Study to Evaluate the Impact of Reactogenicity on Quality of Life (QoL), After Administration of GSK Biologicals' Candidate Herpes Zoster Subunit (HZ/su) Vaccine (GSK1437173A) in Adults ≥ 50 Years of Age
Phase: PHASE3
Conditions: Herpes Zoster
Sponsor: GlaxoSmithKline

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1
Cli ni c al St u d y Pr ot o c ol
S p o n s or:
Gl a x o S mit h Kli n e Bi ol o gi c al s
R ue de l’I nstit ut 8 9, 1 3 3 0 Ri xe nsart, Bel gi u m
Pri m ar y St u d y v acci ne 
( a n d n u m ber)
Gla x o S mit h Kli ne ( G S K) Bi ol o gicals’ l yo p hilize d 
f or m ulati o n of t he Her pes Z oster s u b u nit ( H Z/s u) 
vacci ne ( G S K 1 4 3 7 1 7 3 A)
e Tr ac k st u d y n u m ber a n d 
A b bre vi ate d Title
2 0 4 9 2 8 (Z O S T E R -0 6 3 )
I n vesti g ati o n al Ne w Dr u g 
(I N D) n u m ber
B B -I N D 1 3 8 5 7
D ate of pr ot oc ol
Fi nal Versi o n 1 : 2 2 J u ne 2 0 1 6
D ate of pr ot oc ol a me n d me nt
A me n d me nt 1 Fi nal: 2 2 A u g ust 2 0 1 6
A me n d me nt 2 Fi nal: 1 6 N o ve m ber 2 0 1 6
Title
St u d y  t o e val uate t he i m pact of react o ge nicit y o n 
Q ualit y  of Life ( Q o L), after a d mi nistrati o n of G S K 
Bi ol o gicals’ ca n di date Her pes Z oster s u b u nit 
( H Z/s u) vacci ne ( G S K 1 4 3 7 1 7 3 A) i n a d ults ≥5 0 
ye ars of a ge.
Det aile d Title
A p hase III, o pe n la bel, m ultice n ter st u d y t o 
e val uate t he i m pact of react o ge nicit y o n Q ualit y o f 
Life ( Q o L), after i ntra m usc ular a d mi nistrati o n of 
G S K Bi ol o gicals’ ca n di date Her pes Z oster s u b u nit 
( H Z/s u) vacci ne ( G S K 1 4 3 7 1 7 3 A) i n a d ults ≥5 0 
ye ars of a ge.
C o -or di n ati n g a ut h or

Scie ntific Writer ( A me n de d 
1 6 N o ve m ber 2 0 1 6)
C o ntri b uti n g a ut h ors
( A me n de d 1 6 N o ve m ber 2 0 1 6)

, Cli nic al Rese arc h a n d 
Devel o p me nt Le a d

, Cli nical Researc h a n d 
De vel o p me nt Lea d

, Cli nical Researc h a n d 
De vel o p me nt Lea d

, Pr oject St atistici a n

, Pr oject Statisticia n

, Healt h Ec o n o mics
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
P P D
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1
1 6- N O V- 2 0 1 6
P P D
P P D
P P D
P P D
P P D
P P D

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
2
e Tr ac k st u d y n u m ber a n d 
A b bre vi ate d Title
2 0 4 9 2 8 ( Z O S T E R - 0 6 3)
I n vesti g ati o n al Ne w Dr u g 
(I N D) n u m ber
B B -I N D 1 3 8 5 7
Det aile d Title
A p hase III, o pe n la bel, m ultice nter st u d y  t o 
e val uate t he i m pact of react o ge nicit y o n Q ualit y of 
Life ( Q o L), after i ntra m usc ular a d mi nistrati o n of 
G S K Bi ol o gicals’ ca n di date Her pes Z oster s u b u nit 
( H Z/s u) vacci ne ( G S K 1 4 3 7 1 7 3 A) i n a d ults ≥5 0
ye ars of a ge.
C o ntri b uti n g a ut h ors
(c o nti n ue d)
( A me n de d 1 6 N o ve m ber 2 0 1 6)

, St u d y  Deli ver y Lea d

, St u d y Deli ver y Lea d

, St u d y Deli ver y Lea d, 
C o ntract or f or G S K Bi ol o gicals

, St u d y  Deli ver y Ma na ger , 
S y nteract H C R, C o ntract or f or G S K 
Bi ol o gicals

, Vacci ne S u p pl y C o or di nat or

, Safety re prese ntati ve

, Oversi g ht Data Ma na ger , 
Ke y r us Bi o p har ma, C o ntract or f or G S K 
Bi ol o gicals

, U S Re g ulat or y  Affairs

, Gl o bal Re g ulat or y  Affairs

, U S Me dical Affairs

, Gl o bal Me dical Affairs

, Gl o bal Pate nt

, Gl o bal Vacci ne Cli nical 
La b orat ories Cli nical rea d o ut Tea m Lea d

, Lea d Statisticia n

, Cli nical a n d E pi de mi ol o g y 
Pr oject Lea der ( C E P L) , Bel gia n R D C
G S K Bi ol o gic als’ Pr ot oc ol D S v 1 4. 1. 1
C o p yri g ht 2 0 1 6 t he Gl a x o S mit h Kli ne gr o u p of c o m p a nies. All ri g hts reser ve d. U n a ut h orise d 
c o p yi n g or use of t his i nf or m ati o n is pr o hi bite d.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
P P D
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
2
1 6- N O V- 2 0 1 6
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
3
Pr ot o c ol A m e n d m e nt 2 S p o n s or Si g n at or y A p pr o v al
e Tr ac k st u d y n u m ber a n d 
A b bre vi ate d Title
2 0 4 9 2 8 ( Z O S T E R - 0 6 3)
I N D n u m ber
B B -I N D 1 3 8 5 7
D ate of pr ot oc ol a me n d me nt
A me n d me nt 2 Fi nal: 1 6 N o ve m ber 2 0 1 6
Det aile d Title 
A p hase III, o pe n la bel, m ultice nter st u d y  t o e val uate 
t he i m pact of react o ge nicit y o n Q uality of Life 
( Q o L), after i ntra m usc ular a d mi nistrati o n of G S K 
Bi ol o gicals’ ca n di date Her pes Z oster s u b u nit ( H Z/s u) 
vacci ne ( G S K 1 4 3 7 1 7 3 A) i n a d ults ≥5 0 y ears of a ge.
S p o ns or si g n at or y
Li dia O ost v o gels, M D
Direct or, Cli nical a n d E pi de mi ol o g y  Pr oject Lea der, 
Z oster Pr o gra m, Bel gia n R D C
Si g n at ure
D ate
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
3
1 6- N O V- 2 0 1 6
- ---------------- C hec ks u m----------------! Ver.! Create d O n -   -
6 7 d 8 3 9 1faef 6 4e 9 d 0 5f d 1c 8f 3a 9 b 9 3 8 7 3 2f d d 1 8a 2. 0 1 1/ 2 5/ 2 0 1 6 3: 4 5: 4 5 P M -   -
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F or i nter nal use o nl y

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
4
Pr ot o c ol A m e n d m e nt 2 R ati o n al e
A m e n d me nt n u m ber:
A me n d me nt 2
R a ti o n ale/ b ac k gr o u n d f or c h a n ges:

T he sa m ple E Q -5 D q uesti o n naire i n A P P E N DI X B of t he pr ot oc ol was missi n g t he 
Vis ual A nal o g ue S cale ( V A S). Ima ges of pa ges fr o m a sa m ple E Q -5 D 
q uesti o n naire, i ncl u di n g t he V A S, are n o w pr o vi de d t o re place t he E Q -5 D 
q uesti o n naire te xt, t o better re prese nt t he a p peara nce of t he E Q - 5 D q uesti o n naire 
t hat will be use d i n t his st u d y.

T o c o m ple me nt the i ma ges of a n E Q - 5 D sa m ple q uesti o n naire i n A P P E N DI X B, 
i ma ges of pa ges fr o m a sa m ple S F- 3 6 q uesti o n naire are n o w pr o vi de d t o re place 
t he S F-3 6 q uesti o n naire te xt i n A P P E N DI X A, t o better re prese nt t he a p peara nce 
of t he S F -3 6 q uesti o n naire t hat will be use d i n t his st u d y.

T he ter m V A S has bee n a d de d t o t he List of A b bre viati o ns a n d Secti o n 1 0. 6. 2. 4 
si nce it has n o w bee n i ncl u de d i n t he E Q-5 D q uesti o n naire use d i n t his st u d y .

Refere nces t o h y perte xt li n ks f or e xa m ples of t he S F -3 6 a n d E Q - 5 D q uesti o n naires 
i n Secti o ns 1 0. 6. 2. 3 a n d 1 0. 6. 2. 4, res pecti vely as well as i n t he Refere nce Secti o n 
ha ve bee n delete d, si nce i ma ges of pa ges f or t hese q uesti o n naires are pr o vi de d as 
e xa m ples i n A P P E N DIX A a n d B.

T y p o gra p hic err ors were c orrecte d a n d ot her mi n or m o dificati o ns were ma de 
t hr o u g h o ut f or clarificati o n.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
4
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
5
Pr ot o c ol A m e n d m e nt 2 I n v e sti g at or A gr e e m e nt
I a gree:

T o c o n d uct t he st u d y i n c o m plia nce wit h t his pr ot oc ol, a n y f ut ure pr ot oc ol 
a me n d me nts or pr ot oc ol a d mi nistrati ve c ha n ges, wit h t he ter ms of t he cli nical trial 
a gree me nt a n d wit h a n y ot her st u d y  c o n d uct pr oce d ures a n d/ or st u dy c o n d uct 
d oc u me nts pr o vi de d b y Gla x o S mit h Kli ne ( G S K) Bi ol o gicals.

T o ass u me res p o nsi bilit y f or t he pr o per c o n d uct of t he st u d y  at t his site.

T hat I a m a ware of, a n d will c o m pl y  wit h, ‘ G o o d Cli nical Practice’ ( G C P) a n d all 
a p plica ble re g ulat or y re q uire me nts.

T o e ns ure t hat all pers o ns assisti n g me wit h t he st u d y  are a de q uately i nf or me d a b o ut 
t he G S K Bi ol o gicals’ i n vesti gati o nal vacci ne a n d ot her st u d y-relate d d uties a n d 
f u ncti o ns as descri be d i n t he pr ot oc ol.

T o ac q uire t he refere nce ra n ges f or la b orat or y  tests perf or me d l ocally a n d, if re q uire d 
b y  l ocal re g ulati o ns, o btai n t he la b orat or y’s c urre nt certificati o n or Q ualit y 
Ass ura nce pr oce d ure ma n ual.

T o e ns ure t hat n o cli nical sa m ples (i ncl u di n g ser u m sa m ples) are retai ne d o nsite or 
else w here wit h o ut t he a p pr o val of G S K Bi ol o gicals a n d t he e x press writte n i nf or me d 
c o nse nt of t he s u bject a n d/ or t he s u bject’s le g all y acce pta ble re prese ntati ve.

T o perf or m n o ot her bi ol o gical assa y s o n t he cli nical sa m ples e xce pt t h ose descri be d 
i n t he pr ot oc ol or its a me n d me nt(s).

T o c o -o perate wit h a re prese ntati ve of G S K Bi ol o gicals i n t he m o nit ori n g pr ocess of 
t he st u d y a n d i n res ol uti o n of q ueries a b o ut t he data.

T hat I ha ve bee n i nf or me d t hat certai n re g ulat or y  a ut h orities re q uire t he s p o ns or t o 
o btai n a n d s u p pl y , as necessar y, details a b o ut t he i n vesti gat or’s o w ners hi p i nterest i n 
t he s p o ns or or t he i n vesti gati o nal vacci ne, a n d m ore ge nerally a b o ut his/ her fi na ncial 
ties wit h t he s p o ns or. G S K Bi ol o gicals will use a n d discl ose t he i nf or mati o n s olel y  
f or t he p ur p ose of c o m pl yi n g wit h re g ulat or y re q uire me nts.
He nce I:

A gree t o s u p pl y G S K Bi ol o gicals wit h a n y necessar y  i nf or mati o n re gar di n g 
o w ners hi p i nterest a n d fi na ncial ties (i ncl u di n g t h ose of m y s p o use a n d de pe n de nt 
chil dre n).

A gree t o pr o m ptl y u p date t his i nf or mati o n if a n y rele va nt c ha n ges occ ur d uri n g t he 
c o urse of t he st u d y a n d f or o ne year f oll o wi n g c o m pleti o n of t he st u d y.

A gree t hat G S K Bi ol o gicals ma y  discl ose a n y i nf or mati o n it has a b o ut s uc h 
o w ners hi p i nteres ts a n d fi na ncial ties t o re g ulat or y a ut h orities.

A gree t o pr o vi de G S K Bi ol o gicals wit h a n u p date d C urric ul u m Vitae a n d ot her 
d oc u me nts re q uire d b y re g ulat or y a ge ncies f or t his st u d y.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
5
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
6
e Tr ac k st u d y n u m ber a n d 
A b bre vi ate d Title
2 0 4 9 2 8 ( Z O S T E R - 0 6 3)
I N D n um ber
B B -I N D 1 3 8 5 7
D ate of pr ot oc ol a me n d me nt
A me n d me nt 2 Fi nal : 1 6 N o ve m ber 2 0 1 6
Det aile d Title
A p hase III, o pe n la bel, m ultice nter st u d y  t o e val uate 
t he i m pact of react o ge nicit y o n Q uality of Life 
( Q o L), after i ntra m usc ular a d mi nistrati o n of G S K 
Bi ol o gicals’ ca n di date Her pes Z oster s u b u nit ( H Z/s u) 
vacci ne ( G S K 1 4 3 7 1 7 3 A) i n a d ults ≥5 0 y ears of a ge.
I n vesti g at or n a me
Si g n at ure
D ate
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
6
1 6- N O V- 2 0 1 6
- ---------------- C hec ks u m----------------! Ver.! Create d O n -   -
6 7 d 8 3 9 1faef 6 4e 9 d 0 5f d 1c 8f 3a 9 b 9 3 8 7 3 2f d d 1 8a 2. 0 1 1/ 2 5/ 2 0 1 6 3: 4 5: 4 5 P M -   -
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F or i nter nal use o nl y

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S p o n s or I nf or m ati o n
1.
S p o ns or
Gla x o S mit h Kli ne Bi ol o gicals
R ue de l’I nstit ut 8 9, 1 3 3 0 Ri xe nsart, Bel gi u m
2.
S p o ns or Me dical E x pert f or t he St u d y
Refer t o t he l ocal st u d y  c o ntact i nf or mati o n d oc u me nt.
3.
S p o ns or St u d y  M o nit or
Refer t o t he l ocal st u d y c o ntact i nf or mati o n d oc u me nt.
4.
S p o ns or St u d y  C o ntact f or Re p orti n g of a Seri o us A d verse E ve nt
G S K Bi ol o gicals Ce ntral Bac k -u p St u d y  C o ntact f or Re p orti n g S A Es: refer t o pr ot oc ol 
Secti o n 8. 4. 2 .
 
C O N FI D E N TI A L
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6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
7
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
8
S Y N O P SI S
Det aile d Title
A p hase III, o pe n la bel, m ultice nter st u d y  t o e val uate t he 
i m pact of react o ge nicity o n Q ualit y  of Life ( Q o L), after 
i ntra m usc ular a d mi nistrati o n of G S K Bi ol o gicals’ ca n di date 
Her pes Z oster s u b u nit ( H Z/s u) vacci ne ( G S K 1 4 3 7 1 7 3 A) i n 
a d ults ≥5 0 y ears of a ge.
I n dic ati o n
Pre ve nti o n of Her pes Z oster ( H Z) a n d relate d c o m plicati o ns 
i n a d ults a ge d 5 0 ye ars a n d ol der a n d i n 
i m m u n oc o m pr o mise d (I C) a d ults a ge d 1 8 years a n d ol der.
R ati o n ale f or t he 
st u d y a n d st u d y 
desi g n

Rati o nale f or t he st u d y
Varicella -Z oster Vir us ( V Z V) ca uses t w o dist i nct diseases. 
Varicella (c hic ke n p o x) occ urs s h ortl y after pri mar y V Z V 
i nfecti o n a n d is c haracterize d b y sys te mic ill ness a n d a 
wi del y  disse mi nate d ras h. H Z (s hi n gles) occ urs w he n V Z V 
reacti vates fr o m late nc y. Vacci nati o n as a mea ns t o re d uce 
ris k of H Z has bee n e xa mi ne d i n b ot h ol der a n d i m m u n o-
c o m pr o mise d pers o ns.
H Z is c haracterize d b y ras h, a n d pai n / or pr urit us. T he t ypical 
H Z ras h, vesicles i n a l ocalize d, der mat o mal ba n d o n o ne 
si de of t he b o dy, lasts 2 t o 4 wee ks a n d is ofte n acc o m pa nie d 
b y  se vere pai n t hat is descri be d as b ur ni n g, s h o oti n g, or 
sta b bi n g. I n s o me patie nts, e ve n li g htly t o uc hi n g t he affecte d 
area ma y ca use pai n, a p he n o me n o n k n o w n as all o d ynia. 
Pr urit us, w hic h ca n als o be se vere, ma y  be as c o m m o n as 
pai n. P ai n t hat persists after t he res ol uti o n of t he H Z ras h is 
calle d p ost her petic ne ural gia ( P H N). N ota bl y, P H N ca n last 
f or m o nt hs or e ve n ye ars.
Half of all H Z cases occ ur i n i n di vi d uals ≥6 0 years of a ge 
( Y O A). In di vi d uals w h o reac h 8 5 ye ars ol d ha ve a 
5 0 % c ha nce of ha vi n g H Z d uri n g t heir lifeti me. T he ris k f or 
P H N is als o hi g hest i n ol der pe o ple wit h H Z, occ urri n g i n 
1 8- 5 0 % of t h ose ≥7 0 Y O A . Si nce t he l oss of V Z V -s pecific 
T- cell res p o nses as a res ult of a gi n g lea ds t o hei g hte ne d 
s usce pti bilit y t o H Z, vacci nati o n is c o nsi dere d as a mea ns t o 
re d uce t he ris k of H Z i n ol der a d ults.
Ass ociate d wit h H Z a n d its c o m plicati o ns is a s u bsta ntial 
ne gati ve i m pact o n patie nts’ Q ualit y  of Life ( Q o L) a n d t heir 
a bilit y t o e n ga ge i n Acti vities of Dail y Li vi n g ( A D L). I n 
a d ditio n t o t he m or bi dit y  e nc o u ntere d b y t he i n di vi d ual wit h 
H Z, i ncl u di n g pr o d ucti vit y  l oss, it ca n als o ha ve si g nifica nt 
c o nse q ue nces f or t he care gi vers of patie nts , i ncl u di n g 
part ners a n d relati ves of pe o ple wit h H Z . Ac ute H Z a n d H Z-
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
8
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
9
relate d c o m plicati o ns s uc h as P H N ha ve a c o nsi dera ble 
ec o n o mic c ost t o healt hcare s ys te ms cari n g f or H Z a n d P H N 
patie nts . T hese healt hcare c osts will m ost li kel y i ncrease d ue 
t o t he a gi n g p o p ulati o n, w here a ge -relate d diseases s uc h as 
H Z are bec o mi n g a gr o wi n g ec o n o mic b ur de n i n t he 
de vel o pi n g w orl d .
A li ve atte n uate d V Z V vacci ne, Z ost av ax ( Merc k & C o), is 
lice nse d i n t he U nite d States ( U S) t o pre ve nt H Z i n pers o ns 
≥5 0 Y O A . Li ve atte n uate d vacci ne is c o ntrai n dicate d i n 
i m m u n os u p presse d or i m m u n o deficie nt in di vi d uals.
Gla x o S mit h Kli ne ( G S K) Bi ol o gicals’ H Z ca n di date vacci ne 
is a n a dj u va nte d rec o m bi na nt V Z V e n vel o pe gl yc o pr otei n E 
( g E) s u b u nit vacci ne, hereafter referre d t o as H Z/s u. T he 
a nti ge n c o m p o ne nt of t he st u d y  vacci ne is a tr u ncate d f or m 
of g E. T he a dj u va nt is A S 0 1 B , w hic h c o nsists of li p os o mes i n 
c o m bi nati o n wit h 5 0 µ g 3- O- desc y l- 4’-M o n o p h os p h or y l 
Li pi d A ( M P L) a n d 5 0 µ g Q uill aj a s a p o n ari a , M oli na, 
fracti o n 2 1 ( p urifie d nat ural sa p o ni n m olec ule e xtracte d fr o m 
t he S o ut h A merica n tree, Q uill aj a s a p o n ari a ) ( Q S 2 1) per 0. 5 
m L  d ose.
T he G S K Bi ol o gicals’ H Z/s u ca n di date vacci ne has bee n 
e val uate d i n se veral st u dies i n healt h y  a n d 
i m m u n oc o m pr o mise d a d ults. In t hese st u dies it elicite d
str o n g cell ular a n d h u m oral i m m u ne res p o nses. F urt her m ore, 
t he safety a n d rea ct o ge nicit y pr ofile of t he ca n di date vacci ne 
was acce pta ble.
T w o lar ge pi v otal p hase III trials Z O E -5 0 ( Z O S T E R -0 0 6) 
a n d Z O E-7 0 ( Z O S T E R -0 2 2) t hat e nr olle d s u bjects 5 0 a n d 
7 0 Y O A , res pecti vely, e val uate d t he vacci ne efficac y , 
i m m u n o ge nicity a n d safet y of G S K Bi ol o gicals’ H Z/s u 
vacci ne. T hese ra n d o mize d trials t o get her e nr olle d m ore t ha n 
3 0, 0 0 0 s u bjects w h o eit her recei ve d t he H Z/s u vacci ne or 
place b o o n a 0, 2 -m o nt h sc he d ule.
T he fi nal a nal y sis of t he Z O S T E R-0 0 6 pri mar y  efficac y 
o bjecti ve ( Q 4 2 0 1 4) de m o ns trate d t hat t he vacci ne is hi g hl y 
efficaci o us i n a d ults ≥5 0 Y O A , wit h efficac y a gai nst H Z of 
9 7. 2 % ( 9 5 % c o nfi de nce i nter val ( CI) of 9 3. 7 -9 9. 0). I n 
a d diti o n, efficac y a gai nst H Z was bet wee n 9 6. 6 % a n d 9 7. 9 % 
f or all pre-s pecifie d a ge gr o u ps ( 5 0- 5 9, 6 0-6 9 a n d
≥7 0 Y O A ). T he res ults fr o m Z O S T E R-0 2 2 i n dicate d t hat t he 
pri mar y  o bjecti ves were als o s uccessf ull y met, de m o nstrati n g 
8 9. 8 % ( 9 5 % CI of 8 4. 2 -9 3. 7) efficac y  a gai nst H Z i n s u bjects 
≥7 0 Y O A a n d are t heref ore c o nsiste nt wit h t he res ults of 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
9
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 0
Z O S T E R -0 0 6. I n a d d iti o n, t he first pri mar y o bjecti ve of pre-
s pecifie d p o ole d a nalys is of Z O S T E R-0 0 6 a n d Z O S T E R - 0 2 2 
de m o nstrate d t hat H Z/s u effecti vel y pre ve nts P H N. H Z/s u 
was de m o nstrate d t o be 8 8. 8 % ( 9 5 % CI of 6 8. 7 -9 7. 1) 
efficaci o us i n pre ve nti n g P H N i n pe o ple ≥7 0 Y O A . N o
safety c o ncer ns ha ve bee n raise d.
I n t he p o ole d a nalys is of t he Z O S T E R-0 0 6 a n d Z O S T E R -
0 2 2 st u dies t he m ost c o m m o n si de effects were at t he site of 
i njecti o n, i ncl u di n g pai n, re d ness, a n d s welli n g. U p t o 7 0 % 
of pe o ple w h o recei ve d t he H Z/s u vacci ne ha d pai n at t he 
i njecti o n site. T hese sy m p t o ms were us ually mil d a n d 
res ol ve d wit hi n a b o ut 3 da ys o n a vera ge. T he i nci de nce of 
gra de 3 s olicite d l ocal pai n, was a b o ut 4 %, wit h a n a vera ge 
d urati o n of less t ha n 2 da y s. Gra de 3 react o ge nicit y is 
defi ne d as pre ve nti n g A D L . Ot her si de effects see n i n more 
t ha n 1 0 % of pe o ple w h o recei ve d t he vacci ne i ncl u de d 
m y al gia, fati g ue, hea dac he, s hi veri n g, fe ver a n d 
gastr oi ntesti nal s y m pt o ms s uc h as na usea, v o miti n g, 
diarr h oea a n d/ or a b d o mi nal pai n. T he i nci de nce of m y al gia 
a n d fati g ue was a b o ut 3 3 % ( o verall/ d ose) a n d ha d a n a vera ge 
d urati o n of 2. 5 da y s. T he i nci de nce of gra de 3 s olicite d 
ge neral s y m pt o ms was 3 % or less ( o verall/ d ose) wit h 
a vera ge d urati o ns of less t ha n 2 da y s.
W hile g ra de 3 react o ge nicit y is defi ne d as pre ve nti n g A D L, 
t here is n o clear u n dersta n di n g o n h o w t his i m pact s t he dail y
P h y sical F u ncti o ni n g ( P F) of a n i n di vi d ual. As s uc h t his 
st u d y is desi g ne d t o q ua ntif y t he i m pact of react o ge nicit y i n 
ter ms of P F (e. g., wal ki n g carr yi n g gr oceries, cli m bi n g stairs, 
etc.). The Q ualit y -a dj uste d life year ( QA L Y) l oss ass ociate d 
wit h a H Z case t hat di d n ot lea d t o P H N has bee n esti mate d 
t o be a p pr o xi matel y 3. 6 5 da y s. F or H Z cases t hat le d t o P H N , 
it was bet wee n 3 8. 6 9 a n d 5 6. 9 4 da y s, res ulti n g i n Q A L Y 
l osses of 0. 1 0 6– 0. 1 5 6 de pe n di n g o n a ge f or n o n- vacci nees .
T his Q A L Y l oss ca n be a v oi de d b y pre ve nti n g H Z a n d P H N 
t hr o u g h vacci nati o n. H o we ver re d ucti o ns i n Q A L Y l oss b y  
pre ve nt i n g H Z a n d P H N t hr o u g h H Z/s u a d mi nistrati o n c o ul d 
be partiall y offset b y t he Q A L Y l oss relate d t o react o ge nicit y
t hat is ass ociate d wit h vacci nati o n.

Rati o nale f or t he st u d y desi g n
T he i m pact o n Q o L or Q A L Y l oss d ue t o t he react o ge nicit y 
will be c o m pare d t o t he i m pact o n Q o L or Q A L Y l oss d ue t o 
H Z a n d its c o m plicati o ns , n ota bl y  P H N. T his i m p orta nt 
i nf or mati o n will be use d t o better assess t he p u blic healt h 
i m pact of H Z/s u . F or t his p ur p ose, S F-3 6 a n d E Q -5 D 
q uesti o n naires – t he sa me q uesti o n naires use d i n t he 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 0
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 1
Z O S T E R -0 0 6 a n d Z O S T E R -0 2 2 st u dies t o meas ure t he 
i m pact of H Z an d P H N o n Q o L  – will be c ollecte d d uri n g 
t his st u d y.
T he st u d y will esti mate a n y  c ha n ges i n Q o L or Q A L Y l oss 
wit hi n t he sa me s u bjects bet wee n bef ore a n d after H Z/s u 
vacci nati o n, a n d t heref ore a place b o c o ntr ol will n ot be 
i ncl u de d.
O bjecti ve s
Pri m ar y

T o e sti mate t he c ha n ge i n t he S F - 3 6 P h y sical 
F u ncti o ni n g ( S F - 3 6 P F) scale sc ore fr o m baseli ne sc ore 
t o t he mea n sc ore o ver t he peri o d da y  1 t o da y 7
f oll o wi n g t he first H Z/s u vacci nati o n i n s u bjects ≥5 0 
ye ars of a ge ( Y O A) o verall.
Sec o n d ar y

T o esti mate t he c ha n ge i n t he S F - 3 6 P F scale sc ore fr o m 
baseli ne sc ore t o t he mea n sc ore o ver t he peri o d da y  1 t o 
da y  7 f oll o wi n g t he sec o n d H Z/s u vacci nati o n i n 
s u bjects ≥5 0 Y O A o verall .

T o esti mate t he c ha n ge i n t he S F - 3 6 P F scale sc ore i n 
s u bjects ≥5 0 Y O A b y  a ge, ge n der a n d react o ge nicit y 
gra de a n d t y p e of s y m pt o m (l ocal, s y ste mic) fr o m 
baseli ne sc ore t o t he mea n sc ore o ver t he peri o d da y  1 t o 
da y  7 f oll o wi n g b ot h H Z/s u vacci nati o ns 1 a n d 2.

T o esti mate t he c ha n ge i n S F - 3 6 P F si n gle ite m sc ores i n 
s u bjects ≥5 0 Y O A o verall, b y  a ge, ge n der a n d 
react o ge nicit y gra de a n d t ype of s y m pt o m (l ocal, 
s yste mic) fr o m baseli ne sc ore t o t he mea n sc ore o ver t he 
peri o d da y  1 t o da y 7 f oll o wi n g b ot h H Z/s u vacci nati o ns 
1 a n d 2.

T o esti mate t he c ha n ge i n S F - 3 6 Role P h y sical sc ores i n 
s u bjects ≥5 0 Y O A o verall, b y  a ge, ge n der a n d 
react o ge nicit y gra de a n d t ype of s y m pt o m (l ocal, 
s yste mic) fr o m baseli ne sc ore t o t he sc ore o n da y  7 
f oll o wi n g b ot h H Z/s u vacci nati o ns 1 a n d 2.

T o esti mate t he Q A L Y c ha n ge i n s u bjects ≥5 0 Y O A
o verall, b y a ge, ge n der, react o ge nicit y gra de a n d t y pe of 
s ym pt o m (l ocal, s ys te mic) fr o m baseli ne sc ore t o t he 
c o m bi ne d sc ore o n da ys 1 t o 7 f oll o wi n g b ot h H Z/s u 
vacci nati o ns 1 a n d 2.

T o assess t he i m pact of react o ge nicit y o n t he healt hcare 
res o urce utilizati o n (i.e., h os pitalizati o n, Ge neral 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 1
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 2
Practiti o ners a n d s pecialist visits, me dicati o n i nta ke) i n 
s u bjects ≥5 0 Y O A o verall, b y  a ge, ge n der 
react o ge nicit y gra de a n d t ype of s y m pt o m (l ocal, 
s yste mic) f oll o wi n g b ot h H Z/s u vacci nati o ns 1 a n d 2.

T o esti mate t he w or k l oss i n s u bjects ≥5 0 Y O A o verall, 
b y  a ge, ge n der, react o ge nicit y gra de a n d ty pe of 
s ym pt o m (l ocal, s ys te mic) f oll o wi n g b ot h H Z/s u 
vacci nati o ns 1 a n d 2.

T o esti mate t he w or k l oss f or n o n-de dicate d care gi vers 
(e. g., fa mily me m ber) of s u b jects ≥5 0 Y O A o verall, b y  
ge n der, react o ge nicit y  gra de a n d ty pe of s y m pt o m (l ocal, 
s yste mic) f oll o wi n g b ot h H Z/s u vacci nati o ns 1 a n d 2.

T o esti mate t he e xtra w or k f or de dicate d care gi vers of 
s u bjects ≥5 0 Y O A o verall, b y  ge n der, react o ge nicit y 
gra de a n d t ype of s y m pt o m (l ocal, s y ste mic) f oll o wi n g 
b ot h H Z/s u vacci nati o ns 1 a n d 2.

T o e val uate t he safet y a n d react o ge nicit y f oll o wi n g 
a d mi nistrati o n of t he H Z/s u vacci ne i n s u bjects 
≥5 0 Y O A .
St u d y desi g n

E x peri me ntal desi g n: P hase III, o pe n la bel, m ulti-ce nter 
st u d y wit h a si n gle gr o u p.

D urati o n of t he st u d y:  A p pr o xi matel y 1 4 m o nt hs.

E p oc h 0 0 1 : Pri mar y starti n g at Visit 1 ( Da y -7) a n d 
e n di n g at t he St u d y c o ncl usi o n c o ntact ( M o nt h 1 4).

Pri mar y  c o m pleti o n Date ( P C D): Visit 3.

E n d of St u d y  ( E o S): Last data release d f or all s u bjects 
fr o m t he M o nt h 1 4 p h o ne c o ntact.

St u d y  gr o u ps:
S y n o p si s T a bl e 1
St u d y  gr o u p a n d e p o c h f or e s e e n i n t h e st u d y
St u d y gr o u p s
N u m b er of 
s u bj e ct s
A g e ( Mi ni m u m)
E p o c h s
E p oc h 0 0 1
H Z/s u
4 0 0
≥5 0 y e ars
x
S y n o p si s T a bl e 2
St u d y  gr o u p a n d tr e at m e nt f or e s e e n i n t h e st u d y
Tr e at m e nt n a m e
V a c ci n e/ Pr o d u ct n a m e
St u d y Gr o u p
H Z/s u
H Z/s u
V Z V g E
x
A S 0 1 B
x

C o ntr ol: Pre -vacci nati o n baseli ne c o ntr ol.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 2
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 3

Vacci nati o n sc he d ule: M o nt hs 0 a n d 2.

Treat me nt all ocati o n:
Eli gi ble s u bjects will be e nr olle d i nt o t he si n gle st u d y  
gr o u p.

Bli n di n g:
S y n o p si s T a bl e 3
Bli n di n g of st u d y  e p o c h s
St u d y E p o c h s
Bli n di n g
E p oc h 0 0 1
o p e n

Sa m pli n g sc he d ule:

A uri ne s peci me n will be c ollecte d fr o m all fe male 
s u bjects of c hil d-beari n g p ote ntial at Visit 2 a n d Visit 
4. If a ser u m pre g na nc y  test i nstea d of a uri ne 
pre g na nc y  test is re q uire d b y l ocal or et hics c o m mittee 
re g ulati o ns, a bl o o d sa m ple will be c ollecte d fr o m 
w o me n of c hil d -beari n g p ote ntial at Visit 2 a n d Visit 4 
a n d use d f or t he test as per l ocal g ui da nce .

T y pe of st u d y : self-c o ntai ne d.

Data c ollecti o n: Electr o nic Case Re p ort F or m ( e C R F).
N u m ber of s u bjects
Tar get e nr ol me nt is 4 0 0 eli gi ble s u bjects.
E n d p oi nts
Pri m ar y

C ha n ge i n mea n S F - 3 6 P F scale sc ore.

Baseli ne * vers us mea n sc ore o ver t he peri o d d a y  1 t o 
da y  7 * * after first vacci nati o n .
Sec o n d ar y

C ha n ge i n mea n S F - 3 6 P F scale sc ore.

Baseli ne * vers us mea n sc ore o ver t he peri o d da y 1 t o 
da y  7 * * after sec o n d vacci nati o n .

C ha n ge i n mea n S F - 3 6 P F si n gle ite m sc ores.

Baseli ne * vers us mea n sc ore o ver t he peri o d da y  1 t o 
da y  7 * * after eac h vacci nati o n .

C ha n ge i n S F - 3 6 Role P h ys ical sc ores.

Baseli ne * vers us sc ore o n da y 7 * * after eac h 
vacci nati o n .

C ha n ge i n t he Q A L Y.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 3
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 4

Baseli ne * vers us c o m bi ne d sc ore o ver t he peri o d da y  1 
t o da y  7 * * assess me nt after eac h vacci nati o n .

Healt hcare res o urce utilizati o n (i.e., h os pitalizati o n, 
tele p h o ne calls, me dical visits a n d s pecialist visits, 
me dicati o n i nta ke ).

D a y s 0 t o 6 after eac h vacci nati o n.

W or k l oss f or s u bjects.

D a y s 0 t o 6 after eac h vacci nati o n.

W or k l oss f or t he n o n- de dicate d care gi vers.

D a y s 0 t o 6 after eac h vacci nati o n.

E xtra w or k f or de dicate d care gi vers.

D a y s 0 t o 6 after eac h vacci nati o n.

S olicite d l ocal a n d ge neral s y m pt o ms i n s u bjects.

Occ urre nce, i nte nsit y  a n d d urati o n of s olicite d l ocal 
s ym pt o ms wit hi n 7 da y s ( Da ys 0- 6 * *) after eac h 
vacci nati o n.

Occ urre nce, i nte nsit y , d urati o n a n d relati o ns hi p t o 
vacci nati o n of s olicite d ge neral s y m pt o ms wit hi n 7 
da y s ( Da ys 0- 6 * *) after eac h vacci nati o n.

U ns olicite d a d verse e ve nts ( A Es) i n s u bjects.

Occ urre nce, i nte nsit y  a n d relati o ns hi p t o vacci nati o n 
d uri n g 3 0 da y s ( Da ys 0-2 9) after eac h vacci nati o n, 
acc or di n g t o t he Me dical Dicti o nar y  f or Re g ulat or y 
Acti vities ( Me d D R A) classificati o n.

Occ urre nce of seri o us a d verse e ve nts ( S A Es).

Occ urre nce a n d relati o ns hi p t o vacci nati o n of all S A Es 
fr o m t he first vacci nati o n u p t o t he st u d y e n d.

Occ urre nce of a d verse e ve nts of s pecific i nterest ( A E SI s): 
p ote ntial I m m u ne -Me diate d Diseases ( p I M Ds).

