o nal a d diti o nal researc h .  T h e o pti o nal 
a d diti o nal researc h d oes n ot re q uire t he c ollecti o n of a n y f urt her sa m ples.  T he i n vesti gat or o r 
a ut h orize d d esi g nee will e x plai n t o eac h p artici pa nt t he o bjecti ves of t he a d diti o nal researc h.  
Partici pa nts will be t ol d t hat t he y are free t o ref use t o partici pat e a n d m a 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 .   
T his st u d y is pla n ne d t o o btai n i nf or m c o nse nt t otall y re m otel y, t he partici pa nt will “self -
c o nse nt” o n a sec ure platf or m  a n d t he partici pa nt will self -re p ort a n d a ns w er t he q uesti o ns f or 
i ncl usi o n/e xcl usi o n criteria. It w o ul d b e e x p ecte d f or t he i n vesti gat or or desi g nate d st u d y 
me m ber t o b e a vaila ble f or a n y q uesti o ns t hat t he partici pa nt mi g ht h a ve d uri n g t he c o nse nt 
pr ocess i n t he f or m of virt ual c o ntact. T he c o nse nt d oc u me nt will ha v e t he c o ntact n u m ber 
w hic h will i n dicate h o w t o get i n c o ntact wit h  t he i n vesti gat or if t he partici pa nts ha ve a n y 
q uesti o ns re gar di n g t he c o nse nt a n d t he i ncl usi o n/e xcl usi o n criteria. It will be re q uir e d f or t h e 
i n vesti gat or or desi g nate d st u d y me m ber t o c o-si g n eac h i nf or me d c o nse nt d oc u me nt. 
1 0. 1. 6.  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 niz ati o nal a n d tec h nical meas ures t o e ns ure pr otecti o n of p artici pa nt data.  
Partici pa nts’ pers o n al dat a will be st ore d at t he st u d y site i n  e ncr y pte d electr o nic a n d/ or  p a per 
f or m a n d will be pass w or d pr otecte d or sec ure d i n a l oc ke d r o o m t o e ns ure t hat o nl y a ut h orize d 
st u d y staff ha ve access.  T he st u d y site will i m ple me nt a p pr o priate tec h nical a n d or ga nizati o nal 
meas ures t o e ns ure t hat t he pers o n al data ca n b e rec o vere d i n t he e ve nt of disaster.  I n t he e ve nt 
of a p ote ntial pers o nal d ata breac h, t he st u d y site will be res p o nsi ble f or deter mi ni n g w het her 
a pers o nal d ata breac h h as 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 uir e d 
b y la w.  
T o pr otect t he ri g hts a n d free d o ms of p artici pa nts 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 

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 4 6   
partici pa nt rec or ds or dat a sets t hat are tr a nsferre d t o t he s p o ns or will c o ntai n t he n u merical 
c o de; partici pa nt n a mes will n ot be tr a nsferre d.  All ot her i de ntifia bl e dat a 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 d e.  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, li n ki n g eac h p artici pa nt’s 
n u merical c o de t o his or her act ual i de ntit y a n d t he partici pa nt’s site st u d y rec or d i de ntificati o n.  
I n cas e of data tra nsf er, 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. 7.  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 u dra C T, a n d/ or 
w w w. pfiz er.c o m, a n d 
ot her 
p u blic re gistries i n acc or da n ce 
wit h a p plica ble l o cal 
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 S OPs.  
I n all cases, st u d y res ults are re p orte d b y 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 g ar 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 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 safet y a n d/ or effi cac y of a pr o d uct, re gar dless 
of t he ge o gra p hic al l ocati o n i n w hic h t he st u d y is c o n d ucte d.  T hese res ult s are s u b mitte d f or 
p osti n g i n acc or da n ce wit h t he f or mat a n d ti meli nes set f ort h b y U S la w.  
E u dra C T  
Pfizer p osts cli nical trial res ults o n E u dra C T f or Pfizer  -s p o ns ore d i nter ve nti o nal st u dies i n 
acc or da nce wit h t he f or m at a n d ti meli nes set f ort h b y E U re q uire m e nts. 
w w w. pfiz er.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 h at 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 v e d) o n w w w. pfizer.c o m f or Pfizer -s p o ns or e d 
i nter ve nti o nal st u dies at t he sa me ti me the c orres p o n di n g st u d y res ults are 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 g es/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 M A we bsite.  Cli nical  dat a, 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 nt ai 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 nc e 0 1  Ja n uar y 2 0 1 5 a n d 

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 4 7   
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. 
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 d e scie ntific researc h ” t hat c o ntri b utes t o t he scie ntific u n dersta n di n g of t he disease, 
tar get, or c o m p ou n d class.  Pfizer will ma ke a vaila ble data fr o m t hes e trials 2 4  m o nt hs after 
st u d y c o m pleti o n.  Patie nt -le vel d ata will be a n o n y mize d i n acc or da n ce 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 nall y i de ntifia ble i nf or mati o n re dacte d . 
Data re q uests are c o nsi d ere d fr o m q u alifie d researc hers wit h t he a p pr o priate c o m pete n cies t o 
perf or m t he pr o p os e d a n al 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 os es.  
1 0. 1. 8.  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 nically (e. g., la b orat or y d ata  a n d e Diar y ). 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 ni call 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 nt ati o n (s o urce d ata) t hat s u p p ort s t he 
i nf or mati o n e ntere d i n t h e 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 a n d/ or pa p er f or m a n d are pass w or d pr ot ecte d or s ec ure d i n a l o c k e d r o o m  t o pre v e 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 o c 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 rel e 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 m a na ge me nt a n d miti gati o n strate gies a n d a nal ytical ris k  -b ase 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 d e d i n t he m o nit ori n g 
pla n .  
T he s p o ns or or d esi g nee is res p o nsi ble f or t he d ata 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 d ata.  
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 p artici pa nts are bei n g pr otecte d; a n d t hat t he st u d y is 

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 4 8   
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 m e nts, I C H G C P, a n d all a p plica ble re g ulat or y re q uire m e nts.  
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 years after st u d y c o m pleti o n u nless l ocal re g ulati o ns or 
i nstit uti o nal p olicies re q uire a l o n ger rete nti o n p eri o d.  N o rec or ds ma y be destr o y e 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 p art y 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 urel y f or as l o n g as t he y are mai ntai ne d.  
W he n p artici pa nt d ata 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 bl y 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 v esti gat or will c o o perate 
wit h t he s p o ns or or its a g e nts t o pre p are 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 nci es 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 site st u d y rec or ds.  T he i n v esti gat or will pr o m ptl y 
pr o vi de c o pi es of t he i ns pecti o n fi n di n gs t o t h e 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 r es p o nses t o a n y s uc h fi n di n gs.  
1 0. 1. 9.  S o urce D oc u me nts  
I n t his st u d y, t he site st u d y rec or d, e Diar y a n d electr o nic q uesti o n nair es  will ser ve as a s o urce 
d oc u me nt. A d oc u me nt s h o ul d be a vaila ble at t he i n vesti gat or site a n d at  Pfizer t hat clearl y 
i de ntifies a n y a d diti o nal rec or ds mai ntai n e d at t he i n vesti gat or site t hat mi g ht als o act as 
s u p p orti ve d oc u me ntati o n. 
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 h e partici pa nt a n d s u bsta ntiate t he 
i nte grit y of t he data c ollecte d.   
Data re p orte d o n t he C R F or e ntere d i n t he e C R F t hat are 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 d s, d e pe n di n g o n t he st u d y.  
Als o, a partici pa nt’s c urre nt site  st u d y rec or d m ust be a vaila ble.  
Defi niti o n of w hat c o nstit utes s o urce data ca n b e f o u n d i n t he st u d y m o nit ori n g pla n. 
Descri pti o n of t he use of c o m p uterize d s yste m is d oc u me nte d i n t he Dat a Ma n a ge me nt Pla n  
1 0. 1. 1 0.  St u d y a n d Site St art a n d Cl os ure  
T he st u d y site start date is t he date o n w hic h t he cli nical st u d y will be o pe n f or recr uit me nt of 
partici pa nts st u d y site.  
T he first act of recr uit me nt is t he date of t he first st u d y partici pa nt’s first visit a n d will be t he 
st u d y start date. 