Occ urre nce a n d relati o ns hi p t o vacci nati o n of a n y 
pI M Ds fr o m first vacci nati o n u p t o t he st u d y  e n d.
* N ote: baseli ne f or d ose 1 is defi ne d as t he mea n of t he 
assess me nts at da y -7 a n d da y  0; f or d ose 2 baseli ne is defi ne d 
as t he mea n of t he t hree assess me nts at da y  -7, da y 0 a n d da y  6 0 
( da y 0 f or d ose 2 ). F urt her details o n baseli ne calc ulati o n will 
be gi ve n i n t he Statistical A nal y sis Pla n ( S A P).
* * N ote: T he p ost -vacci nati o n c o m pleti o n of S F -3 6 a n d E Q -5 D 
q uesti o n naires br o u g ht h o me b y  t he s u bjects will be o n da ys 1 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 4
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 5
t o da y 6, wit h da y  7 t o be fille d i n at t he site ( d uri n g Visits 3 
a n d 5); w hile t he p ost -vacci nati o n rec or di n g of s olicite d A Es o n 
t he diar y  car d br o u g ht h o me b y t he s u bjects will be o n da ys 0 t o 
da y  6.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 5
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 6
T A B L E O F C O N T E N T S
P A G E
S P O N S O R I N F O R M A TI O N ............................................................................................7
S Y N O P SI S ......................................................................................................................8
LI S T O F A B B R E VI A TI O N S ...........................................................................................2 2
G L O S S A R Y O F T E R M S ...............................................................................................2 5
T R A D E M A R K S .............................................................................................................2 9
1.
I N T R O D U C TI O N....................................................................................................3 0
1. 1.
B a c k gr o u n d ................................................................................................3 0
1. 2.
R ati o n al e f or t h e st u d y a n d st u d y d e si g n ....................................................3 1
1. 2. 1.
R ati o n al e f or t h e st u d y .................................................................3 1
1. 2. 2.
R ati o n al e f or t h e st u d y d e si g n ......................................................3 2
1. 3.
B e n efit : Ri s k A s s e s s m e nt ..........................................................................3 3
1. 3. 1.
Ri s k A s s e s s m e nt .........................................................................3 3
1. 3. 2.
B e n efit A s s e s s m e nt .....................................................................3 4
1. 3. 3.
O v er all B e n efit: Ri s k C o n cl u si o n ...................................................3 4
2.
O B J E C TI V E S .........................................................................................................3 4
2. 1.
Pri m ar y o bj e cti v e ........................................................................................3 4
2. 2.
S e c o n d ar y o bj e cti v e s ..................................................................................3 4
3. 
S T U D Y D E SI G N O V E R VI E W
................................................................................3 6
4.
S T U D Y C O H O R T ...................................................................................................3 8
4. 1.
N u m b er of s u bj e ct s/ c e nt er s .......................................................................3 8
4. 2.
I n cl u si o n crit eri a f or e nr ol m e nt....................................................................3 8
4. 3.
E x cl u si o n crit eri a f or e nr ol m e nt ...................................................................3 9
5.
C O N D U C T O F T H E S T U D Y ..................................................................................4 0
5. 1.
R e g ul at or y a n d et hi c al c o n si d er ati o n s, i n cl u di n g t h e i nf or m e d 
c o n s e nt pr o c e s s ..........................................................................................4 0
5. 2.
S u bj e ct i d e ntifi c ati o n a n d r a n d o mi z ati o n of tr e at m e nt .................................4 1
5. 2. 1.
S u bj e ct i d e ntifi c ati o n ....................................................................4 1
5. 2. 2.
R a n d o mi z ati o n of tr e at m e nt .........................................................4 1
5. 2. 2. 1.
R a n d o mi z ati o n of s u p pli e s ..........................................4 1
5. 2. 2. 2.
Tr e at m e nt all o c ati o n t o t h e s u bj e ct .............................4 1
5. 2. 2. 2. 1.
St u d y gr o u p a n d tr e at m e nt 
n u m b er all o c ati o n ...................................4 1
5. 2. 2. 2. 2.
Tr e at m e nt n u m b er all o c ati o n f or 
s u b s e q u e nt d o s e s ..................................4 2
5. 3.
G e n er al st u d y a s p e ct s ................................................................................4 2
5. 3. 1.
D at a c oll e cti o n .............................................................................4 3
5. 3. 1. 1.
Q u e sti o n n air e s a n d Di ar y c ar d s ..................................4 3
5. 4.
O utli n e of st u d y pr o c e d ur e s ........................................................................4 4
5. 5.
D et ail e d d e s cri pti o n of st u d y pr o c e d ur e s ....................................................4 7
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 6
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 7
5. 5. 1.
Pr o c e d ur e s d uri n g Vi sit 1 .............................................................4 7
5. 5. 1. 1.
I nf or m e d c o n s e nt........................................................4 7
5. 5. 1. 2.
C h e c k i n cl u si o n a n d e x cl u si o n crit eri a ........................4 7
5. 5. 1. 3.
Tr ai ni n g o n t h e c o m pl eti o n of S F -3 6 a n d E Q -
5 D q u e sti o n n air e s .......................................................4 7
5. 5. 1. 4.
Di stri b uti o n a n d c o m pl eti o n of S F -3 6 a n d E Q -
5 D q u e sti o n n air e s .......................................................4 8
5. 5. 1. 5.
P h y si c al e x a mi n ati o n a n d a s s e s s m e nt of fr ailt y 
st at u s ..........................................................................4 8
5. 5. 1. 6.
R e c or d d e m o gr a p hi c d at a ..........................................4 8
5. 5. 1. 7.
M e di c al hi st or y ...........................................................4 8
5. 5. 1. 8.
Di stri b uti o n, tr ai ni n g, c o m pl eti o n a n d c oll e cti o n 
of  pr e -v a c ci n ati o n di ar y c ar d .......................................4 8
5. 5. 1. 9.
R e vi e w a n d tr a n s cri b e pr e -v a c ci n ati o n di ar y 
c ar d s ..........................................................................4 9
5. 5. 2.
Pr o c e d ur e s d uri n g Vi sit 2 .............................................................4 9
5. 5. 2. 1.
R e -c h e c k i n cl u si o n a n d e x cl u si o n crit eri a ...................4 9
5. 5. 2. 2.
Di stri b uti o n, c o m pl eti o n a n d c oll e cti o n of 
s e c o n d pr e- v a c ci n ati o n di ar y c ar d ..............................4 9
5. 5. 2. 3.
R e vi e w a n d tr a n s cri b e pr e -v a c ci n ati o n di ar y 
c ar d s ..........................................................................4 9
5. 5. 2. 4.
Di stri b uti o n a n d c o m pl eti o n of S F -3 6 a n d E Q -
5 D q u e sti o n n air e s at Vi sit 2 ........................................4 9
5. 5. 2. 5.
C h e c k c o ntr ai n di c ati o n s ..............................................5 0
5. 5. 2. 6.
Pr e g n a n c y t e st ...........................................................5 0
5. 5. 2. 7.
A s s e s s pr e -v a c ci n ati o n b o d y t e m p er at ur e ..................5 0
5. 5. 2. 8.
St u d y v a c ci n e a d mi ni str ati o n ......................................5 0
5. 5. 2. 9.
C h e c k a n d r e c or d c o n c o mit a nt 
m e di c ati o n/ v a c ci n ati o n ...............................................5 1
5. 5. 2. 1 0.
R e c or di n g of A E s, S A E s, pr e g n a n ci e s a n d 
pI M D s .........................................................................5 1
5. 5. 2. 1 1.
Di stri b uti o n a n d c o m pl eti o n o f S F-3 6 a n d E Q -
5 D q u e sti o n n air e s p o st -v a c ci n ati o n ............................5 1
5. 5. 3.
St u d y c o n cl u si o n ..........................................................................5 2
6.
S T U D Y V A C CI N E A N D A D MI NI S T R A TI O N ...........................................................5 2
6. 1.
D e s cri pti o n of st u d y v a c ci n e .......................................................................5 2
6. 2.
St or a g e a n d h a n dli n g of st u d y v a c ci n e .......................................................5 2
6. 3.
D o s a g e a n d a d mi ni str ati o n of st u d y v a c ci n e ...............................................5 3
6. 4.
C o ntr ai n di c ati o n s t o s u b s e q u e nt v a c ci n ati o n ..............................................5 3
6. 5.
C o n c o mit a nt m e di c ati o n s/ pr o d u ct s a n d c o n c o mit a nt v a c ci n ati o n s ..............5 4
6. 5. 1.
R e c or di n g of c o n c o mit a nt m e di c ati o n s/ pr o d u ct s a n d 
c o n c o mit a nt v a c ci n ati o n s .............................................................5 4
6. 5. 2.
C o n c o mit a nt v a c ci n e s t h at m a y l e a d t o t h e eli mi n ati o n of a 
s u bj e ct fr o m A T P a n al y s e s ..........................................................5 5
7.
H E A L T H E C O N O MI C S ..........................................................................................5 6
8.
S A F E T Y .................................................................................................................5 6
8. 1.
S af et y d efi niti o n s ........................................................................................5 6
8. 1. 1.
D efi niti o n of a n a d v er s e e v e nt ......................................................5 6
8. 1. 2.
D efi niti o n of a s eri o u s a d v er s e e v e nt ...........................................5 7
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 7
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 8
8. 1. 3.
S oli cit e d a d v er s e e v e nt s ..............................................................5 8
8. 1. 3. 1.
S oli cit e d l o c al (i nj e cti o n -sit e) a d v er s e e v e nt s ..............5 8
8. 1. 3. 2.
S oli cit e d g e n er al a d v er s e e v e nt s ................................5 9
8. 1. 4.
Cli ni c al l a b or at or y p ar a m et er s a n d ot h er a b n or m al 
a s s e s s m e nt s q u alif yi n g a s a d v er s e e v e nt s or s eri o u s 
a d v er s e e v e nt s ............................................................................5 9
8. 1. 5. 
A d v er s e e v e nt s of s p e cifi c i nt er e st ...............................................5 9
8. 1. 5. 1.
P ot e nti al i m m u n e -m e di at e d di s e a s e s .........................5 9
8. 2.
E v e nt s or o ut c o m e s n ot q u alif yi n g a s a d v er s e e v e nt s or s eri o u s 
a d v er s e e v e nt s ...........................................................................................6 1
8. 2. 1.
Pr e g n a n c y ...................................................................................6 1
8. 3.
D et e cti n g a n d r e c or di n g a d v er s e e v e nt s, s eri o u s a d v er s e e v e nt s 
a n d pr e g n a n ci e s .........................................................................................6 2
8. 3. 1.
Ti m e p eri o d f or d et e cti n g a n d r e c or di n g a d v er s e e v e nt s, 
s eri o u s a d v er s e e v e nt s a n d pr e g n a n ci e s .....................................6 2
8. 3. 2.
P o st -St u d y a d v er s e e v e nt s a n d s eri o u s a d v er s e e v e nt s ..............6 4
8. 3. 3.
E v al u ati o n of a d v er s e e v e nt s a n d s eri o u s a d v er s e e v e nt s ...........6 4
8. 3. 3. 1.
A cti v e q u e sti o ni n g t o d et e ct a d v er s e e v e nt s 
a n d s eri o u s a d v er s e e v e nt s ........................................6 4
8. 3. 3. 2.
A s s e s s m e nt of a d v er s e e v e nt s ...................................6 5
8. 3. 3. 2. 1.
A s s e s s m e nt of i nt e n sit y ..........................6 5
8. 3. 3. 2. 2.
A s s e s s m e nt of c a u s alit y .........................6 6
8. 3. 3. 3.
A s s e s s m e nt of o ut c o m e s ............................................6 7
8. 3. 3. 4.
M e di c all y att e n d e d vi sit s .............................................6 8
8. 4.
R e p orti n g of s eri o u s a d v er s e e v e nt s, pr e g n a n ci e s, a n d ot h er e v e nt s .........6 8
8. 4. 1.
Pr o m pt r e p orti n g of s eri o u s a d v er s e e v e nt s, pr e g n a n ci e s, 
a n d ot h er e v e nt s t o G S K Bi ol o gi c al s ............................................6 8
8. 4. 2.  
C o nt a ct i nf or m ati o n f or r e p orti n g s eri o u s a d v er s e e v e nt s, 
pr e g n a n ci e s a n d pI M D s ...............................................................6 9
8. 4. 3.
C o m pl eti o n a n d tr a n s mi s si o n of S A E r e p ort s t o G S K 
Bi ol o gi c al s ...................................................................................6 9
8. 4. 3. 1.
B a c k -u p s y st e m i n c a s e t h e el e ctr o ni c r e p orti n g 
s y st e m d o e s n ot w or k .................................................6 9
8. 4. 4.
C o m pl eti o n a n d tr a n s mi s si o n of pr e g n a n c y r e p ort s t o G S K 
Bi ol o gi c al s ...................................................................................7 0
8. 4. 5.
R e p orti n g of pI M D s t o G S K Bi ol o gi c al s ........................................7 0
8. 4. 6.
U p d ati n g of S A E, pr e g n a n c y, a n d pI M D i nf or m ati o n aft er 
r e m o v al of writ e a c c e s s t o t h e s u bj e ct’ s e C R F.............................7 0
8. 4. 7.
R e g ul at or y r e p orti n g r e q uir e m e nt s f or s eri o u s a d v er s e 
e v e nt s ..........................................................................................7 0
8. 5.
F oll o w -u p of a d v er s e e v e nt s, s eri o u s a d v er s e e v e nt s, a n d 
pr e g n a n ci e s ................................................................................................7 1
8. 5. 1.
F oll o w -u p of a d v er s e e v e nt s a n d s eri o u s a d v er s e e v e nt s ............7 1
8. 5. 1. 1.
F oll o w -u p d uri n g t h e st u d y ..........................................7 1
8. 5. 1. 2.
F oll o w -u p aft er t h e s u bj e ct i s di s c h ar g e d fr o m 
t h e st u d y.....................................................................7 1
8. 5. 2.
F oll o w -u p of pr e g n a n ci e s .............................................................7 2
8. 6.
Tr e at m e nt of a d v er s e e v e nt s ......................................................................7 2
8. 7.
S u bj e ct c ar d ................................................................................................7 2
9.
S U B J E C T C O M P L E TI O N A N D W I T H D R A WA L .....................................................7 2
9. 1.
S u bj e ct c o m pl eti o n .....................................................................................7 2
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 8
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 9
9. 2.
S u bj e ct wit h dr a w al ......................................................................................7 2
9. 2. 1.
S u bj e ct wit h dr a w al fr o m t h e st u d y ................................................7 2
9. 2. 2.
S u bj e ct wit h dr a w al fr o m i n v e sti g ati o n al v a c ci n e ...........................7 3
1 0.
S T A TI S TI C A L M E T H O D S ......................................................................................7 4
1 0. 1.
Pri m ar y e n d p oi nt .........................................................................................7 4
1 0. 2.
S e c o n d ar y e n d p oi nt s ..................................................................................7 4
1 0. 3.
D et er mi n ati o n of s a m pl e si z e ......................................................................7 5
1 0. 4.
C o h ort s f or A n al y s e s ...................................................................................7 6
1 0. 4. 1.
T ot al v a c ci n at e d c o h ort ................................................................7 6
1 0. 4. 2.
A c c or di n g -t o-pr ot o c ol c o h ort f or a n al y si s of s af et y .......................7 6
1 0. 5.
D eri v e d a n d tr a n sf or m e d d at a .....................................................................7 6
1 0. 6.
St ati sti c al a n al y s e s .....................................................................................7 6
1 0. 6. 1.
A n al y si s of d e m o gr a p hi c s/ b a s eli n e c h ar a ct eri sti c s ......................7 6
1 0. 6. 2.
Q u alit y of lif e ................................................................................7 7
1 0. 6. 2. 1.
A n al y si s of Q A L Y ( Utilit y) ............................................7 7
1 0. 6. 2. 2.
A s s e s s m e nt of fr ailt y st at u s ........................................7 7
1 0. 6. 2. 3.
S F -3 6 h e alt h s ur v e y ...................................................7 8
1 0. 6. 2. 4.
E Q -5 D q u e sti o n n air e ..................................................7 8
1 0. 6. 3.
A n al y si s of s af et y .........................................................................7 9
1 0. 7.
I nt er pr et ati o n of a n al y s e s............................................................................8 0
1 0. 8.
C o n d u ct of a n al y s e s ...................................................................................8 0
1 0. 8. 1.
S e q u e n c e of a n al y s e s ..................................................................8 0
1 0. 8. 2.
St ati sti c al c o n si d er ati o n s f or i nt eri m a n al y s e s ..............................8 0
1 1.
A D MI NI S T R A TI V E M A T T E R S ...............................................................................8 0
1 1. 1.
el e ctr o ni c C a s e R e p ort F or m i n str u cti o n s ...................................................8 0
1 1. 2.
St u d y M o nit ori n g b y G S K Bi ol o gi c al s ..........................................................8 1
1 1. 3.
R e c or d r et e nti o n .........................................................................................8 1
1 1. 4.
Q u alit y a s s ur a n c e .......................................................................................8 2
1 1. 5.
P o sti n g of i nf or m ati o n o n p u bli cl y a v ail a bl e cli ni c al tri al r e gi st er s a n d 
p u bli c ati o n p oli c y ........................................................................................8 2
1 1. 6.
Pr o vi si o n of st u d y r e s ult s t o i n v e sti g at or s ...................................................8 3
1 2.
C O U N T R Y S P E CI FI C R E Q UI R E M E N T S ...............................................................8 3
1 3.
R E F E R E N C E S ( A m e n d e d 1 6 N O V E M B E R 2 0 1 6) .................................................8 3
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 9
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
2 0
LI S T O F T A B L E S
P A G E
T a bl e 1
St u d y gr o u p a n d e p o c h f or e s e e n i n t h e st u d y ........................................3 7
T a bl e 2
St u d y gr o u p a n d tr e at m e nt f or e s e e n i n t h e st u d y ...................................3 7
T a bl e 3
Bli n di n g of st u d y e p o c h s ........................................................................3 7
T a bl e 4
N u m b er of s u bj e ct s r e q uir e d f or e nr ol m e nt .............................................4 2
T a bl e 5
Li st of st u d y pr o c e d ur e s .........................................................................4 4
T a bl e 6
I nt er v al s b et w e e n st u d y vi sit s.................................................................4 7
T a bl e 7
St u d y v a c ci n e .........................................................................................5 2
T a bl e 8
D o s a g e a n d a d mi ni str ati o n .....................................................................5 3
T a bl e 9
S oli cit e d l o c al a d v er s e e v e nt s ................................................................5 8
T a bl e 1 0
S oli cit e d g e n er al a d v er s e e v e nt s ............................................................5 9
T a bl e 1 1
Li st of p ot e nti al i m m u n e -m e di at e d di s e a s e s ...........................................6 0
T a bl e 1 2
R e p orti n g p eri o d s f or c oll e cti n g s af et y i nf or m ati o n .................................6 3
T a b l e 1 3
I nt e n sit y s c al e s f or s oli cit e d s y m pt o m s i n a d ult s.....................................6 5
T a bl e 1 4
Ti m efr a m e s f or s u b mitti n g s eri o u s a d v er s e e v e nt, pr e g n a n c y a n d 
ot h er e v e nt s r e p ort s t o G S K Bi ol o gi c al s .................................................6 8
T a bl e 1 5
C o n str u cti o n of t h e ei g ht s c al e s g e n er at e d fr o m t h e S F -3 6 ....................7 8
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
2 0
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
2 1
LI S T O F A P P E N DI C E S
P A G E
A P P E N DI X A
S F -3 6 ( V er si o n 2. 0 S A M P L E) ( A m e n d e d 1 6 N o v e m b er 2 0 1 6) ...............8 5
A P P E N DI X B
E Q -5 D ( E n gli s h V er si o n U S S A M P L E) ( A m e n d e d 1 6 N o v e m b er 
2 0 1 6) ......................................................................................................9 1
A P P E N DI X C
A M E N D M E N T S A N D A D MI NI S T R A TI V E C H A N G E S T O T H E 
P R O T O C O L ...........................................................................................9 4
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
2 1
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
2 2
LI S T O F A B B R E VI A TI O N S
A D L:
Acti vities of Dail y  Li vi n g
A E:
A d verse E ve nt
A E SI :
A d verse E ve nt of S pecific I nterest
A N C A:
A nti- Ne utr o p hil C y t o plas mic A nti b o dies
A S 0 1 B :
M P L , Q S 2 1, li p os o me base d A dj u va nt S y ste m ( 5 0 μ g M P L  a n d 
5 0 μ g Q S 2 1)
A T P:
Acc or di n g -T o -Pr ot oc ol
B MI:
B o d y Mass I n de x
C D C:
Ce nters f or Disease C o ntr ol
C E S D - R:
Ce nter f or E pi de mi ol o gic St u dies De pressi o n Scale – Re vise d
CI:
C o nfi de nce I nter val
C R E S T:
Calci n osis, Ra y na u d's p he n o me n o n, Es o p ha geal d y s m otilit y, 
Scler o dact yl y a n d Tela n giectasia (s y n dr o me)
D:
D o mi na nt
D C:
Diar y  Car d
e C R F:
electr o nic Case Re p ort F or m
E D D:
Esti mate d Date of D eli ver y
E G A:
Esti mate d Gestati o nal A ge
E o S:
E n d of St u d y
E Q -5 D:
E ur o Q ol fi ve di me nsi o n healt h q uesti o n naire
e T D F:
Electr o nic Te m perat ure e xc ursi o n Decisi o n F or m
F D A:
F o o d a n d Dr u g A d mi nistrati o n, U nite d States of A merica
FI:
Frailt y I n de x
G C P:
G o o d Cli nical Practice
g E:
V Z V e n vel o pe gl yc o pr otei n E
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
2 2
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
2 3
G S K:
Gla x o S mit h Kli ne
H C P:
Healt h Care Pr o vi der
H Z:
Her pes Z oster
H Z/s u:
Her pes Z oster s u b u nit vacci ne
I B:
I n vesti gat or Br oc h ure
I C:
I m m u n oc o m pr o mise d
I C F:
I nf or me d C o nse nt F or m
I C H:
I nter nati o nal C o nfere nce o n Har m o nizati o n
I E C:
I n de pe n de nt Et hics C o m mittee
I M:
I ntra m usc ular
I M P:
I n vesti gati o nal Me dici nal Pr o d uct
I N D:
I n vesti gati o nal Ne w Dr u g
I R B:
I nstit uti o nal Re vie w B oar d
L L:
L o wer Li mit
L M P:
Last Me nstr ual Peri o d
L S L V:
Last S u bject Last Visit
M A C D P:
Metr o p olita n Atla nta C o n ge nital Defects Pr o gra m
M A T E X:
M A Terial E Xcelle nce
Me d D R A:
Me dical Dicti o nar y  f or Re g ulat or y Acti vities
m L :
Millilit er
M o C a:
M o ntreal C o g niti ve Assess me nt
M P L:
3- O -desac y l- 4’-M o n o p h os p h or y l Li pi d A
N- D:
N o n - d o mi na nt
P C D:
Pri mar y  C o m pleti o n Date
P F:
P h y sical F u ncti o ni n g
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
2 3
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
2 4
P F P:
P h y sical Frailt y P he n ot y pe
P H N:
P ost her petic Ne ural gia
pI M D:
P ote ntial I m m u ne -Me diate d Disease
P T:
Preferre d T er ms
Q A L Y:
Q ualit y -a dj uste d life ye ar
Q o L:
Q ualit y  of Life
Q S 2 1 :
Q uill aj a s a p o n ari a M oli na, fracti o n 2 1 ( A nti ge nics, Dela ware, 
U S A)
S A E:
Seri o us A d verse E ve nt
S A P:
Statistical A nal y sis Pla n
S A S:
Statistical A nal y sis S yste m
S BI R:
Ra n d o mizati o n S y ste m o n Inter net
S D V:
S o urce D oc u me nt Verificati o n
S F - 3 6:
A S h ort F or m 3 6- ite m healt h s ur ve y
S P M:
St u d y  Pr oce d ures Ma n ual
T Vc:
T otal Vacci nate d c o h ort
U L:
U p per Li mit
U S:
U nite d States ( of A merica)
V A S:
Vis u al A n al o g ue Sc ale ( A me n de d 1 6 N o ve m ber 2 0 1 6 )
V Z V:
Varicella -Z oster Vir us
Y O A:
Years of a ge
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
2 4
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
2 5
G L O S S A R Y O F T E R M S
A de q u ate c o ntr ace pti o n:
A de q uate c o ntrace pti o n is defi ne d as a c o ntrace pti ve 
met h o d wit h fail ure rate of less t ha n 1 % per y ear w he n 
use d c o nsiste ntl y  a n d c orrectly a n d w he n a p plica ble, i n 
acc or da nce wit h t he pr o d uct la bel f or e xa m ple: 

a bsti ne nce fr o m pe nile-va gi nal i nterc o urse, w he n t his 
is t heir preferre d a n d us ual lifest yle,

oral c o ntrace pti ves, eit her c o m bi ne d or pr o gest o ge n 
al o ne,

i njecta ble pr o gest o ge n,

i m pla nts of ete n o gestrel or le v o n or gestrel,

estr o ge nic va gi nal ri n g,

perc uta ne o us c o ntrace pti ve patc hes,

i ntra uteri ne de vice or i ntra uteri ne s ys te m,

male part ner sterili zati o n pri or t o t he fe male s u bject’s 
e ntr y i nt o t he st u d y, a n d t his male is t he s ole part ner 
f or t hat s u bject,
T he i nf or mati o n o n t he male sterilit y  ca n c o me fr o m 
t he site pers o n nel’s re vie w of t he s u bject’s me dical 
rec or ds; or i nter vie w wit h t he s u bject o n her me dical 
hist or y .

male c o n d o m c o m bi ne d wit h a va gi nal s per mici de 
(f oa m, gel, fil m, crea m or s u p p osit or y),