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T he s p o ns or 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 n y 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 st u d y  -site cl os ure visit has bee n perf or m e d. 
T he i n vesti gat or ma y i nitiate st u d y  -site cl os ur e at a n y ti me u p o n n otificati o n t o t he s p o ns or if 
re q ueste d t o d o s o by 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 h e 
healt h of st u d y partici pa nts.  
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 o l, t he re q uire me nts of t he I R 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 n a de q uat e 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 de vel o p me nt.  
If t he st u d y is pre mat urel y ter mi nate d or s us pe n de d, t he s p o ns or s hall pr o m ptl y i nf or m t he 
i n vesti gat ors, t he E Cs/I R Bs, t he re g ulat or y a ut h orities, a n d a n y C R O(s) us e d i n t he st u d y of 
t he reas o n f or ter mi nati o n or s us pe nsi o n, as s pecifie d b y t he a p plica ble re g ulat or y 
re q uire me nts.  T he i n vesti gat or s hall pr o m ptl y i nf or m t he partici pa nt a n d s h o ul d ass ure 
a p pr o priate p artici pa nt t h era p y a n d/ or f oll o w -u p.  
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 o nflict 
bet wee n t he c o ntract a n d t his pr ot oc ol, t he c o ntra ct will c o ntr ol as t o ter mi nati o n ri g hts.  
1 0. 1. 1 1.  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 pres e nte d at s cie ntific meeti n gs b y 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 t he 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 m es 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 t he s p o ns or 3 0 da ys 
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  relat e d 
i nf or mati o n necessar y f or t he a p pr o priat e scie ntifi c pres e ntati o n or u n derst a n di n g of t he st u d y 
res ults. 
F or all p u blicati o ns rel ati 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 ni n 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 bli s he d b y t he 
I nter nati o nal C o m mittee of Me dical J o ur n al 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 nce wit h sta n dar d e dit orial a n d et hical practice, t he 
s p ons 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 h eir e ntiret y a n d n ot as 

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i n di vi d ual site data.  I n 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 m e 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 m e nt a n d i n li ne wit h I nt er 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 o n p olic y set o ut i n t his 
secti o n will n ot a p pl y. 

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1 0. 2.  A p pe n di x 2 : 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  
1 0. 2. 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 a st u dy 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 bl e a n d u ni nte n d e 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), s y m pt o m, or diseas e ( ne w or e xacer bate d) te m p orall y 
ass ociate d wit h a 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 nicall y si g nifica nt i n t he 
me dical a n d s cie ntific j u d g me nt of t he i n vesti g at or . A n y a b n or mal la b orat or y test 
res ults t hat meet a n y of t he c o n diti o ns bel o w m ust be rec or de d as a n A E: 
o  Is ass ociate d wit h acc o m pa n yi n g s y m pt o ms. 
o  Re q uire s a d diti o nal dia g n ostic testi n g or me dical/s ur gical i nter ve nti o n. 
o  Le a ds t o a c h a n ge i n t he st u dy i nterve nti o n sc he d ule ( o utsi de of a ny 
pr ot oc ol -s pecifie d a dj ust me nts) or disc o nti n u ati o n fr o m t he st u dy, 
si g nific a nt a d diti o n al c o nc o mit a nt dr u g tre at me nt, or ot her t her a py.  
o  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 ncreas e 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 he cli nica l se q uelae of a s us pecte d 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 a c o n c o mita nt 
me dicati o n.  O v er d ose p er se will n ot be re p orte d as a n A E/ S A E u nl ess 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 g ar dless of s e q uelae.  
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 safet y 
assess me nts w hic h are ass ociate d wit h t he u n d erl yi n g disea se, u nless j u d ge d b y t he 
i n vesti gat or t o be m ore s e vere t h a n e x pecte d f or t he partici pa nt’s c o n diti o n. 

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•  T he diseas e/ dis or der 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 o r t he p artici 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 d ect o m y): t he c o n diti o n t hat 
lea ds t o t he 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 da 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 h e st u d y t hat d o n ot w orse n.  
1 0. 2. 2.  Defi niti o n of S A E  
If a n e v e 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 s eri 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 diseas e u n der st u d y, d eat h 
d ue t o pr o gressi o n of dis ease).  
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 hr eate ni n g” i n t he d efi niti o n of “s eri o us” refers t o a n e ve nt i n w hic h t he 
partici pa nt w as at ris k of deat h at t he ti me of t he e ve nt.  It d oes n ot refer t o a n e v e nt 
t hat h y p ot heticall y mi g ht ha ve ca use d deat h if it were m or e 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 n eral, h os pitalizati o n si g nifies t hat t he partici pa nt has bee n detai n e 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 n c y war d f or o bser vati on 
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 ysicia n’s office or 
o ut patie nt setti n g.  C o m plicati o ns t hat occ ur d uri n g h os pitalizati 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 electi 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 n cl u de e x perie nces of rel ati vel y mi n or me dical 
si g nifica nce s uc h as u nc o m plicate d hea dac h e, na usea, v o miti n g, diarr hea, 

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i nfl ue nza, a n d acci d e 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 v er y da 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 a ti o ns: 
•  Me dical or scie ntific j u d g me nt s h o ul d be e x ercise 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 diatel y life  t hreate ni n g or res ult i n deat h or h os pitalizati o n b ut 
ma y je o pa r di ze t h e partici pa nt or ma y re q uire m e dical or s ur gical i nter ve nti o n t o 
pre ve nt o n e of t he ot her o utc o mes liste d i n t he a b o ve d efi 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 v e nts i ncl u de i n vasi ve or mali g na nt ca ncers, i n te nsi ve tr eat me nt 
i n a n e mer ge n c 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 v el o p me nt of dr u g 
de pe n de n c y or dr u g a b us e.  
g.  Rese arc h Rel ate d I nj ur y  
S h o ul d a partici pa nt, i n t he i n vesti gat or’s o pi ni o n, s uffer a me dicall y i m p orta nt 
researc h relate d i nj ur y ca use d b y t heir p artici pati o n i n t he st u d y, t he d esi g nate d Pfizer 
cli nicia n or me dical m o nit or m ust be n otifie d i m me diatel y b y tele p h o ne or e mail.  
A me dicall y i m p orta nt researc h r elate d i nj ur y is a n y u nt o war d me dical occ urre nce t hat:  
•  Res ults i n deat h;  
•  Is life t hreat e ni n g (i m me diate ris k of deat h); 
•  Re q uires i n patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n;  
•  Res ults i n persiste nt or si g nifica nt disa bilit y/i nca paci t y (s u bsta ntial disr u pti o n 
of t he a bilit y t o c o n d uct n or mal life f u ncti o ns) ; 
•  Res ults i n c o n ge nital a n o mal y/ birt h defect.  
Me dical a n d scie ntific j u d g me nt is e xercise d i n d eter mi ni n g w het her a n i nj ur y is a n 
i m p orta nt me dical e ve nt.  A n i m p orta nt me dical e ve n t ma y n ot be i m me diatel y life 
t hreate ni n g a n d/ or res ult i n deat h or h os pitalizati o n.  H o we ver, if it is deter mi ne d t hat 
t he e ve nt ma y je o par dize t he partici pa nt or ma y re q uire 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 defi niti o n a b o ve, t he i m p orta nt me dical e v e nt s h o ul d 
be re p ort e d as a researc h relate d i nj ur y.  
A n i n vesti gat or ma y be re q ueste d b y t he d esi g nate d Pfizer cli nicia n or me di cal m o nit or 
t o o btai n s pecific a d diti o nal 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.   I n ge neral, 
t his will i ncl u de a descri pti o n of t he i nj ur y 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 