male c o n d o m c o m bi ne d wit h a fe male dia p hra g m, 
eit her wit h or wit h o ut a va gi nal s per mici de (f oa m, 
gel, fil m, crea m, or s u p p osit or y ). 
A de q uate c o ntrace pti o n d oes n ot a p pl y  t o s u bjects of 
c hil d beari n g p ote ntial wit h sa me se x part ners, w he n t his 
is t heir preferre d a n d us ual lifest yle.
A d verse e ve nt:
A n y  u nt o war d me dical occ urre nce i n a patie nt or cli nical 
i n vesti gati o n s u bject, te m p orall y ass ociate d wit h t he use 
of a me dici nal pr o d uct, w het her or n ot c o nsi dere d re late d 
t o t he me dici nal pr o d uct.
A n a d verse e ve nt ( A E) ca n t heref ore be a n y u nfa v o ura ble 
a n d u ni nte n de d si g n (i ncl u di n g a n a b n or mal la b ora t or y 
fi n di n g), sy m pt o m, or disease ( ne w or e xacer bate d) 
te m p orall y ass ociate d wit h t he use of a me dici nal pr o d uct. 
F or mar kete d me dici nal pr o d ucts, t his als o i ncl u des 
fail ure t o pr o d uce e x pecte d be nefits (i.e., lac k of 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
2 5
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
2 6
efficac y), a b use or mis use.
Bli n di n g :
A pr oce d ure i n w hic h o ne or m ore parties t o t he trial are 
ke pt u na ware of t he treat me nt assi g n me nt i n or der t o 
re d uce t he ris k of biase d st u d y o utc o mes. T he le vel of 
bli n di n g is mai ntai ne d t hr o u g h o ut t he c o n d uct of t he trial, 
a n d o nl y w he n t he data are clea ne d t o a n acce pta ble le vel 
of q ualit y  will a p pr o priate pers o n nel be u n bli n de d or 
w he n re q uire d i n case of a seri o us a d verse e ve nt. I n a n 
o pe n -la bel st u dy, n o bli n d is use d. B ot h t he i n vesti gat or 
a n d t he s u bject k n o w t he i de ntit y  of t he treat me nt 
assi g ned.
De dic ate d C are gi ver
A care gi ver t hat ma y  be a me m ber of a n or ga nizati o n, or 
w or ki n g i n de pe n de ntl y as a v ol u nteer care gi ver, or ma y 
be a n e m pl o ye d pr ofessi o nal .
Eli gi ble:
Q ualifie d f or e nr ol me nt i nt o t he st u d y  base d u p o n strict 
a d here nce t o i ncl usi o n/excl usi o n criteria.
E n d of St u d y
( S y n o n y m of E n d of 
Tri al)
F or st u dies wit h o ut c ollecti o n of h u ma n bi ol o gicals 
sa m ples or i ma gi n g data E o S is t he Last S u bject Last 
Visit ( L S L V).
F or st u dies wit h c ollecti o n of H u ma n Bi ol o gicals 
Sa m ples or i ma gi n g data, E o S is defi ne d as t he date of 
t he last testi n g/rea di n g release d of t he H u ma n Bi ol o gical 
Sa m ples or i ma gi n g data, relate d t o pri mar y  a n d 
sec o n dar y e n d p oi nts. E o S m ust be ac hie ve d n o later t ha n 
8 m o nt hs after L S L V.
E p oc h:
A n e p oc h is a self -c o ntai ne d set of c o nsec uti ve 
ti me p oi nts or a si n gle ti me p oi nt fr o m a si n gle pr ot oc ol. 
Self -c o ntai ne d mea ns t hat data c ollecte d f or all s u bjects 
at all ti me p oi nts wit hi n t hat e p oc h all o ws t o dra w a 
c o m plete c o ncl usi o n t o defi ne or precise t he tar gete d 
la bel of t he pr o d uct. T y pical e xa m ples of e p oc hs are 
pri mar y  vacci nati o ns, b o osters, yearl y i m m u n o ge nicit y  
f oll o w-u ps, a n d s ur veilla nce peri o ds f or efficac y  or 
safety.
e Tr ac k:
G S K’s trac ki n g t o ol f or cli nical trials.
E v al u a ble:
Meeti n g all eli gi bilit y  criteria, c o m plyi n g wit h t he 
pr oce d ures defi ne d i n t he pr ot oc ol, a n d, t heref ore, 
i ncl u de d i n t he acc or di n g-t o-pr ot oc ol ( A T P) a nal ysis (see 
Secti o ns 6. 5. 2 a n d 1 0. 4 f or details o n criteria f or 
e val ua bilit y).
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
2 6
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
2 7
Fr ailt y:
Frailt y is a ter m use d i n g eriatric m e dici ne t o i de ntif y 
ol der a d ults w h o are at i ncrease d ris k of p o or cli nical 
o utc o mes, s uc h as i nci de nt disa bilit y , c o g niti ve decli ne, 
falls, h os pitalizati o n, i nstit uti o nalizati o n, or i ncrease d 
m ortalit y. Frailt y  re prese nts a re d ucti o n i n resista nce t o 
stress ors lea di n g t o i ncrease d cli nical v ul nera bilit y a n d 
a d verse healt h o utc o mes .
I n vesti g ati o n al v acci ne :
( S y n o n y m of 
I n vesti g ati o n al Me dici n al 
Pr o d uct)
A p har mace utical f or m of a n acti ve i n gre die nt or place b o 
bei n g teste d or use d as a refere nce i n a cli nical trial, 
i ncl u di n g a pr o d uct wit h a mar keti n g a ut h orizati o n w he n 
use d i n a wa y  differe nt fr o m t he a p pr o ve d f or m, or w he n 
use d f or a n u na p pr o ve d i n dicati o n, or w he n use d t o gai n 
f urt her i nf or mati o n a b o ut a n a p pr o ve d use.
Me n o p a use:
Me n o pa use is t he a ge ass ociate d wit h c o m plete cessati o n 
of me nstr ual c y cles, me nses, a n d i m plies t he l oss of 
re pr o d ucti ve p ote ntial b y o varia n fail ure. A practical 
defi niti o n acce pts me n o pa use after 1 ye ar wit h o ut me nses 
wit h a n a p pr o priate cli nical pr ofile at t he a p pr o priate a ge 
e. g., > 4 5 ye ars.
N o n -De dic ate d 
C are gi ver
A care gi ver t hat is n ot a me m ber of a n or ga nizati o n or 
e m pl o ye d t hr o u g h a pr ofessi o nal a ge nc y ; has n o f or mal 
trai ni n g; f or e xa m ple, t he y ma y be a fa mil y me m ber or 
frie n d.
P ote nti al I m m u ne-
Me di ate d Dise ase:
P ote ntial i m m u ne -me diate d diseases ( p I M Ds) are a s u bset 
of A Es t hat i ncl u de a ut oi m m u ne diseases a n d ot her 
i nfla m mat or y a n d/ or ne ur ol o gic dis or ders of i nterest 
w hic h ma y  or ma y n ot ha ve a n a ut oi m m u ne aeti ol o g y.
Pri m ar y c o m pleti o n 
d ate:
T he date t hat t he fi nal s u bject was e xa mi ne d or recei ve d 
a n i nter ve nti o n f or t he p ur p ose of fi nal c ollecti o n of data 
f or t he pri mar y o utc o me, w het her t he cli nical trial 
c o ncl u de d acc or di n g t o t he pre -s pecifie d pr ot oc ol or was 
ter mi nate d.
Pr ot oc ol a me n d me nt:
T he I nter nati o nal C o nfere nce o n Har m o ni zati o n (I C H) 
defi nes a pr ot oc ol a me n d me nt as: ‘ A writte n descri pti o n 
of a c ha n ge(s) t o or f or mal clarificati o n of a pr ot oc ol.’ 
G S K Bi ol o gicals f urt her details t his t o i ncl u de a c ha n ge 
t o a n a p pr o ve d pr ot oc ol t hat affects t he safety of s u bjects, 
sc o pe of t he i n vesti gati o n, st u d y desi g n, or scie ntific 
i nte grity of t he st u d y.
Pr ot oc ol a d mi nistr ati ve 
c h a n ge:
A pr ot oc ol a d mi nistrati ve c ha n ge a d dresses c ha n ges t o 
o nl y  l o gistical or a d mi nistrati ve as pects of t he st u d y.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
2 7
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
2 8
R a n d o mi zati o n:
Pr ocess of ra n d o m attri b uti o n of treat me nt t o s u bjects i n 
or der t o re d uce bias of selecti o n.
Self -c o nt ai ne d st u d y:
St u d y  wit h o bjecti ves n ot li n ke d t o t he data of a n ot her 
st u d y.
Site M o nit or:
A n i n di vi d ual assi g ne d b y t he s p o ns or w h o is res p o nsi ble 
f or ass uri n g pr o per c o n d uct of cli nical st u dies at o ne or 
m ore i n vesti g ati o nal sites.
S olicite d a d verse e ve nt:
A Es t o be rec or de d as e n d p oi nts i n t he cli nical st u d y . T he 
prese nce/ occ urre nce/i nte nsit y  of t hese e ve nts is acti vel y 
s olicite d fr o m t he s u bject or a n o bser ver d uri n g a 
s pecifie d p ost-vacci nati o n f oll o w -u p peri o d.
S u bject:
Ter m use d t hr o u g h o ut t he pr ot oc ol t o de n ote a n 
i n di vi d ual w h o has bee n c o ntacte d i n or der t o partici pate 
or partici pates i n t he cli nical st u d y , eit her as a reci pie nt of 
t he vacci ne or as a c o ntr ol.
S u bject n u m ber:
A u ni q ue n u m ber i de ntif y i n g a s ubject, assi g ne d t o eac h 
s u bject c o nse nti n g t o partici pate i n t he st u d y.
Tre at me nt:
Ter m use d t hr o u g h o ut t he cli nical st u d y  t o de n ote a set of 
i n vesti gati o nal pr o d uct(s) or mar kete d pr o d uct(s) or 
place b o i nte n de d t o be a d mi nistere d t o a s u bject, 
i de ntifie d b y  a u ni q ue n u m ber, acc or di n g t o t he st u d y 
ra n d o mizati o n or treat me nt all ocati o n.
Tre at me nt n u m ber:
A n u m ber i de ntif y i n g a treat me nt t o a s u bject, acc or di n g 
t o t he st u d y ra n d o mizati o n or treat me nt all ocati o n.
U ns olicite d a d verse 
e ve nt:
A n y  A E re p orte d i n a d diti o n t o t h ose s olicite d d uri n g t he 
cli nical st u d y. Als o a ny ‘s olicite d’ s ym pt o m wit h o nset 
o utsi de t he s pecifie d peri o d of f oll o w -u p f or s olicite d 
s ym pt o ms will be re p orte d as a n u ns olicite d a d verse 
e ve nt.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
2 8
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
2 9
T R A D E M A R K S
T he f oll o wi n g tra de mar ks are us e d i n t he prese nt pr ot oc ol.
N ote: I n t he b o d y  of t he pr ot oc ol (i ncl u di n g t he s yn o psis), t he na mes of t he 
vacci nes/ pr o d ucts a n d/ or me dicati o n s will be writte n wit h o ut t he s u perscri pt s y m b ol ™ 
or ® a n d i n it alics.
Tr a d e m ar k s n ot o w n e d b y t h e 
Gl a x o S mit h Kli n e gr o u p of c o m p a ni e s
G e n eri c d e s cri pti o n
Z ost av ax ® (M erck & C o ., I nc.)
H er p es z ost er v acci n e c o nsisti n g of hi g h -
titr e liv e att e n u at e d V aric ell a-z ost er vir us 
( Ok a str ai n)
Q S -2 1: Q uill aj a s a p o n ari a M oli n a, fr acti o n 
2 1 ( Lic e ns e d by G S K fr o m A nti g e nics I nc, a 
w h olly o w n e d s u bsi di ary of A g e n us I nc., a 
D el a w ar e, U S A c or p or ati o n)
Trit er p e n e glyc osi d e i m m u n e e n h a nc er
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
2 9
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
3 0
1.
I N T R O D U C TI O N
1. 1.
B a c k gr o u n d
Varicella -Z oster Vir us ( V Z V) ca uses t w o disti nct diseases. Vari cella (c hic ke n p o x) occ urs 
s h ortl y after pri mar y V Z V i nfecti o n a n d is c haracterize d b y sys te mic ill ness a n d a wi dely 
disse mi nate d ras h. H Z (s hi n gles) occ urs w he n V Z V reacti vates fr o m late nc y. Vacci nati o n 
as a mea ns t o re d uce ris k of H Z has bee n e xa mi ne d i n b ot h ol der a n d i m m u n o-
c o m pr o mise d pers o ns.
H Z is c haracterize d b y ras h, a n d pai n/ or pr urit us. T he t y pical H Z ras h, vesicles i n a 
l ocalize d, der mat o mal ba n d o n o ne si de of t he b o d y, lasts 2 t o 4 wee ks a n d is ofte n
acc o m pa nie d b y se vere pai n t hat is descri be d as b ur ni n g, s h o oti n g, or sta b bi n g. I n s o me 
patie nts, e ve n li g htl y t o uc hi n g t he affecte d area ma y  ca use pai n, a p he n o me n o n k n o w n as 
all o d ynia. Pr urit us, w hic h ca n als o be se vere, ma y be as c o m m o n as pai n. Pai n t hat 
persists after t he res ol uti o n of t he H Z ras h is calle d p ost her petic ne ural gia ( P H N). 
N ota bl y , P H N ca n last f or m o nt hs or e ve n years.
Half of all H Z cases occ ur i n i n di vi d uals ≥6 0 years of a ge ( Y O A) . In di vi d uals w h o reac h 
8 5 ye ars ol d ha ve a 5 0 % c ha nce of ha vi n g H Z d uri n g t heir lifeti me [ O x ma n , 2 0 0 5]. T he 
ris k f or P H N is als o hi g hest i n ol der pe o ple wit h H Z, occ urri n g i n 1 8-5 0 % of t h ose 
≥7 0 Y O A [O x ma n , 2 0 0 5; Sc ott , 2 0 0 6; D w or ki n , 2 0 0 7]. Si nce t he l oss of V Z V -s pecific 
T- cell res p o nses as a res ult of a gi n g lea ds t o hei g hte ne d s usce pti bilit y  t o H Z, vacci nati o n 
is c o nsi dere d as a mea ns t o re d uce t he ris k of H Z i n ol der a d ults [O x ma n , 2 0 0 5; S per ber , 
1 9 9 2].
Ass ociate d wit h H Z a n d its c o m plicati o ns is a s u bsta ntial ne gati ve i m pact o n patie nts’ 
Q ualit y  of Life ( Q o L) a n d t heir a bilit y t o e n ga ge i n Acti vities of Dail y Li vi n g ( A D L). I n 
a d diti o n t o t he m or bi dit y e nc o u ntere d b y t he i n di vi d ual wit h H Z, i ncl u di n g pr o ducti vit y  
l oss, it ca n als o ha ve si g nifica nt c o nse q ue nces f or t he care gi ver(s) of patie nts i ncl u di n g 
part ners a n d relati ves of pe o ple wit h H Z [Gater , 2 0 1 5]. Ac ute H Z a n d H Z-relate d 
c o m plicati o ns s uc h as P H N ha ve a c o nsi dera ble ec o n o mic c ost t o healt hcare s yste ms 
cari n g f or H Z a n d P H N patie nts. T hese healt hcare c osts will m ost li kel y i ncrease d ue t o 
t he a gi n g p o p ulati o n, w here a ge -relate d diseases s uc h as H Z are bec o mi n g a gr o wi n g 
ec o n o mic b ur de n i n t he de vel o pi n g w orl d [ Sz ucs , 2 0 1 3].
A li ve atte n uate d V Z V vacci ne, Z ost av ax ( Merc k & C o), is lice nse d i n t he U nite d States 
( U S) t o pre ve nt H Z i n pers o ns ≥5 0 Y O A [Z ost av ax Prescri bi n g I nf or mati o n, 2 0 1 1]. Li v e
atte n uate d vacci ne is c o ntrai n dicate d i n i m m u n os u p presse d or i m m u n o deficie nt 
i n di vi d uals [Kr o ger , 2 0 1 1].
Gla x o S mit h Kli ne ( G S K) Bi ol o gicals’ H Z ca n di date vacci ne is a n a dj u va nte d 
rec o m bi na nt V Z V e n vel o pe glyc o pr otei n E ( g E) s u b u nit vacci ne, hereafter referre d t o as 
H Z/s u. T he a nti ge n c o m p o ne nt of t he st u d y  vacci ne is a tr u ncate d f or m of g E. T he 
a dj u va nt is A S 0 1 B , w hic h c o nsists of li p os o mes i n c o m bi nati o n wit h 5 0 µ g 3 - O-desc y l-
4’- M o n o p h os p h or y l Li pi d A ( M P L) a n d 5 0 µ g Q uill aj a s a p o n ari a , M oli na, fracti o n 2 1 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
3 0
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
3 1
( p urifie d nat ural sa p o ni n m olec ule e xtracte d fr o m t he S o ut h A merica n tree, Q uill aj a 
s a p o n ari a) ( Q S 2 1) per 0. 5 m L d ose.
T he G S K Bi ol o gicals’ H Z/s u ca n di date vacci ne has bee n e val uate d i n se veral st u dies i n 
healt h y  a n d i m m u n oc o m pr o mise d a d ults. In t hese st u dies it elicite d str o n g cell ular a n d
h u m oral i m m u ne res p o nses. F urt her m ore, t he safet y  a n d react o ge nicity pr ofile of t he 
ca n di date vacci ne was acce pta ble.
T w o lar ge pi v otal p hase III trials Z O E -5 0 ( Z O S T E R -0 0 6) a n d Z O E -7 0 ( Z O S T E R -0 2 2) 
t hat e nr olle d s u bjects 5 0 a n d 7 0 Y O A , res pecti vel y, e val uate d t he vacci ne efficac y, 
i m m u n o ge nicity a n d safet y of G S K Bi ol o gicals’ H Z/s u vacci ne. T hese ra n d o mize d trials 
t o get her e nr olle d m ore t ha n 3 0, 0 0 0 s u bjects w h o eit her recei ve d t he H Z/s u vacci ne or 
place b o o n a 0, 2 -m o nt h sc he d ule.
T he fi nal a nal y sis of t he Z O S T E R-0 0 6 pri mar y  efficac y o bjecti ve (Q 4 2 0 1 4) 
de m o nstrate d t hat t he vacci ne is hi g hly efficaci o us i n a d ults ≥5 0 Y O A , wit h efficac y 
a gai nst H Z of 9 7. 2 % ( 9 5 % c o nfi de nce i nter val ( CI) of 9 3. 7 -9 9. 0). I n a d diti o n, efficac y  
a gai nst H Z was bet wee n 9 6. 6 % a n d 9 7. 9 % f or all pre -s pecifie d a ge gr o u ps ( 5 0- 5 9, 6 0- 6 9 
a n d ≥7 0 Y O A ) [Lal , 2 0 1 5]. T he res ults fr o m Z O S T E R-0 2 2 i n dicate d t hat t he pri mar y 
o bjecti ves ha ve als o bee n s uccessf ull y m et, de m o nstrati n g 8 9. 8 % ( 9 5 % CI of 8 4. 2- 9 3 . 7) 
efficac y a gai nst H Z i n s u bjects ≥7 0 Y O A a n d are t heref ore c o nsiste nt wit h t he res ults of 
Z O S T E R -0 0 6. I n a d diti o n, t he first pri mar y  o bjecti ve of pre-s pecifie d p o ole d a nalys is of 
Z O S T E R -0 0 6 a n d Z O S T E R -0 2 2 de m o n strate d t hat H Z/s u effecti vel y pre ve nts P H N. 
H Z/s u was de m o nstrate d t o be 8 8. 8 % ( 9 5 % CI of 6 8. 7 -9 7. 1) efficaci o us i n pre ve nti n g 
P H N i n pe o ple ≥7 0 Y O A . N o safety c o ncer ns ha ve bee n raise d.
Please refer t o t he c urre nt I n vesti gat or Br oc h ure (I B) f or i nf or mati o n re gar di n g t he pre-
cli nical a n d cli nical st u dies of H Z/s u vacci ne.
1. 2.
R ati o n al e f or t h e st u d y  a n d st u d y d e si g n
1. 2. 1.
R ati o n al e f or t h e st u d y
N earl y 2 2, 9 0 0 s u bjects recei ve d t he acti ve H Z/s u st u d y vacci ne i n cli nical trials 
w orl d wi de , m ost of w h o m ( 9 5 %) were ≥5 0 Y O A . D ue t o the hi g h efficac y of t he 
vacci ne , m ost H Z a n d P H N cases were pre ve nte d , t h us a v oi di n g a ny ne gati ve i m pact o n
Q o L  i n t h ose s u bjects. N o i m bala nce bet wee n t he vacci ne a n d t he place b o ar ms were
f o u n d i n ter ms of S A Es, p ote ntial I m m u n e-Me diate d D iseases ( p I M Ds) or deat h d uri n g 
t he e ntire d urati o n of t he st u dies. T he vacci ne was ge nerall y well t olerate d. H o we ver, t he 
vacci ne was m o re react o ge nic t ha n place b o (sali ne s ol uti o n).
I n t he p o ole d a nalys is of t he Z O S T E R -0 0 6 a n d Z O S T E R -0 2 2 st u d ies the m ost c o m m o n 
si de effects were at t he site of i njecti o n, i ncl u di n g pai n, re d ness, a n d s welli n g. U p t o 7 0 % 
of pe o ple w h o recei ve d t he H Z/s u vacci ne ha d pai n at t he i njecti o n site. T hese s y m pt o ms 
were us uall y  mil d a n d res ol ve d wit hi n ab o ut 3 da ys o n a vera ge . T he i nci de nce of gra de 3 
s olicite d l ocal pai n, was a b o ut 4 %, wit h a n a vera ge d urati o n of less t ha n 2 da y s. Gra de 3 
react o ge nicit y is defi ne d as pre ve nti n g A D L. Ot her si de effects see n i n m ore t ha n 1 0 % of 
pe o ple w h o recei ve d t he vacci ne i ncl u de d m yal gia, f ati g ue, hea dac he, s hi veri n g, fe ver 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
3 1
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
3 2
a n d gastr oi ntesti nal s ym pt o ms s uc h as na usea, v o miti n g, diarr h oea a n d/ or a b d o mi nal 
pai n. T he i nci de nce of m yal gia a n d fati g ue was a b o ut 3 3 % ( o verall/ d ose) a n d ha d a n 
a vera ge d urati o n of 2. 5 da ys. T he i nci de nce of gra de 3 s olicite d ge neral s y m pt o ms was 
3 % or less ( o verall/ d ose) wit h a vera ge d urati o ns of less t ha n 2 da ys. T he react o ge nicit y is 
li kel y t o be sec o n dar y t o t he e n ha nce d i n nate i m m u ne res p o nses elicite d at t he site of 
i njecti o n a n d t heref ore is e x pecte d [Di dierla ure nt , 2 0 1 4]. T his is c o nsiste ntl y o bser ve d i n 
st u dies e val uati n g A S 0 1 – (a n d ot her) a dj u va nte d vacci nes, i n w hic h hi g her 
react o ge nicit y is o bser ve d wit h a dj u va nte d vers us n o n- a dj u va nte d vacci nes [Stassij ns , 
2 0 1 6].
W hile g ra de 3 react o ge nicit y is defi ne d as pre ve nti n g A D L, t here is n o clear 
u n dersta n di n g a vaila ble o n h o w t his tra nslates t o i m pact o n t he dail y P h y sical 
F u ncti o ni n g ( P F) of a n i n di vi d ual. As s uc h t his st u d y  is desi g ne d t o q ua ntif y t he i m pact 
of react o ge nicity i n ter ms of P F (e. g., wal ki n g, carr y i n g gr oceries, cli m bi n g stairs, etc.).
I n a d diti o n, the Q ualit y -a dj uste d life year ( Q A L Y) l oss ass ociate d f or b ot h Z ost av ax -
vacci n ate d a n d n o n- vacci nate d s u bjects wit h a H Z case t hat di d n ot lea d t o P H N , has 
bee n esti mate d t o be a p pr o xi matel y  0.0 1 (i.e., 3. 6 5 da y s) [Pellissier , 2 0 0 7]. F or H Z cases 
t hat le d t o P H N, it was bet wee n 3 8. 6 9 a n d 5 6. 9 4 da y s, res ulti n g i n Q A L Y l osses of 
0. 1 0 6 – 0. 1 5 6 de pe n di n g o n a ge f or n o n- vacci nate d s u bjects , [Pellissier , 2 0 0 7]. Si milar
res ults were o bser ve d i n t he Z O S T E R- 0 0 6 a n d Z O S T E R - 0 2 2 st u dies wit h t he H Z/s u 
vacci ne . As s uc h , Q A L Y l oss ca n be a v oi de d b y pre ve nt i n g H Z a n d P H N, t hr o u g h H Z/s u 
vacci nati o n . H o we ver re d ucti o ns i n Q A L Y l oss b y  pre ve nt i n g H Z a n d P H N t hr o u g h 
H Z/s u a d mi nistrati o n c o ul d be partiall y  offset b y t he Q A L Y l oss relate d t o react o ge nicit y
t hat is ass ociate d wit h vacci na ti o n.
I n assessi n g t he i m pact o n Q o L, t he Q A L Y l oss d ue t o a d verse e ve nts is a n i m p orta nt 
para meter t o i ncl u de w he n calc ulat i n g t he c ost/effecti ve ness of H Z/s u c o m pare d t o n o 
vacci nati o n . T hese data will be i ncl u de d i n m o dels w hic h a nalyz e net Q A L Y l oss a v oi de d 
b y  pre ve nti n g H Z a n d P H N b y  vacci nati n g wit h H Z/s u. F urt her m ore, o nl y li mite d data 
are a vaila ble t o assess t he i m pact of t he react o ge nicit y  o n t he Q ualit y of Life ( Q o L) a n d 
P F of i n di vi d uals e x p ose d t o t he H Z/s u vacci ne or vacci nati o n i n ge neral. T hese data are 
i m p orta nt t o b ot h Healt h Care Pr o vi ders ( H C Ps) a n d p olic y ma kers. A d diti o nal 
c haracterizati o n of t he react o ge nicit y will all o w vacci nat ors t o better i nf or m vacci nees 
bef ore t he a d mi nistrati o n of t he vac ci ne. T heref ore, t his st u d y will be c o n d ucte d t o 
e n ha nce o ur u n dersta n di n g of H Z/s u vacci ne react o ge nicit y, a n d t o pr o vi de m ore 
c o m plete i nf or mati o n t o vacci nat ors a n d pers o ns w h o will recei ve t he vacci ne .
1. 2. 2.
R ati o n al e f or t h e st u d y  d e si g n
T he i m pact o n Q o L a n d Q A L Y l oss d ue t o t he react o ge nicity will be c o m pare d t o t he 
i m pact o n Q o L or Q A L Y l oss d ue t o H Z a n d its c o m plicati o ns , n ota bl y  P H N. T his 
i nf or mati o n will be use d t o better assess t he p u blic healt h i m pact of H Z/s u . F or t his 
p ur p ose, S F - 3 6 [A P P E N DI X A ] a n d E Q-5 D [ A P P E N DI X B q uesti o n naires – t he sa me 
q uesti o n naires use d i n t he Z O S T E R- 0 0 6 a n d Z O S T E R -0 2 2 st u dies t o meas ure t he i m pact 
of H Z a n d P H N o n Q o L – will be c ollecte d d uri n g t his st u d y .
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
3 2
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
3 3
T he st u d y  will esti mate c ha n ges i n Q o L or Q A L Y l oss wit hi n t he sa me s u bject s bet wee n 
bef ore a n d after H Z/s u vacci nati o n, a n d t heref ore a place b o c o ntr ol will n ot be i ncl u de d.
( A me n de d 1 6 N o ve m ber 2 0 1 6 )
S u bjects i n t he ge neral p o p ulati o n (es peciall y ol der a d ults), are o n a vera ge u na ble t o 
ac hie ve perfect Q o L sc ores , beca use ma n y s u bjects ma y  be s o me w hat li mite d i n 
“cli m bi n g se veral fli g hts of stairs” or “ b e n di n g, k neeli n g, or st o o pi n g”. T o esti mate t he 
i m pact of react o ge nicity o n a n i n di vi d ual’s S F - 3 6 P F a n d Q o L, we will c o m pare t w o 
peri o ds, i.e., pre -vacci nati o n a n d p ost -vacci nati o n. T he differe nce is c o nsi dere d t o be t he 
effect of vacci nati o n a n d react o ge nicit y  o n t he S F - 3 6 P F a n d Q o L. T o c haracterize t he 
st u d y p o p ulati o n a n d deter mi ne if frailt y ma y i nfl ue nce react o ge nicity a n d c o nse q ue ntl y 
t he i m pact o n Q o L sc ores, t he s u bjects’ frailt y stat us will be assesse d at i ncl usi o n (see 
Secti o n 1 0. 6. 2. 2 ).
In a d diti o n t o t he S F -3 6 a n d E Q -5 D q uesti o n naires, a m ore c o m plete c haracterizati o n of 
t he react o ge nicity of t he vacci ne will be ac hie ve d b y  i ncl u di n g a detaile d c ollecti o n of t he
use of healt hcare res o urces a n d t he occ urre nce of s y m pt o ms t hr o u g h diar y  car d data 
c ollecti o n (see Secti o n 5. 3. 1. 1 ). Im pact o n da y s of w or k l oss, b ot h f or t he s u bject or f or a 
care gi ver, as a p plica ble, will be assesse d.
1. 3.
B e n efit : Ri s k A s s e s s m e nt
Please refer t o t he c urre nt I B f or t he s u m mar y of p ote ntial ris ks a n d be nefits of H Z/s u 
vacci ne .
T he f oll o wi n g secti o n o utli nes t he ris k assess me nt a n d miti gati o n strate g y  f or t his st u d y 
pr ot oc ol:
1. 3. 1.
Ri s k A s s e s s m e nt
I m p ort a nt 
P ot e nti al/I d e ntifi e d Ri s k
D at a/ R ati o n al e f or Ri s k
Miti g ati o n Str at e g y
I nv esti g ati o n al H Z/s u v acci n e
T h e or etic al risk of ac q uiri n g a 
v acci n e i n d uc e d a ut oi m m u n e 
dis e as e aft er v acci n ati o n.
N o c o nfir m e d si g n als r el at e d t o 
t his p ot e nti al risk h av e b e e n 
i d e ntifi e d d uri n g t h e cli nic al 
pr o gr a m. Av ail a bl e cli nic al d at a 
d o n ot hi g hli g ht a ny c o nc er n.
Cl os e m o nit ori n g of pI M Ds as p er 
st u dy pr ot oc ol.
T h e p ot e nti al risk of ev e nts of 
p ossi bl e a ut oi m m u n e eti ol o gy 
occ ur ri n g is m e nti o n e d i n t h e I C F. 
I n a d diti o n, t h e I C F a dvis es 
s u bj ects t o c o nt act t h e st u dy 
d oct or or t h e st u dy st aff 
i m m e di at ely, s h o ul d t h ey d ev el o p 
a ny sy m pt o ms t h at t h ey f e el 
m ay b e s eri o us.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
3 3
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
3 4
1. 3. 2.
B e n efit A s s e s s m e nt
Be nefits i ncl u de:

Recei vi n g t he H Z/s u st u d y vacci ne t hat ma y  pr o vi de t he pre ve nti o n of H Z.

Me dical e val uati o ns/assess me nts ass ociate d wit h st u d y pr oce d ures [e. g., p h y sical 
e xa mi nati o n].
1. 3. 3.
O v er all B e n efit: Ri s k C o n cl u si o n
Ta ki n g i nt o acc o u nt t he meas ures t o mi ni mize ris k t o s u bjects partici pati n g i n t his st u d y , 
t he p ote ntial or rec o g nize d ris ks i de ntifie d i n ass ociati o n wit h t he i n vesti gati o nal H Z/s u 
vacci ne a n d st u d y  pr oce d ures are offset b y t he be nefits ( pre ve nti o n of H Z a n d relate d 
c o m plicati o ns) t hat ma y  be aff or de d t o t he s u bject(s) recei vi n g H Z/s u.
2.
O B J E C TI V E S
2. 1.
Pri m ar y  o bj e cti v e

T o esti mate t he c ha n ge i n t he S F - 3 6 P h y sical F u ncti o ni n g (S F - 3 6 P F) scale sc ore 
fr o m baseli ne sc ore t o t he mea n sc ore o ver t he peri o d da y  1 t o da y 7 f oll o wi n g t he 
first H Z/s u vacci nati o n i n s u bjects ≥5 0 y ears of a ge ( Y O A) o verall.
Refer t o Secti o n 1 0. 1 f or t he defi niti o n of t he pri mar y e n d p oi nt.
2. 2.
S e c o n d ar y  o bj e cti v es

T o esti mate t he c ha n ge i n t he S F - 3 6 P F scale sc ore fr o m baseli ne sc ore t o t he mea n
sc ore o ver t he peri o d da y 1 t o da y  7 f oll o wi n g t he sec o n d H Z/s u vacci nati o n i n 
s u bjects ≥5 0 Y O A o verall.

T o esti mate t he c ha n ge i n t he S F - 3 6 P F scale sc ore i n s u bjects ≥5 0 Y O A b y  a ge, 
ge n der a n d react o ge nicit y  gra de a n d ty p e of s y m pt o m (l ocal, s y ste mic) fr o m baseli ne 
sc ore t o t he mea n sc ore o ver t he peri o d da y  1 t o da y 7 f oll o wi n g b ot h H Z/s u 
vacci nati o ns 1 a n d 2.

T o esti mate t he c ha n ge i n S F - 3 6 P F si n gle ite m sc ores i n s u bjec ts ≥5 0 Y O A o verall, 
b y  a ge, ge n der a n d react o ge nicit y gra de a n d t ype of s y m pt o m (l ocal, s ys te mic) fr o m 
baseli ne sc ore t o t he mea n sc ore o ver t he peri o d da y  1 t o da y 7 f oll o wi n g b ot h H Z/s u 
vacci nati o ns 1 a n d 2.

T o esti mate t he c ha n ge i n S F - 3 6 R ole P h y sical sc ores i n s u bjects ≥5 0 Y O A o verall, 
b y  a ge, ge n der a n d react o ge nicit y gra de a n d t ype of s y m pt o m (l ocal, s ys te mic) fr o m 
baseli ne sc ore t o t he sc ore o n da y  7 f oll o wi n g b ot h H Z/s u vacci nati o ns 1 a n d 2.

T o esti mate t he Q A L Y c ha n ge i n s u bjects ≥5 0 Y O A o v erall, b y a ge, ge n der, 
react o ge nicit y gra de a n d t ype of s y m pt o m (l ocal, s y ste mic) fr o m baseli ne sc ore t o 
t he c o m bi ne d sc ore o n da ys 1 t o 7 f oll o wi n g b ot h H Z/s u vacci nati o ns 1 a n d 2.

T o assess t he i m pact of react o ge nicit y o n t he healt hcare res o urce utilizati o n (i.e., 
h os pitalizati o n, Ge neral Practiti o ners a n d s pecialist visits, me dicati o n i nta ke) i n 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
3 4
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
3 5
s u bjects ≥5 0 Y O A o verall, b y  a ge, ge n der react o ge nicit y gra de a n d t ype of s y m pt o m 
(l ocal, sys te mic) f oll o wi n g b ot h H Z/s u vacci nati o ns 1 a n d 2.

T o esti mate t he w or k l oss i n s u bjects ≥5 0 Y O A o verall, b y a ge, ge n der, 
react o ge nicit y gra de a n d t ype of s y m pt o m (l ocal, s y ste mic) f oll o wi n g b ot h H Z/s u 
vacci nati o ns 1 a n d 2.

T o esti mate t he w or k l oss f or n o n- de dicate d care gi vers (e. g., fa mil y  me m ber) of 
s u bjects ≥5 0 Y O A o verall, b y  ge n der, react o ge nicit y gra de a n d ty pe of s y m pt o m 
(l ocal, sys te mic) f oll o wi n g b ot h H Z/s u vacci nati o ns 1 a n d 2.

T o esti mate t he e xtra w or k f or de dicate d care gi vers of s u bjects ≥5 0 Y O A o verall, b y  
ge n der, react o ge nicit y  gra de a n d ty pe of s ym pt o m (l ocal, s ys te mic) f oll o wi n g b ot h
H Z/s u vacci nati o ns 1 a n d 2.

T o e val uate t he safet y a n d react o ge nicit y f oll o wi n g a d mi nistrati o n of t he H Z/s u 
vacci ne i n s u bjects ≥5 0 Y O A .
Refer t o Secti o n 1 0. 2 f or t he defi niti o n of t he sec o n dar y e n d p oi nts.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
3 5
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
3 6
3.
S T U D Y D E SI G N O V E R VI E W
D C = Di ary C ar d.
† Visit 3 at D ay 7 is d efi n e d as 7 d ays p ost d os e 1 at Visit 2 ( M o nt h 0) a n d Visit 5 at D ay 6 7 is d efi n e d as 7 d ays p ost d os e 2 at Visit 4 ( M o nt h 2) ( R ef er t o T a bl e 6 f or visit i nt erv als).
‡ Di ary C ar ds distri b ut e d at Visit 2 a n d Visit 4 f or s olicit e d a dv ers e ev e nts ( D ays 0– 6) will b e c oll ect e d o n D ay 7 a n d D ay 6 7 ( Visit 3 a n d Visit 5) , r es p ectiv ely ( R ef er t o T a bl e 5 ).
¥ Q u esti o n n air es distri b ut e d at Visit 2 a n d Visit 4 will b e c oll ect e d o n D ay 7 a n d D ay 6 7 ( Visit 3 a n d Visit 5), r es p ectiv ely ( R ef er t o T a bl e 5 a n d S ecti o n 5. 5. 2. 1 1 ).
* T h e M o nt h 3 c o nt act will occ ur w h e n t h e p ost -v acci n ati o n 2 ( D ays 0 -2 9) di ary c ar ds h av e b e e n r ec eiv e d by sit e (r et ur n e d by m ail) .
H Z/ s u Gr o u p ( N =4 0 0)
Vi sit 2
M o nt h 0
V ac cinatio n 1
Di str ibut e D Cs & 
Qu estio n n air es
Visit 3
D a y 7 †
C ol lect DCs ‡ & 
Qu estion n air es¥
Visit 4
M o nt h 2
Vaccination 2
Di strib ut e D Cs & 
Qu estio n n air es
Ph o n e C o nt ac t
M o nt h 8
S af ety 
F o llow- U p
Ph o n e C o nt ac t
M o nt h 1 4
S af ety  
F o llow- U p
St u dy C o nclusion
Ep och 0 0 1: Pr i mar y
Visit 5
D a y 6 7 †
C ol lect DCs ‡ & 
Qu esti o n n air es¥
Visit  1
D a y - 7
Pr e vaccinatio n D Cs
Qu esti o n n air es 
Fr a ilty Assess m e nt
Pr i mary A n alysis
P h o n e C o nt ac t
M o nt h 3*
S af ety 
F o llow- U p
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
3 6
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
3 7
Pr ot oc ol wai vers or e xe m pti o ns are n ot all o we d wit h t he e xce pti o n of i m me diate safet y  
c o ncer ns. T heref ore, a d here nce t o t he st u d y d esi g n re q uire me nts, i ncl u di n g t h ose 
s pecifie d i n t he o utli ne of st u d y pr oce d ures ( Secti o n 5. 4 ), are esse ntial a n d re q uire d f or 
st u d y c o n d uct.

E x peri me ntal desi g n: P hase III, o pe n la bel, m ulti-ce nter st u d y wit h a si n gle gr o u p.

D urati o n of t he st u d y:  A p pr o xi matel y 1 4 m o nt hs.
E p oc h 0 0 1 : Pri mar y starti n g at Visit 1 ( Da y -7) a n d e n di n g at t he St u d y  c o ncl usi o n 
c o ntact ( M o nt h 1 4).

Pri mar y  c o m pleti o n Date ( P C D): Visit 3.
Refer t o t he gl ossar y  of ter ms f or t he defi niti o n of P C D.

E n d of St u d y  ( E o S): Last data release d f or all s u bjects fr o m t he M o nt h 1 4 p h o ne 
c o ntact .
Refer t o t he gl ossar y  of ter ms f or t he defi niti o n of E o S.

St u d y  gr o u p:
T a bl e 1
St u d y  gr o u p a n d e p o c h f or e s e e n i n t h e st u d y
St u d y gr o u p
N u m b er of 
s u bj e ct s
A g e ( Mi ni m u m)
E p o c h s
E p oc h 0 0 1
H Z/s u
4 0 0
≥5 0 y e ars
x
T a bl e 2
St u d y  gr o u p a n d tr e at m e nt f or e s e e n i n t h e st u d y
Tr e at m e nt 
n a m e
V a c ci n e/ Pr o d u ct n a m e
St u d y Gr o u p
H Z/s u
H Z/s u
V Z V g E
x
A S 0 1 B
x

C o ntr ol: Pre -vacci nati o n baseli ne c o ntr ol.

Vacci nati o n sc he d ule: M o nt hs 0 a n d 2.

Treat me nt all ocati o n: Eli gi ble s u bjects will be e nr olle d i nt o t he si n gle st u d y  gr o u p.

Bli n di n g:
T a bl e 3
Bli n di n g of st u d y  e p o c h s
St u d y E p o c h
Bli n di n g
E p oc h 0 0 1
o p e n

Sa m pli n g sc he d ule:

A uri ne s peci me n will be c ollecte d fr o m all fe male s u bjects of c hil d -beari n g 
p ote ntial at Visit 2 a n d Visit 4 . If a ser u m pre g na nc y test i nstea d of a uri ne 
pre g na nc y  test is re q uire d b y l ocal or et hics c o m mittee re g ulati o ns, a bl o o d 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
3 7
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
3 8
sa m ple will be c ollected fr o m w o me n of c hil d- beari n g p ote ntial at Visit 2 a n d 
Visit 4 a n d use d f or t he test as per l ocal g ui da nce .
N ote: t he res ult of t he uri ne/ ser u m pre g na nc y test m ust be o btai ne d bef ore 
vacci nati o n.

T y pe of st u d y : self-c o ntai ne d.

Data c ollecti o n: Electr o nic Case Re p ort F or m ( e C R F).
4.
S T U D Y C O H O R T
4. 1.
N u m b er of s u bj e ct s/ c e nt e r s
Tar get e nr ol me nt is 4 0 0 eli gi ble s u bjects. Refer t o Secti o ns 4. 2 a n d 4. 3 f or eli gi bilit y 
criteria. Refer t o Secti o n 1 0. 3 f or a descri pti o n of t he criteria use d i n t he esti mati o n of 
sa m ple size.
O ver vie w of t he recr uit me nt pl a n:
E nr ol me nt tar get n u m bers per st u d y  ce nter will be assi g ne d at t he st u d y start a n d ma y be 
a dj uste d d uri n g t he st u d y. T he recr uit me nt rate will be m o nit ore d usi n g a st u d y-s pecific 
ce ntral ra n d o mizati o n s yste m o n t he I nter net ( S BI R).
Tra nsfer of s u p plies will be trac ke d b y t he ce ntral ra n d o mizati o n s y ste m. M o nit ori n g visit 
fre q ue nc y will be a da pte d t o t he pace of e nr ol me nt. Vacci ne d oses will be distri b ute d t o 
eac h st u d y site res pecti n g t he bl oc k size.
4. 2.
I n cl u si o n crit eri a f or e nr ol m e nt
De viati o ns fr o m i ncl usi o n criteria are n ot all o we d beca use t he y  ca n p ote ntiall y je o par dize 
t he scie ntific i nte grit y of t he st u d y, re g ulat or y acce pta bilit y or s u bject safet y. T heref ore, 
a d here nce t o t he criteria as s pecifie d i n t he pr ot oc ol is esse ntial.
All s u bjects m ust satisf y  A L L t he f oll o wi n g criteria at st u d y e ntr y:

S u bjects w h o, i n t he o pi ni o n of t he i n vesti gat or, ca n a n d will c o m pl y  wit h t he 
re q uire me nts of t he pr otoc ol (e. g., c o m pleti o n of t he q uesti o n naires a n d diar y  car ds).

Writte n i nf or me d c o nse nt o btai ne d fr o m t he s u bject pri or t o perf or ma nce of a n y  
st u d y s pecific pr oce d ure.

A male or fe male a ge d ≥5 0 Y O A at t he ti me of c o nse nt.

Fe male s u bjects of n o n -c hild beari n g p ote ntial ma y be e nr olle d i n t he st u d y.

F or t his st u d y  p o p ulati o n, n o n-c hil d beari n g p ote ntial is defi ne d as c urre nt t u bal 
li gati o n, hys terect o m y, o variect o my or p ost -me n o pa use.
Please refer t o t he gl ossar y  of ter ms f or t he defi niti o n of me n o pa use.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
3 8
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
3 9

Fe male s u bjects of c hil d beari n g p ote ntial ma y  be e nr olle d i n t he st u d y, if t he s u bject:

has practice d a de q uate c o ntrace pti o n f or 3 0 da y s pri or t o vacci nati o n, a n d

has a ne gati ve pre g na nc y test o n t he da y  of vacci nati o n, a n d

has a gree d t o c o nti n ue a de q uate c o ntrace pti o n d uri n g t he e ntire treat me nt peri o d 
a n d f or 2 m o nt hs after c o m pleti o n of t h e vacci nati o n series.
Please refer t o t he gl ossar y  of ter ms f or t he defi niti o n of a de q uate c o ntrace pti o n.
4. 3.
E x cl u si o n crit eri a f or e nr ol m e nt
De viati o ns fr o m e xcl usi o n criteria are n ot all o we d beca use t he y  ca n p ote ntiall y 
je o par dize t he scie ntific i nte grity of t he st u d y, re g ulat or y acce pta bilit y or s u bject safet y. 
T heref ore, a d here nce t o t he criteria as s pecifie d i n t he pr ot oc ol is ess e ntial.
T he f oll o wi n g criteria s h o ul d be c hec ke d at t he ti me of st u d y  e ntr y. If A N Y e xcl usi o n 
criteri o n a p plies, t he s u bject m ust n ot be i ncl u de d i n t he st u d y :

A n y  c o n diti o n w hic h, i n t he j u d g me nt of t he i n vesti gat or, w o ul d ma ke i ntra m usc ular 
(I M) i njecti on u nsafe.

Use or pla n ne d use of a n y i n vesti gati o nal or n o n -re gistere d pr o d uct ( dr u g or vacci ne) 
ot her t ha n t he st u d y vacci ne or c urre nt partici pati o n or pla n ne d c o nc urre nt 
partici pati o n i n a n ot her cli nical st u d y, i n w hic h t he s u bject has bee n or will be 
e x p ose d t o a n i n vesti gati o nal or a n o n -i n vesti gati o nal pr o d uct ( p har mace utical 
pr o d uct or de vice) d uri n g t he peri o d starti n g 3 0 da ys bef ore t he first d ose of st u d y  
vacci ne a n d t he st u d y e n d.

Use or a ntici pate d use of i m m u n os u p pressa nts or ot her i m m u ne-m o dif y i n g dr u gs 
d uri n g t he peri o d starti n g 1 8 0 da y s pri or t o st u d y start a n d d uri n g t he w h ole st u d y 
peri o d. T his i ncl u des c hr o nic a d mi nistrati o n of c ortic oster oi ds ( > 1 4 c o nsec uti ve 
da y s of pre d nis o ne at a d ose of ≥2 0 m g/ da y  [ or e q ui vale nt]), l o n g-acti n g i m m u ne-
m o dif y i n g a ge nts (e. g., i nfli xi ma b) or i m m u n os u p pressi ve/c yt ot o xic t hera p y (e. g., 
me dicati o ns use d d uri n g ca ncer c he m ot hera p y, or ga n tra ns pla ntati o n or t o treat 
a ut oi m m u ne dis or ders). I n hale d, t o pical a n d i ntra-artic ular c ortic oster oi ds are 
all o we d.

A n y  c o nfir me d or s us pecte d i m m u n os u p pressi ve or i m m u n o deficie nt c o n diti o n 
res ulti n g fr o m disease (e. g., mali g na nc y, h u ma n i m m u n o deficie nc y vir us [ HI V] 
i nfecti o n) or i m m u n os u p pressi ve/c yt ot o xic t hera p y (e. g., me dicati o ns use d d uri n g 
ca ncer c he m ot h era p y, or ga n tra ns pla ntati o n or t o treat a ut oi m m u ne dis or d ers).

A d mi nistrati o n of i m m u n o gl o b uli ns a n d/ or a n y bl o o d pr o d ucts i n t he peri o d starti n g 
9 0 da y s prece di n g t he first d ose of st u d y vacci ne or plan ne d a d mi nistrati o n d uri n g 
t he st u d y peri o d.

A d mi nistrati o n or pla n ne d a d mi nistrati o n of a li ve vacci ne i n t he peri o d starti n g 3 0 
da y s bef ore t he first d ose of st u d y vacci ne a n d en di n g 3 0 da y s after t he last d ose of 
st u d y vacci ne, or, a d mi nistrati o n or pla n ne d a d mi nistrati o n of a n o n-re plicati n g 
vacci n e * i n t he peri o d starti n g 1 5 da y s pri or t o a n d e n di n g 1 4 da ys after eit her d ose 
of st u d y  vacci ne.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
3 9
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
4 0
* E. g., i nacti vate d a n d s u b u nit vacci nes, i ncl u di n g i nacti vate d a n d s u b u nit i nfl ue nza 
vacci nes f or seas o nal or pa n de mic fl u, wit h o ut a dj u va nt, a n d p ne u m oc occal 
c o nj u gate vacci nes.

Pre vi o us or pla n ne d a d mi nistrati o n of a vacci ne a gai nst H Z (i ncl u di n g a n 
i n vesti gati o nal or n o n-re gistere d vacci ne) ot her t ha n t he st u d y vacci ne, d uri n g t he 
entire st u d y  peri o d.

Hist or y  of H Z.

Hist or y  of a n y reacti on or h y perse nsiti vit y  li kely t o be e xacer bate d b y a n y 
c o m p o ne nt of t he vacci ne.

Fe male pla n ni n g t o bec o me pre g na nt or pla n ni n g t o disc o nti n ue c o ntrace pti ve 
preca uti o ns.

Pre g na nt or lactati n g fe male.

Si g nifica nt u n derl y i n g ill ness re q uiri n g me dicati o ns t hat mi g ht c o nf o u n d t he 
e val uati o n of ge neral/ l ocal A Es, or i n t he o pi ni o n of t he i n vesti gat or, w o ul d be 
e x pecte d t o pre ve nt c o m pleti o n of t he st u d y .

A n y  ot her c o n diti o n t hat, i n t he o pi ni o n of t he i n vesti gat or, mi g ht i nterfere wit h t he 
e val uati o ns re q uire d by t he st u d y.
5.
C O N D U C T O F T H E S T U D Y
5. 1.
R e g ul at or y  a n d et hi c al c o n si d er ati o n s, i n cl u di n g t h e 
i nf or m e d c o n s e nt pr o c e s s
T he st u d y  will be c o n d ucte d i n acc or da nce wit h all a p plica ble re g ulat or y re q uire me nts.
T he st u d y  will be c o n d ucte d i n acc or da nce with t he I C H G ui deli ne f or G o o d Cli nical 
Practice ( G C P), all a p plica ble s u bject pri vac y  re q uire me nts a n d t he g ui di n g pri nci ples of 
t he Declarati o n of Helsi n ki.
G S K will o btai n fa v o ura ble o pi ni o n/a p pr o val t o c o n d uct t he st u d y  fr o m t he a p pr o priate 
re g ulat or y a ge nc y, i n acc or da nce wit h a p plica ble re g ulat or y re q uire me nts, pri or t o a site 
i nitiati n g t he st u d y i n t hat c o u ntr y.
C o n d uct of t he st u d y  i ncl u des, b ut is n ot li mite d t o, t he f oll o wi n g:

I nstit uti o nal Re vie w B oar d (I R B)/I n de pe n de nt Et hics C o m mittee (IE C) re vi e w a n d 
fa v o ura ble o pi ni o n/a p pr o val of st u d y pr ot oc ol a n d a n y s u bse q ue nt a me n d me nts.

S u bject i nf or me d c o nse nt.