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ca usalit y.   I nf or mati o n o n ot her p ossi ble ca uses of t he e v e nt, s uc h as c o nc o mita nt 
treat me nts, vacci nes, a n d/ or 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 v aila 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 or its desi g nate d re pres e ntati ve. 
Defi niti o n of Me dic ati o n Err or:  
A me dicati o n err or is a n y u ni nte nti o nal err or i n t he prescri bi n g, dis pe nsi n g, or a d mi nistrati o n 
of a me di ci nal pr o d u ct t hat ma y ca use or lea d t o i na p pr o priate me dicati o n use or patie nt har m 
w hile i n t he c o ntr ol of t h e healt hcare pr ofessi o nal, patie nt, or c o ns u mer. S uc h e v e nts ma y b e 
relate d t o:  
•  pr ofessi o nal pr actice,  
•  pr oce d ures,  
•  s yste ms, i ncl u di n g: 
o  Prescri bi n g  
o  Or der c o m m u nicati o n   
o  Pr o d uct la beli n g, pac ka gi n g, a n d n o me nclat ure  
o  Dis pe nsi n g  
o  Distri b uti o n  
o  A d mi nistrati o n  
o  E d ucati o n  
o  M o nit ori n g  
o  Use  
Me dicati o n err ors i ncl u d e near -misses i n v ol vi n g or n ot i n v ol vi n g a patie nt directl y or  
c o nf usi o n re g ar di n g i n ve nte d na mes (e. g., tr a de n a me, bra n d n a me).  
 
Defi niti o n of O ver d ose  
 
A n o ver d ose is a n a d mi nistrati o n of a q ua ntit y of a me dici nal pr o d uct gi ve n  per a d mi nistrati o n 
or c u m ulati vel y t hat is a b o ve t he ma xi m u m rec o m me n de d d ose acc or di n g t o t he a ut h orize d 
pr o d uct i nf or mati o n . 

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1 0. 2. 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 D uri n g t he Acti ve C ollecti o n Peri o d  
T he ta b le 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 vers e e ve nts o n t he NI S A E R e p ort f or m  t o Pfizer Safet y t hr o u g h o ut t he 
acti ve c ollecti o n peri o d(s).  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 a Pfizer pr o d uct use d u n der r o uti ne 
care d uri n g pre g n a nc y or breastfee di n g.  
It s h o ul d be n ot e d t hat t he NI 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 g e of t he C R F. W here ver t he s a me data or i nf or mati o n are t o be 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, w he n referri n g t o a s pecific e ve nt, t he s a 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 NI S A E Re p ort f or m.  
S afet y E ve nt  
Rec or d o n t he C R F  
Re p ort o n t he NI 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  
A n y S A E t hat occ urs 
d uri n g t he acti ve c ollecti o n 
peri o d(s).  
A n y S A E t hat occ urs 
o utsi de t he acti ve 
c ollecti o n peri o d(s) t h at 
t he i n vesti gat or s us pects 
ma y be relat e d t o t he  
pr ot oc ol -re q uir e d 
pr oce d ure/i nter ve nti o n.  
 
A n y S A E t hat t h e i n vesti gat or 
s us pects ma y be relate d t o a n y 
Pfizer pr o d uct us e d b y t he 
partici pa nt u n der r o uti ne care 
d uri n g a n d o utsi de a n y acti ve 
c ollecti o n peri o d.  
 
 
N o n -seri o us A Es 
A n y n o n -seri o us A E t hat 
occ urs d uri n g t he acti ve 
c ollecti o n peri o d(s).  
A n y A E t hat occ urs 
o utsi de t he acti ve 
c ollecti o n peri o d(s) t h at 
t he i n vesti gat or s us pects 
ma y be relat e d t o t he 
pr ot oc ol -re q uir e d 
pr oce d ure/i nter ve nti o n.  
 
N o ne  

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S afet y E ve nt  
Rec or d o n t he C R F  
Re p ort o n t he NI 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  
Sce nari os i n v ol vi n g 
e x p os ure d uri n g 
pre g na nc y ( E D P) a n d 
e x p os ure d uri n g breast 
fee di n g ( E D B).  
I nsta n ces of E D P or E D B 
are n ot ca pt ure d i n t he 
C R F.  
All i nsta nces of E D P ( w h et her or 
n ot t here is a n ass oci ate d S A E). *  
All i nsta nces of E D B are re p orte d 
( w het her or n ot t here is a n 
ass ociate d A E/ S A E). * *  
* E D P  ( wit h or wit h o ut a n ass ociate d A E or S A E): a n y pre g na n c y i nf or mati o n is re p orte d 
t o Pfizer Safet y usi n g t he NI S A E Re p ort F or m a n d t he E D P S u p ple me ntal F or m; if t he 
E D P is ass ociate d wit h a n S A E, t he n t he  S A E is re p orte d t o Pfizer Safet y usi n g t he NI S 
A E Re p ort F or m.  
* * E D B  is re p orte d t o Pfizer Safet y usi n g t he NI S A E Re p ort F or m, w hi c h w o ul d als o 
i ncl u de details of a n y S A E t hat mi g ht be ass ociate d wit h t he E D B.  
 
•  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 v e 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 NI S A E Re p ort f or m  or t he A d verse 
E ve nt  C R F pa ge.  
•  T here ma y b e i nsta nces w he n c o pies of me dical rec or ds f or certai n case s are re q u este d 
b y Pfizer Safet y.  I n t his case, all partici pa nt i de ntifiers, wit h t he e xce pti o n of t he 
partici pa nt n u m ber, will be re d acte 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 att e m pt t o esta blis h  a dia g n osis of t he e v e nt bas e d o n si g ns, 
s y m 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 y m pt o ms) will be d oc u me nte d as t he A E/ S A E. 
Assess m e 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 da y acti vities.  

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•  M o derate: A n e v e nt t hat ca uses s ufficie nt disc o mf ort a n d i nterferes wit h n or mal 
e ver y da y acti vities.  
•  Se vere: A n e ve nt t hat pre ve nts n or mal e v er y da y acti vities.  A n A E t hat is assesse d as 
se vere s h o ul d n ot b e 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 h e 
i nte nsit y 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 d efi ne d o utc o mes as 
descri be d i n t he d efi niti o n of a n S A E, N O T w h e n it is rate d as se vere.  
Assess m e nt of C a us alit y  
•  T he i n vesti gat or is o bli gate d t o assess t h e relati o ns hi p bet wee n a n y st u d y i nter ve nti o n 
( or Pfizer pr o d uct use d u n der r o uti ne care) a n d eac h occ urre n ce 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 m e nts t o s u g gest a ca usal relati o ns hi p, rat her t h a n a relati o ns hi p ca n n ot b e 
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 us es, 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 w ell as t h e 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.  
•  I n ma ki n g his/ her assess me nt, t he i n vesti gat or will als o c o ns ult t he pr o d uct i nf or mati o n 
f or a mar k ete d Pfizer pr o d uct use d u n der r o uti ne care.  
•  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 h e 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 ve sti 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 uir e 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 h a 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 h at a n S A E is 
ass ociate d wit h st u d y pr oce d ure/i nter ve nti o n, t he i n vesti gat or m ust rec or d t his ca usal 

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relati o ns hi p i n t he s o ur ce d oc u me nts a n d C R F, a n d re p ort s u c h a n assess me nt i n t he 
NI 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 n at ure a n d/ or ca usalit y of t he A E or S A E as f ull y as 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 o vi ders.  
•  If a p artici 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 ni ze d f oll o w u p 
p eri 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 d ate 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 o r wit hi n 2 4 h o urs of 
recei pt of t h e i nf or mati o n. 
1 0. 2. 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 m ec ha nis m f or re p orti n g a n S A E t o Pfizer Safet y will be t h e electr o nic 
data c ollecti o n t o ol.  
•  If t he ele ctr o nic s yste 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 s ecti 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 el ectr o nic s yste m as s o o n as t he data bec o m e 
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 offli ne t o pr e ve nt t he e ntr y of n e 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 v es u p date d 
data  o n a pre vi o usl y re p orte d S A E aft er t he electr o nic data c ollecti o n t o ol has bee n 
ta ke n offli 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 NI S A E Re p ort F or m  
•  Facsi mile tr a ns missi o n of t he NI 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. 

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•  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 b y tele p h o ne is 
acce pta ble wit h a c o p y of t he NI S A E Re p ort f o r m se nt b y o v er ni g ht mail or c o urier 
ser vice. 
•  I nitial n otificati o n via t ele p h o ne d oes n ot re place t he nee d f or t h e i n vesti gat or t o 
c o m plete a n d si g n t he NI 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. 