I n vesti gat or re p orti n g re q uire me nts as state d i n t he pr ot oc ol.
G S K will pr o vi de f ull details of t he a b o ve pr oce d ures t o t he i n vesti gat or, eit her ver ball y , 
i n writi n g, or b ot h.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
4 0
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
4 1
Freel y  gi ve n a n d writte n or wit nesse d i nf or me d c o nse nt m ust be o btai ne d fr o m eac h 
s u bject, as a p pr o priate, pri or t o partici pati o n i n t he st u d y.
G S K Bi ol o gicals will pre pare a m o del I nf or me d C o nse nt F or m (I C F) w hic h will e m b o d y 
t he IC H G C P a n d G S K Bi ol o gicals re q uire d ele me nts. W hile it is str o n gl y  rec o m me n de d 
t hat t his m o del IC F is t o be f oll o we d as cl osel y  as p ossi ble, t he i nf or me d c o nse nt 
re q uire me nts gi ve n i n t his d oc u me nt are n ot i nte n de d t o pre-e m pt a n y l ocal re g ulati o ns 
w hic h re q uire a d diti o nal i nf or mati o n t o be discl ose d f or i nf or me d c o nse nt t o be le gall y 
effecti ve. Cli nical j u d ge me nt, l ocal re g ulati o ns a n d re q uire me nts s h o ul d g ui de t he fi nal 
str uct ure a n d c o nte nt of t he l ocal versi o n of t he I C F.
T he i n vesti gat or has t he fi nal res p o nsi bilit y f or t he fi nal prese ntati o n of t he I C F, 
res pecti n g t he ma n dat or y re q uire me nts of l ocal re g ulati o ns. T he I C F ge nerate d b y t he 
i n vesti gat or wit h t he assista nce of t he s p o ns or’s re prese ntati ve m ust be acce pta ble t o 
G S K Bi ol o gicals a n d be a p pr o ve d (al o n g wit h t he pr ot oc ol, a n d a n y ot her necessar y  
d oc u me ntati o n) b y t he I R B/I E C.
5. 2.
S u bj e ct i d e ntifi c ati o n a n d r a n d o mi z ati o n of tr e at m e nt
5. 2. 1.
S u bj e ct i d e ntifi c ati o n
S u bject i de ntificati o n n u m bers will be assi g ne d se q ue ntiall y  t o t he s u bjects w h o ha ve 
c o nse nte d t o partici pate i n t he st u d y, acc or di n g t o t he ra n ge of s u bject i de ntificati o n 
n u m bers all ocate d t o eac h st u d y  ce nter. A ge gr o u p will be use d as a stratificati o n fact or 
t o e ns ure recr uit me nt of t he pre-s pecifie d n u m ber of s u bjects i n eac h a ge gr o u p (refer t o
Ta ble 4 ).
5. 2. 2.
R a n d o mi z ati o n of tr e at m e nt
E ve n t h o u g h t here will be n o ra n d o m izati o n of treat me nt, S BIR will be use d f or treat me nt 
n u m ber all ocati o n a n d f or e nr ol me nt trac ki n g p ur p oses.
5. 2. 2. 1.
R a n d o mi z ati o n of s u p pli e s
T he ra n d o mi z ati o n of s u p plies wit hi n bl oc ks will be perf or me d at G S K Bi ol o gicals, usi n g 
M A Terial E Xcelle nce ( M A T E X), a pr o gra m de vel o pe d f or use i n Statistical A nal ys is 
S y ste m ( S A S® ) ( Car y, N C, U S A) b y G S K Bi ol o gicals. E ntire bl oc ks of s u p plies wil l be 
s hi p pe d t o t he st u d y ce nters / ware h o use(s).
5. 2. 2. 2.
Tr e at m e nt all o c ati o n t o t h e s u bj e ct
T he treat me nt n u m bers will be all ocate d b y d ose .
5. 2. 2. 2. 1.
St u d y gr o u p a n d tr e at m e nt n u m b er all o c ati o n
T he tar get will be t o e nr ol a p pr o xi matel y  4 0 0 eli gi ble s u bjects a ge d ≥5 0 ye ars.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
4 1
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
4 2
T he e nr ol me nt will be perf or me d t o e ns ure e q ual distri b uti o n of t he p o p ulati o n acr oss t he 
t hree a ge strata ( 5 0-5 9 Y O A vers us 6 0 -6 9 Y O A vers us 7 0 Y O A ). T heref ore t he 
e x pecte d distri b uti o n of s u bjects is as s h o w n i n Ta ble 4 .
T a bl e 4
N u m b er of s u bj e ct s r e q uir e d f or e nr ol m e nt
A g e str at a
S a m pl e siz e
5 0 -5 9 Y O A
≈1 3 4
6 0 -6 9 Y O A
≈1 3 3
7 0 Y O A
≈1 3 3
All
≈4 0 0
T he s u bject will be e ntere d i nt o t he a p plica ble a ge strat u m ( 5 0-5 9 Y O A vers us 6 0 - 6 9 
Y O A vers us 7 0 Y O A ) i n S BI R at t he i n vesti gat or site.
After o btai ni n g t he si g ne d a n d date d I C F fr o m t he s u bject a n d ha vi n g c hec ke d t he 
eli gi bilit y of t he s u bject, t he st u d y staff i n char ge of t he vacci ne a d mi nistrati o n will 
access S BI R. U p o n pr o vi di n g t he a ge ( 5 0 -5 9 Y O A vers us 6 0 -6 9 Y O A vers us 7 0 Y O A ) 
a n d t he s u bject i de ntificati o n n u m ber, t he ra n d o mi zati o n s yste m will pr o vi de t he 
treat me nt n u m ber t o be use d f or t he first d ose.
T he n u m ber of eac h a d mi nistere d treat me nt m ust be rec or de d i n t he e C R F o n t he Vacci ne 
A d mi nistrati o n scree n.
W he n S BI R is n ot a vaila ble, please refer t o t he S BI R user g ui de or t he St u d y  Pr oce d ures 
Ma n ual ( S P M) f or s pecific i nstr ucti o ns.
N ote t hat as s o o n as t he tar get n u m ber of s u bjects i n a s pecific a ge gr o u p has bee n 
reac he d, t he e nr ol me nt will be fr oze n f or t his a ge gr o u p.
5. 2. 2. 2. 2.
Tr e at m e nt n u m b er all o c ati o n f or s u b s e q u e nt d o s e s
F or eac h d ose s u bse q ue nt t o t he first d ose, t he st u d y  staff i n c har ge of t he vacci ne 
a d ministrati o n will access S BI R, pr o vi de t he s u bject i de ntificati o n n u m ber, a n d t he 
s yste m will pr o vi de a treat me nt n u m ber.
T he n u m ber of eac h a d mi nistere d treat me nt m ust be rec or de d i n t he e C R F o n t he Vacci ne 
A d mi nistrati o n scree n.
5. 3.
G e n er al st u d y  a s p e ct s
S u p ple me ntar y  st u d y c o n d uct i nf or mati o n n ot ma n date d t o be prese nt i n t his pr ot oc ol is 
pr o vi de d i n t he acc o m pa n y i n g S P M. T he S P M pr o vi des t he i n vesti gat or a n d t he site 
pers o n nel wit h a d mi nistrati ve a n d detaile d tec h nical i nf or mati o n t hat d oes n ot i m pact t h e 
safety of t he s u bjects.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
4 2
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
4 3
5. 3. 1.
D at a c oll e cti o n
5. 3. 1. 1.
Q u e sti o n n air e s a n d Di ar y  c ar d s
T he q uesti o n naires ( S F-3 6 [ A P P E N DI X A ] a n d E Q-5 D [ A P P E N DI X B ]) a n d diar y car ds,
t hat will be distri b ute d a n d e x plai ne d b y  t he i n vesti gator or his/ her dele gate , are t o be 
c o m plete d b y t he s u bject/ s u bject’s care gi ver. A n y s u p plie d q uesti o n naires a n d diar y 
car ds s h o ul d be prefera bl y c o m plete d b y t he s u bject t he msel ves.
F oll o wi n g vacci nati o n, 7- d a y  a n d 3 0-d a y  diar y car ds will be dis pe nse d t o be c o m plete d 
b y  t he s u bjects/ s u bjects’ care gi ver. T he 7-d a y  diar y car ds will be c o m plete d f or s olicite d 
A Es (fr o m Da y  0 t o Da y 6 after eac h vacci nati o n) a n d t he 3 0-d a y  diar y car ds will be 
c o m plete d f or u ns olicite d A Es (fr o m Da y  0 t o Da y 2 9 after eac h vacci nati o n) a n d a ny 
c o nc o mita nt me dicati o n a n d vacci nati o n ta ke n fr o m Da y  0 t o Da y 2 9 after eac h 
vacci nati o n (see Ta ble 5 a n d Ta ble 1 2 ). T hese diar y  car ds will all o w a detaile d
c haracterizati o n of t he vacci ne react o ge nicit y t hr o u g h a detaile d c ollecti o n of t he 
occ urre nce of s y m pt o ms a n d a n y use of healt hcare res o urces. Please refer t o t he S P M f or 
m ore i nf or mati o n o n diar y  car d a n d q uesti o n naire data c ollecti o n.
T he q uesti o n naires will be fille d i n b y  t he s u bject/s u bjects care gi ver o n site at eac h visit. 
I n a d diti o n, t he s u bject/s u bjects care gi ver will be re q uire d t o c o mplete t he S F - 3 6 P F 
c o m p o ne nt of t he S F- 3 6 q uesti o n naire (i .e., ite ms 3a t o 3j, see Ta ble 1 5 ) a n d t he E Q -5 D 
q uesti o n naire at h o me o n da ys 1 t o 6 f oll o wi n g eac h vacci nati o n.
W he n t he c o m plete d q uesti o n naires a n d diar y car ds are ret ur ne d t o t he st u d y staff, t he 
st u d y staff will as k t he s u bject (at t he ti me of ret ur n or at s u bse q ue nt c o ntact) if he/s he 
recei ve d a ny assista nce i n c o m pleti n g q uesti o n nai res or diar y  car ds. If t he s u bject ha d 
assista nce c o m pleti n g t he q uesti o n naires a n d/ or diar y car d (e. g., by a care gi ver), it s h o ul d 
be n ote d i n t he e C R F. W he n q uesti o n naires or pre -v acci n ati o n di ary c ar ds are 
c o m plete d at t he st u d y site, st u d y staff ca n as sist i n rea di n g t he q uesti o ns ( ver bati m).
(A m e n de d 1 6 N o ve m ber 2 0 1 6 )
Als o, w he n t he c o m plete d di ary c ar ds are ret ur ne d t o t he st u dy st aff t he st u dy st aff will 
revie w it t o get her wit h t he s u bject. (A me n de d 1 6 N o ve m ber 2 0 1 6 )
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
4 3
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
4 4
5. 4.
O utli n e of st u d y  pr o c e d ur e s
Ta ble 5 s u m marizes t he list of pr oce d ures t o be f oll o we d d uri n g t he st u dy.
T a bl e 5
Li st of st u d y  pr o c e d ur e s
E p o c h
Pri m ar y
T y p e of c o nt a ct
Vi sit 1
Vi sit 2
Vi sit 3
Vi sit 4
Vi sit 5
M 3 C o nt a ct
M 8 C o nt a ct
M 1 4 C o nt a ct
Ti m e p oi nt( s)
D a y -7 M o nt h 0
D a y 7 1
M o nt h 2
D a y 6 7 1
M o nt h 3 2
M o nt h 8
M o nt h 1 4
I nf or m e d c o ns e nt (s e e S ecti o n 5. 5. 1. 1 )
●
C h eck i ncl usi o n / excl usi o n crit eri a (s e e S ecti o ns 5. 5. 1. 2 a n d 5. 5. 2. 1 )
●
O
Tr ai ni n g o n c o m pl eti o n of S F -3 6 a n d E Q -5 D q u esti o n n air es (s e e S ecti o n 5. 5. 1. 3 )
O
O
O
O
O
O n sit e c o m pl eti o n of S F -3 6 a n d E Q -5 D q u esti o n n air es by t h e s u bj ect
O
O
O
O
O
Tr a nscri pti o n of S F -3 6 a n d E Q -5 D q u esti o n n air es by i nv esti g at or/ d esi g n e e
●
●
●
●
●
P hysic al ex a mi n ati o n i ncl u di n g h ei g ht a n d w ei g ht (s e e S ecti o n 5. 5. 1. 5 ) ( A m e n d e d 1 6 
N o v e m b er 2 0 1 6 )
●
Ass ess m e nt of fr ailty st at us by m e a ns of a s p ecific t o ol 3
●
R ec or d d e m o gr a p hic d at a i ncl u di n g s u bj ect’s w orki n g st at us a n d if t h ey h av e a 
c ar e giv er (s e e S ecti o n 5. 5. 1. 6 )
●
M e dic al hist ory a n d r ec or d m e dic ati o ns t ak e n by t h e s u bj ect (s e e S ecti o n 5. 5. 1. 7 )
●
T r ai ni n g of s u bj ects o n t h e c o m pl eti o n of pr e-v acci n ati o n di ary c ar ds (s e e S ecti o ns 
5. 5. 1. 8 a n d 5. 5. 2. 2 )
O
O n sit e c o m pl eti o n of pr e -v acci n ati o n di ary c ar ds by t h e s u bj ect (s e e S ecti o ns 5. 5. 1. 9
a n d 5. 5. 2. 2 )
O 
O
R evi e w a n d tr a nscri pti o n of pr e -v acci n ati o n di ary c ar ds (s e e S ecti o n 5. 5. 2. 3 )
●
●
C h eck c o ntr ai n dic ati o ns
4 (s e e S ecti o n 5. 5. 2. 5 )
●
●
Pr e g n a ncy t est 5
●
●
Pr e -v acci n ati o n b o dy t e m p er at ur e ( or al r o ut e pr ef err e d) 6 (s e e S ecti o n 5. 5. 2. 7 )
●
●
Assi g n m e nt/r ec or di n g of tr e at m e nt n u m b er
●
●
V acci n ati o n (s e e S ecti o n 5. 5. 2. 8 )
●
●
Tr ai ni n g o n c o m pl eti o n of di ary c ar ds
O
O
Distri b uti o n of di ary c ar ds
O
O
Distri b uti o n of p ost -v acci n ati o n d aily S F-3 6 a n d E Q -5 D q u esti o n n air es (s e e S ecti o n 
5. 5. 2. 1 1 )
O
O
D aily p ost -v acci n ati o n c o m pl eti o n of S F-3 6 a n d E Q -5 D q u esti o n n air es by s u bj ect
O
O
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
4 4
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
4 5
E p o c h
Pri m ar y
T y p e of c o nt a ct
Vi sit 1
Vi sit 2
Vi sit 3
Vi sit 4
Vi sit 5
M 3 C o nt a ct
M 8 C o nt a ct
M 1 4 C o nt a ct
Ti m e p oi nt( s)
D a y -7 M o nt h 0
D a y 7 1
M o nt h 2
D a y 6 7 1
M o nt h 3 2
M o nt h 8
M o nt h 1 4
D aily p ost -v acci n ati o n r ec or di n g of s olicit e d A Es ( D ays 0 -6) by s u bj ects o n di ary c ar d
O
O
D aily p ost -v acci n ati o n r ec or di n g of u ns olicit e d A Es a n d c o nc o mit a nt 
m e dic ati o n/v acci n ati o n ( D ays 0 -2 9) by s u bj ects o n di ary c ar d
O 
O
O 
O
O
R et ur n of d aily S F -3 6 a n d E Q -5 D q u esti o n n air es (s e e S ecti o ns 5. 5. 1. 4 , 5. 5. 2. 4 a n d 
5. 5. 2. 1 1 )
O
O
Tr a nscri pti o n of d aily S F -3 6 a n d E Q -5 D q u esti o n n air es by i nv esti g at or/ d esi g n e e (s e e 
S ecti o n 5. 5. 2. 1 1 )
●
●
R et ur n of di ary c ar ds
O
O
O
O
7
R evi e w a n d tr a nscri pti o n of s olicit e d a dv ers e ev e nts wit hi n 7 d ays ( D ays 0 -6) p ost -
v acci n ati o n, fr o m di ary c ar ds by i nv esti g at or/sit e st aff
●
●
R evi e w a n d tr a nscri pti o n of n o n -s eri o us a dv ers e ev e nts wit hi n 3 0 d ays ( D ays 0 -2 9) 
p ost -v acci n ati o n, fr o m di ary c ar ds by i nv esti g at or/ sit e st aff
●
●
R ec or d a ny c o nc o mit a nt m e dic ati o n/v acci n ati o n ( R ef er t o S ecti o n 6. 5 )
●
●
●
●
●
●
●
●
R ec or di n g of s eri o us a dv ers e ev e nts ( S A Es) by i nv esti g at or ( R ef er t o T a bl e 1 2 ) 8
●
●
●
●
●
●
●
●
R ec or di n g of p ot e nti al i m m u n e -m e di at e d dis e as es ( pI M Ds) ( R ef er t o S ecti o n 8. 1. 5 a n d
T a bl e 1 1 )
● 
● 
● 
● 
● 
● 
●
R ec or di n g of pr e g n a nci es ( R ef er t o S ecti o n 8. 2. 1 a n d T a bl e 1 2 )
●
●
●
●
●
●
●
I n v e sti g at or si g n off f or t h e a n alysis ( A m e n d e d 1 6 N o v e m b er 2 0 1 6 )
●
●
St u dy C o ncl usi o n
●
N ot e: T h e d o u bl e -li n e b or d er f oll o wi n g Visit 3 D ay 7 i n dic at es t h e a n alys es w hic h will b e p erf or m e d o n all d at a (i. e., d at a t h at ar e as cl e a n as p ossi bl e) o bt ai n e d u p t o Visit 3 (s e e 
S ecti o n 1 0. 8. 1 ).
● is us e d t o i n dic at e a st u dy pr oc e d ur e t h at r e q uir es d oc u m e nt ati o n i n t h e i n divi d u al e C R F.
O is us e d t o i n dic at e a st u dy pr oc e d ur e t h at d o es n ot r e q uir e d oc u m e nt ati o n i n t h e i n divi d u al e C R F. H o w ev er, it e ms wit h t his d esi g n ati o n s h o ul d b e n ot e d i n t h e s u bj ect’s s o urc e 
d oc u m e nt ati o n.
1 Visit 3 at D ay 7 is d efi n e d as 7 d ays p ost d os e 1 at Visit 2 ( M o nt h 0) a n d Visit 5 at D ay 6 7 is d efi n e d as 7 d ays p ost d os e 2 at Visit 4 ( M o nt h 2) ( R ef er t o T a bl e 6 f or visit i nt erv als).
2 T h e M o nt h 3 c o nt act will occ ur w h e n t h e p ost -v acci n ati o n 2 ( D ays 0-2 9) di ary c ar ds h av e b e e n r ec eiv e d by sit e (r et ur n e d by m ail) a n d will all o w t h e sit e st aff t o r evi e w a n d v erify  t h e 
p ost -v acci n ati o n 2 ( D ays 0-2 9) di ary c ar ds by disc ussi n g t h e m wit h t h e s u bj ect/ s u bj ect’s c ar e gi v er.
3 A n ass ess m e nt of fr ailty st at us d efi n e d t hr o u g h a Fr ailty I n d ex ( FI) d escri b e d as acc u m ul ati o n of d eficits, i ncl u di n g b ut n ot li mit e d t o a s eri es of c ertifi e d t ests, will b e p erf or m e d at 
i ncl usi o n a n d d at a r ec or d e d i n t h e e C R F(s e e S ecti o n 1 0. 6. 2. 2 ).
4 A ny s u bj ect wit h a cli nic ally di a g n os e d H Z e pis o d e b et w e e n Visit 1 a n d Visit 4 s h o ul d n ot r ec eiv e t h e s u bs e q u e nt d os e(s).
5 O nly f or w o m e n of c hil d-b e ari n g p ot e nti al . A s er u m pr e g n a ncy t est i nst e a d of a uri n e pr e g n a ncy t est s h o ul d o nly b e c o nsi d er e d if r e q uir e d by l oc al or et hics c o m mitt e e r e g ul ati o ns
(s e e S ecti o n 5. 5. 2. 6 ).
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
4 5
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
4 6
6 Pr e -v acci n ati o n t e m p er at ur es s h o ul d al w ays b e r ec or d e d or ally at st u dy sit es. I n r ar e sit u ati o ns w h e n t h er e is n o ot h er alt er n ati v e, t h e t e m p er at ur e m ay b e r ec or d e d by ot h er r o ut e. If 
t h e t e m p er at ur e is t ak e n by a n ot h er r o ut e ( axill ary, r ect al or ty m p a nic), t h e r o ut e s h o ul d b e d oc u m e nt e d.
7 T h e p ost -v acci n ati o n 2 di ary c ar ds f or d aily r ec or di n g of u ns olicit e d A Es a n d c o nc o mit a nt m e dic ati o n/v acci n ati o n ( D ays 0 -2 9) by s u bj ects will b e r et ur n e d by m ail .
8 S A Es r el at e d t o st u dy p artici p ati o n or G S K c o nc urr e nt m e dic ati o n/v acci n e ar e t o b e r ec or d e d fr o m t h e ti m e t h e s u bj ect c o ns e nts t o p artici p at e i n t h e st u dy.
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
4 6
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
4 7
Ti me i nter vals bet wee n st u d y  visits/c o ntact relate d t o st u d y pr oce d ures perf or me d i n 
s u bjects partici pati n g i n t he st u d y are prese nte d i n Ta ble 6 .
T a bl e 6
I nt er v al s b et w e e n st u d y vi sit s
I nt er v al
O pti m al l e n gt h of i nt er v al 1
All o w e d i nt er v al
(r a n g e i n d a y s)
Visit 1 ( D ay -7) 
Visit 2 ( M o nt h 0)
7 d ays
7 – 1 0 2
Visit 2 ( M o nt h 0) 
Visit 3 ( D ay 7) 3
7 d ays
7 – 1 0
Visit 2 ( M o nt h 0) 
Visit 4 ( M o nt h 2)
6 0 d ays
4 9 – 8 3
Visit 4 ( M o nt h 2) 
Visit 5 ( D ay 6 7) 3
7 d ays
7 – 1 0
Visit 4 ( M o nt h 2) 
M 3 C o nt act ( M o nt h 3)
3 5 d ays 4
3 0 – 6 0
Visit 4 ( M o nt h 2) 
M 8 C o nt act ( M o nt h 8)
1 5 0 d ays
1 2 0 – 1 8 0
Visit 4 ( M o nt h 2) 
St u dy c o ncl usi o n M 1 4 C o nt act ( M o nt h 1 4) 3 6 5 d ays
3 3 5 – 3 9 5
1 W h e n ev er p ossi bl e t h e i nv esti g at or s h o ul d arr a n g e st u dy visits wit hi n t his i nt erv al.
2 T his i nt erv al c a n b e ext e n d e d u p t o 1 4 d ays if s u bj ect is n ot a bl e t o b e v acci n at e d at Visit 2 a n d n e e ds t o b e 
r esc h e d ul e d.
3 Visit 3 at D ay 7 is d efi n e d as 7 d ays p ost d os e 1 at Visit 2 ( M o nt h 0) a n d Visit 5 at D ay 6 7 is d efi n e d as 7 d ays p ost 
d os e 2 at Visit 4 ( M o nt h 2).
4 T h e M o nt h 3 c o nt act will o cc ur w h e n t h e p ost-v acci n ati o n 2 ( D ays 0-2 9) di ary c ar ds h av e b e e n r ec eiv e d by sit e 
(r et ur n e d by m ail).
5. 5.
D et ail e d d e s cri pti o n of st u d y pr o c e d ur e s
5. 5. 1.
Pr o c e d ur e s d uri n g V i sit 1
N ote t hat Visit 1 will ta ke place at least 7 d a y s bef ore t he first vacci nati o n Visit ( Visit 2) 
(see Ta ble 6 f or visit i nter vals).
5. 5. 1. 1.
I nf or m e d c o n s e nt
T he si g ne d/ wit nesse d i nf or me d c o nse nt of t he s u bject m ust be o bt ai ne d bef ore st u d y 
partici pati o n. Refer t o Secti o n 5. 1 f or t he re q uire me nts o n h o w t o o btai n i nf or me d 
c o nse nt.
5. 5. 1. 2.
C h e c k i n cl u si o n a n d e x cl u si o n crit eri a
C hec k all i ncl usi o n a n d e xcl usi o n criteria as descri be d i n Secti o ns 4. 2 a n d 4. 3 bef ore 
e nr ol me nt.
5. 5. 1. 3.
Tr ai ni n g o n t h e c o m pl eti o n of S F -3 6 a n d E Q -5 D q u e sti o n n air e s
S u bjects/ s u bjects’ care gi ver(s) will be trai ne d o n c o m pleti n g t he S F -3 6 a n d E Q -5 D 
q uesti o n naires at Visits 1, 2, 3, 4 a n d 5 (see Secti o n s 1 0. 6. 2. 3 a n d 1 0. 6. 2. 4 f or
i nf or mati o n o n t he S F -3 6 a n d E Q -5 D q uesti o n naires , res pecti vel y).
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
4 7
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
4 8
5. 5. 1. 4.
Di stri b uti o n a n d c o m pl eti o n of S F -3 6 a n d E Q -5 D q u e sti o n n air e s
S u bjects /s u bjects’ care gi ver(s) will c o m plete t he S F -3 6 a n d E Q - 5 D q uesti o n naires (see 
Secti o ns 1 0. 6. 2. 3 a n d 1 0. 6. 2. 4 ). T he S F - 3 6 a n d E Q- 5 D q uesti o n naires will be distri b ute d 
t o s u bjects at t he Pre-Vacci nati o n Visit 1. S u bjects will be as ke d t o c o m plete b ot h S F - 3 6 
a n d E Q- 5 D q uesti o n naires o n Da y  -7 ( Visit 1) . C o m plete d q uesti o n naires will be 
c ollecte d at Visit 1 a n d s u bject res p o nses tra nscri be d i nt o t he e C R F.
5. 5. 1. 5.
P h y si c al e x a mi n ati o n a n d a s s e s s m e nt of fr ailt y  st at u s
Perf or m a p h y sical e xa mi nati o n of t he s u bject at Visit 1 i ncl u di n g wei g ht a n d hei g ht
(b o d y  mass i n de x [B MI ] will be calc ulate d). T he p h ysical e xa mi nati o n ca n be perf or me d 
per t he site’s me dical j u d g me nt a n d sta n dar d of care. C ollecte d i nf or mati o n nee ds t o be 
rec or de d i n t he e C R F. ( A me n de d 1 6 N o ve m ber 2 0 1 6 )
Treat me nt of a n y a b n or malit y o bser ve d d uri n g p h ysical e xa mi nati o n has t o be perf or me d 
acc or di n g t o l ocal me dical practice o utsi de t his st u d y  or by referral t o a n a p pr o priate 
healt h care pr o vi der.
A n assess me nt of frailt y  stat us defi ne d t hr o u g h a Frailt y I n de x ( FI) descri be d as 
acc u m ulati o n of deficits , i ncl u di n g b ut n ot li mite d t o a series of certifie d tests will be 
d o ne at Visit 1 a n d data rec o rde d i n t he e C R F (see Secti o n 1 0. 6. 2. 2 , a n d refer t o t he 
S P M f or det ails o n t he assess me nt of fr ailty st at us ). ( A me n de d 1 6 N o ve m ber 2 0 1 6 )
5. 5. 1. 6.
R e c or d d e m o gr a p hi c d at a
Rec or d de m o gra p hic data s uc h as date of birt h, ge n der , ge o gra p hic a ncestr y a n d 
et h nicit y*. W or ki n g stat us of t he s u bject, if t he s u bject has a care gi ver (as well as t he 
w or ki n g stat us of t he care gi ver if a p plica ble) will als o be i ncl u de d i n t he s u bject’s e C R F.
* Si nce differe nces i n t he safety a n d efficac y of certai n me dical pr o d ucts ha ve bee n 
o bser ve d i n raciall y a n d et h nicall y disti nct s u b gr o u ps of t he U S p o p ulati o n, et h nicit y  will 
be c ollecte d.
5. 5. 1. 7.
M e di c al hi st or y
O btai n t he s u bject’s me dical hist or y b y i nter vie w a n d/ or re vie w of t he s u bject’s me dical 
rec or ds a n d rec or d a ny pre -e xisti n g c o n diti o ns or si g ns a n d/ or s y m pt o ms prese nt i n a 
s u bject pri or t o t he first visit i n t he e C R F. Me dicati o ns ta ke n b y  t he s u bject m ust als o be 
rec or de d.
5. 5. 1. 8.
D i stri b uti o n, tr ai ni n g, c o m pl eti o n a n d c oll e cti o n of pr e -v a c ci n ati o n 
di ar y  c ar d
A p re-vacci nati o n diar y  car d will be dis pe nse d t o eac h s u bject pri or t o t he first st u d y 
vacci nati o n a n d s u bjects/ s u bjects’ care gi ver will be i nf or me d h o w t o c o m plete t his car d 
b y  t he site staff. Th is p re- vacci nati o n diar y  car d will o nl y  q uer y ge neral s ym pt o ms a n d
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
4 8
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
4 9
s h oul d be c o m plete d b y t he s u bject / s u bjects’ care gi ver(s) a n d c ollecte d b y t he site staff 
at Visit 1.
5. 5. 1. 9.
R e vi e w a n d tr a n s cri b e pr e -v a c ci n ati o n di ar y  c ar d s
T he i n vesti gat or/st u d y  staff will e ns ure t hat s u bject has c o m plete d t he Visit 1 pre -
vacci nati o n diar y  car d. T he i n vesti gat or or desi g nee will tra nscri be t he i nf or mati o n t hat 
t he s u bject d oc u me nte d o n t he diar y car d i nt o t he e C R F.
5. 5. 2.
Pr o c e d ur e s d uri n g Vi sit 2
N ote t hat t he first vacci nati o n at Visit 2 will ta ke place at least 7 da y s after t he first visit 
( Visit 1) (see Ta ble 6 f or visit i nter vals).
5. 5. 2. 1.
R e - ch e c k i n cl u si o n a n d e x cl u si o n crit eri a
I ncl usi o n a n d e xcl usi o n criteria are re-c hec ke d at Visit 2 f or a ny c ha n ges c o m pare d t o 
Visit 1. I n case t he s u bject is n o l o n ger eli gi ble at Visit 2 , t he s u bject will be wit h dra w n 
fr o m t he st u d y a n d the reas o n f or t his will be rec or de d i n t he e C R F. If t he i n vesti gat or or 
dele gate deter mi nes t hat t he s u bject’s healt h o n t he da y  of a d mi nistrati o n te m poraril y  
precl u des vacci ne a d mi nistrati o n, t he visit will be resc he d ule d wit hi n t he all o we d i nter val 
f or t his visit (refer t o Ta ble 6 f or visit i nter vals).
5. 5. 2. 2.
Di stri b uti o n , c o m pl eti o n a n d c oll e cti o n of s e c o n d pr e- v a c ci n ati o n di ar y  
c ar d
A sec o n d p r e-vacci nati o n diar y  car d will be dis pe nse d t o eac h s u bject at Visit 2. T he car d
will o nl y  q uer y ge neral s ym pt o ms a n d s h oul d be c o m plete d b y  t he s u bject /s u bjects’ 
care gi ver(s) a n d c ollecte d b y t he site staff pri or t o t he first st u d y vacci nati o n.
5. 5. 2. 3.
R e vi e w a n d tr a n s cri b e pr e -v a c ci n ati o n di ar y  c ar d s
T he i n vesti gat or/st u d y  staff will e ns ure t hat s u bject has c o m plete d t he ( Visit 2) pre -
vacci nati o n diar y  car ds pri or t o Vacci nati o n 1. T he i n vesti gat or or desi g nee will 
tra nscri be t he i nf or mati o n t hat t he s u bject d oc u me nte d o n t he diar y car d pri or t o t he visit 
i nt o t he e C R F.
5. 5. 2. 4.
Di stri b uti o n a n d c o m pl eti o n of S F -3 6 a n d E Q -5 D q u e sti o n n air e s at 
Vi sit 2
T he S F - 3 6 a n d E Q- 5 D q uesti o n naires will be distri b ute d t o s u bjects a gai n at Visit 2. 
S u bjects will be as ke d t o c o m plete t he e ntire S F- 3 6 a n d E Q - 5 D q uesti o n naires o n site j ust 
bef ore vacci nati o n at Visit 2. C o m plete d q uesti o n naires will t he n be c ollecte d a n d s u bject 
res p o nses will be tra nscri be d i nt o t he e- C R F. T he sa me pr oce d ure f or q uesti o n naires will 
be f oll o we d at Visit 4 (see Secti o n 5. 5. 2. 1 1 ).
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
4 9
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
5 0
5. 5. 2. 5.
C h e c k c o ntr ai n di c at i o n s
C o ntrai n dicati o ns m ust be c hec ke d at t he be gi n ni n g of eac h vacci nati o n visit. Refer t o 
Secti o n 6. 4 f or m ore details.
5. 5. 2. 6.
P r e g n a n c y t e st
Fe male s u b jects of c hil d beari n g p ote ntial are t o ha ve a uri ne pre g na nc y test* pri or t o a n y  
st u d y vacci ne a d mi nistrati o n. T he st u d y vacci ne m a y  o nly be a d mi nistere d if t he 
pre g na nc y  test is ne gati ve. N ote: T he uri ne pre g na nc y test m ust be perf or me d e ve n if t he 
s u bject is me nstr uati n g at t he ti me of t he st u d y visit.
* A uri ne pre g na nc y  test is s ufficie nt. A ser u m pre g na nc y test, i nstea d of a uri ne 
pre g na nc y  test, s h o ul d o nl y be c o nsi dere d if re q uire d b y l ocal or et hics c o m mittee 
re g ulati o ns.
5. 5. 2. 7.
A s s e s s pr e -v a c ci n ati o n b o d y  t e m p er at ur e
T he b o d y  te m perat ure of all s u bjects nee ds t o be meas ure d pri or t o a n y st u d y vacci ne 
a d mi nistrati o n. Pre -vacci nati o n te m perat ures s h o ul d al wa y s be rec or de d orall y. I n rare 
sit uati o ns w he n t here is n o ot her alter nati ve, t he te m perat ure ma y be rec or de d b y ot her 
r o ute. If t he te m perat ure is ta ke n b y a n ot her r o ute (a xillar y, rectal or ty m pa nic), t he r o ute 
s h o ul d be d oc u me nte d a n d j ustifie d. If t he s u bject has a fe ver (fe ver is defi ne d as 
te m perat ure 3 7. 5° C/ 9 9. 5° F b y oral r o ute, a xillar y or t y m pa ni c setti n g, or 
≥3 8. 0° C/ 1 0 0. 4° F o n rectal setti n g) o n t he d a y  of vacci nati o n, t he vacci nati o n visit will be 
resc he d ule d wit hi n t he all o we d i nter val f or t his visit (see Ta ble 6 f or visit i nter vals).
5. 5. 2. 8.
St u d y  va c ci n e a d mi ni str ati o n

After c o m pleti n g all prere q uisite pr oce d ures pri or t o vacci nati o n, o ne d ose(s) of 
H Z/s u st u d y vacci ne will be a d mi nistere d I M i n t he delt oi d of t he n o n -d o mi na nt ar m 
(refer t o Secti o n 6. 3 f or detaile d descri pti o n of t he vacci ne a d mi nistrati o n 
pr oce d ure). If t he i n vesti gat or or dele gate deter mi nes t hat t he s u bject’s healt h o n t he 
da y  of a d mi nistrati o n te m p oraril y precl u des vacci ne a d mi nistrati o n, t he visit will be 
resc he d ule d wit hi n t he allo we d i nter val f or t his visit (refer t o Ta ble 6 f or visit 
i nter vals). I n t hat case, all acti vities t hat nee d t o be perf or me d o n t he da y of 
vacci nati o n (e. g., pre g na nc y test, q uesti o n naires c o m pleti o n, …) will als o ha ve t o be 
p ost p o ne d u ntil vacci nati o n da y .

T he s u bjects will be o bser ve d cl osel y f or at least 3 0 mi n utes f oll o wi n g t he 
a d mi nistrati o n of t he vacci ne(s), wit h a p pr o priate me dical treat me nt rea d il y a vaila ble 
i n case of a na p hyl a xis.

A n y  s u bjects wit h a n e ve nt of H Z bet wee n Visit 1 ( Da y -7) a n d a n y d ose of H Z/s u 
vacci ne s h o ul d n ot recei ve t he u pc o mi n g d ose(s) of t he H Z/s u vacci ne.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
5 0
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
5 1
5. 5. 2. 9.
C h e c k a n d r e c or d c o n c o mit a nt m e di c ati o n/ v a c ci n ati o n
C o nc o mita nt me di cati o n/ vacci nati o n m ust be c hec ke d a n d rec or de d i n t he e C R F as 
descri be d i n Secti o n 6. 5 .
5. 5. 2. 1 0.
R e c or di n g of A E s, S A E s, pr e g n a n ci e s a n d pI M D s

Refer t o Secti o n 8. 3 f or pr oce d ures f or t he i n vesti gat or t o rec or d A Es, S A Es, 
pre g na ncies a n d pI M Ds. Refer t o Secti o n 8. 4 f or g ui deli nes a n d h o w t o re p ort S A E, 
pre g na nc y  a n d pI M D re p orts t o G S K Bi ol o gicals.

T he s u bjects/s u bjects’ care gi ver(s) will be i nstr ucte d t o c o ntact t he i n vesti gat or 
i m me diatel y s h o ul d t he s u bjects ma nifest a n y si g ns or s ym pt o ms t he y  percei ve as 
seri o us.

At eac h vacci nati o n visit, diar y  car ds will be pr o vi de d t o t he s u bject/s u bject’s 
care gi ver(s) see Secti o n 5. 3. 1. 1 ). T he s u bject/s u bject’s care gi ver(s) will rec or d b o d y
( oral r o ute preferre d) te m perat ure a n d a ny s olicite d l ocal/ ge neral A Es (i.e. , o n t he 
da y  of vacci nati o n a n d d uri n g t he ne xt 6 da ys) or a n y u ns olicite d A Es (i.e., o n t he 
da y  of vacci nati o n a n d d uri n g t he ne xt 2 9 da y s occ urri n g after vacci nati o n). If t he 
te m perat ure is ta ke n by a n ot her r o ute (a xillar y, rectal or t y m pa nic), t he r o ute s h o ul d 
be d oc u me nte d wit h a n e x pla nati o n f or w h y  it was differe nt fr o m t he oral r o ute. T he 
s u bject/s u bject’s care gi ver(s) will be i nstr ucte d t o ret ur n t he c o m plete d diar y  car ds.

T he s u bject/s u bject’s care gi ver(s) will be i nstr ucte d t o ret ur n t he c o m plete d diar y  
car d t o t he i n vesti gat or at t he ne xt st u d y  visit. T he p ost-vacci nati o n 2 diar y  car ds f or 
dail y  rec or di n g of u ns olicite d A Es a n d c o nc o mita nt me dicati o n/ vacci nati o n ( Da y s 0-
2 9) b y  s u bjects will be ret ur ne d b y mail.

C ollecti o n a n d verificati o n of c o m plete d diar y  car ds will occ ur d uri n g disc ussi o n 
wit h t he s u bject/ s u bject’s care gi ver(s) a t t he visit f oll o wi n g eac h vacci nati o n visit
(e xce pt f or t he p ost-vacci nati o n 2 diar y  car ds f or dail y rec or di n g of u ns olicite d A Es 
a n d c o nc o mita nt me dicati o n/ vacci nati o n ( Da y s 0-2 9) w hic h will be ret ur ne d b y  mail
a n d disc usse d d uri n g t he M o nt h 3 p h o ne c o nt act).