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1 0. 3.  A p pe n di x 3 : Li ver S afet y: S u g geste d Acti o ns a n d F oll o w -u p Assess me nts  
L F Ts are n ot re q uir e d as a r o uti ne s afet y m o nit ori n g pr oce d ure i n t his st u d y.  H o we v er, s h o ul d 
a n i n vesti gat or d ee m it n ecessar y t o assess L F Ts beca use a partici p a nt prese nts wit h cli nical 
si g ns/s y m pt o ms t hat t he i n vesti gat or s us pects ma y be d ue t o a Pfizer pr o d uct use d u n der 
r o uti ne care, t he n, s uc h L F T res ults s h o ul d be ma na ge d a n d f oll o we d as des cri be d bel o w. 
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 n e d b y ele vati o ns i n 
transa mi nases) are t er me d “t olerat ors,” w hile t h ose w h o s h o w tra nsie nt li v er 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 DI LI.  Partici pa nts w h o 
e x perie n ce a tra nsa mi nas e ele vati o n a b o ve 3  × 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 bl e.”  
I n t he maj orit y of DI LI cases, el e vati o ns i n A S T a n d/ or A L T prece d e T Bili ele vati o ns ( > 2 × 
U L N) b y se veral da ys or wee ks.  T he i ncreas e i n T Bili t y picall 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 (i.e., 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 s a m ple).  I n rare i nsta n ces, b y t he ti m e T Bili ele vati o ns are d etecte d, A S T/ A L T 
val ues mi g ht ha ve d ecrease 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) cas es  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 v e nts, e ve n b ef ore all ot her p ossi ble ca uses of li ver i nj ur y 
ha ve bee n e xcl u d e d . 
T he t hres h ol d of la b orat or y a b n or m alities f or a p ot e ntial DI LI cas e d e pe n ds o n t he partici pa nt’s 
i n di vi d ual baseli ne val u es a n d u n d erl 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 b n or malities s h o ul d be e val uate d f urt her as p ote ntial DI LI ( H y’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 u es:  
•  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 A S 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 ysis 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 us e 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 u es are a b o ve t he U L N at baseli ne:  
o  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 b aseli ne val ues A N D > 3 × U L N; or > 8  ×  U L N ( w hic he ver is 
s maller). 
o  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 ncreas e 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 h es > 3 ×  U L N 
( w hic he ver is s maller). 

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Ri ses 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 assess e 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 pres e nts a p ote ntial H y’s la w cas e s h o ul d be re vie we d wit h t he s p o ns or.   
T he part ici 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 n ess 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 t ests, detaile d hist or y, a n d p h ysical assess me nt.   
I n a d ditio 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, C K, direct a n d i n direct bilir u bi n, G G T, 
P T/I N R, t otal bile aci ds, a n d al kali ne p h os p hatas e.  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 d e d, f or f urt her c o nte m p ora ne o us a n al yses 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, acet a mi n o p he n/ paraceta m ol (eit her b y itself or as a c o -f or m ulate d pr o d uct 
i n prescri pti o n or --o v er -t he-c o u nter me dicati o ns) , recreati o nal dr u g, s u p pl e me nt ( her bal) us e 
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 ot e ntial 
occ u pati o nal e x p os ure t o c he micals, s h o ul d be c oll ecte d.  F urt h er testi n g f or ac ute h e 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 ples 
f or aceta mi n o p he n/ paraceta m ol dr u g a n d/ or pr otei n a d d uct le vels ma y be warra nt e 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 criteri a of A S T/ A L T 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) cas es if n o ot her 
reas o n f or t he L F T a b n or malities has yet bee n f o 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 bil it 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 nl y after all res ults of reas o na ble 
i n vesti gati o ns ha ve bee n recei v e d a n d ha v e e x cl u de d a n alter nati ve eti ol o g y.  
 