A n y  u nret ur ne d diar y car ds will be s o u g ht fr o m t he s u bject/s u bject’s care gi ver(s)
t hr o u g h tele p h o ne call(s) or a ny ot her c o n ve nie nt pr oce d ure. T he i n vesti gat or a n d/ or 
dele gate will tra nscri be t he c ollecte d i nf or mati o n i nt o t he e C R F.
5. 5. 2. 1 1.
Di stri b uti o n a n d c o m pl eti o n of S F -3 6 a n d E Q -5 D q u e sti o n n air e s p o st -
v a c ci n ati o n
T he S F - 3 6 P F c o m p o ne nt of t he S F -3 6 q uesti o n naire ( o nly q uesti o ns 3a t hr o u g h 3j , see 
Ta ble 1 5 ) a n d E Q- 5 D dail y q uesti o n naires will be distri b ute d t o t he s u bjects t o ta ke h o me
f oll o wi n g b ot h vacci nati o ns at Visit 2 a n d Visit 4. T hese q uesti o n naires will nee d t o be 
c o m plete d o n a dail y basis ( Da y s 1 t o 6) a n d m ust be ret ur ne d at t he ne xt visits ( Visit 3 
a n d Visit 5). A d diti o nall y , d uri n g Visits 3 a n d 5, s u bjects will be as ke d t o o nce a gai n fill 
i n t he e ntire S F-3 6 a n d E Q -5 D q uesti o n naires o n site. C o m plete d q ues ti o n naires, 
c ollecte d at Visits 3 a n d Visit 5, will be tra nscri be d i nt o t he e C R F (see Secti o ns 1 0. 6. 2. 3
a n d 1 0. 6. 2. 4 ).
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
5 1
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
5 2
5. 5. 3.
St u d y c o n cl u si o n
T he i n vesti gat or will:

R e vie w data c ollecte d t o e ns ure acc urac y  a n d c o m plete ness,

C o m plete t he St u d y  C o ncl usi o n scree n i n t he e C R F.
6.
S T U D Y V A C CI N E A N D A D M I NI S T R A TI O N
6. 1.
D e s cri p ti o n of st u d y va c ci n e
T he ca n di date vacci ne t o be use d has bee n de vel o pe d a n d ma n ufact ure d b y G S K 
Bi ol o gicals.
T he Q ualit y  C o ntr ol Sta n dar ds a n d Re q uire me nts f or t he ca n di date vacci ne are descri be d 
i n se parate Q ualit y Ass ura nce d oc u me nts (e. g., release pr ot oc ols, certificate of a nalys is) 
a n d t he re q uire d a p pr o vals ha ve bee n o btai ne d.
T he vacci ne is la belle d a n d pac ke d acc or di n g t o a p plica ble re g ulat or y re q uire me nts.
T he c haracteristics of t he st u d y  vacci ne are detaile d i n Ta ble 7 .
T a bl e 7
St u d y  v a c ci n e
Tr e at m e nt 
n a m e
V a c ci n e n a m e
F or m ul ati o n
Pr e s e nt ati o n
V ol u m e t o b e 
a d mi ni st er e d
N u m b er 
of d o s e s
H Z/s u
V Z V g E
g E = 5 0 µ g
Ly o p hiliz e d p ell et 
i na vi al
0. 5 m L
2
A S 0 1 B
M P L = 5 0 µ g; Q S 2 1 = 5 0 µ g; 
Li p os o m es
Li q ui d i n a m o n o -
d os e vi al
H Z/s u = H er p es Z ost er s u b u nit v acci n e; V Z V = V aric ell a Z ost er Vir us; g E = r ec o m bi n a nt p urifi e d e nv el o p e g lyc o pr ot ei n
E; μ g = micr o gr a m; m L = millilit er ; A S 0 1B = A dj uv a nt Syst e m A S 0 1 B ; M P L = 3- O-d es acyl -4’ -m o n o p h os p h oryl li pi d A; 
Q S 2 1 = Q uill aj a s a p o n ari a M oli n a, fr acti o n 2 1 ( p urifi e d s a p o ni n extr act fr o m t h e S o ut h A m eric a n tr e e).
6. 2.
St or a g e a n d h a n dli n g of st u d y  va c ci n e
T he st u d y  vacci ne m ust be st ore d at t he res p ecti ve la bel st ora ge te m perat ure c o n diti o ns i n 
a safe a n d l oc ke d place. Access t o t he st ora ge s pace s h o ul d be li mite d t o a ut h orize d st u d y  
pers o n nel. T he st ora ge c o n diti o ns will be assesse d d uri n g pre -st u d y acti vities u n der t he 
res p o nsi bilit y of t he s p o ns or st u d y c o ntact. T he st ora ge te m perat ure s h o ul d be 
c o nti n u o usl y m o nit ore d wit h cali brate d (if n ot vali date d) te m perat ure m o nit ori n g 
de vice(s) a n d rec or de d. Refer t o t he M o d ule o n Cli nical Trial S u p plies i n t he S P M f or 
m ore details o n st ora ge of t he st u d y  vacci ne.
Te m perat ure e xc ursi o ns m ust be re p orte d i n de gree Celsi us.
A n y  te m perat ure e xc ursi o n o utsi de t he ra n ge of 0. 0 t o + 8. 0C (f or + 2 t o + 8° C/ + 3 6 t o 
+ 4 6° F la bel st ora ge c o n diti o n) i m pacti n g i n vesti gati o nal me dici nal pr o d ucts (I M Ps) m ust 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
5 2
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
5 3
be re p orte d i n t he a p pr o priate (electr o nic) te m perat ure e xc ursi o n decisi o n f or m ([e] T D F). 
T he i m pacte d I M Ps m ust n ot be use d a n d m ust be st ore d i n q uara nti ne at la bel 
te m perat ure c o n diti o ns u ntil usa ge a p pr o val has bee n o btai ne d fr o m t he s p o ns or.
I n case of te m perat ure e xc ursi o n bel o w + 2. 0° C d o w n t o 0. 0° C i m pacti n g I M P(s) t here is 
n o nee d t o re p ort i n (e) T D F, b ut a de q uate acti o ns m ust be ta ke n t o rest ore t he + 2 t o 
+ 8° C/ + 3 6 t o + 4 6° F la bel st ora ge te m perat ure c o n diti o ns . T he i m pacte d IM P(s) ma y  still 
be a d mi nistere d, b ut t he site s h o ul d a v oi d re-occ urre nce of s uc h te m perat ure e xc ursi o n.
Refer t o t he M o d ule o n Cli nical Trial S u p plies i n t he S P M f or m ore details o n acti o ns t o 
ta ke.
Refer t o t he M o d ule o n Cli nical Trial S u p plies i n t he S P M f or details a n d i nstr ucti o ns o n 
t he te m perat ure e xc ursi o n re p orti n g a n d usa ge decisi o n pr ocess, pac ka gi n g a n d 
acc o u nta bilit y of t he st u d y vacci ne.
6. 3.
D o s a g e a n d a d mi ni str ati o n of st u d y  va c ci n e
After re m o val of t he vacci ne c o m p o ne nts fr o m t he te m perat ure m o nit ore d refri gerat or, 
t he vacci ne s h o ul d be rec o nstit ute d a n d a d mi nistere d wit hi n 6 h o urs, a n d s h o ul d be ke pt 
at r o o m te m perat ure ( bet wee n 2° C/ 3 6° F a n d 3 0° C/ 8 6° F).
Vacci ne will be a d mi nistere d as i n dicate d i n Ta ble 8 .
T a bl e 8
D o s a g e a n d a d mi ni str ati o n
T y p e of c o nt a ct 
a n d ti m e p oi nt
St u d y gr o u p
Tr e at m e nt n a m e
V ol u m e t o b e 
a d mi ni st er e d
R o ut e 1
Sit e 2
Si d e 3
Visit 2 ( M o nt h 0)
H Z/s u
H Z/s u
0. 5 m L
I M
D 
N- D
Visit 4 ( M o nt h 2)
1 I ntr a m usc ul ar (I M)
2 D elt oi d ( D)
3 N o n -d o mi n a nt ( N -D)
m L = millilitr e; H Z/s u = H er p es Z ost er s u b u nit v acci n e.
T he rec o nstit ute d vacci ne ( 0. 5 m L) s h o ul d be a d mi nistere d b y  IM i njecti o n i nt o t he 
delt oi d ( D) m uscle of t he n o n - d o mi na nt ( N- D) ar m usi n g a sta n dar d ase ptic tec h ni q ue. I n 
rare sit uati o ns w he n t here is n o alter nati ve, t he i njecti o n ma y be gi ve n i n t he d o mi na nt 
ar m.
6. 4.
C o ntr ai n di c ati o n s t o s u b s e q u e nt v a c ci n ati o n
T he f oll o wi n g e ve nts c o nstit ute a bs ol ute c o ntrai n dicati o ns t o f urt her a d mi nistrati o n of
H Z/s u vacci ne . If a ny of t hese e ve nts occ ur d uri n g t he st u d y , t he s u bject m ust n ot recei ve 
a d diti o nal d oses of vacci ne b ut ma y c o nti n ue ot her st u d y pr oce d ures at t he discreti o n of 
t he i n vesti gat or (see Secti o n 8. 5 ).

A na p h yl a xis f oll o wi n g t he a d mi nistrati o n of vacci ne.

Pre g na nc y  (see Secti o n 8. 2. 1 ).
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
5 3
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
5 4

A n y  c o n diti o n t hat i n t he j u d g me nt of t he i n vesti gat or w o ul d ma ke i ntra m usc ular 
i njecti o n u nsafe.

If t he s u bject e x perie nces a n S A E j u d ge d t o be vacci ne-relate d by t he i n vesti gat or/ 
dele gate.

If t he s u bject e x perie nces a n e ve nt of H Z bef ore a d mi nistra ti o n of t he first d ose of 
t he vacci ne or bet wee n t he first a n d t he sec o n d d ose of vacci ne.

A n y  c o nfir me d or s us pecte d i m m u n os u p pressi ve or i m m u n o deficie nt c o n diti o n, 
i ncl u di n g HI V i nfecti o n.

Occ urre nce of a ne w pI M D or t he e xacer bati o n of a n e xisti n g pI M D t hat, i n t he 
o pi ni o n of t he i n vesti gat or, e x p ose t he s u bject t o u nacce pta ble ris k fr o m s u bse q ue nt 
vacci nati o n. I n s uc h cases, t he i n vesti gat or s h o ul d use his/ her cli nical j u d g me nt pri or 
t o a dmi nisteri n g t he ne xt d ose of t he vacci ne. Refer t o Secti o n 8. 1. 5. 1 f or t he 
defi niti o n of pI M Ds.
T he f oll o wi n g e ve nts c o nstit ute c o ntrai n dicati o ns t o a d mi nistrati o n of H Z/s u vacci ne at 
t hat p oi nt i n ti me; if a n y of t hese e ve nts occ ur at t he ti me sc he d ule d f or vacci nati o n, t he 
s u bject ma y be vacci nate d at a later date, wit hi n t he ti me wi n d o w s pecifie d i n t he 
pr ot oc ol (see Secti o n 5. 4 ), or t he s u bject ma y be wit h dra w n at t he discreti o n of t he 
i n vesti gat or (see Secti o n 8. 5 ).

Ac ute disease a n d/ or fe ver at t he ti me of vacci nati o n.

Fe ver is defi ne d as te m perat ure 3 7. 5° C/ 9 9. 5° F f or oral, a xillar y  or t ym pa nic 
setti n g, or 3 8. 0° C/ 1 0 0. 4° F f or rectal r o ute. T he preferre d r o ute f or rec or di n g 
te m perat ure i n t his st u d y will be oral.

S u bjects wit h a mi n or ill ness (s uc h as mil d diarr hea, mil d u p per res pirat or y 
i nfecti o n) wit h o ut fe ver ca n be a d mi nistere d all vacci nes/ pr o d ucts.
6. 5.
C o n c o mit a nt m e di c ati o n s / pr o d u cts a n d c o n c o mit a nt 
v a c ci n ati o n s
At eac h st u d y visit/c o ntact, t he i n vesti gat or s h o ul d q uesti o n t he s u bject a n d/ or t he 
s u bject’s care gi ver a b o ut a n y me dicati o ns/ pr o d ucts ta ke n a n d vacci nati o ns recei ve d by 
t he s u bject.
6. 5. 1.
R e c or di n g of c o n c o mit a nt m e di c ati o n s/ pr o d u ct s a n d 
c o n c o mit a nt v a c ci n ati o n s
T he f oll o wi n g c o nc o mita nt me dicati o n(s)/ pr o d uct(s)/ vacci ne(s) m ust be rec or de d i n 
t he e C R F.

All c o nc o mita nt me dicati o ns/ pr o d ucts, e xce pt vita mi ns a n d dietar y  s u p ple me nts, 
a d mi nistere d starti n g 7 da y s bef ore t he first d ose a n d d uri n g t he peri o d 3 0 da y s (Da y  
0 t o Da y  2 9) f oll o wi n g eac h d ose of st u d y vacci ne.

A n y  c o nc o mita nt vacci nati o n a d mi nistere d i n t he peri o d starti n g 3 0 d a y s bef ore 
e nr ol me nt a n d e n di n g at o ne m o nt h p ost d ose 2.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
5 4
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
5 5

Pr o p h y lactic me dicati o n (i.e., me dicati o n a d mi nistere d i n t he a bse nce of A NY 
s ym pt o m a n d i n a ntici pati o n of a reacti o n t o t he vacci nati o n).
E. g. , a n a nti-p y retic is c o nsi dere d t o be pr o p h ylactic w he n it is gi ve n i n t he a bse nce 
of fe ver a n d a n y ot her s y m pt o m, t o pre ve nt fe ver fr o m occ urri n g [fe ver is defi ne d as 
te m perat ure 3 7. 5° C/ 9 9. 5° F f or oral r o ute, a xillar y  or ty m pa nic setti n g, or 
3 8. 0° C/ 1 0 0. 4° F o n rectal setti n g. T he preferre d r o ute f or rec or di n g te m perat ure i n 
t his st u d y will be oral].

A n y  i n vesti gati o nal or n o n-re gistere d pr o d uct ( dr u g or vacci ne) ot her t ha n t he st u d y 
vacci ne.

A n y  c o nc o mita nt me dicati o ns/ pr o d ucts/ vacci nes liste d i n Secti o n 6. 5. 2 .

A n y  c o nc o mita nt me dicati o ns/ pr o d ucts/ vacci nes rele va nt t o a S AE/ pI M D t o be 
re p orte d as per pr ot oc ol or a d mi nistere d d uri n g t he st u d y peri o d f or t he treat me nt of 
a S A E / pIM D. I n a d diti o n, c o nc o mita nt me dicati o ns rele va nt t o S A Es a n d pIM D 
nee d t o be rec or de d o n t he e x pe dite d A d verse E ve nt re p ort.
6. 5. 2.
C o n c o mit a nt v a c ci n e s t h at m a y  l e a d t o t h e eli mi n ati o n of a 
s u bj e ct fr o m A T P a n al y s e s
T he use of t he f oll o wi n g c o nc o mita nt vacci nes will n ot re q uire wit h dra wal of t he s u bject 
fr o m t he st u d y b ut ma y deter mi ne a s u bject’s e val ua bilit y i n t he A T P a nalysis. See 
Secti o n 1 0. 4 f or c o h orts t o be a nalys e d.

A n y  i n vesti gati o nal or n o n-re gistere d pr o d uct ( dr u g or vacci ne) ot her t ha n t he st u d y 
vacci ne use d d uri n g t he st u d y  peri o d.

A d mi nistrati o n of a li ve vacci ne i n t he peri o d starti n g 3 0 da y s bef ore t he first d ose of 
st u d y vacci ne a n d e n di n g 3 0 da ys after t he last d ose of st u d y vacci ne, or, 
a d mi nistrati o n of a n o n -re plicati n g vacci ne * wit hi n 1 5 da ys pri or t o or wit hi n 1 4 
da y s after either d ose of st u d y  vacci ne. * E. g., i nacti vate d a n d s u b u nit vacci nes, 
i ncl u di n g i nacti vate d a n d s u b u nit i nfl ue nza vacci nes f or seas o nal or pa n de mic fl u, 
wit h o ut a dj u va nt, a n d p ne u m oc occal c o nj u gate vacci nes.

I n case a n e mer ge nc y mass vacci nati o n f or a n u nf oresee n p u blic healt h t hreat (e. g.: a 
pa n de mic) is or ga nize d b y t he p u blic healt h a ut h orities, o utsi de t he r o uti ne 
i m m u nizati o n pr o gra m, t he ti me peri o d descri be d a b o ve ca n be re d uce d if necessar y 
f or t hat vacci ne pr o vi de d it is lice nse d a n d use d acc or di n g t o its Prescri bi n g 
I nf or mati o n a n d acc or di n g t o t he l ocal g o ver n me ntal rec o m me n dati o ns a n d pr o vi de d 
a writte n a p pr o val of t he S p o ns or is o btai ne d.

Recei pt of a vacci ne a gai nst H Z ot her t ha n t he st u d y  vacci ne fr o m e nr ol me nt t o 1 
m o nt h p ost -d ose 2.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
5 5
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
5 6
7.
H E A L T H E C O N O MI C S
Direct me dical a n d i n direct c ost (t he n u m ber of da ys of w or k l oss) data relate d t o t he 
react o ge nicit y will be esti mate d base d o n t he c orres p o n di n g i nf or mati o n rec or de d i n t he 
C R F. Res o urce use data t o be c ollecte d i ncl u de:

Direct me dical c osts:

Me dicati o n , i.e., t he c ha n ge i n me dicati o n pre-vacci nati o n a n d p ost -vacci nati o n 
will be a nal ys e d t o i de ntif y w hic h me dicati o n is ass ociate d wit h react o ge nicit y.

Me dicall y  Atte n de d Visits (i.e., h os pitalizati o n, Ge neral Practiti o ners a n d 
s pecialist visits).

Tele p h o ne co ntact s f or healt hcare reas o ns will be rec or de d i n t he diar y car ds a n d 
t he n tra nscri be d i nt o t he e C R F.

I n direct c osts:

Misse d ti me fr o m w or k (s u bject a n d care gi ver) . T he perce nta ge of s u bjects wit h 
l oss of w or ki n g da ys will be ta b ulate d.

A n a p pr o xi mate d m o nt hl y salar y  (f or f ull-ti me a n d self-e m pl o ye d w or kers) or 
a vera ge dail y wa ge (f or part -ti me w or kers) will be esti mate d base d o n s u bject’s 
ty pe of w or k, h o urs w or ke d, a ge, etc., c ollecte d o n Da y - 7 ( Visit 1).
F urt her details of c ost a nal y sis will be detaile d i n a Healt h Ec o n o mics a nal ysis pla n.
8.
S A F E T Y
T he i n vesti gat or or site staff is/are res p o nsi ble f or t he detecti o n, d oc u me ntati o n a n d 
re p orti n g of e ve nts meeti n g t he criteria a n d defi niti o n of a n A E or S A E as pr o vi de d i n 
t his pr ot oc ol.
Eac h s u bject/s u bject’s care gi ver will be i nstr ucte d t o c o ntact t he i n vesti gat or i m me diatel y  
s h o ul d t he y/t he s u bject ma nifest a n y si g ns or sy m pt o ms t he y  percei ve as seri o us.
8. 1.
S af et y d efi niti o n s
8. 1. 1.
D efi niti o n of a n a d v er s e e v e nt
A n A E is a ny u nt o war d me dical occ urre nce i n a cli nical i n vesti gati o n s u bject, te m p orall y 
ass ociate d wit h t he use of a me dici nal pr o d uct, w het her or n ot c o nsi dere d relate d t o t he 
me dici nal pr o d uct.
A n A E ca n t heref ore be a n y  u nfa v o ura ble a n d u ni nte n de d si g n (i ncl u di n g a n a b n or mal 
la b orat or y fi n di n g), sy m pt o m, or disease ( ne w or e xacer bate d) te m p orall y ass ociate d wit h 
t he use of a me dici nal pr o d uct. F or mar kete d me dici nal pr o d ucts, t his als o i ncl u des 
fail ure t o pr o d uce e x pecte d be nefits (i.e., lac k of efficac y ), a b use or mis use.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
5 6
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
5 7
E xa m ples of a n A E i ncl u de:

E xacer bati o n of a c hr o nic or i nter mitte nt pre-e xisti n g c o n diti o n i ncl u di n g eit her a n 
i ncrease i n fre q ue nc y a n d/ or i nte nsit y of t he c o n diti o n.

Ne w c o n diti o ns detecte d or dia g n ose d after i n vesti gati o nal vacci ne(s)/ pr o d uct(s) 
a d mi nistrati o n e ve n t h o u g h t he y ma y ha ve bee n prese nt pri or t o t he start of t he st u d y.

Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d i nteracti o n.

Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d o ver d ose of eit h er 
i n vesti gati o nal vacci ne(s)/ pr o d uct(s) or a c o nc urre nt me dicati o n ( o ver d ose per se 
s h o ul d n ot be re p orte d as a n A E/ S A E).

Si g ns, s y m pt o ms te m p orall y  ass ociate d wit h vacci ne a d mi nistrati o n.

Pre - or p ost -treat me nt e ve nts t hat occ ur as a res ult of pr ot oc ol- ma n date d pr oce d ures 
(i.e., i n vasi ve pr oce d ures, m o dificati o n of s u bject’s pre vi o us t hera pe utic re gi me n).
A Es t o be rec or de d as e n d p oi nts (s olicite d A Es) are descri be d i n Secti o n 8. 1. 3 . All ot her 
A Es will be rec or de d as U N S O LI CI T E D A Es.
E xa m ples of a n A E D O N O T i ncl u de:

Me dical or s ur gical pr oce d ures (e. g., e n d osc o p y, a p pe n dect o m y); t he c o n diti o n t hat 
lea ds t o t he pr oce d ure is a n A E/ S A E.

Sit uati o ns w her e a n u nt o war d me dical occ urre nce di d n ot occ ur (e. g., s ocial a n d/ or 
c o n ve nie nce a d missi o n t o a h os pital, a d missi o n f or r o uti ne e xa mi nati o n).

A ntici pate d da y -t o-d a y  fl uct uati o ns of pre-e xisti n g disease(s) or c o n diti o n(s) prese nt 
or detecte d at t he start of t he st u d y t hat d o n ot w orse n.

Pre -e xisti n g c o n diti o ns or si g ns a n d/ or s y m pt o ms prese nt i n a s u bject pri or t o t he 
first st u d y vacci nati o n. T hese e ve nts will be rec or de d i n t he me dical hist or y secti o n 
of t he e C R F .
8. 1. 2.
D efi niti o n of a s eri o u s a d v er s e e v e nt 
A S A E is a n y u nt o war d me dical occ urre nce t hat:
a.
Res ults i n deat h,
b.
Is life-t hreate ni n g,
N ote: T he ter m ‘life-t hreate ni n g’ i n t he defi niti o n of ‘seri o us’ refers t o a n e ve nt i n 
w hic h t he s u bject was 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 ve nt, w hic h h y p ot heticall y  mi g ht ha ve ca use d deat h, ha d it bee n m ore se vere.
c.
Re q uires h os pitaliz ati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n,
N ote: I n ge neral, h os pitali z ati o n si g nifies t hat t he s u bject has bee n a d mitte d at t he 
h os pital or e mer ge nc y war d f or o bser vati o n a n d/ or treat me nt t hat w o ul d n ot ha ve 
bee n a p pr o priate i n t he p h y sicia n’s office or i n a n o ut- patie nt setti n g. C o m plicati o ns 
t hat occ ur d uri n g h os pitaliz ati o n are als o c o nsi dere d A Es. If a c o m plicati o n pr ol o n gs 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
5 7
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
5 8
h os pitali z ati o n or f ulfils a n y ot her seri o us criteria, t he e ve nt will als o be c o nsi dere d 
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 pital izati o n f or electi ve treat me nt of a pre-e xisti n g c o n diti o n ( k n o w n or 
dia g n ose d pri or t o i nf or me d c o nse nt si g nat ure) t hat di d n ot w orse n fr o m baseli ne is 
N O T c o nsi dere d a n A E.
d.
Res ults i n disa bilit y /i nca pacit y, O R
N ote: T he ter m disa bilit y mea ns a s u bsta ntial disr u pti o n of a pers o n’s a bilit y  t o 
c o n d uct n or mal life f u ncti o ns. T his defi niti o n is n ot i nte n de d t o i ncl u de e x perie nces 
of relati vel y mi n or me dical si g nifica nce s uc h as u nc o m plicate d hea dac he, na usea, 
v o miti n g, diarr h oea, i nfl ue nza li ke ill ness, a n d acci de ntal tra u ma (e. g. , s prai ne d 
a n kle) w hic h ma y i nterfere or pre ve nt e ver yd a y  life f u ncti o ns b ut d o n ot c o nstit ute a 
s u bsta ntial disr u pti o n.
e.
Is a c o n ge nital a n o maly/ birt h defect i n t he offs pri n g of a st u d y  s u bject.
Me dical or scie ntific j u d ge me nt s h o ul d be e xercise d i n deci di n g w het her re p orti n g is 
a p pr o priate i n ot he r 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 par dise t he 
s u bject or ma y re q uire me dical or s ur gical i nter ve nti o n t o pre ve nt o ne of t he ot her 
o utc o mes liste d i n t he a b o ve defi niti o n. T hese s h o ul d als o be c o nsi dere d seri o us. 
E xa m ples of s uc h e ve nts are i n vasi ve or mali g na nt ca ncers, i nte nsi ve treat me nt i n a n 
e mer ge nc y r o o m or at h o me f or aller gic br o nc h os pas m, bl o o d d yscrasias or c o n v ulsi o ns 
t hat d o n ot res ult i n hos pitali z ati o n.
8. 1. 3.
S oli cit e d a d v er s e e v e nt s
8. 1. 3. 1.
S oli cit e d l o c al (i nj e cti o n -sit e) a d v er s e e v e nt s
T he f oll o wi n g l ocal (i njecti o n- site) A Es will be s olicite d:
T a bl e 9
S oli cit e d l o c al a d v er s e e v e nt s
P ai n at i nj ecti o n sit e
R e d n ess at i nj ecti o n sit e
S w elli n g at i nj ecti o n sit e
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
5 8
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
5 9
8. 1. 3. 2.
S oli cit e d g e n er al a d v er s e e v e nt s
T he f oll o wi n g ge neral A Es will be s olicite d:
T a bl e 1 0
S oli cit e d g e n er al a d v er s e e v e nt s
F ati g u e
F ev er
G astr oi nt esti n al sy m pt o ms †
H e a d ac h e
My al gi a
S hiv eri n g
†G astr oi nt esti n al sy m pt o ms i ncl u d e n a us e a, v o miti n g, di arr h e a a n d/ or a b d o mi n al p ai n.
N ote: Te m perat ure ( oral) will be rec or de d i n t he e ve ni n g. S h o ul d a d diti o nal te m perat ure 
meas ure me nts be perf or me d at ot her ti mes of da y, t he hi g hest te m perat ure will be 
recor de d i n t he e C R F.
T he ti me of first o nset of t he s olicite d l ocal a n d ge neral A E s nee ds t o be rec or de d i n t he 
d iar y car ds a n d e C R F.
8. 1. 4.
Cli ni c al l a b or at or y  p ar a m et er s a n d ot h er a b n or m al a s s e s s m e nt s 
q u alif y i n g a s a d v er s e e v e nt s or s eri o u s a d v er s e e v e nt s
I n a bsence of dia g n osis, a b n or mal la b orat or y  fi n di n gs (e. g., cli nical c he mistr y, 
hae mat ol o g y , uri nalys is) or ot her a b n or mal assess me nts t hat are j u d ge d b y t he 
i n vesti gat or t o be cli nicall y si g nifica nt will be rec or de d as A E or S A E if t he y meet t he 
defi niti o n of a n A E or S A E (refer t o Secti o n s 8. 1. 1 a n d 8. 1. 2 ). 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 assess me nts t hat are prese nt at baseli ne 
a n d si g nifica ntl y w orse n f oll o wi n g t he start of t he st u d y will als o be re p orte d as A Es or 
S A Es .
T he i n vesti gat or will e xercise his or her me dical a n d scie ntific j u d ge me nt i n deci di n g 
w het her a n a b n or mal la b orat or y fi n di n g or ot her a b n or mal assess me nt is cli nicall y  
si g nifica nt.
8. 1. 5.
A d v er s e e v e nt s of s p e cifi c i nt er e st
8. 1. 5. 1.
P ot e nti al i m m u n e -m e di at e d di s e a s e s
P ote ntial i m m u ne -me diate d diseases ( pI M Ds) are a s u bset of A Es t hat i ncl u de 
a ut oi m m u ne diseases a n d ot her i nfla m mat or y  a n d/ or ne ur ol o gic dis or ders of i nterest 
w hic h ma y  or ma y n ot ha ve a n a ut oi m m u ne aeti ol o g y. A Es t hat nee d t o be rec or de d a n d 
re p orte d as pI M Ds i ncl u de t h ose liste d i n Ta ble 1 1 .
H o we ver, t he i n vesti gat or will e xercise his/ her me dical a n d scie ntific j u d ge me nt i n 
deci di n g w het her ot her diseases ha ve a n a ut oi m m u ne ori gi n ( i.e., pat h o p h ysi ol o g y  
i n v ol vi n g s yste mic or or ga n-s pecific pat h o ge nic a ut oa nti b o dies) a n d s h o ul d als o be 
rec or de d as a pI M D.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
5 9
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
6 0
T a bl e 1 1 
Li st of p ot e nti al i m m u n e -m e di at e d di s e a s e s
N e ur oi nfl a m m at or y di s or d er s
M u s c ul o s k el et al di s or d er s
S ki n di s or d er s

Cr a ni al n erv e dis or d ers, i ncl u di n g 
p ar alys es/ p ar esis ( e. g., B ell’s 
p alsy) 

O ptic n e uritis

M ulti pl e scl er osis

Tr a nsv ers e my elitis

G uill ai n -B arr é sy n dr o m e, i ncl u di n g 
Mill er Fis h er sy n dr o m e a n d ot h er 
v ari a nts

Ac ut e diss e mi n at e d 
e nc e p h al o my elitis, i ncl u di n g sit e 
s p ecific v ari a nts: e. g., n o n -
i nf ecti o us e nc e p h alitis, 
e nc e p h al o my elitis, my elitis, 
my el or a dic ul o n e uritis

My ast h e ni a gr avis, i ncl u di n g 
L a m b ert -E at o n my ast h e nic 
sy n dr o m e 

I m m u n e-m e di at e d p eri p h er al 
n e ur o p a t hi es a n d pl ex o p at hi es, 
(i ncl u di n g c hr o nic i nfl a m m at ory 
d e my eli n ati n g p oly n e ur o p at hy, 
m ultif oc al m ot or n e ur o p at hy a n d 
p oly n e ur o p at hi es ass oci at e d wit h 
m o n ocl o n al g a m m o p at hy).

N arc ol e psy

Syst e mic l u p us eryt h e m at os us 
a n d ass oci at e d c o n diti o ns

S yst e mic scl er od er m a
( Syst e mic scl er osis), i ncl u di n g 
diff us e syst e mic f or m a n d 
C R E S T sy n dr o m e
I di o p at hic i nfl a m m at ory 
my o p at hi es, i ncl u di n g 
d e r m at o my ositis 

P oly my ositis 

A ntisy nt h et as e sy n dr o m e

R h e u m at oi d art hritis, a n d 
ass oci at e d c o n diti o ns i ncl u di n g 
juv e nil e c hr o nic a rt hritis a n d 
Still’s dis e as e

P oly my al gi a r h e u m atic a

S p o n dyl o art hritis, i ncl u di n g 
a nkyl osi n g s p o n dylitis, r e activ e 
art hritis ( R eit er's Sy n dr o m e) 
a n d u n diff er e nti at e d 
s p o n dyl o art hritis 

Ps ori atic art hr o p at hy

R el a psi n g p olyc h o n dritis

Mix e d c o n n ectiv e tiss u e 
d is or d er

Ps ori asis

Vitili g o

Eryt h e m a n o d os u m

A ut oi m m u n e b ull o us ski n 
dis e as es (i ncl u di n g 
p e m p hi g us, p e m p hi g oi d 
a n d d er m atitis 
h er p etif or mis)

Al o p eci a ar e at a

Lic h e n pl a n us

S w e et’s sy n dr o m e

L oc alis e d Scl er o d er m a 
(M or p h o e a )
V a s c uliti d e s
Bl o o d di s or d er s
Ot h er s

L ar g e v ess els v asc ulitis 
i ncl u di n g: gi a nt c ell art eritis s uc h 
as T ak ay as u's art eritis a n d 
t e m p or al art eritis. 

M e di u m siz e d a n d/ or s m all 
v ess els v asc ulitis i ncl u di n g: 
p oly art eritis n o d os a, K a w as aki's 
dis e as e, micr osc o pic 
p oly a n giitis, W e g e n er's 
gr a n ul o m at osis, C h ur g – Str a uss 
sy n dr o m e ( all er gic 
gr a n ul o m at o us a n giitis), 
B u er g er’s dis e as e 
(t hr o m b o a n giitis o blit er a ns), 
n ecr otizi n g v asc ulitis a n d a nti -
n e utr o p hil cyt o pl as mic a nti b o dy 
( A N C A) p ositiv e v asc ulitis (ty p e 
u ns p ecifi e d), H e n oc h -Sc h o nl ei n 
p ur p ur a, B e hc et's sy n dr o m e, 
l e uk ocyt ocl astic v asc ulitis.

A ut oi m m u n e h e m olytic 
a n e mi a

A ut oi m m u n e 
t hr o m b ocyt o p e ni a

A nti p h os p h oli pi d 
sy n dr o m e

P er nici o us a n e mi a

A ut oi m m u n e a pl astic 
a n a e mi a

A ut oi m m u n e 
n e utr o p e ni a 

A ut oi m m u n e 
p a ncyt o p e ni a

A ut oi m m u n e gl o m er ul o n e p hritis
(i ncl u di n g I g A n e p hr o p at hy, 
gl o m er ul o n e p hritis r a pi dly 
pr o gr essiv e, m e m br a n o us 
gl o m er ul o n e p hritis, 
m e m br a n o pr olif er ativ e 
gl o m er ul o n e p hritis, a n d 
m es a n gi o pr olif er ativ e 
gl o m er ul o n e p hritis)

Oc ul ar a ut oi m m u n e dis e as es 
(i ncl u di n g a ut oi m m u n e uv eitis a n d 
a ut oi m m u n e r eti n o p at hy)

A ut oi m m u n e 
my oc ar ditis/c ar di o my o p at hy S arc oi d o
sis

St ev e ns -J o h ns o n sy n dr o m e

Sj ö gr e n’s sy n dr o m e

I di o p at hic p ul m o n ary fi br osis

G o o d p ast ur e sy n dr o m e

R ay n a u d’s p h e n o m e n o n
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
6 0
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
6 1
Li v er di s or d er s
G a str oi nt e sti n al di s or d er s
E n d o cri n e di s or d er s

A ut oi m m u n e h e p atitis

Pri m ary bili ary cirr h osis

Pri m ary scl er osi n g 
c h ol a n gitis

A ut oi m m u n e c h ol a n gitis

I nfl a m m at ory B o w el dis e as e, 
i ncl u di n gCr o h n’s dis e as e, 
ulc er ativ e c olitis, micr osc o pic 
c olitis, ulc er ativ e pr octitis 

C eli ac dis e as e

A ut oi m m u n e p a ncr e atitis

A ut oi m m u n e t hyr oi ditis (i ncl u di n g 
H as hi m ot o t hyr oi ditis)

Gr av e's or B as e d o w’s dis e as e

Di a b et es m ellit us ty p e I

A d dis o n’s dis e as e

P oly gl a n d ul ar a ut oi m m u n e sy n dr o m e

A ut oi m m u n e hy p o p hysitis
W he n t here is e n o u g h e vi de nce t o ma ke a n y of t he a b o ve dia g n oses, t he A E m ust be 
re p orte d as a pI M D. Sy m pt o ms, si g ns or c o n diti o ns w hic h mi g ht ( or mi g ht n ot) re prese nt 
t he a b o ve dia g n oses, s h o ul d be rec or de d a n d re p orte d as A Es b ut n ot as pI M Ds u ntil t he 
fi nal or defi niti ve dia g n osis has bee n deter mi ne d, a n d alter nati ve dia g n oses ha ve bee n 
eli mi nate d or s h o w n t o be less li kel y.
I n or der t o facilitate t he d oc u me ntati o n of pI M Ds i n t he e C R F, a pI M D sta n dar d 
q uesti o n naire a n d a list of preferre d ter ms ( P Ts) a n d P T c o des c orres p o n di n g t o t he a b o ve 
dia g n oses will be a vaila ble t o i n vesti gat ors at st u d y start.
8. 2.
E v e nt s or o ut c o m e s n ot q u alif y i n g a s a d v er s e e v e nt s or 
s eri o u s a d v er s e e v e nt s
8. 2. 1.
Pr e g n a n c y
Fe male s u bjects w h o are pre g na nt or lactati n g at t he ti me of vacci nati o n m ust n ot recei ve 
a d diti o nal d oses of st u d y vacci ne b ut ma y  c o nti n ue ot her st u d y pr oce d ures at t he 
discreti o n of t he i n vesti gat or.
W hile pre g na nc y  itself is n ot c o nsi dere d a n A E or S A E, a n y a d verse pre g na nc y o utc o me 
or c o m plicati o n or electi ve ter mi nati o n of a pre g na nc y  f or me dical reas o ns will be 
rec or de d a n d re p orte d as a n A E or a S A E.
N ote: T he pre g na nc y  itself s h o ul d al wa ys be rec or de d o n electr o nic pre g na nc y re p ort.
T he f oll o wi n g s h o ul d al wa y s be c o nsi dere d as S A E a n d will be re p orte d as descri be d i n 
Secti o ns 8. 4. 1 a n d 8. 4. 3 :

S p o nta ne o us pre g na nc y  l oss, i ncl u di n g:

s p o nta ne o us a b orti o n, (s p o nta ne o us pre g na nc y l oss bef ore/at 2 2 wee ks of 
gestati o n)

ect o pic a n d m olar pre g na nc y

still birt h (i ntra uteri ne deat h of f oet us after 2 2 wee ks of gestati o n).
N ote: t he 2 2 wee ks c ut -off i n gestati o nal a ge is base d o n W H O -I CD 1 0 n ote d i n t he 
E M A G ui deli ne o n pr e g na nc y e x p os ure [E M A , 2 0 0 6]. It is rec o g nize d t hat nati o nal 
re g ulati o ns mi g ht be differe nt.

A n y  early ne o natal deat h ( i.e., deat h of a li ve b or n i nfa nt occ urri n g wi t hi n t he first 7 
da y s of life).
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
6 1
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
6 2

A n y  c o n ge nital a n o maly or birt h defect (as per [ C D C M A C D P 2 0 0 7 ] g ui deli nes) 
i de ntifie d i n t he offs pri n g of a st u d y s u bject (eit her d uri n g pre g na nc y, at birt h or 
later) re gar dless of w het her t he f oet us is deli vere d dea d or ali ve. T his i ncl u des 
a n o malies i de ntifie d b y pre natal ultras o u n d, a m ni oce ntesis or e xa mi nati o n of t he 
pr o d ucts of c o nce pti o n after electi ve or s p o nta ne o us a b ort i o n.
F urt her m ore, a n y S A E occ urri n g as a res ult of a p ost -st u d y pre g na nc y A N D c o nsi dere d 
b y  t he i n vesti gat or t o be reas o na bly relate d t o t he i n vesti gati o nal vacci ne will be re p orte d 
t o G S K Bi ol o gicals as descri be d i n Secti o n 8. 4. 3 . W hile t he i n vesti gat or is n ot o bli gate d 
t o acti vel y see k t his i nf or mati o n fr o m f or mer st u d y partici pa nts, he/s he ma y lear n of a 
pre g na nc y  t hr o u g h s p o nta ne o us re p orti n g.
8. 3.
D et e cti n g a n d r e c or di n g a d v er s e e v e nt s, s eri o u s a d v er s e 
e v e nt s a n d pr e g n a n ci e s
8. 3. 1.
Ti m e p eri o d f or d et e cti n g a n d r e c or di n g a d v er s e e v e nt s, s eri o u s 
a d v er s e e v e nt s a n d pr e g n a n ci e s
All A Es starti n g 3 0 d a y s f oll o wi n g a d mi nistrati o n of eac h d ose of st u d y  vacci ne m ust be 
rec or de d i nt o t he a p pr o priate secti o n of t he e C R F, irres pecti ve of i nte nsit y or w het her or 
n ot t he y  are c o nsi dere d vacci nati o n-relate d.
T he ti me peri o d f or c ollecti n g a n d rec or di n g S A Es will be gi n at t he first recei pt of st u d y  
vacci ne a n d will e n d a p pr o xi matel y  1 2 m o nt hs f oll o wi n g a d mi nistrati o n of t he last d ose 
of st u d y  vacci ne f or eac h s u bject. See Secti o n 8. 4 f or i nstr ucti o ns o n re p orti n g of S A Es.
All A Es/ S A Es lea di n g t o wit h dra wal fr o m t he st u d y will be c ollecte d a n d rec or de d fr o m 
t he ti me of t he first recei pt of st u d y vacci ne .
I n a d diti o n t o t he a b o ve- me nti o ne d re p orti n g re q uire me nts a n d i n or der t o f ulfil 
i nter nati o nal re p orti n g o bli gati o ns, S A Es t hat are relate d t o st u d y partici pati o n (i.e., 
pr ot oc ol -ma n date d pr oce d ures, i n vasi ve tests, a c ha n ge fr o m e xisti n g t hera p y ) or are 
relate d t o a c o nc urre nt G S K me dicati o n/ vacci ne will be c ollecte d a n d rec or de d fr o m t he 
ti me t he s u bject c o nse nts t o partici pate i n t he st u d y u ntil s he/ he is disc har ge d fr o m t he 
st u d y.
T he ti me peri o d f or c ollecti n g a n d rec or di n g pre g na ncies will be gi n at t he first recei pt of 
st u d y vacci ne a n d will e n d 1 2 m o nt hs f oll o wi n g a d mi nistrati o n of t he last d ose of st u d y  
vacci ne . See S ecti o n 8. 4 f or i nstr ucti o ns o n re p orti n g of pre g na ncies.
T he ti me peri o d f or c ollecti n g a n d rec or di n g of pI M Ds will be gi n at t he first recei pt of 
st u d y vacci ne a n d will e n d 1 2 m o nt hs f oll o wi n g a d mi nistrati o n of t he last d ose of st u d y  
vacci ne . See S ecti o n 8. 4 f or i nstr ucti o ns o n re p orti n g of pI M Ds.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
6 2
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
6 3
A n o ver vie w of t he pr ot oc ol -re q uire d re p orti n g peri o ds f or A Es, S A Es, a n d pre g na ncies is gi ve n i n Ta ble 1 2 .
T a bl e 1 2
R e p orti n g p eri o d s f or c oll e cti n g s af et y i nf or m ati o n
Ti m e p oi nt
Vi sit 1
D a y - 7
Vi sit 2
M o nt h 0
Vi sit 3
D a y 7
M o nt h 1
Vi sit 4
M o nt h 2
Vi sit 5
D a y 6 7
C o nt a ct
M o nt h 3
C o nt a ct
M o nt h 8
C o nt a ct
M o nt h 1 4
Ti mi n g of r e p orti n g / St u d y a cti vit y
D ay -7
D ay 0
D ay 6
D ay 2 9
D ay 6 0
D ay 6
D ay 2 9
S af ety
St u dy
Pr e -V acc .
D o s e 1
p ost -D os e 1
p ost -D os e 1
D o s e 2
p ost -D os e 2
p ost -D os e 2
F oll o w -U p
C o ncl usi o n
S olicit e d g e n er al A Es ( s e e S e cti o n s 
5. 3. 1. 1 a n d 5. 5. 1. 8 ) ( A m e n d e d 1 6 
N o v e m b er 2 0 1 6 )
S olicit e d l oc al A Es
U ns olicit e d A Es a
A Es/ S A Es l e a di n g t o wit h dr a w al fr o m t h e 
st u dy
S A Es
S A Es r el at e d t o t h e i nv esti g ati o n al 
v acci n e
S A Es r el at e d t o st u dy p artici p ati o n or 
c o nc urr e nt G S K m e dic ati o n/v acci n e b
Pr e g n a nci es
pI M Ds (s e e S ecti o n 8. 1. 5. 1 a n d T a bl e 1 1 )
V acc. = V acci n ati o n; A E = A dv ers e Ev e nt; S A E = S eri o us A dv ers e Ev e nt; G S K = Gl ax o S mit h Kli n e; pI M Ds = p ot e nti al I m m u n e M e di at e d Dis e as es.
a T h e p ost -v acci n ati o n 2 di ary c ar ds f or d aily r ec or di n g of u ns olicit e d A Es a n d c o nc o mit a nt m e dic ati o n/v acci n ati o n ( D ays 0 -2 9) by s u bj ects will b e r et ur n e d by m ail.
b T h e r e p orti n g p eri o d of t h es e ev e nts st arts fr o m t h e ti m e t h e s u bj ect c o ns e nts t o p artici p at e i n t h e st u dy.
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
6 3
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
6 4
8. 3. 2.
P o st -St u d y a d v er s e e v e nt s a n d s eri o u s a d v er s e e v e nt s
A p ost -st u d y A E/ S A E is defi ne d as a n y e ve nt t hat occ urs o utsi de of t he A E/ S A E 
re p orti n g peri o d defi ne d i n Ta ble 1 2 . I n vesti gat ors are n ot o bli gate d t o acti vel y see k A Es 
or S A Es i n f or mer st u d y partici pa nts. H o we ver, if t he i n vesti gat or lear ns of a n y S A E at 
an y  ti me after a s u bject has bee n disc har ge d fr o m t he st u d y, a n d he/s he c o nsi ders t he 
e ve nt reas o na bl y relate d t o t he i n vesti gati o nal vacci ne , t he i n vesti gat or will pr o m ptl y 
n otif y  t he St u d y C o ntact f or Re p orti n g S A Es.
8. 3. 3.
E v al u ati o n of a d v er s e e v e nt s a n d s eri o u s a d v er s e e v e nt s
8. 3. 3. 1.
A c ti v e q u e sti o ni n g t o d et e ct a d v er s e e v e nt s a n d s eri o u s a d v er s e 
e v e nt s
As a c o nsiste nt met h o d of c ollecti n g A Es, t he s u bject s h o ul d be as ke d a n o n -lea di n g 
q uesti o n s uc h as:
‘H ave y o u felt differe nt i n a ny w ay si nce receivi n g t he v acci ne or si nce t he previ o us visit ?
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  a n d dia g n ostics re p orts) relati ve 
t o t he e ve nt. T he i n vesti gat or will t he n rec or d all rele va nt i nf or mati o n re gar di n g a n 
A E/ S A E i n t he e C R F. T he i n vesti gat or is n ot all o we d t o se n d p h ot oc o pies of t he 
s u bject’s me dical rec or ds t o G S K Bi ol o gicals i nstea d of a p pr o priately c o m pleti n g t he 
e C R F. H o we ver, t here ma y  be i nsta nces w he n c o pies of me dical rec or ds f or certai n cases 
are re q ueste d b y G S K Bi ol o gicals. I n t his i nsta nce, all s u bject i de ntifiers will be bli n de d 
o n t he c o pies of t he me dical rec or ds pri or t o s u b missi o n t o G S K Bi ol o gicals.
T he i n vesti gat or will atte m pt t o esta blis h a dia g n osis perta i ni n g t o t he e ve nt base d o n 
si g ns, sy m pt o ms, a n d/ or ot her cli nical i nf or mati o n. I n s uc h cases, t he dia g n osis s h o ul d be 
d oc u me nte d as t he A E/ S A E a n d n ot t he i n di vi d ual si g ns/s y m pt o ms.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
6 4
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
6 5
8. 3. 3. 2.
A s s e s s m e nt of a d v er s e e v e nt s
8. 3. 3. 2. 1.
A s s e s s m e nt of i nt e n sit y
T he i nte nsit y  of t he f oll o wi n g s olicite d A Es will be assesse d as descri be d i n Ta ble 1 3 .
T a bl e 1 3
I nt e n sit y s c al e s f or s oli cit e d s ym pt o m s i n a d ult s
A d v er s e E v e nt
I nt e n sit y gr a d e
P ar a m et er
P ai n at i nj ecti o n sit e
0
N o n e
1
Mil d: A ny p ai n n eit h er i nt erf eri n g wit h n or pr ev e nti n g 
n or m al ev ery d ay activiti es.
2
M o d er at e: P ai nf ul w h e n li m b is m ov e d a n d i nt erf er es wit h 
ev ery d ay activiti es.
3
S ev er e: Si g nific a nt p ai n at r est. Pr ev e nts n or m al ev ery 
d ay activiti es.
R e d n ess at i nj ecti o n sit e
R ec or d gr e at est s urf ac e di a m et er i n m m
S w elli n g at i nj ecti o n sit e
R ec or d gr e at est s urf ac e di a m et er i n m m
F ev er*
R ec or d t e m p er at ur e i n ° C/° F
H e a d ac h e
0
N or m al
1
Mil d: H e a d ac h e t h at is e asily t ol er at e d
2
M o d er at e: H e a d ac h e t h at i nt erf er es wit h n or m al activity
3
S ev er e: H e a d ac h e t h at pr ev e nts n or m al activity
F ati g u e
0
N or m al
1
Mil d: F ati g u e t h at is e asily t ol er at e d
2
M o d er at e: F ati g u e t h at i nt erf er es wit h n or m al activity
3
S ev er e: F ati g u e t h at pr ev e nts n or m al activity
G astr oi nt esti n al sy m pt o ms
0
N or m al
( n a us e a, v o miti n g, di arr h o e a a n d/ or 
a b d o mi n al p ai n)
1
Mil d: G astr oi nt esti n al sy m pt o ms t h at ar e e asily t ol er at e d
2
M o d er at e: G astr oi nt esti n al sy m pt o ms t h at i nt erf er e wit h 
n or m al activity
3
S ev er e: G astr oi nt esti n al sy m pt o ms t h at pr ev e nt n or m al 
activity
My al gi a
0
N or m al
1
Mil d: My al gi a t h at is e asily t ol er at e d
2
M o d er at e: My al gi a t h at i nt erf er es wit h n or m al activity
3
S ev er e: My al gi a t h at pr ev e nts n or m al activity
S hiv eri n g
0
N o n e
1
S hiv eri n g t h at is e asily t ol er at e d
2
S hiv eri n g t h at i nt erf er es wit h n or m al activity
3
S hiv eri n g t h at pr ev e nts n or m al activity
* T h e pr ef err e d r o ut e f or r ec or di n g t e m p er at ur e i n t his st u dy is or al. W h e n t h er e is n o ot h er alt er n ativ e, t h e t e m p er at ur e 
m ay b e r ec or d e d by ot h er r o ut e. If t h e t e m p er at ur e is t ak e n by a n ot h er r o ut e ( axill ary, r ect al or ty m p a nic), t h e r o ut e 
s h o ul d b e d oc u m e nt e d.
N ot e: T e m p er at ur e will b e r ec or d e d i n t h e ev e ni n g. S h oul d a d diti o n al t e m p er at ur e m e as ur e m e nts b e p erf or m e d at 
ot h er ti m es of d ay, t h e hi g h est t e m p er at ur e will b e r ec or d e d i n t h e e C R F a n d t h e ti m e w h e n t h e t e m p er at ur e w as 
r ec or d e d.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
6 5
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
6 6
T he ma xi m u m i nte nsit y  of l ocal i njecti o n site re d ness/s welli n g will be sc ore d at G S K 
Bi ol o gicals as f oll o ws usi n g G S K Bi ol o gicals’ sta n dar d gra di n g scale base d o n t he U S
F o o d a n d Dr u g A d mi nistrati o n ( F D A) g ui deli nes f or T o xicit y  Gra di n g Scale f or Healt h y 
A d ult a n d A d olesce nt V ol u nteers e nr olle d i n Pre ve nti ve Vacci ne Cli nical Trials [ F D A , 
2 0 0 7]:
0 
: 
< 2 0 m m dia meter
1 
:
2 0 m m t o 5 0 m m dia meter
2 
:
> 5 0 m m t o 1 0 0 m m dia meter
3 
: 
> 1 0 0 m m dia meter
T he i n vesti gat or will assess t he ma xi m u m i nte nsit y t hat occ urre d o ver t he d urati o n of t he 
e ve nt f or all u ns olicite d A Es (i ncl u di n g S A Es) rec or de d d uri n g t he st u d y. T he assess me nt 
will be base d o n t he i n vesti gat or’s cli nical j u d ge me nt.
T he i nte nsit y  s h o ul d be assi g ne d t o o ne of t he f oll o wi n g cate g ories:
1 ( mil d)
=
A n A E w hic h is easil y t olerate d b y t he s u bject, ca usi n g mi ni mal 
disc o mf ort a n d n ot i nterferi n g wit h e ver y d a y  acti vities.
2 ( m o derate)
=
A n A E w hic h is s ufficie ntl y  disc o mf orti n g t o i nterfere wit h 
n or mal e ver y d a y  acti vities.
3 (se vere)
=
A n A E w hic h pre ve nts n or mal, e ver y d a y  acti vities. Suc h a n A E 
w o ul d, f or e xa m ple, pre ve nt atte n da nce at w or k a n d w o ul d 
necessitate t he a d mi nistrati o n of c orrecti ve t hera p y.)
A n A E t hat is assesse d as Gra de 3 (se vere) s h o ul d n ot be c o nf use d wit h a S A E. Gra de 
3 is a cate g or y  use d f or rati n g t he i nte nsity of a n e ve nt; a n d b ot h A Es a n d S A Es ca n be 
assesse d as Gra de 3. A n e ve nt is defi ne d as ‘seri o us’ w he n it meets o ne of t he pre -
defi ne d o utc o mes as descri be d i n Secti o n 8. 1. 2 .
8. 3. 3. 2. 2.
A s s e s s m e nt of c a u s alit y
T he i n vesti gat or is o bli gate d t o assess t he relati o ns hi p bet wee n i n vesti gati o nal 
vacci ne/ pr o d uct a n d t he occ urre nce o f eac h A E/ S A E. 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 pla usi ble ca uses, s uc h as nat ural 
hist or y  of t he u n derlyi n g diseases, c o nc o mita nt t hera p y , ot her ris k fact ors, a n d t he 
te m p oral relati o ns hi p of t he e ve nt t o t he i n vesti gati o nal vacci ne/ pr o d uct will be 
c o nsi dere d a n d i n vesti gate d. T he i n vesti gat or will als o c o ns ult t he I B t o deter mi ne his/ her 
assess me nt.
T here ma y  be sit uati o ns w he n a 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 G S K Bi ol o gicals. H o we ver, it is ver y 
i m p orta nt t hat t he i n vesti gat or al wa ys ma kes a n assess me nt of ca usalit y f or e ver y e ve nt 
pr i or t o s u b missi o n of t he Ex pe dite d A dverse Eve nts Re p ort t o G S K Bi ol o gicals. T he 
i n vesti gat or ma y c ha n ge his/ her o pi ni o n of ca usalit y i n li g ht of f oll o w-u p i nf or mati o n a n d 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
6 6
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
6 7
u p date t he S A E i nf or mati o n acc or di n gl y. T he ca usalit y assess me nt is o ne of t he crite ria 
use d w he n deter mi ni n g re g ulat or y  re p orti n g re q uire me nts.
I n case of c o nc o mita nt a d mi nistrati o n of m ulti ple vacci nes, it m a y  n ot be p ossi ble t o 
deter mi ne t he ca usal relati o ns hi p of ge neral A Es t o t he i n di vi d ual vacci nes a d mi nistere d. 
T he i n vesti gat or s h o ul d, t heref ore, assess w het her t he A E c o ul d be ca usall y relate d t o 
vacci nati o n rat her t ha n t o t he i n di vi d ual vacci nes.
All s olicite d l ocal (i njecti o n site) reacti o ns will be c o nsi dere d ca usall y relate d t o 
vacci nati o n. Ca usalit y of all ot her A Es s h o ul d be assesse d b y t he i n vesti gat or usi n g t he 
f oll o wi n g q uesti o n:
Is t here a re as o n a ble p ossi bility t h at t he A E m ay h ave bee n c a use d by t he i nvesti g ati o n al 
v acci ne/ pr o d uct ?
Y E S
:
T here is a reas o na ble p ossi bilit y  t hat t he vacci ne(s) c o ntri b ute d t o 
t he A E.
N O
:
T here is n o reas o na ble p ossi bilit y  t hat t he A E is ca usall y relate d t o 
t he a d mi nistrati o n of t he st u d y vacci ne(s). T here are ot her, m ore 
li kel y ca uses a n d a d mi nistrati o n of t he st u d y vacci ne(s) is n ot 
s us pecte d t o ha ve c o ntri b ute d t o t he A E.
If a n e ve nt meets t he criteria t o be deter mi ne d as ‘seri o us’ (see Secti o n 8. 1. 2 ), a d diti o nal 
e xa mi nati o ns/tests will be perf or me d b y t he i n vesti gat or i n or der t o d eter mi ne A L L 
p ossi ble c o ntri b uti n g fact ors f or eac h S A E.
P ossi ble c o ntri b uti n g fact ors i ncl u de:

Me dical hist or y .

Ot her me dicati o n.

Pr ot oc ol re q uire d pr oce d ure.

Ot her pr oce d ure n ot re q uire d b y  t he pr ot oc ol.

Lac k of efficac y  of t he vacci ne, if a p plica ble.

Er r o ne o us a d mi nistrati o n.

Ot her ca use (s pecif y ).
8. 3. 3. 3.
A s s e s s m e nt of o ut c o m e s
T he i n vesti gat or will assess t he o utc o me of all u ns olicite d A Es (i ncl u di n g S A Es) 
rec or de d d uri n g t he st u d y as:

Rec o vere d/res ol ve d.

Rec o veri n g/res ol vi n g.

N ot rec o vere d/ n ot res ol ve d.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
6 7
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
6 8

Rec o vere d wit h se q uelae/res ol ve d wit h se q uelae.

Fatal ( S A Es o nl y).
8. 3. 3. 4.
M e di c all y  att e n d e d vi sit s
T he s u bject s will be as ke d if t he y recei ve d me dical atte nti o n defi ne d as h os pitalizati o n, 
a n e mer ge nc y r o o m visit or a visit t o me dical pers o n nel ( me dical d oct or) f or a n y reas o n, 
ot her t ha n r o uti ne healt h care visits, fr o m t he first vacci nati o n u ntil M o nt h 1 4, a n d t his 
i nf or mati o n will be rec or de d i n t he e C R F.
I n a d diti o n, f or s olicite d A Es s pecific i nf or mati o n o n react o ge nicit y-tri g gere d me dical 
atte nti o n ( p h o ne ca lls, visits t o a ge neral practiti o ner/e mer ge nc y r o o m, h os pitalizati o ns 
a n d s pecialists’ visits) will be c ollecte d fr o m da y  0-6 a n d rec or de d i n t he e C R F.
8. 4.
R e p orti n g of s eri o u s a d v er s e e v e nt s, pr e g n a n ci e s, a n d 
ot h er e v e nt s
8. 4. 1.
Pr o m pt r e p orti n g of s eri o u s a d v er s e e v e nt s, pr e g n a n ci e s, a n d 
ot h er e v e nt s t o G S K Bi ol o gi c al s
S A Es t hat occ ur i n t he ti me peri o d defi ne d i n Secti o n 8. 3 will be re p orte d pr o m ptl y  t o 
G S K wit hi n t he ti mefra mes descri be d i n Ta ble 1 4 , o nce t he i n vesti gat or deter mi nes t hat 
t he e ve nt meets t he pr ot oc ol defi niti o n of a S A E.
Pre g na ncies t hat o cc ur i n t he ti me peri o d defi ne d i n Secti o n 8. 3 will be re p orte d pr o m ptl y  
t o G S K wit hi n t he ti mefra mes descri be d i n Ta ble 1 4 , o nce t he i n vesti gat or bec o mes 
a ware of t he pr e g na nc y.
pI M Ds t hat occ ur i n t he ti me peri o d defi ne d i n Secti o n 8. 3 will be re p orte d pr o m ptl y  t o 
G S K wit hi n t he ti mefra mes descri be d i n Ta ble 1 4 , o nce t he i n vesti gat or dete r mi nes t hat 
t he e ve nt meets t he pr ot oc ol defi niti o n of a pI M D.
T a bl e 1 4
Ti m efr a m e s f or s u b mitti n g s eri o u s a d v er s e e v e nt, pr e g n a n c y  a n d 
ot h er e v e nt s r e p ort s t o G S K Bi ol o gi c al s
T y p e of E v e nt
I niti al R e p ort s
F oll o w -u p of R el e v a nt I nf or m ati o n o n a 
Pr e vi o u s R e p ort
Ti m efr a m e
D o c u m e nt s
Ti m efr a m e
D o c u m e nt s
S A E s
2 4 h o urs* ‡
el ectr o nic Ex p e dit e d 
A dv ers e Ev e nts R e p ort
2 4 h o urs*
el ectr o nic Ex p e dit e d A dv ers e 
Ev e nts R e p ort
Pr e g n a n ci e s
2 w e eks*
el ectr o nic pr e g n a ncy r e p ort 
2 w e eks*
el ectr o nic pr e g n a ncy r e p ort 
pI M D s
2 4 h o urs** ‡
el ectr o nic Ex p e dit e d 
A dv ers e Ev e nts R e p ort
2 4 h o urs*
el ectr o nic Ex p e dit e d A dv ers e 
Ev e nts R e p ort
* Ti m efr a m e all o w e d aft er r ec ei pt or a w ar e n ess of t h e i nf or m ati o n.
**Ti m efr a m e all o w e d o nc e t h e i nv esti g at or d et er mi n es t h at t h e ev e nt m e ets t h e pr ot oc ol d efi niti o n of a pI M D .
‡ T h e i nv esti g at or will b e r e q uir e d t o c o nfir m r evi e w of t h e S A E/ pI M D c a us ality by ticki n g t h e ‘r evi e w e d’ b ox i n t h e 
el ectr o nic Ex p e dit e d A dv ers e Ev e nts R e p ort wit hi n 7 2 h o urs of s u b missi o n of t h e S A E/ pI M D.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
6 8
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
6 9
8. 4. 2.
C o nt a ct i nf or m ati o n f or r e p orti n g s eri o u s a d v er s e e v e nt s, 
pr e g n a n ci e s a n d pI M D s
St u d y C o nt act f or Re p orti n g S A Es , pre g n a ncies a n d pI M Ds
Refer t o t he l ocal st u d y c o ntact i nf or mati o n d oc u me nt.
B ac k - u p St u d y C o nt act f or Re p orti n g S A Es, pre g n a ncies a n d pI M Ds
2 4/ 2 4 h o ur a n d 7/ 7 da y  a vaila bilit y:
G S K Bi ol o gicals Cli nical Safet y  & P har mac o vi gila nce
U S sites o nl y:
Fa x: 
S A E s = S eri o us A dv ers e Ev e nt s; pI M Ds = p ot e nti al I m m u n e M e di at e d Dis e as es.
8. 4. 3.
C o m pl eti o n a n d tr a n s mi s si o n of S A E r e p ort s t o G S K Bi ol o gi c al s
O nce a n i n vesti gat or bec o mes a ware t hat a S A E has occ urre d i n a st u d y s u bject, t he 
i n vesti gat or ( or desi g nate) m ust c o m plete t he i nf or mati o n i n t he electr o nic E x pe dite d 
A d verse E ve nts Re p ort WI T HI N 2 4 H O U R S. T he re p ort will al wa y s be c o m plete d as 
t h or o u g hly as p ossi ble wit h all a vaila ble details of t he e ve nt. E ve n if t he i n vesti gat or d oes 
n ot ha ve all i nf or mati o n re gar di n g a S A E, t he re p ort s h o ul d still be c o m plete d wit hi n 2 4 
h o urs. O nce a d di ti o nal rele va nt i nf or mati o n is recei ve d, t he re p ort s h o ul d be u p date d 
WI T HI N 2 4 H O U R S.
T he i n vesti gat or will al wa y s pr o vi de a n assess me nt of ca usality at t he ti me of t he i nitial 
re p ort. T he i n vesti gat or will be re q uire d t o c o nfir m t he re vie w of t he S A E ca u salit y b y 
tic ki n g t he ‘re vie we d’ b o x i n t he electr o nic E x pe dite d A d verse E ve nts Re p ort wit hi n 7 2 
h o urs of s u b missi o n of t he S A E.
8. 4. 3. 1.
B a c k -u p s y st e m i n c a s e t h e el e ctr o ni c r e p orti n g s y st e m d o e s n ot w or k
If t he electr o nic re p orti n g sys te m d oes n ot w or k, t he i n vesti gat or ( or desi g nate) m ust 
c o m plete, t he n date a n d si g n a pa per E x pe dite d A d verse E ve nts Re p ort a n d fa x it t o t he 
St u d y  C o ntact f or Re p orti n g S A Es (refer t o t he S p o ns or I nf or mati o n ) or t o G S K 
Bi ol o gicals Cli nical Safet y  a n d P har mac o vi gila nce de part me nt wit hi n 2 4 h o urs.
T his bac k - u p sys te m s h o ul d o nl y be use d if t he electr o nic re p orti n g sys te m is n ot w or ki n g 
a n d n ot if t he s yste m is sl o w. As s o o n as t he electr o nic re p orti n g sys te m is w or ki n g a gai n, 
t he i n vesti gat or ( or desi g nate) m ust c o m plete t he electr o nic E x pe dite d A d verse E ve nts 
Re p ort wit hi n 2 4 h o urs. T he fi nal vali d i nf or mati o n f or re g ulat or y  re p orti n g will be t he 
i nf or mati o n re p orte d t hr o u g h t he electr o nic S A E re p orti n g sys te m.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
P P D
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
6 9
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
7 0
8. 4. 4.
C o m pl eti o n a n d tr a n s mi s si o n of pr e g n a n c y  r e p ort s t o G S K 
Bi ol o gi c al s
O nce t he i n vesti gat or bec o mes a ware t hat a s u bject is pre g na nt, t he i n vesti gat or ( or 
desi g nate) m ust c o m plete t he re q uire d i nf or mati o n o nt o t he electr o nic p re g na nc y re p ort 
WI T HI N 2 W E E K S.
N ote: C o n ve nti o nall y , t he esti mate d gestati o nal a ge ( E G A) of a pre g na nc y is date d fr o m 
t he first da y of t he last me nstr ual peri o d ( L M P) of t he c ycle i n w hic h a w o ma n c o ncei ves. 
If t he L M P is u ncertai n or u n k n o w n, dati n g of EG A a n d t he esti mate d date of deli ver y  
( E D D) s h o ul d be esti mate d b y ultras o u n d e xa mi nati o n a n d rec or de d i n t he pre g na nc y 
re p ort.
8. 4. 5.
R e p orti n g of pI M D s t o G S K Bi ol o gi c al s
O nce a p I M D is dia g n ose d (seri o us or n o n-seri o us) i n a st u d y s u bject, t he i n vesti gat or ( or
desi g nate) m ust c o m plete t he i nf or mati o n i n t he electr o nic E x pe dite d A d verse E ve nts 
Re p ort WI T HI N 2 4 H O U R S after he/s he bec o mes a ware of t he dia g n osis. T he re p ort 
all o ws t o s pecif y t hat t he e ve nt is a pI M D a n d w het her it is seri o us or n o n-seri o us. T he 
re port will al wa y s be c o m plete d as t h or o u g hl y as p ossi ble wit h all a vaila ble details of t he 
e ve nt, i n acc or da nce wit h t he pI M D sta n dar d q uesti o n naire pr o vi de d. E ve n if t he 
i n vesti gat or d oes n ot ha ve all i nf or mati o n re gar di n g a pI M D, t he re p ort s h o ul d still be
c o m plete d wit hi n 2 4 h o urs. O nce a d diti o nal rele va nt i nf or mati o n is recei ve d, t he re p ort 
s h o ul d be u p date d WIT HI N 2 4 H O U R S.
T he i n vesti gat or will al wa y s pr o vi de a n assess me nt of ca usality at t he ti me of t he i nitial 
re p ort. T he i n vesti gat or will be re q uire d t o c o nfir m t he re vie w of t he pI M D ca usality b y 
tic ki n g t he ‘re vie we d’ b o x i n t he electr o nic E x pe dite d A d verse E ve nts Re p ort wit hi n 7 2 
h o urs of s u b missi o n of t he pI M D.
Refer t o Secti o n 8. 4. 3. 1 f or bac k- u p sys te m i n case t he electr o nic re p orti n g s yste m d oes 
n ot w or k.
8. 4. 6.
U p d ati n g of S A E, pr e g n a n c y , a n d pI M D i nf or m ati o n aft er r e m o v al 
of wr it e a c c e s s t o t h e s u bj e ct’ s e C R F
W he n a d diti o nal S A E, pre g na nc y , or pI M D i nf or mati o n is recei ve d after re m o val of t he 
write access t o t he s u bject’s e C R F, ne w or u p date d i nfor mati o n s h o ul d be rec or de d o n t he 
a p pr o priate pa per re p ort , wit h all c ha n ges si g ne d a n d date d b y t he i n vesti gat or. T he 
u p date d re p ort s h o ul d be fa xe d t o t he St u d y  C o ntact f or Re p orti n g S A Es (refer t o t he
S p o ns or I nf or mati o n ) or t o G S K Bi ol o gicals Cli nical Safet y a n d P har mac o vi gila nce 
de part me nt wit hi n t he desi g nate d re p orti n g ti me fra mes s pecifie d i n Ta ble 1 4 .
8. 4. 7.
R e g ul at or y  r e p orti n g r e q uir e m e nt s f or s eri o u s a d v er s e e v e nt s
T he i n vesti gat or will pr o m ptl y  rep ort all S A Es t o G S K i n acc or da nce wit h t he pr oce d ures 
detaile d i n Secti o n 8. 4. 1 . G S K Bi ol o gicals has a le gal res p o nsi bilit y t o pr o m ptl y n otif y, 
as a p pr o priate, b ot h t he l ocal re g ulat or y  a ut h ority a n d ot her re g ulat or y a ge ncies a b o ut t he 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
7 0
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
7 1
safety of a pr o d uct u n der cli nical i n vesti gati o n. Pr o m pt n otificati o n of S A Es b y  t he 
i n vesti gat or t o t he St u dy C o ntact f or Re p orti n g S A Es is esse ntial s o t hat le gal o b li gati o ns 
a n d et hical res p o nsi bilities t o war ds t he safet y of ot her s u bjects are met.
I n vesti gat or safet y re p orts are pre pare d acc or di n g t o t he c urre nt G S K p olic y a n d are 
f or war de d t o i n vesti gat ors as necessar y. A n i n vesti gat or safety re p ort is pre pare d f or a 
S A E(s) t hat is b ot h attri b uta ble t o t he i n vesti gati o nal vacci ne a n d u ne x pecte d. T he 
p ur p ose of t he re p ort is t o f ulfil s pecific re g ulat or y a n d G C P re q uire me nts, re gar di n g t he 
pr o d uct u n der i n vesti gati o n.
8. 5.
F oll o w -u p of a d v er s e e v e nt s, s eri o u s a d v er s e e v e n t s, a n d 
pr e g n a n ci e s
8. 5. 1.
F oll o w -u p of a d v er s e e v e nt s a n d s eri o u s a d v er s e e v e nt s
8. 5. 1. 1.
F oll o w- u p d uri n g t h e st u d y
After t he i nitial A E/ S A E re p ort, t he i n vesti gat or is re q uire d t o pr oacti vel y f oll o w eac h 
s u bject a n d pr o vi de a d diti o nal rele va nt i nf or mati o n o n t he s u bject’s c o n diti o n t o G S K 
Bi ol o gicals ( wit hi n 2 4 h o urs f or S A Es; refer t o Ta ble 1 4 ).
All S A Es a n d pI M Ds (seri o us or n o n -seri o us) d oc u me nte d at a pre vi o us vi sit/c o ntact a n d 
desi g nate d as n ot rec o vere d/ n ot res ol ve d or rec o veri n g/res ol vi n g will be re vie we d at 
s u bse q ue nt visits/c o ntacts u ntil t he e n d of t he st u d y.
All A Es d oc u me nte d at a pre vi o us visit/c o ntact a n d desi g nate d as n ot rec o vere d/ n ot 
res ol ve d or rec o veri n g/res ol vi n g will be re vie we d at s u bse q ue nt visits/c o ntacts u ntil 3 0 
da y s after t he last vacci nati o n.
8. 5. 1. 2.
F oll o w- u p aft er t h e s u bj e ct i s di s c h ar g e d fr o m t h e st u d y
T he i n vesti gat or will f oll o w s u bjects:

wit h S A Es, pI M Ds (seri o us or n o n -seri o us), or s u bjects wit h dra w n fr o m t he st u d y  as 
a res ult of a n A E, u ntil t he e ve nt has res ol ve d, s u bsi de d, sta bilise d, disa p peare d, or 
u ntil t he e ve nt is ot her wise e x plai ne d, or t he s u bject is l ost t o f oll o w - u p.
If t he i n vesti gat or recei ves a d diti o nal rele va nt i nf or mati o n o n a pre vi o usl y re p orte d S A E, 
he/s he will pr o vi de t his i nf or mati o n t o G S K Bi ol o gicals usi n g a pa per/ electr o nic 
E x pe dite d A d verse E ve nts Re p ort a n d/ or pre g na nc y  re p ort as a p plica ble.
G S K Bi ol o gicals ma y  re q uest t hat t he i n vesti gat or perf or ms or arra n ges t he co n d uct of 
a d diti o nal cli nical e xa mi nati o ns/tests a n d/ or e val uati o ns t o el uci date as f ull y  as p ossi ble 
t he nat ure a n d/ or ca usalit y of t he A E or S A E. T he i n vesti gat or is o bli ge d t o assist. If a 
s u bject 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 gnise d f oll o w- u p peri o d, 
G S K Bi ol o gicals will be pr o vi de d wit h a n y a vaila ble p ost -m orte m fi n di n gs, i ncl u di n g 
hist o pat h ol o g y .
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
7 1
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
7 2
8. 5. 2.
F oll o w -u p of pr e g n a n ci e s
Pre g na nt s u bjects will be f oll o we d t o deter mi ne t he o utc o me of t he pre g na nc y . At t he e n d 
of t he pre g na nc y , w het her f ull -ter m or pre mat ure, i nf or mati o n o n t he stat us of t he m ot her 
a n d c hil d will be f or war de d t o G S K Bi ol o gicals usi n g t he electr o nic pre g na nc y re p ort a n d 
t he E x pe dite d A d verse E ve nts Re p ort if a p plica ble. Ge nerally, t he f oll o w -u p peri o d 
d oes n’t nee d t o be l o n ger t ha n si x t o ei g ht wee ks after t he esti mate d date of deli ver y .
Re gar dless of t he re p orti n g peri o d f or S A Es f or t his st u d y, if t he pre g na nc y o utc o me is a 
S A E, it s h o ul d al wa y s be re p orte d as S A E.
8. 6.
Tr e at m e nt of a d v er s e e v e nt s
Treat me nt of a n y A E is at t he s ole discreti o n of t he i n vesti gat or a n d acc or di n g t o c urre nt 
g o o d me dical practice. A n y  me dicati o n a d mi nistere d f or t he treat me nt of a n A E s h o ul d 
be rec or de d i n t he s u bject’s e C R F (refer t o Secti o n 6. 5 ).
8. 7.
S u bj e ct c ar d
St u d y  s u bjects / s u bjects’ care gi ver(s) m ust be pr o vi de d wit h t he a d dress a n d tele p h o ne 
n u m ber of t he mai n c o ntact f or i nf or mati o n a b o ut t he cli nical st u d y .
T he i n vesti gat or ( or desi g nate) m ust t heref ore pr o vi de a “s u bject car d” t o eac h s u bject/ 
s u bject’s care gi ver(s). I n a n e mer ge nc y sit uati o n t his car d ser ves t o i nf or m t he 
res p o nsi ble atte n di n g p h ysicia n t hat t he s u bject is i n a cli nical st u d y a n d t hat rele va nt 
i nf or mati o n ma y be o btai ne d b y c o ntacti n g t he i n vesti gat or.
S u bjects / s u bjects’ care gi ver(s) m ust be i nstr ucte d t o kee p s u bject car ds i n t heir 
p ossessi o n at all ti mes.
9.
S U B J E C T C O M P L E TI O N A N D WI T H D R A W A L
9. 1.
S u bj e ct c o m p l eti o n
A s u bject w h o is a vaila ble f or t he c o ncl u di n g c o ntact f oresee n i n t he pr ot oc ol is 
c o nsi dere d t o ha ve c o m plete d t he st u d y .
9. 2.
S u bj e ct w it h dr a w al
Wit h dra wals will n ot be re place d.
9. 2. 1.
S u bj e ct w it h dr a w al fr o m t h e st u d y
Fr o m a n a nal ys is pers pecti ve, a ‘ wit h drawal’ fr o m t he st u d y  refers t o a n y s u bject w h o 
was n ot a vaila ble f or t he c o ncl u di n g c o ntact f oresee n i n t he pr ot oc ol .
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
7 2
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
7 3
All data c ollecte d u ntil t he date of wit h dra wal/last c o ntact of t he s u bject will be use d f or 
t he a nalys is.
A s u bject is c o nsi dere d a ‘ wit h d ra wal’ fr o m t he st u d y w he n n o st u d y pr oce d ure has 
occ urre d, n o f oll o w -u p has bee n perf or me d a n d n o f urt her i nf or mati o n has bee n c ollecte d 
f or t his s u bject fr o m t he date of wit h dra wal/last c o ntact.
I n vesti gat ors will ma ke a n atte m pt t o c o ntact t h ose s u bjects w h o d o n ot ret ur n f or 
sc he d ule d visits or f oll o w- u p.
I nf or mati o n relati ve t o t he wit h dra wal will be d oc u me nte d i n t he e C R F. T he i n vesti gat or 
will d oc u me nt w het her t he decisi o n t o wit h dra w a s u bject fr o m t he st u d y was ma de b y 
t he s u bject hi mself/ herself, b y  t he s u bject’s care gi ver(s), or b y t he i n vesti gat or, as well as 
w hic h of t he f oll o wi n g p ossi ble reas o ns was res p o nsi ble f or wit h dra wal:

Seri o us a d verse e ve nt.

N o n -seri o us a d verse e ve nt.

Pr ot oc ol vi olati o n (s pecif y ).

C o nse nt wit h dra wal, n ot d ue t o a n a d ve rse e ve nt *.

M o ve d fr o m t he st u d y area.

L ost t o f oll o w - u p.

Ot her (s pecif y ).
*I n case a s u bject is wit h dra w n fr o m t he st u d y  beca use he/s he/t he s u bject’s car gi ver(s)
has wit h dra w n c o nse nt, t he i n vesti gat or will d oc u me nt t he reas o n f or wit h dra wal of 
c o nse nt, if s pecifie d b y t he s u bject /s u bject’s care gi ver(s), i n t he e C R F.
S u bjects w h o are wit h dra w n fr o m t he st u d y  beca use of S A Es/ A Es m ust be clearly 
disti n g uis he d fr o m s u bjects w h o are wit h dra w n f or ot her reas o ns. I n vesti gat ors will 
f oll o w s u bjects w h o are wit h dra w n fr o m t he st u d y as res ult of a S A E/ A E u ntil res ol uti o n 
of t he e ve nt (see Secti o n 8. 5. 1. 2 ).
9. 2. 2.
S u bj e ct w it h dr a w al fr o m i n v e sti g ati o n al v a c ci n e
A ‘ wit h dra wal’ fr o m t he i n vesti gati o nal vacci ne refers t o a n y s u bject w h o d oes n ot 
recei ve t he c o m plete treat me nt, i.e., w he n n o f urt her pla n ne d d ose is a d mi nistere d fr o m 
t he date of wit h dra wal. A s u bject wit h dra w n fr o m t he i n vesti gati o nal vacci ne m a y  n ot 
necessaril y  be wit h dra w n fr o m t he st u d y as f urt her st u d y pr oce d ures or f oll o w-u p ma y  be 
perf or me d (safet y or i m m u n o ge nicit y) if pla n ne d i n t he st u d y  pr ot oc ol.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
7 3
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
7 4
I nf or mati o n relati ve t o pre mat ure disc o nti n uati o n of t he i n vesti gati o nal vacci ne will be 
d oc u me nte d o n t he Vacci ne A d mi nistrati o n pa ge/scree n of t he e C R F. T he i n vesti gat or 
will d oc u me nt w het her t he decisi o n t o disc o nti n ue f urt her vacci nat i o n/treat me nt was 
ma de b y t he s u bject hi mself/ herself, b y t he s u bject’s care gi ver(s), or by t he i n vesti gat or, 
as well as w hic h of t he f oll o wi n g p ossi ble reas o ns was res p o nsi ble f or wit h dra wal:

Seri o us a d verse e ve nt.