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 6 2   
1 0. 4.  A p pe n di x 4 : A b bre vi ati o ns 
T he f oll o wi n g is a list of a b bre viati o ns t hat ma y b e use d i n t he pr ot oc ol.   
A b bre vi ati o n  
Defi niti o n  
A cRI S  
Ac ute Res pirat or y Ill n ess S ur veilla nce  
AI C  
A kai ke inf or mati o n criteria 
A E  
a d verse e ve nt  
A L T  
alani ne a mi n otra nsferas e  
A S T  
as partate a mi n otra nsferas e  
BI C  
Ba yesia n i nf or mati o n crit eria  
C LI A  
Cli nical La b orat or y I m pr o ve me nt A me n d me nts  
C F R  
C o de of Fe d eral Re g ulati o ns  
CI O M S  
C o u ncil f or I nter nati o nal Or ga nizati o ns of M e dical 
Scie nces  
C K  
creati ne ki n ase  
C R F  
case re p ort f or m  
C R O  
C o ntract  Researc h  Or g a nizati o n  
C O VI D -1 9  
C or o na vir us Disease 2 0 1 9  
C S R  
Cli nical St u d y Re p ort  
DI LI  
d r u g-i n d uce d li ver i nj ur y 
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 B  
e x p os ure d uri n g breastf ee di n g  
e Diar y  
electr o nic diar y  
E D P  
e x p os ure d uri n g pre g na n c y  

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 6 3   
E M A  
E ur o pea n Me dici nes A ge nc y  
E O S  
E n d of St u d y  
E U A  
e mer ge n c y use a ut h ori zati o n  
E u dra C T   
E ur o pea n U ni o n Dr u g Re g ulati n g A ut h orities Cli nical 
Trials Data bas e  
G C P  
G o o d Cli nical Practice  
G G T  
ga m ma -gl uta m yl tra nsferase  
H C P  
healt h care pr o vi der  
HI P A A  
Healt h I ns ura nce P orta bilit y a n d Acc o u nta bilit y A ct  
I A 
i nteri m a nal ysis 
I C H 
I nter nati o nal C o u ncil f or Har m o nisati o n of Tec h nical 
Re q uire me nts f or P har m ace uticals f or H u ma n Us e  
I C D 
i nf or me d c o nse nt d oc u m e nt 
I N R 
i nter nati o nal n or malize d rati o 
I R B 
I nstit uti o nal Re vie w B oar d 
L F T  
li ver f u ncti o n tests 
 
 
n, N  
n u m ber  
N/ A  
n ot a p plica ble  
NI S  
n o n -i nter ve nti o nal st u d y 
P T  
pr ot hr o m bi n ti me  
R RI  
researc h relate d i nj ur y 
R T -P C R  
re verse tra nscri pti o n p ol y merase c hai n reacti o n 
R S V  
res pirat or y s y n c ytial vir us 
S A E  
seri o us a d verse e v e nt 
C CI

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 6 4   
S A P  
statistical a nal ysis pla n 
S A R S -C o V -2  
se vere ac ute res pirat or y s y n dr o me c or o na vir us 2 
S o A  
sc he d ule of acti vities 
S O P  
sta n dar d o perati n g pr oce d ures 
S R S D  
si n gle refere nce safet y doc u me nt  
T Bili  
t otal bilir u bi n 
U L N  
u p per li mit of n or mal  
 
 
y/ o  
years ol d  
 
C CI

Pr ot oc ol X 9 0 0 1 2 9 3 L O W -I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
 
Pr ot oc ol A me n d me nt # 1, 2 8 Se pte m ber 2 0 2 1  
 
P FI Z E R C O N FI D E N TI A L  
 
Pa ge 6 5   
1 1.  R E F E R E N C E S  
1.  
Ba n h olzer M L, Wa n del  C, Barr o w P, et al. Cli nical trial c o nsi derati o ns o n male 
c o ntrace pti o n a n d c ollecti o n of pre g na n c y i nf or mati o n fr o m fe male part ner: u p date. 
Cli n Tra nsl Me d 2 0 1 6; 5( 1) : 2 3-3 7.  
2.  
V o gel, A. P. et al., A C o m parati ve St u d y of T w o Ac o ustic Meas ures of H y per nasalit y. 
J. S peec h, L a n g. He ar. R es.  ( 2 0 0 9) 
3.  
Lee, G. S. et al., Effect of nasal dec o n g esti o n o n v oice s pectr u m of a nas al c o ns o na nt -
v o wel. J. V oice 1 9,  7 1 – 7 7 ( 2 0 0 5)  
4.  
Trace y B. et al., V oice Bi o mar kers of R ec o ver y fr o m Ac ute Res pirat or y Ill ness. 
M a n uscri pt s u b mitte d , 2 0 2 1