N o n -seri o us a d verse e ve nt.

Ot her (s pecif y).
1 0.
S T A TI S TI C A L M E T H O D S
1 0. 1.
Pri m ar y  e n d p oi nt

C ha n ge i n mea n S F - 3 6 P F scale sc ore.

Baseli ne * vers us mea n sc ore o ver t he peri o d da y  1 t o da y 7 * * after first
vacci nati o n .
1 0. 2.
S e c o n d ar y  e n d p oi nt s

C ha n ge i n mea n S F - 3 6 P F scale sc ore. ( A me n de d 1 6 N o ve m ber 2 0 1 6 )

Baseli ne * vers us mea n sc ore o ver t he peri o d da y  1 t o da y 7 * * after sec o n d 
vacci nati o n .

C ha n ge i n mea n S F - 3 6 P F si n gle ite m sc ores.

Baseli ne * vers us mea n sc ore o ver t he peri o d da y  1 t o da y 7 * * after eac h 
vacci nati o n .

C ha n ge i n S F - 3 6 R ole P h y sical sc ores.

Baseli ne * vers us sc ore o n da y 7 * * after eac h vacci nati o n.

C ha n ge i n t he Q A L Y.

Baseli ne * vers us c o m bi ne d sc ore o ver t he peri o d da y  1 t o da y 7 * * after eac h 
vacci nati o n .

Healt hcare res o urce utilizati o n (i.e., h os pitalizati o n, tele p h o ne calls, me dical visits 
a n d s pecialist visits, me dicati o n i nta ke).

D a y s 0 t o 6 after eac h vacci nati o n.

W or k l oss f or s u bjects .

D a y s 0 t o 6 after eac h vacci nati o n.

W or k l oss f or t he n o n- de dicate d care gi vers.

D a y s 0 t o 6 after eac h vacci nati o n.

E xtra w o r k f or de dicate d care gi vers.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
7 4
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
7 5

D a y s 0 t o 6 after eac h vacci nati o n.

S olicite d l ocal a n d ge neral s y m pt o ms i n s u bjects.

Occ urre nce, i nte nsit y  a n d d urati o n of s olicite d l ocal s ym pt o ms wit hi n 7 da y s 
( Da ys 0- 6 * *) after eac h vacci nati o n.

Occ urre nce, i nte nsit y , d urati o n a n d relati o ns hi p t o vacci nati o n of s olicite d 
ge neral s y m pt o ms wit hi n 7 da y s ( Da ys 0- 6 * *) after eac h vacci nati o n.

U ns olicite d a d verse e ve nts ( A Es) i n s u bjects.

Occ urre nce, i nte nsit y  a n d relati o ns hi p t o vacci nati o n d uri n g 3 0 da y s ( Da ys 0-2 9) 
after eac h vacci nati o n, acc or di n g t o t he Me dical Dicti o nar y  f or Re g ulat or y 
Acti vities ( Me d D R A) classificati o n.

Occ urre nce of seri o us a d verse e ve nts ( S A Es).

Occ urre nce a n d relati o ns hi p t o vacci nati o n of all S A Es fr o m t he first 
vacci n ati o n u p t o t he st u d y e n d.

Occ urre nce of a d verse e ve nts of s pecific i nterest ( A E SI s): p ote ntial I m m u ne-
Me diate d Diseases ( pI M Ds).

Occ urre nce a n d relati o ns hi p t o vacci nati o n of a n y pI M Ds fr o m first vacci nati o n 
u p t o t he st u d y  e n d.
* N ote: baseli ne f or d ose 1 is defi ne d as t he mea n of t he assess me nts at da y - 7 a n d da y 0; 
f or d ose 2 baseli ne is defi ne d as t he mea n of t he t hree assess me nts at da y  -7, da y 0 a n d 
da y 6 0 ( da y  0 f or d ose 2). F urt her details o n baseli ne calc ulati o n will be gi ve n i n t he 
Statistical A nal y sis Pla n ( S A P).
* * N ote: T he p ost -vacci nati o n c o m pleti o n of S F -3 6 a n d E Q - 5 D q uesti o n naires br o u g ht 
h o me b y  t he s u bjects will be o n da ys 1 t o da y 6, wit h da y  7 t o be fille d i n at t he site 
( d uri n g Visits 3 a n d 5); w hile t he p ost - vacci nati o n rec or di n g of s olicite d A Es o n t he diar y  
car d br o u g ht h o me b y t he s u bjects will be o n da ys 0 t o da y  6.
1 0. 3.
D et er mi n ati o n of s a m pl e si z e
T o esti mate t he o verall c ha n ge i n P F sc ores i n H Z/s u vacci nate d s u bjects, t he l oss i n P F 
sc ores d ue t o t he react o ge nicit y fr o m t he H Z/s u vacci nati o n will be e val uate d b y t he 
differe nce i n P F scale sc ores i n s u bjects bef o re a n d after H Z/s u vacci nati o n.
T he P F sc ore will be esti mate d as t he c ha n ge i n mea n P F sc ore bet wee n baseli ne a n d 
mea n sc ore o ver t he peri o d da y  1 t o da y 7 after first vacci nati o n.
I n t he ol der a d ult p o p ulati o n fr o m Z O S T E R-0 0 6 a n d base d o n t he assess me nt of P F at 
M o nt h 0, 1 4, 2 6 a n d 3 8, t he baseli ne mea n P F sc ore a n d t he sta n dar d de viati o n are 
esti mate d as 8 1. 8 a n d 1 8. 4 5, res pecti vel y. T his st u d y  is desi g ne d t o pr o vi de a n esti mate 
of precisi o n ar o u n d t he mea n c ha n ge i n P F sc ores. Ass u mi n g a sta n dar d de viati o n of 2 1. 2 
f or t he c ha n ge i n P F sc ores t his all o ws us t o ge nerate a n esti mate of t he mea n wit h a
precisi o n of 2. 2 wit h a sa m ple size of 3 6 0 s u bjects. Ass u mi n g a n o n-e val ua ble pr o p orti o n 
of a p pr o xi matel y  1 0 % of s u bjects a t otal of 4 0 0 s u bjects nee d t o be e nr olle d i n t he st u d y.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
7 5
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
7 6
1 0. 4.
C o h ort s f or A n al y s e s
1 0. 4. 1.
T ot al v a c ci n at e d c o h ort
T he t otal vacci nate d c o h ort ( T Vc) will i ncl u de all vacci nate d s u bjects wit h res pect t o t he 
va cci ne act uall y a d mi nistere d.
T he T Vc f or a nal y sis of safety will i ncl u de all s u bjects wit h at least o ne vacci ne d ose
a d mi nistere d.
T he T Vc f or a nal y sis of react o ge nicit y will i ncl u de all s u bjects wit h at least o ne vacci ne 
d ose a d mi nist ere d a n d d oc u me nte d ( wit h t he 7 da y diar y  car d a vaila ble).
1 0. 4. 2.
A c c or di n g -t o-pr ot o c ol c o h ort f or a n al y si s of s af et y
T he A T P c o h ort f or a nal ysis of safet y will i ncl u de all s u bjects:

w h o ha ve recei ve d at least o ne d ose of st u d y  vacci ne;

f or w h o m a d mi nistrati o n site of st u d y vacci ne is k n o w n;

w h o ha ve n ot recei ve d ot her vacci ne f or bi d de n i n t he pr ot oc ol ( Secti o n 6. 5. 2 );

W h o ha ve recei ve d t he st u d y  vacci ne c orrectl y rec o nstit ute d.
1 0. 5.
D eri v e d a n d tr a n sf or m e d d at a
T he calc ulati o n of t he Q A L Y will be base d o n t he E Q -5 D q uesti o n naire . T he E Q-5 D is a 
ge neric meas ure of healt h stat us t hat pr o vi des a si m ple descri pti o n pr ofile base d o n t he 
f oll o wi n g 5 ite ms: m o bilit y , self- care, us ual acti vities, pai n/ disc o mf ort a n d 
a n xiet y/ de pressi o n.
F or eac h da y , t he c o m bi nati o n of t he sc ores rec or de d i n eac h of t hese 5 ite ms, will be 
tra nsf or me d i n a si n gle i n de x val ue.
T he Q A L Y/ wee k is calc ulate d f or eac h s u bject usi n g t he f oll o wi n g f or m ula:
A U C 0- 6= ∑( 0 t o 6) (tk + 1- tk ) * ( Yk + Y k + 1 )/ 2
w here Y k is t he sc ore at da y k a n d t is ti me at da y k.
1 0. 6.
St ati sti c al a n al y s e s
1 0. 6. 1.
A n al y si s of d e m o gr a p hi c s/ b a s eli n e c h ar a ct eri sti c s

De m o gra p hic c haracteristics (a ge, ge n der, ge o gra p hic a ncestr y a n d et h nicit y) will be
ta b ulate d.

T he mea n a ge ( pl us ra n ge a n d sta n dar d de viati o n) of t he e nr olle d s u bjects, as a 
w h ole, a n d stratifie d b y a ge gr o u p will be calc ulate d.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
7 6
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
7 7

T he distri b uti o n of s u bjects e nr olle d a m o n g t he st u d y  sites will be ta b ulate d as a 
w h ole.
1 0. 6. 2.
Q u alit y  of lif e
T he a nal ys is of Q o L will be base d o n the T Vc. A n a nal ys is of t he i m pact o n 
react o ge nicit y a n d Q o L of frailt y stat us will be perf or me d if data all o ws (see Secti o n 
1 0. 6. 2. 2 ). Details of t his s u b-a nal ys is will be ela b orate d u p o n i n t he S A P.
1 0. 6. 2. 1.
A n al y si s of Q A L Y ( Utilit y )
T he 9 5 % CI f or Q A L Y mea n l oss will be o btai ne d usi n g a m ulti ple re gressi o n m o del o n 
t he c ha n ge fr o m baseli ne utilit y sc ores. T he m o del will i ncl u de a ge strata, ge n der a n d 
frailt y stat us as t he fi xe d effect.
T he 9 5 % CI f or utilit y  sc ores will be o btai ne d pre- a n d p ost-vacci nati o n se paratel y 
ass u mi n g t hat utilit y sc ores were n or mally distri b ute d wit h u n k n o w n varia nce.
1 0. 6. 2. 2.
A s s e s s m e nt of fr ailt y  st at u s
A n assess m e nt of frailt y stat us will be d o ne at Visit 1. Frailt y  stat us will be meas ure d i n 
relati o n t o t he acc u m ulati o n of deficits usi n g an FI calc ulate d acc or di n g t o t he m o del 
pr o p ose d b y Mit nits ki et al. [ Mit nits ki , 2 0 0 1]. T he differe nt as pects of frailt y c o m p osi n g 
t he FI will be assesse d t hr o u g h a series of certifie d tests a n d s pecific q uesti o ns i n t he 
f oll o wi n g d o mai ns:

C o g niti o n: a 3 0 -p oi nt q uesti o n naire t hat is use d e xte nsi vel y  i n cli nical a n d researc h 
setti n gs t o meas ure c o g niti ve i m pair me nt calle d t he M o ntreal C o g niti ve Assess me nt 
( M o Ca);

P h y sical stat us: criteria f or t he defi niti o n of frailt y de vel o pe d b y Frie d et al . [Frie d , 
2 0 0 1] t o cat e g orize t he p h ysical frailty p he n ot y pe ( P F P) , t he p hys ical f u ncti o ni n g 
cate g or y of t he S F -3 6 q uesti o n naire will be use d as meas ure of t h e p h ys ical acti vit y 
of t he s u bject [R y b , 2 0 1 2];

De pressi o n a n d e x ha usti o n: a scree ni n g test f or de pressi o n a n d de pressi ve dis or der 
calle d t he Ce nter f or E pi de mi ol o gic St u dies De pressi o n Scale – Re vise d ( C E S D - R);

M ulti m or bi dit y : occ urre nce of a s pecific a ge de pe n de nt list of diseases base d o n t he 
p u blis he d w or k [Mit nits ki , 2 0 0 1];

Disa bilit y : assess me nt of t he s u bjects’ de pe n de nce o n ot hers t o perf or m a list of 
s pecific daily acti vities ( base d o n t he p u blis he d w or k [Mit nits ki , 2 0 0 1; Searle , 
2 0 0 8]).
I n t he u nli kely e ve nt t hat a n y of t he a b o ve me nti o ne d tests f or c o g niti o n, p h y sical stat us 
or de pressi o n are u na ble t o be i m ple me nte d i n t he pr ot oc ol, a s uita ble re place me nt will be 
s u bstit ute d as a n alter nati ve.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
7 7
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
7 8
1 0. 6. 2. 3.
S F -3 6 h e alt h s ur v e y
T he S F -3 6 ® is a m ulti -p ur p ose healt h s ur ve y  wit h 3 6 q uesti o ns (refer t o A P P E N DI X A
[Ware , 2 0 0 1] t hat will be use d t o e val uate P F usi n g q uesti o ns 3a t hr o u g h 3j . (A m e n de d 
1 6 N o ve m ber 2 0 1 6 ) T he c o nce pts u n derl y i n g t he c o nstr ucti o n of t he S F-3 6 scales a n d 
s u m mar y meas ures i nc or p orates a ta x o n o m y of t hree le vels: ( 1) 3 6 ite ms; ( 2) ei g ht scales 
(see Ta ble 1 5 f or details); a n d, ( 3) t w o s u m mar y  meas ures ( P h ysical C o m p o ne nt a n d 
Me ntal C o m p o ne nt Sc ores) t hat a g gre gate scales. All b ut o ne of t he 3 6 ite ms (self -
re p orte d healt h tra nsiti o n) are use d t o sc ore t he ei g ht S F-3 6 scales. Eac h ite m is use d i n 
sc ori n g o nly o ne scale. Scale sc ores will be c o nstr ucte d f oll o wi n g t he s u m mate d rati n gs 
a n d sta n dar dize d S F-3 6 sc ori n g al g orit h ms.
T a bl e 1 5
C o n str u cti o n of t h e ei g ht s c al e s g e n er at e d fr o m t h e S F-3 6
S c al e
It e m s
R e s p o n s e C at e g ori e s P er It e m
P hysic al F u ncti o ni n g ( P F)
3 a, 3 b, 3c, 3 d, 3 e, 3f, 3 g, 3 h, 3i, 3j
3
R ol e P hysic al ( R P)
4 a, 4 b, 4c, 4 d
5
B o dily P ai n ( B P)
7*, 8*
6, 5
G e n er al H e alt h ( G H)
1*, 1 1 a, 1 1 b*, 1 1c, 1 1 d*
5
Vit ality ( V T)
9 a*, 9 e*, 9 g, 9i
5
S oci al f u ncti o ni n g ( S F)
6*, 1 0
5
R ol e E m oti o n al ( R E)
5 a, 5 b, 5c
5
M e nt al H e alt h ( M H)
9 b, 9c, 9 d*, 9f, 9 h*
5
* It e m R ev ers e d
T he S F -3 6 healt h s ur ve y  q uesti o n naires will be c o m plete d b y all s u bjects at eac h st u dy 
visits (i.e. , Visit 1 Da y  -7, Visit 2 M o nt h 0 ( bef ore t he vacci nati o n), Visit 3 Da y 7, Visit 4 
M o nt h 2 ( bef ore t he vacci nati o n) a n d Visit 5 Da y  6 7). A d diti o nall y, after eac h 
vacci nati o n, t he s u bjects will be gi ve n t he S F - 3 6 q uesti o n naires t o ta ke h o me a n d as ke d 
t o c o m plete o nl y  q uesti o ns 3a t hr o u g h 3j o n a dail y  basis o n Da ys 1 t o 6 . S u bjects will be 
as ke d t o ret ur n t he c o m plete d q uesti o n naires at t he ne xt visit ( Visits 3 a n d 5). C o m plete d 
q uesti o n naires are t o be c ollecte d a n d t he s u bject res p o nses tra nscri be d i nt o t he e- C R F.
1 0. 6. 2. 4.
E Q -5 D q u e sti o n n air e
T he E Q -5 D q uesti o n naire is a ge neric meas ure of healt h stat us t hat pr o vi des a si m ple 
descri pti ve pr ofile a n d a si n gle i n de x val ue (refer t o A P P E N DI X B [Ki n d , 1 9 9 6]. T he 
E Q -5 D defi nes healt h i n ter ms of m o bilit y , self-care, us ual acti vities, pai n/ disc o mf ort 
a n d a n xiet y/ de pressi o n. T he 5 ite ms are c o m bi ne d to ge nerate healt h pr ofiles, i.e., a 
res p o n de nt w h o res p o n ds 1 ( n o pr o ble m\ n o sy m pt o m) t o all 5 ite ms has a pr ofile “ 1 1 1 1 1” 
a n d si milarl y a s u bject w h o res p o n ds wit h t he hi g hest le vel of diffic ulty or s y m pt o m t o 
all ite ms has a pr ofile “ 3 3 3 3 3”. T hese pr ofil es are s u bse q ue ntl y c o n verte d t o a c o nti n u o us 
si n gle i n de x utilit y sc ore usi n g a o ne t o o ne matc hi n g, e. g., “ 1 1 1 1 1” = 1. 0 0, “ 2 2 2 2 2” = 0. 5 2 
a n d “ 3 3 3 3 3” = -0. 5 9, usi n g val ue sets (i.e., matc hi n g pr ofiles t o si n gle i n de x utilit y  sc ores 
usi n g c o u ntr y  s pecific val ue sets). N ote, hi g her sc ores re prese nt a better Q o L, a n d refer 
t o Secti o n 1 0. 5 f or h o w t he c alc ul ati o n of t he Q A L Y will be b ase d o n t he E Q- 5 D 
q uesti o n n aire . T he E Q -5 D als o i ncl u des a Vis u al A n al o g ue Sc ale ( V A S) r a n gi n g fr o m 
0 t o 1 0 0, wit h 1 0 0 re prese nti n g t he best i m a gi n a ble he alt h st ate a n d 0 re prese nti n g t he 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
7 8
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
7 9
w orst i m a gi n a ble he alt h st ate. F urt her det ails will be pr ovi de d i n t he S A P . (A m e n de d 
1 6 N o ve m ber 2 0 1 6 )
T he E Q -5 D q uesti o n naires will be c o m plete d b y all s u bjects at eac h st u d y visits (i.e., 
Visit 1 Da y  -7, Visit 2 M o nt h 0 ( bef ore t he vacci nati o n), Visit 3 Da y  7, Visit 4 M o nt h 2 
( bef ore t he vacci nati o n) a n d Visit 5 Da y 6 7). A d diti o nall y, after eac h vacci nati o n, t he 
s u bjects will be gi ve n t he E Q -5 D q uesti o n naires t o ta ke h o me a n d as ke d t o c o m plete t he 
e ntire E Q-5 D q ue sti o n naire o n a dail y basis o n Da ys 1 t o 6 . S u bjects will be as ke d t o 
ret ur n t he c o m plete d q uesti o n naires at t he ne xt visit ( Visits 3 a n d 5). C o m plete d 
q uesti o n naires are t o be c ollecte d a n d t he s u bject res p o nses tra nscri be d i nt o t he e- C R F.
(A m e n de d 1 6 N o ve m ber 2 0 1 6 )
1 0. 6. 3.
A n al y si s of s af et y
T he pri mar y  a nalys is f or safety will be base d o n t he T Vc. If t he perce nta ge of t he 
vacci nate d s u bjects e xcl u de d fr o m t he A T P c o h ort f or safet y is m ore t ha n 5 %, a sec o n d 
a nal ys is base d o n t he A T P c o h ort f or safety will be p erf or me d.
T he f oll o wi n g a nal ys es will be perf or me d f or safet y e n d p oi nts:

T he perce nta ge of s u bjects wit h at least o ne l ocal s olicite d A E, wit h at least o ne 
ge neral s olicite d A E a n d wit h a n y  s olicite d A E d uri n g t he s olicite d 7-d a y  f oll o w- u p 
peri o d will be t a b ulate d wit h e xact 9 5 % CI after eac h vacci ne d ose a n d o verall. T he 
sa me ta b ulati o n will be perf or me d f or gra de 3;

T he perce nta ge of s u bjects wit h at least o ne l ocal A E (s olicite d a n d u ns olicite d), wit h 
at least o ne ge neral a d verse e ve nt (s olicite d a n d u ns olicite d) a n d wit h a n y A E d uri n g 
t he s olicite d 7-d a y  f oll o w- u p peri o d will be ta b ulate d wit h e xact 9 5 % CI after eac h 
vacci ne d ose a n d o verall. T he sa me ta b ulati o n will be perf or me d f or gra de 3;

T he perce nta ge of s u bjects re p orti n g eac h i n di vi d ual s olicite d l ocal a n d ge neral A E 
d uri n g t he s olicite d 7 -d a y -f oll o w-u p peri o d will be ta b ulate d wit h e xact 9 5 % CI . F or 
all s olicite d s ym pt o ms, t he sa me ta b ulati o n will be perf or me d f or gra de 3 s olicite d 
A Es a n d f or s olicite d ge neral A Es wit h relati o ns hi p t o vacci nati o n;

T he perce nta ge of s u bjects wit h at least o ne re p ort of u ns olicite d A E classifie d b y  t he 
Me d D R A Preferre d Ter ms a n d re p orte d u p t o 3 0 da y s after eac h vacci nati o n will be 
ta b ulate d wit h e xact 9 5 % CI. T he sa me ta b ulati o n will be perf or me d f or gra de 3 
u ns ol icite d A Es a n d f or u ns olicite d A Es wit h a relati o ns hi p t o vacci nati o n. T he 
pr o p orti o n of u ns olicite d A Es res ulti n g i n a me dicall y  atte n de d visit (s uc h as 
e mer ge nc y r o o m, o ut- patie nt visit, site i n vesti gat or, etc.) will als o be ta b ulate d;

T he perce nta ge of s u bjects w h o starte d t o use t he me dicati o ns wit hi n t he 3 0-d a y s 
p ost -vacci nati o n will be ta b ulate d.

T he perce nta ge of s u bjects wit h at least o ne re p ort of seri o us a d verse e ve nt classifie d 
b y  t he Me d D R A Preferre d Ter ms a n d re p orte d d uri n g t he w h ole p ost-vacc i nati o n 
f oll o w u p peri o d will be ta b ulate d wit h e xact 9 5 % CI;

S A Es will be descri be d i n details;
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
7 9
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
8 0

T he pr o p orti o n of s u bjects wit h at least o ne re p ort of pI M Ds classifie d b y t he 
Me d D R A Preferre d Ter ms a n d re p orte d d uri n g t he w h ole p ost -vacci nati o n peri o d 
wil l be ta b ulate d wit h e xact 9 5 % CI .

pI M Ds will be descri be d i n detail.
1 0. 7.
I nt er pr et ati o n of a n al ys e s
T here is n o pre -defi ne d s uccess criteri o n f or t he pri mar y  o bjecti ve assess me nt. T he 
a nal ys es re mai n descri pti ve.
1 0. 8.
C o n d u ct of a n al y s e s
A n y  de viati o n(s) or c ha n ge(s) fr o m t he ori gi nal statistical pla n o utli ne d i n t his pr ot oc ol 
will be descri be d a n d j ustifie d i n t he fi nal st u d y  re p ort.
1 0. 8. 1.
S e q u e n c e of a n al y s e s
T w o f or mal a nal y ses are pla n ne d: a first a nal ysis a n d a n e n d of st u d y a nal ysis.
T he first a nal ys is will be perf or me d w he n t he react o ge nicity a n d Q o L c ollecte d fr o m 
d ose 1 u p t o Visit 3 are a vaila ble.
T he e n d of st u d y a nal ysis of Q o L a n d safet y data will be perf or me d w he n all data u p t o 
t he st u d y e n d ( St u d y c o ncl usi o n c o ntact) will be a vaila ble.
1 0. 8. 2.
St ati sti c al c o n si d er ati o n s f or i nt eri m a n al y s e s
N o i nteri m a nal ys is is pla n ne d.
1 1.
A D M I NI S T R ATI V E M A T T E R S
T o c o m pl y  wit h I C H G C P a d mi nistrati ve o bli gati o ns relati n g t o data c ollecti o n, 
m o nit ori n g, arc hi vi n g data, a u dits, c o nfi de ntialit y  a n d p u blicati o ns m ust be f ulfille d.
1 1. 1.
el e ctr o ni c C a s e R e p ort F or m i n str u cti o n s
A vali date d G S K defi ne d electr o nic data c ollecti o n t o ol will be use d as t he met h o d f or 
data c ollecti o n.
I n all cases, s u bject i nitials will n ot be c ollecte d n or tra ns mitte d t o G S K. S u bject data 
necessar y  f or a nalys is a n d re p orti n g will be e ntere d/tra ns mitte d i nt o a vali date d data base 
or data s ys te m. Cli nical data ma na ge me nt will be perf or me d i n acc or da nce wit h 
a p plica ble G S K sta n dar ds a n d data clea ni n g pr oce d ures.
W hile c o m plete d e C R Fs are re vie we d b y a G S K Bi ol o gica ls’ Site M o nit or at t he st u d y 
site, o missi o ns or i nc o nsiste ncies detecte d by s u bse q ue nt e C R F re vie w ma y necessitate 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
8 0
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
8 1
clarificati o n or c orrecti o n of o missi o ns or i nc o nsiste ncies wit h d oc u me ntati o n a n d 
a p pr o val b y t he i n vesti gat or or a p pr o priatel y q ualifie d d esi g nee. I n all cases, t he 
i n vesti gat or re mai ns acc o u nta ble f or t he st u d y data.
T he i n vesti gat or will be pr o vi de d wit h a C D- R O M of t he fi nal versi o n of t he data 
ge nerate d at t he i n vesti gati o nal site o nce t he data base is arc hi ve d a n d t he st u d y  re p ort is 
c o mplete a n d a p pr o ve d b y  all parties.
1 1. 2.
St u d y M o nit ori n g b y  G S K Bi ol o gi c al s
G S K will m o nit or t he st u d y  t o verif y t hat, a m o n gst ot hers, t he:

Data are a ut he ntic, acc urate, a n d c o m plete.

Safet y  a n d ri g hts of s u bjects are bei n g pr otecte d.

St u d y  is 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 ny ot her 
st u d y a gree me nts, G C P a n d all a p plica ble re g ulat or y re q uire me nts.
T he i n vesti gat or a n d t he hea d of t he me dical i nstit uti o n ( w here a p plica ble) a grees t o 
all o w t he m o nit or direct access t o all rele va nt d oc u me nts.
T he i n vesti gat or m ust e ns ure pr o visi o n of reas o na ble ti me, s pace a n d q ualifie d pers o n nel 
f or m o nit ori n g visits.
Direct access t o all st u d y- site relate d a n d s o urce data is ma n dat or y f or t he p ur p ose of 
m o nit ori n g re vie w. T he m o nit or will perf or m a e C R F re vie w a n d a S o urce D oc u me nt 
Verificati o n ( S D V). B y  S D V we u n dersta n d verif yi n g e C R F e ntries  b y c o m pari n g t he m 
wit h t he s o urce data t hat will be ma de a vaila ble b y t he i n vesti gat or f or t his p ur p ose.
T he S o urce D oc u me ntati o n A gree me nt F or m descri bes t he s o urce data f or t he differe nt 
data i n t he e C R F. T his d oc u me nt s h o ul d be c o m plete d a n d si g ne d b y t he site m o nit or a n d 
i n vesti gat or a n d s h o ul d be file d i n t he m o nit or’s a n d i n vesti gat or’s st u dy file. A n y data 
ite m f or w hic h t he e C R F will ser ve as t he s o ur ce m ust be i de ntifie d, a gree d a n d 
d oc u me nte d i n t he s o urc e d oc u me ntati o n a gree me nt f or m.
F or e C R F, t he m o nit or freezes c o m plete d a n d a p pr o ve d scree ns at eac h visit.
U p o n c o m pleti o n or pre mat ure disc o nti n uati o n of t he st u d y , t he m o nit or will c o n d uct site 
clos ure acti vities wit h t he i n vesti gat or or site staff, as a p pr o priate, i n acc or da nce wit h 
a p plica ble re g ulati o ns, G C P, a n d G S K pr oce d ures.
1 1. 3.
R e c or d r et e nti o n
F oll o wi n g cl os ure of t he st u d y , t he i n vesti gat or m ust mai ntai n all site st u d y rec or ds 
(e xce pt f or t h ose re q uire d b y l ocal re g ulati o ns t o be mai ntai ne d else w here) i n a safe a n d 
sec ure l ocati o n. T he rec or ds m ust be easil y accessi ble, w he n nee de d (e. g., a u dit or 
i ns pecti o n), a n d m ust be a vaila ble f or re vie w i n c o nj u ncti o n wit h assess me nt of t he 
facilit y, s u p p orti n g sys te ms, a n d staff. W here per mitte d b y a p plica ble la ws/re g ulati o ns or 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
8 1
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
8 2
i nstit uti o nal p olic y, s o me or all of t hese rec or ds ca n be mai ntai ne d i n a vali date d f or mat 
ot her t ha n har d c o p y ( e. g., micr ofic he, sca n ne d, electr o nic); h o we ver, ca uti o n nee ds t o be 
e xercise d bef ore s uc h acti o n is ta ke n. T he i n vesti gat or m ust e ns ure t hat all re pr o d ucti o ns 
are le gi ble a n d are a tr ue a n d acc urate c o p y of t he ori gi nal a n d meet accessi bilit y  a n d 
retrie val sta n dar ds, i ncl u di n g re-ge nerati n g a har d c o p y , if re q uire d. F urt her m ore, t he 
i n vesti gat or m ust e ns ure t hat a n acce pta ble bac k-u p of t he re pr o d ucti o ns e xists a n d t hat 
t here is a n acce pta ble q ualit y c o ntr ol pr oce d ure i n place f or ma ki n g t hese re pr o d ucti o ns.
G S K will i nf or m t he i n vesti gat or/i nstit uti o n of t he ti me pe ri o d f or retai ni n g t hese rec or ds 
t o c o m pl y wit h all a p plica ble re g ulat or y re q uire me nts. H o we ver, t he 
i n vesti gat or/i nstit uti o n s h o ul d see k t he writte n a p pr o val of t he s p o ns or bef ore pr ocee di n g 
wit h t he dis p osal of t hese rec or ds. T he mi ni m u m rete nti o n ti me w ill meet t he strictest 
sta n dar d a p plica ble t o a partic ular site, as dictate d b y IC H G C P, a n y  i nstit uti o nal 
re q uire me nts, a p plica ble la ws or re g ulati o ns, or G S K sta n dar ds/ pr oce d ures.
T he i n vesti gat or/i nstit uti o n m ust n otif y  G S K of a n y c ha n ges i n t he arc hi val 
arra n ge me nts, i ncl u di n g, b ut n ot li mite d t o arc hi val at a n off -site facilit y, tra nsfer of 
o w ners hi p of t he rec or ds i n t he e ve nt t h e i n vesti gat or lea ves t he site.
1 1. 4.
Q u alit y a s s ur a n c e
T o e ns ure c o m plia nce wit h G C P a n d all a p plica ble re g ulat or y  re q uire me nts, G S K ma y  
c o n d uct a q ualit y ass ura nce a u dit. Re g ulat or y a ge ncies ma y  als o c o n d uct a re g ulat or y 
i ns pecti o n of t his st u d y. S uc h a u dits/i ns pecti o ns ca n occ ur at a n y ti me d uri n g or after 
c o m pleti o n of t he st u d y. If a n a u dit or i ns pecti o n occ urs, t he i n vesti gat or a n d i nstit uti o n 
a gree t o all o w t he a u dit or/i ns pect or direct access t o all rele va nt d oc u me nts a n d t o all ocate 
his/ her ti me a n d t he ti me of his/ her staff t o t he a u dit or/i ns pect or t o disc uss fi n di n gs a n d 
a n y rele va nt iss ues.
1 1. 5.
P o sti n g of i nf or m ati o n o n p u bli cl y a v ail a bl e cli ni c al tri al 
r e gi st er s a n d p u bli c ati o n p oli c y
G S K ass ures t hat t he ke y desi g n ele me nts of t his pr ot oc ol will be p oste d o n t he G S K 
we bsite a n d i n p u blicl y  accessi ble data base(s) s uc h as cli nicaltrials. g o v, i n c o m plia nce 
wit h t he c urre nt re g ula ti o ns.
G S K als o ass ures t hat res ults of t his st u d y  will be p oste d o n t he G S K we bsite a n d i n 
p u blicl y  accessi ble re g ulat or y re gistr y(ies) wit hi n t he re q uire d ti me-fra me, i n c o m plia nce 
wit h t he c urre nt re g ulati o ns. T he mi ni mal re q uire me nt is t o ha ve pri mar y  e n d p oi nt 
s u m mar y res ults discl ose d at latest 1 2 m o nt hs p ost pri mar y c o m pleti o n date ( P C D) a n d t o 
ha ve sec o n dar y  e n d p oi nt discl ose d at latest 1 2 m o nt hs after t he last s u bject last visit 
( LS L V) as descri be d i n t he pr ot oc ol.
G S K als o ai ms t o p u blis h t he res ul ts of t hese st u dies i n searc ha ble, peer re vie we d 
scie ntific literat ure a n d f oll o ws t he g ui da nce fr o m t he Inter nati o nal C o m mittee of 
Me dical J o ur nal E dit ors.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
8 2
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
8 3
1 1. 6.
Pr o vi si o n of st u d y  r e s ult s t o i n v e sti g at or s
W here re q uire d b y a p plica ble re g ulat or y  re q uire me nts, an i n vesti gat or si g nat or y  will be 
i de ntifie d f or t he a p pr o val of t he st u d y re p ort. T he i n vesti gat or will be pr o vi de d 
reas o na ble access t o statistical ta bles, fi g ures, a n d rele va nt re p orts a n d will ha ve t he 
o p p ort u nit y  t o re vie w t he c o m plete st u d y res ults at a G S K site or ot her m ut uall y-
a greea ble l ocati o n.
G S K Bi ol o gicals will als o pr o vi de t he i n vesti gat or wit h t he f ull s u m mar y  of t he st u d y 
res ults. T he i n vesti gat or is e nc o ura ge d t o s hare t he s u m mar y res ults wit h t he st u d y 
s u bjects, as a p pr o priate.
1 2.
C O U N T R Y S P E CI FI C R E Q UI R E M E N T S
N ot a p plica ble.
1 3.
R E F E R E N C E S (A m e n d e d 1 6 N O V E M B E R 2 0 1 6 )
Ce nters f or Disease C o ntr ol a n d Pre ve nti o n Metr o p olita n Atla nta C o n ge nital Defects 
Pr o gra m ( C D C M A C D P) g ui deli nes. Birt h defects a n d ge netic diseases bra nc h 6 -di git 
c o de f or re p orta b le c o n ge nital a n o malies; 2 0 0 7. 
htt p:// w w w.c dc. g o v/ nc b d d d/ birt h defects/ d oc u me nts/ M A C D Pc o de 0 8 0 7. p df . We bsite 
accesse d 1 9 Oct o ber 2 0 1 5 .
Di dierla ure nt A M, C olli g n o n C, B o ur g ui g n o n P, et al. E n ha nce me nt of a da pti ve 
i m m u nit y b y t he h u ma n vacci ne a dj u va nt A S 0 1 de pe n ds o n acti vate d de n dritic cells. J 
I m m u n ol. 2 0 1 4; 1 9 3( 4): 1 9 2 0- 3 0.
D w or ki n R H, J o h ns o n R W, Bre uer J, et al. Rec o m me n dati o ns f or t he ma na ge me nt of 
her pes z oster. Cli n I nfect Dis. 2 0 0 7; 4 4 S u p pl 1: S 1 – 2 6.
E M A G ui deli ne o n t he e x p os ure t o me dici nal pr o d ucts d uri n g pre g na nc y : nee d f or p ost-
a ut h orizati o n data ( D oc. Ref. E M E A/ C H M P/ 3 1 3 6 6 6/ 2 0 0 5 ) ‘a d o pte d at C o m m u nit y  le vel 
i n Ma y 2 0 0 6);
htt p:// w w w.e m a.e ur o p a.e u/ d ocs/e n _ G B/ d oc u me nt _li br ary/ Re g u l at ory _ a n d _ pr oce d ur al _ g
ui deli ne/ 2 0 0 9/ 1 1/ W C 5 0 0 0 1 1 3 0 3. p df . Accesse d 2 4 Oct o ber 2 0 1 6.
F D A, U. S. De part me nt of Healt h a n d H u ma n Ser vices, Ce nter f or Bi ol o gics E val uati o n 
a n d Researc h. G ui da nce f or I n d ustr y : T o xicit y Gra di n g Scale f or Healt hy A d ult a n d 
A d olesce nt V ol u nteers E nr olle d i n Pre ve nti ve Vacci ne Cli nical Trials. Versi o n of 
Se pte m ber 2 0 0 7.
Frie d L P, Ta n ge n C M, Walst o n J, et al., ( Car di o vasc ular Healt h St u d y  C olla b orati ve 
Researc h Gr o u p). Frailt y  i n ol der a d ults: e vi de nce f or a p he n oty p e. J Ger o nt ol A Bi ol Sci 
Me d Sci. 2 0 0 1; 5 6( 3): M 1 4 6- 5 6.
Gater A, U hart M, Mc C o ol R, Préa u d E. T he h u ma nistic, ec o n o mic a n d s ocietal b ur de n 
of her pes z oster i n E ur o pe: a critical re vie w. B M C P u blic Healt h. 2 0 1 5; 1 5: 1 9 3.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
8 3
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
8 4
Ki n d P. T he E ur o Q L i nstr u me nt: A n i n de x of healt h- relate d q ualit y of life. i n: S pil ker B, 
e dit or. Q u ality of Life a n d P h ar m ac oec o n o mics i n Cli nic al Tri als . Sec o n d E diti o n. 
P hila del p hia: L i p pi nc ott- Ra ve n P u blis hers; 1 9 9 6.
Kr o ger A T, S u ma y a C V, Pic keri n g L K, At ki ns o n W L. Ge neral rec o m me n dati o ns o n 
i m m u nizati o n: rec o m me n dati o ns of t he A d vis or y C o m mittee o n Im m u nizati o n Practices 
( A CIP). M M W R Rec o m m Re p . 2 0 1 1; 6 0: 1- 6 1.
Lal H, C u n ni n g ha m A L, G o dea u x O et al. Efficac y of a n A dj u va nte d Her pes Z oste r 
S u b u nit Vacci ne i n Ol der A d ults. N E n gl J Me d. 2 0 1 5: D OI : 1 0. 1 0 5 6/ N EJ M oa 1 5 0 1 1 8 4.
Mit nits ki A B, M o gil ner AJ, R oc k w o o d K. Acc u m ulati o n of deficits as a pr o x y  meas ure 
of a gi n g. Sci W orl d J. 2 0 0 1; 1: 3 2 3 - 3 6.
O x ma n M N, L e vi n MJ, J o h ns o n G R, et al. S hi n gles Pr e ve nti o n St u d y Gr o u p. A vacci ne 
t o pre ve nt her pes z oster a n d p ost her petic ne ural gia i n ol der a d ults. N E n gl J Me d . 2 0 0 5; 
3 5 2: 2 2 7 1 – 8 4.
Pellissier J M, Briss o n M, L e vi n MJ. E val uati o n of t he c ost- effecti ve ness i n t he U nite d 
States of a vacci ne t o pre ve nt her p es z oster a n d p ost her petic ne ural gia i n ol der a d ults. 
V acci ne . 2 0 0 7; 2 5( 4 9): 8 3 2 6 - 3 7.
R y b G E, Disc hi n ger P C, B urc h C A, et al. Frailt y  a n d i nj ur y ca usati o n. A n n A dv A ut o m ot 
Me d . 2 0 1 2; 5 6: 1 7 5- 8 1.
Sc ott F, J o h ns o n R, L ee d ha m-Gree n M, et al. T he b ur de n of her pes z oster: A pr os pecti ve 
p o p ulati o n base d st u d y . V acci ne. 2 0 0 6; 2 4: 1 3 0 8 - 1 4.
Searle S D, Mit nits ki A, Ga h ba uer E A, Gill T M, R oc k w o o d K. A sta n dar d pr oce d ure f or 
creati n g a frailt y i n de x. B M C Geri atr . 2 0 0 8; 8: 2 4- 3 3.
S per ber SJ, S mit h B V, Ha y de n F G. Ser ol o gic res p o nse a n d react o ge nicit y  t o b o oster 
i m m u nizati o n of healt h y ser o p ositi ve a d ults wit h li ve or i nacti vate d varicella vacci ne. 
A ntivir al Res . 1 9 9 2; 1 7: 2 1 - 2 2.
Stassij ns J, B ollaerts K, Baa y  M, Verstraete n T. A s yste matic re vie w a n d meta-a nal ys is 
o n t he safet y of ne wl y a dj u va nte d vacci nes a m o n g c hil dre n. V acci ne . 2 0 1 6; 3 4( 6): 7 1 4-
2 2.
Sz ucs T D, Pfeil A M. A s y ste matic re vie w of t he c ost effecti ve ness of her pes z oster 
vacci nati o n. P har mac oec o n o mics. 2 0 1 3 ( 2): 1 2 5- 3 6.
Ware J E, K osi ns ki M, I nter preti n g S F-3 6 s u m mar y  healt h meas ures: a res p o nse. Q u al 
Life Res , 2 0 01; 1 -( 5): 4 0 5- 1 3.
Z ost av ax [s hi n gles ( her pes z oster) vacci ne (li ve)] Prescri bi n g I nf or mati o n. J u ne 2 0 1 1.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
8 4
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
8 5
A P P E N DI X A
S F -3 6 ( V er si o n 2. 0 S A M P L E)
( Am e n d e d 1 6 
N o v e m b er 2 0 1 6 )
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
8 5
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
8 6
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
8 6
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
8 7
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
8 7
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
8 8
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
8 8
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
8 9
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
8 9
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
9 0
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
9 0
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
9 1
A P P E N DI X B
E Q -5 D ( E n gli s h V er si o n U S S AM P L E) ( Am e n d e d 
1 6 N o v e m b er 2 0 1 6 )
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
9 1
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
9 2
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
9 2
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
9 3
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
9 3
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
9 4
A P P E N DI X C
A M E N D M E N T S A N D A D M I NI S T R ATI V E 
C H A N G E S T O T H E P R O T O C O L
Gl a x o S mit h Kli n e Bi ol o gi c al s
Vacci ne Val ue & Healt h Scie nce ( V V H S)
Pr ot oc ol A me n d me nt 1
e Tr ac k st u d y n u m ber 
a n d A b bre vi ate d Title
2 0 4 9 2 8 ( Z O S T E R - 0 6 3)
I N D n u m ber:
B B -I N D 1 3 8 5 7
A m e n d me nt n u m ber:
A me n d me nt 1
A m e n d me nt d ate:
2 2 A u g ust 2 0 1 6
C o -or di n ati n g a ut h or:
, Scie ntific writer, X P E P har ma & 
Scie nce, C o ntract or f or G S K Bi ol o gicals
R ati o n ale/ b ac k gr o u n d f or c h a n ges:

I n res p o nse t o C B E R fee d bac k, t he o bjecti ves a n d e n d p oi nts were e dite d t o clarif y 
t he ti me p oi nts f or t he meas ure me nt of t he S F- 3 6 P h y sical F u ncti o ni n g ( S F-3 6 P F) 
a n d S F-3 6 P h y sical R ole sc ores i n t he Sy n o psis a n d Secti o ns 2. 1, 2. 2, 1 0. 1 1 0. 2 
a n d 1 0. 2.

T he o bjecti ves a n d e n d p oi nts were e dite d t o re m o ve t he u nit of h o urs f or t he 
esti mate d w or k l oss f or s u bjects a n d n o n -de dicate d care gi vers a n d e xtra w or k f or 
de dicate d care gi vers i n t he S y n o psis a n d Secti o ns 2. 1, 2. 2, 1 0. 1 a n d 1 0. 2.

T he a b bre viati o ns f or t he q uesti o n naires “ E Q - 5 D” a n d “ S F-3 6” were a d de d t o t he 
List of A b bre viati o ns a n d t he ter m “ Frailt y” was defi ne d i n t he Gl ossar y of Te r ms.

Clarificati o n a b o ut t he filli n g o ut t he q uesti o n naires was a d de d t o Secti o ns 5. 3. 1. 1, 
5. 5. 2. 4 a n d 5. 5. 2. 1 1 as well as i n dicati n g t hat t he p h ysical e xa mi nati o n at Visit 1 
ca n be perf or me d acc or di n g t o l ocal practice i n Secti o n 5. 5. 1. 5.

T he bac k -u p st u d y c o ntact Fa x n u m ber f or re p orti n g S A Es, pre g na ncies a n d 
pI M Ds
i n t he U S was a d de d t o Secti o n 8. 4. 2.

A d diti o nal e dits were ma de t o clarif y  h o w t he P F sc ore will be esti mate d i n 
Secti o n 1 0. 3 a n d t hat t he S F -3 6 q uesti o n naire will be use d f or t he meas ure me nt of 
P h y sical F u ncti o ni n g i n Secti o n 1 0. 6. 2. 3.

I n res p o nse t o C B E R fee d bac k, clarificati o n was ma de t o i n dicate t hat t he a nalys is 
of Q ualit y  of Life ( Q o L) data will be base d o n t he T otal Vacci nate d C o h ort ( T Vc) 
i n Secti o ns 1 0. 4. 1 a n d 1 0. 6. 2.

T he ti mefra me f o r q uesti o n 2 has bee n re d uce d fr o m “ o ne year a g o” t o “ o ne wee k 
a g o” a n d t he ti mefra me f or q uesti o ns 4 - 1 0 has bee n re d uce d fr o m “t he past 4 
wee ks” t o “t he past wee k” i n t he sa m ple S F- 3 6 q uesti o n naire ( A p pe n di x A).
A m e n de d te xt h as bee n i ncl u de d i n b ol d i t alics a n d delete d te xt i n stri ket hr o u g h i n 
t he f oll o wi n g secti o ns:
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
P P D
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
9 4
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
9 5
S Y N O P SI S
R ati o n ale f or t he 
st u d y a n d st u d y 
desi g n

Rati o nale f or t he st u d y
Ot her si de effects see n i n m ore t ha n 1 0 % of pe o ple w h o 
g ot receive d t he vacci ne i ncl u de d m yal gia, fati g ue, hea dac he, 
s hi veri n g, fe ver a n d gastr oi ntesti nal s ym pt o ms s uc h as 
na usea, v o miti n g, diarr h oea a n d/ or a b d o mi nal pai n.
O bjecti ve s
Pri m ar y

T o esti mate t he c ha n ge i n t he S F - 3 6 P h y sical 
F u ncti o ni n g ( S F - 3 6 P F) scale sc ores fr o m baseli ne sc ore 
t o t he me a n sc ore over t he peri o d d ay 1 t o d ay 7
f oll o wi n g t he first H Z/s u vacci nati o n i n s u bjects ≥5 0 
ye ars of a ge ( Y O A) o verall.
Sec o n d ar y

T o esti mate t he c ha n ge i n t he S F - 3 6 P F scale sc ore s
fr o m baseli ne sc ore t o t he me a n sc ore over t he peri o d 
d ay 1 t o d ay 7 f oll o wi n g t he sec o n d H Z/s u vacci nati o n 
i n s u bjects ≥5 0 Y O A o verall.

T o esti mate t he c ha n ge i n t he S F - 3 6 P F scale sc ore s i n 
s u bjects ≥5 0 Y O A b y  a ge, ge n der a n d react o ge nicit y 
gra de a n d t y p e of s y m pt o m (l ocal, s y ste mic) fr o m 
baseli ne sc ore t o t he me a n sc ore over t h e peri o d d ay 1 
t o d ay 7 f oll o wi n g b ot h H Z/s u vacci nati o ns 1 a n d 2.

T o esti mate t he c ha n ge i n S F - 3 6 P F si n gle ite m sc ores 
i n s u bjects ≥5 0 Y O A o verall, b y  a ge, ge n der a n d 
react o ge nicit y gra de a n d t ype of s y m pt o m (l ocal, 
s yste mic) fr o m baseli ne sc ore t o t he me a n sc ore over t he 
peri o d d ay 1 t o d ay 7 f oll o wi n g b ot h H Z/s u vacci nati o ns 
1 a n d 2.

T o esti mate t he c ha n ge i n S F - 3 6 rR ole p P h y sical sc ores 
i n s u bjects ≥5 0 Y O A o verall, b y  a ge, ge n der a n d 
react o ge nicit y gra de a n d t ype of s y m pt o m (l ocal, 
s yste mic) fr o m baseli ne sc ore t o t he sc ore o n d ay 7
f oll o wi n g b ot h H Z/s u vacci nati o ns 1 a n d 2.

T o esti mate t he Q A L Y c ha n ge i n s u bjects ≥5 0 Y O A
o verall, b y a ge, ge n der, react o ge n icit y gra de a n d t ype of 
s ym pt o m (l ocal, s ys te mic) fr o m baseli ne sc ore t o t he 
c o m bi ne d sc ore o n d ays 1 t o 7 f oll o wi n g b ot h H Z/s u 
vacci nati o ns 1 a n d 2.

T o esti mate t he w or k l oss ( h o urs) i n s u bjects ≥5 0 Y O A 
o verall, b y a ge, ge n der, react o ge nicit y gra de a n d t y p e of 
s ym pt o m (l ocal, s ys te mic) f oll o wi n g b ot h H Z/s u 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
9 5
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
9 6
vacci nati o ns 1 a n d 2.

T o esti mate t he w or k l oss ( h o urs) f or n o n-de dicate d 
care gi vers (e. g., fa mil y me m ber) of s u bjects ≥5 0 Y O A
o verall, b y ge n der, react o ge nicit y  gra de a n d t ype of 
s ym pt o m (l ocal, s ys temic) f oll o wi n g b ot h H Z/s u 
vacci nati o ns 1 a n d 2.

T o esti mate t he h o urs of e xtra w or k f or de dicate d 
care gi vers of s u bjects ≥5 0 Y O A o verall, b y  ge n der, 
react o ge nicit y gra de a n d t ype of s y m pt o m (l ocal, 
s yste mic) f oll o wi n g b ot h H Z/s u vacci nati o ns 1 a n d 2.
E n d p oi nts
Pri m ar y

C ha n ge i n mea n S F - 3 6 P F scale sc ore s.

Baseli ne * vers us me a n sc ore over t he peri o d d a y s 1 
t o d ay 7 after first vacci nati o n.
Sec o n d ar y

C ha n ge i n mea n S F - 3 6 P F scale sc ore s.

Baseli ne * vers us me a n sc ore over t he peri o d d a y s 1 
t o d ay 7 after sec o n d vacci nati o n.

C ha n ge i n mea n S F - 3 6 P F si n gle ite m sc ores.

Baseli ne * vers us me a n sc ore over t he peri o d d a y s 1 
t o d ay 7 after eac h vacci nati o n.

C ha n ge i n S F - 3 6 rR ole p P h y sical sc ores.

Baseli ne * vers us d a y s 1 a n dsc ore o n d ay 7 after 
eac h vacci nati o n.

C ha n ge i n t he Q A L Y.

Baseli ne * vers us c o m bi ne d sc ore over t he peri o d
da y s 1 t o d ay 7 assess me nt after eac h vacci nati o n.

H o urs of w W or k l oss f or s u bjects.

Da y s 0 t o 6 after eac h vacci nati o n.

H o urs of w W or k l oss f or t he n o n - de dicate d care gi vers.

Da y s 0 t o 6 after eac h vacci nati o n.

H o urs of eE xtra w or k f or de dicate d care gi vers.

Da y s 0 t o 6 after eac h vacci nati o n.
* N ote: baseli ne f or d ose 1 is defi ne d as t he me a n of t he 
assess me nts at d ay - 7 a n d d ay 0; f or d ose 2 b aseli ne is 
defi ne d as t he me a n of t he t hree assess me nts at d ay -7, d ay 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
9 6
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
9 7
0 a n d d ay 6 0 ( d ay 0 f or will be defi ne d f or d ose 1 a n d d ose 
2 )., fF urt her details o n baseli ne calc ulati o n will be gi ve n i n 
t he Statistical A nal ysis Pla n ( S A P).
* * N ote: T he p ost -v acci n ati o n c o m pleti o n of S F -3 6 a n d E Q -
5 D q uesti o n n aires br o u g ht h o me by t he s u bjects will be o n 
d ays 1 t o d ay 6, wit h d ay 7 t o be fille d i n at t he site ( d uri n g 
Visits 3 a n d 5); w hile t he p ost -v acci n ati o n rec or di n g of 
s olicite d A Es o n t he di ary c ar d bro u g ht h o me by t he 
s u bjects will be o n d ays 0 t o d ay 6 .
LI S T O F A B B R E VI A TI O N S
E Q -5 D:
E ur o Q ol five di me nsi o n he alt h q uesti o n n aire
S F - 3 6:
A S h ort F or m 3 6 -ite m he alt h s urvey
G L O S S A R Y O F T E R M S
Fr ailty:
Fr ailty is a ter m use d i n Geri atric Me dici ne t o i de ntify
ol der a d ults w h o are at i ncre ase d ris k of p o or cli nic al 
o utc o mes, s uc h as i nci de nt dis a bility, c o g nitive decli ne, 
f alls, h os pit aliz ati o n, i nstit uti o n aliz ati o n, or i ncre ase d 
m ort ality. Fr ailty re prese nts a re d ucti o n i n resist a nce t o 
stress ors le a di n g t o i ncre ase d cli nic al v ul ner a bility a n d 
a dverse he alt h o utc o mes.
Secti o n 1. 2. 1 .    R ati o n ale f or t he st u d y
Ot her si de effects see n i n m ore t ha n 1 0 % of pe o ple w h o g ot receive d t he vacci ne i ncl u de d
m yal gia, fati g ue , hea dac he, s hi veri n g, fe ver a n d gastr oi ntesti nal s ym pt o ms s uc h as 
na usea, v o miti n g, diarr h oea a n d/ or a b d o mi nal pai n .
Secti o n 1. 2. 2.    R ati o n ale f or t he st u d y desi g n
S u bjects i n t he ge neral p o p ulati o n (es peciall y ol der a d ults), are o n a vera ge u na ble t o 
ac hie ve perfect Q o L sc ores , beca use ma n y s u bjects ma y  be s o me w hat li mite d i n 
“cli m bi n g se veral fli g hts of stairs” or “ b e n di n g, k neeli n g, or st o o pi n g”. T o esti mate t he 
i m pact of react o ge nicity o n a n i n di vi d ual’s S F - 3 6 P F a n d Q o L , we will c o m pare t w o 
peri o ds, i.e. , pre -vacci nati o n a n d p ost - vacci nati o n. T he differe nce is c o nsi dere d t o be t he 
effect of vacci nati o n a n d react o ge nicit y  o n t he S F - 3 6 P F a n d Q o L .
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
9 7
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
9 8
Secti o n 2. 1.     Pri m ar y o bjecti ve

T o esti mate t he c ha n ge i n t he S F - 3 6 P h y sical F u ncti o ni n g (S F - 3 6 P F) scale sc ores
fr o m baseli ne sc ore t o t he me a n sc ore over t he peri o d d ay 1 t o d ay 7 f oll o wi n g t he 
first H Z/s u vacci nati o n i n s u bjects ≥5 0 y ears of a ge ( Y O A) o verall.
Secti o n 2 . 2.    Sec o n d ar y o bjecti ves

T o esti mate t he c ha n ge i n t he S F - 3 6 P F scale sc ore s fr o m baseli ne sc ore t o t he me a n
sc ore over t he peri o d d ay 1 t o d ay 7 f oll o wi n g t he sec o n d H Z/s u vacci nati o n i n 
s u bjects ≥5 0 Y O A o verall.

T o esti mate t he c ha n ge i n t he S F - 3 6 P F scale sc ore s i n s u bjects ≥5 0 Y O A b y  a ge, 
ge n der a n d react o ge nicit y  gra de a n d ty p e of s y m pt o m (l ocal, s yste mic) fr o m baseli ne 
sc ore t o t he me a n sc ore over t he peri o d d ay 1 t o d ay 7 f oll o wi n g b ot h H Z/s u 
vacci nati o ns 1 a n d 2.

T o esti mate t he c ha n ge i n S F - 3 6 P F si n gle ite m sc ores i n s u bjects ≥5 0 Y O A o verall, 
b y  a ge, ge n der a n d react o ge nicit y gra de an d t y pe of s y m pt o m (l ocal, s ys te mic) fr o m 
baseli ne sc ore t o t he me a n sc ore over t he peri o d d ay 1 t o d ay 7 f oll o wi n g b ot h 
H Z/s u vacci nati o ns 1 a n d 2.

T o esti mate t he c ha n ge i n S F - 3 6 rR ole p P h y sical sc ores i n s u bjects ≥5 0 Y O A
o verall, b y a ge, ge n der a n d react o ge nicit y gra de a n d t y pe of s y m pt o m (l ocal, 
s yste mic) fr o m baseli ne sc ore t o t he sc ore o n d ay 7 f oll o wi n g b ot h H Z/s u 
vacci nati o ns 1 a n d 2.

T o esti mate t he Q A L Y c ha n ge i n s u bjects ≥5 0 Y O A o verall, b y  a ge, ge n der, 
react o ge nicit y gra de a n d t ype of s y m pt o m (l ocal, s y ste mic) fr o m baseli ne sc ore t o 
t he c o m bi ne d sc ore o n d ays 1 t o 7 f oll o wi n g b ot h H Z/s u vacci nati o ns 1 a n d 2.

T o esti mate t he w or k l oss ( h o urs) i n s u bjects ≥5 0 Y O A o verall, b y  a ge, ge n der, 
react o ge nicit y gra de a n d ty pe of s y m pt o m (l ocal, s y ste mic) f oll o wi n g b ot h H Z/s u 
vacci nati o ns 1 a n d 2.

T o esti mate t he w or k l oss ( h o urs) f or n o n-de dicate d care gi vers (e. g., fa mil y  me m ber) 
of s u bjects ≥5 0 Y O A o verall, b y  ge n der, react o ge nicit y gra de a n d ty pe of s y m pt o m 
(l ocal, sys te mic) f oll o wi n g b ot h H Z/s u vacci nati o ns 1 a n d 2.

T o esti mate t he h o urs of e xtra w or k f or de dicate d care gi vers of s u bjects ≥5 0 Y O A
o verall, b y ge n der, react o ge nicit y  gra de a n d t ype o f s ym pt o m (l ocal, s ys te mic)
f oll o wi n g b ot h H Z/s u vacci nati o ns 1 a n d 2.
Secti o n 5. 3. 1. 1.    Q uesti o n n aires a n d Di ar y c ar ds
F oll o wi n g vacci nati o n , 7- d a y  a n d 3 0-d a y  diar y car ds will be dis pe nse d t o be c o m plete d 
b y  t he s u bjects/ s u bjects’ care gi ver.
T he q uesti o n n aires will be fille d i n by t he s u bject/s u bjects c are giver o n site at e ac h 
visit. I n a d diti o n, t he s u bject/s u bjects c are giver will be re q uire d t o c o m plete t he S F - 3 6 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
9 8
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
9 9
P F c o m p o ne nt of t he S F - 3 6 q uesti o n n aire (i.e., ite ms 3 a t o 3j, see T a ble 1 5) a n d t he 
E Q -5 D q uesti o n n aire at h o me o n d ays 1 t o 6 f oll o wi n g e ac h v acci n ati o n.
Secti o n 5. 5 . 1.5 .    P h ysic al e x a mi n ati o n a n d assess me nt of fr ailt y st at us
Perf or m a p h y sical e xa mi nati o n of t he s u bject at Visit 1 i ncl u di n g wei g ht a n d hei g ht 
( b o d y mass i n de x [ B MI] will be calc ulate d). T he p hysic al e x a mi n ati o n c a n be 
perf or me d per t he site’s me dic al j u d g me nt a n d st a n d ar d of c are (refer t o t he S P M f or 
det ails of t he p hysic al e x a mi n ati o n) .
Secti o n 5. 5. 2. 4 .    Distri b uti o n a n d c o m pleti o n of S F -3 6 a n d E Q - 5 D 
q uesti o n n aires at Visit 2
T he S F - 3 6 a n d E Q- 5 D q uesti o n naires will be distri b ute d t o s u bjects a gai n at Visit 2. 
S u bjects will be as ke d t o c o m plete t he e ntire S F -3 6 a n d E Q- 5 D q uesti o n naires o n site
j ust bef ore vacci nati o n at Visit 2. C o m plete d q uesti o n naires will t he n be c ollecte d at 
Visit 2, a n d s u bject res p o nses will be tra nscri be d i nt o t he e- C R F.
Secti o n 5. 5. 2. 1 1.      Distri b uti o n a n d c o m pleti o n of S F -3 6 a n d E Q - 5 D 
q uesti o n n aires p ost -v acci n ati o n
T he S F - 3 6 P F c o m p o ne nt of t he S F - 3 6 q uesti o n n aire (o nl y  q uesti o ns 3a t hr o u g h 3j, see 
T a ble 1 5 ) a n d E Q - 5 D dail y q uesti o n naires will be distri b ute d t o t he s u bjects t o ta ke h o me
f oll o wi n g b ot h vacci nati o ns at Visit 2 a n d Visit 4.
Secti o n 6. 1 .    Descri pti o n of st u d y v acci n e
T a bl e 7
St u d y  v a c ci n e
H Z/s u = H er p es Z ost er s u b u nit v acci n e; V Z V = V aric ell a Z ost er Vir us; g E = r ec o m bi n a nt p urifi e d e nv el o p e 
G g lyc o pr ot ei n E; μ g = micr o gr a m; m L = millilit er; A S 0 1 B = A dj uv a nt Syst e m A S 0 1 B ; M P L = 3- O-d es acyl -4’ -
m o n o p h os p h oryl li pi d A; Q S 2 1 = Q uill aj a s a p o n ari a M oli n a, fr acti o n 2 1 ( p urifi e d s a p o ni n extr act fr o m t h e S o ut h 
A m eric a n tr e e).
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
9 9
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 0 0
Secti o n 8. 4. 2.     C o nt act i nf or m ati o n f or re p orti n g seri o us a d verse 
e ve nts, pre g n a ncies a n d pI M Ds
B ac k - u p St u d y C o nt act f or Re p orti n g S A Es, pre g n a ncies a n d pI M Ds
2 4/ 2 4 h o ur a n d 7/ 7 da y  a vaila bilit y:
G S K Bi ol o gicals Cli nical Safet y  & P har mac o vi gila nce
U S sites o nly:
F a x: 
Secti o n 1 0. 1 .    Pri m ar y e n d p oi nt

C ha n ge i n mea n S F - 3 6 P F scale sc ore s.

Baseli ne * vers us mea n sc ore o ver t he peri o d d a y s 1 t o da y 7 after first 
vacci nati o n.
Secti o n 1 0. 2 .    Sec o n d ar y e n d p oi nt s

C ha n ge i n mea n S F - 3 6 P F scale sc ore s.

Baseli ne * vers us me a n sc ore over t he peri o d d a y s 1 t o d ay 7 after sec o n d 
vacci nati o n.

C ha n ge i n mea n S F - 3 6 P F si n gle ite m sc ores.

Baseli ne * vers us me a n sc ore over t he peri o d d a y s 1 t o d ay 7 after eac h 
vacci nati o n.

C ha n ge i n S F - 3 6 rR ole p P h y sical sc ores.

Baseli ne * vers us d a y s 1 a n dsc ore o n d ay 7 after eac h vacci nati o n.

C ha n ge i n t he Q A L Y.

Baseli ne * vers us c o m bi ne d sc ore over t he peri o d da y s 1 t o d ay 7 assess me nt
after eac h vacci nati o n.

H o urs of w W or k l oss f or s u bjects.

D a y s 0 t o 6 after eac h vacci nati o n.

H o urs of w W or k l oss f or t he n o n - de dicate d care gi vers.

D a y s 0 t o 6 after eac h vacci nati o n.

H o urs of eE xtra w or k f or de dicate d care gi vers.

D a y s 0 t o 6 after eac h vacci nati o n.
* N ote: baseli ne f or d ose 1 is defi ne d as t he me a n of t he assess me nts at d ay -7 a n d 
d ay 0; f or d ose 2 b aseli ne is defi ne d as t he me a n of t he t hree assess me nts at d ay - 7, 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
P P D
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 0 0
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 0 1
d ay 0 a n d d ay 6 0 ( d ay 0 f or will be defi ne d f or d ose 1 a n d d ose 2 )., fF urt her details o n 
baseli ne calc ulati o n will be gi ve n i n t he Statistical A nal y sis Pla n ( S A P).
* * N ote: T he p ost -v acci n ati o n c o m pleti o n of S F -3 6 a n d E Q -5 D q uesti o n n aires br o u g ht 
h o me by t he s u bjects will be o n d ays 1 t o d ay 6, wit h d ay 7 t o be fille d i n at t he site 
( d uri n g Visits 3 a n d 5); w hile t he p ost -v acci n ati o n rec or di n g of s olicite d A Es o n t he 
di ary c ar d br o u g ht h o me by t he s u bjects will be o n d ays 0 t o d ay 6 .
Secti o n 1 0. 3 .    Deter mi n ati o n of s a m ple size
T he P F sc ore will be esti mate d as t he c ha n ge i n mea n P F sc ore bet wee n baseli ne a n d 
me a n sc ore over t he peri o d da y s 1 t o d ay 7 after first vacci nati o n .
Secti o n 1 0. 4. 1 .    T ot al v acci n ate d c o h ort
T he T Vc f or a nal y sis of Q o L will i ncl u de all s u bjects wit h at least o ne vacci ne d ose 
a d mi nistere d a n d wit h Q o L  data c ollecte d at pre- a n d p ost-vacci nati o n.
Secti o n 1 0. 6. 2. 1 .    Q u alit y of life
T he a nal ys is of Q o L will be base d o n the T Vc f or a nalys is of Q o L.
Secti o n 1 0. 6. 2. 3 .    S F -3 6 he alt h s ur ve y
T he S F -3 6 ® is a m ulti -p ur p ose healt h s ur ve y  wit h 3 6 q uesti o ns (refer t o A P P E N DI X A
or t he we bsite a d dress htt p:// w w w.sf -3 6. or g/ de m os/ S F - 3 6. ht ml f or a sa m ple of t he 
q uesti o n naire) [ Ware , 2 0 0 1; S F -3 6. or g , 2 0 1 4; S F -3 6 sa m ple , 2 0 1 4] t h at will be use d t o 
ev al u ate P F usi n g q uesti o ns 3 a t hr o u g h 3j .
A P P E N DI X A     S F -3 6 ( Versi o n 2. 0 S A M P L E)
2.
C o m pare d t o o ne ye arwee k a g o, h o w w o ul d y o u rate y o ur healt h i n ge neral n o w?
M uc h better
n o w t ha n o ne
ye arwee k a g o
S o me w hat better
n o w t ha n o ne
ye arwee k a g o
A b o ut t he
sa me as o ne
ye arwee k a g o
S o me w hat w orse
n o w t ha n o ne
ye arwee k a g o
M uc h w orse
n o w t ha n o ne
ye arwee k a g o
4.
D uri n g t he past 4 wee ks , h o w m uc h of t he ti me ha ve yo u ha d a n y  of t he f oll o wi n g 
pr o ble ms wit h y o ur w or k or ot her re g ular dail y acti vities as a res ult of y o ur p h y sical 
healt h?
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 0 1
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 0 2
5.
D uri n g t he past 4 wee ks , h o w m uc h of t he ti me ha ve yo u ha d a n y  of t he f oll o wi n g 
pr o ble ms wit h y o ur w or k or ot her re g ular dail y acti vities as a res ult of a n y e m oti o nal 
pr o ble ms (s uc h as feeli n g de presse d or a n xi o us)?
6.
D uri n g t he past 4 wee ks , t o w hat e xte nt has yo ur p h y sical healt h or e m oti o nal 
pr o ble ms i nterfere d wit h y o ur n or mal s ocial acti vities wit h fa mil y , frie n ds, 
nei g h b ors, or gr o u ps?
7.
H o w m uc h b o dil y  pai n ha ve yo u ha d d uri n g t he past 4 wee k s?
8.
D uri n g t he past 4 wee ks, h o w m uc h di d pai n i nterfere wit h y o ur n or mal w or k 
(i ncl u di n g b ot h w or k o utsi de t he h o me a n d h o use w or k)?
9.
T hese q uesti o ns are a b o ut h o w y o u feel a n d h o w t hi n gs ha ve bee n wit h y o u d uri n g 
t he past 4 wee k s. F or eac h q uesti o n, please gi ve t he o ne a ns wer t hat c o mes cl osest t o 
t he wa y yo u ha ve bee n feeli n g.
H o w m uc h of t he ti me d uri n g t he past 4 wee k s...
1 0. D uri n g t he past 4 wee ks , h o w m uc h of t he ti me has yo ur p h ys ical healt h or 
e m oti o nal pr o ble ms i nterfere d wit h yo ur s ocial acti vities (li ke visiti n g frie n ds, 
relati ves, etc.)?
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 0 2
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 0 3
Gl a x o S mit h Kli n e Bi ol o gi c al s
Vacci ne Val ue & Healt h Scie nce ( V V H S)
Pr ot oc ol A me n d me nt 2
e Tr ac k st u d y n u m ber 
a n d A b bre vi ate d Title
2 0 4 9 2 8 ( Z O S T E R - 0 6 3)
I N D n u m ber:
B B -I N D 1 3 8 5 7
A m e n d me nt n u m ber:
A me n d me nt 2
A m e n d me nt d ate:
1 6 N o ve m ber 2 0 1 6
C o -or di n ati n g a ut h or:
, Scie ntific W riter
R ati o n ale/ b ac k gr o u n d f or c h a n ges:

T he sa m ple E Q -5 D q uesti o n naire i n A P P E N DI X B of t he pr ot oc ol was missi n g t he 
Vis ual A nal o g ue Scale ( V A S). I ma ges of pa ges fr o m a sa m ple E Q -5 D 
q uesti o n naire, i ncl u di n g t he V A S , are n o w pr o vi de d t o re place t he E Q-5 D 
q uesti o n naire te xt, t o better re prese nt t he a p peara nce of t he E Q - 5 D q uesti o n naire 
t hat will be use d i n t his st u d y.

T o c o m ple me nt the i ma ges of a n E Q - 5 D sa m ple q uesti o n naire i n A P P E N DI X B, 
i ma ges of pa ges fr o m a sa m ple S F - 3 6 q uesti o n naire are n o w pr o vi de d t o re place 
t he S F-3 6 q uesti o n naire te xt i n A P P E N DI X A, t o better re prese nt t he a p peara nce 
of t he S F -3 6 q uesti o n naire t hat will be u se d i n t his st u d y.

T he ter m V A S has bee n a d de d t o t he List of A b bre viati o ns a n d Secti o n 1 0. 6. 2. 4 
si nce it has n o w bee n i ncl u de d i n t he E Q-5 D q uesti o n naire use d i n t his st u d y .

Refere nces t o h yperte xt li n ks f or e xa m ples of t he S F -3 6 a n d E Q - 5 D q uesti o n naires 
i n Secti o ns 1 0. 6. 2. 3 a n d 1 0. 6. 2. 4, res pecti vely as well as i n t he R efere nce Secti o n
ha ve bee n delete d, si nce i ma ges of pa ges f or t hese q uesti o n naires are pr o vi de d as 
e xa m ples i n A P P E N DIX A a n d B .

T y p o gra p hic err ors were c orrecte d a n d ot her mi n or m o dificati o ns were ma de 
t hr o u g h o ut f or clarificati o n.
A m e n de d te xt h as bee n i ncl u de d i n b ol d it alics a n d delete d te xt i n stri ket hr o u g h i n 
t he f oll o wi n g secti o ns:
C o ver p a ge
C o -or di n ati n g a ut h or

, Scie ntific W riter, X P E P har ma 
& Scie nce, C o ntract or f or G S K Bi ol o gicals
C o ntri b uti n g a ut h ors

, Cli nic al Rese arc h a n d 
Devel o p me nt Le a d

, Pr oject St atistici a n

, Pr oject Oversi g ht Data Ma na ger , 
Ke y r us Bi o p har ma, C o ntract or f or G S K 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
P P D
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 0 3
1 6- N O V- 2 0 1 6
P P D
P P D
P P D
P P D

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 0 4
Bi ol o gicals
LI S T O F A B B R E VI A TI O N S
V A S:
Vis u al A n al o g ue Sc ale
Secti o n 1. 2. 2.     R ati o n ale f or t he st u d y desi g n
T he st u d y  will esti mate a n y c ha n ges i n Q o L or Q A L Y l oss wit hi n t he sa me s u bject s
bet wee n bef ore a n d after H Z/s u vacci nati o n, a n d t heref ore a place b o c o ntr ol will n ot be 
i ncl u de d.
Sec ti o n 5. 3. 1. 1.     Q uesti o n n aires a n d Di ar y c ar ds
W he n t he c o m plete d q uesti o n naires a n d diar y car ds are ret ur ne d t o t he st u d y staff, t he 
st u d y staff will re vie w it t o get her wit h t he s u bject a n d as k hi m/ her t he s u bject (at t he ti me 
of ret ur n or at s u bse q ue nt c o ntact) if he/s he recei ve d a n y assista nce i n c o m pleti n g 
q uesti o n naires or diar y  car ds. If t he s u bject ha d assista nce c o m pleti n g t he q uesti o n naires
a n d/ or diar y car d (e. g., b y a care gi ver), it s h o ul d be n ote d i n t he e C R F. I n caseW he n 
q uesti o n naires or pre -v acci n ati o n di ary c ar ds are c o m plete d at t he st u d y site, st u d y staff 
ca n assist i n rea di n g t he q uesti o ns ( ver bati m).
Als o, w he n t he c o m plete d di ary c ar ds are ret ur ne d t o t he st u dy st aff t he st u dy st aff will 
revie w it t o get her wit h t he s u bject.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 0 4
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 0 5
Secti o n 5. 4 .    O utli ne of st u d y pr oce d ures
T a ble 5
List of st u d y pr oce d ures
E p o c h
Pri m ar y
T y p e of c o nt a ct
Vi sit 1
Vi sit 2
Vi sit 3
Vi sit 4
Vi sit 5
M 3 C o nt a ct
M 8 C o nt a ct
M 1 4 C o nt a ct
Ti m e p oi nt( s)
D a y -7 M o nt h 0
D a y 7 1
M o nt h 2
D a y 6 7 1
M o nt h 3 2
M o nt h 8
M o nt h 1 4
P hysic al ex a mi n ati o n i ncl u di n g h ei g ht a n d w ei g ht (s e e S ecti o n 5. 5. 1. 5 )
●
O
I n v e sti g at or S s i g n off f or t h e a n alysis
●
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 0 5
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 0 6
Secti o n 5. 5. 1. 5.     P h ysic al e x a mi n ati o n a n d assess me nt of fr ailt y st at us
Perf or m a p h y sical e xa mi nati o n of t he s u bject at Visit 1 i ncl u di n g wei g ht a n d hei g ht 
( b o d y mass i n de x [ B MI] will be calc ulate d). T he p h ysical e xa mi nati o n ca n be perf or me d 
per t he site’s me dical j u d g me nt a n d sta n dar d of care (refer t o t he S P M f or details of t he 
p h y sical e xa mi nati o n). C ollecte d i nf or mati o n nee ds t o be rec or de d i n t he e C R F.
Treat me nt of a n y a b n or malit y o bs er ve d d uri n g p h ysical e xa mi nati o n has t o be perf or me d 
acc or di n g t o l ocal me dical practice o utsi de t his st u d y  or by referral t o a n a p pr o priate 
healt h care pr o vi der.
A n assess me nt of frailt y  stat us defi ne d t hr o u g h a Frailt y I n de x ( FI) descri be d as 
acc u m ulati o n of deficits , i ncl u di n g b ut n ot li mite d t o a series of certifie d tests will be 
d o ne at Visit 1 a n d data rec or de d i n t he e C R F (see Secti o n 1 0. 6. 2. 2 , a n d refer t o t he 
S P M f or det ails o n t he assess me nt of fr ailty st at us ).
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 0 6
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R -0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 0 7
Secti o n 8. 3. 1 .    Ti me peri o d f or detecti n g a n d rec or di n g a d verse e ve nts, seri o us a d verse e ve nts a n d 
pre g n a ncies
T a ble 1 2
Re p orti n g peri o ds f or c ollecti n g s afet y i nf or m ati o n
Ti m e p oi nt
Vi sit 1
D a y - 7
Vi sit 2
M o nt h 0
Vi sit 3
D a y 7
M o nt h 1
Vi sit 4
M o nt h 2
Vi sit 5
D a y 6 7
C o nt a ct
M o nt h 3
C o nt a ct
M o nt h 8
C o nt a ct
M o nt h 1 4
Ti mi n g of r e p orti n g / St u d y a cti vit y
D ay -7
D ay 0
D ay 6
D ay 2 9
D ay 6 0
D ay 6
D ay 2 9
S af ety
St u dy
Pr e -V acc .
D o s e 1
p ost -D os e 1
p ost -D os e 1
D o s e 2
p ost -D os e 2
p ost -D os e 2
F oll o w -U p
C o ncl usi o n
S olicit e d g e n er al A Es ( s e e S e cti o n s 
5. 3. 1. 1 a n d 5. 5. 1. 8)
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 0 7
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R-0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 0 8
Secti o n 1 0. 2 .    Sec o n d ar y e n d p oi nts

C ha n ge i n mea n S F - 3 6 P F scale sc ore s.
Secti o n 1 0. 6. 2. 3     S F -3 6 he alt h s ur ve y
T he S F -3 6 ® is a m ulti -p ur p ose healt h s ur ve y  wit h 3 6 q uesti o ns (refer t o A P P E N DI X A
or t he we bsite a d dress htt p:// w w w.sf-3 6. or g/ de m os/ S F - 3 6. ht ml f or a sa m ple of t he 
q uesti o n naire) [Ware , 2 0 0 1; S F -3 6. or g , 2 0 1 4; S F -3 6 sa m ple , 2 0 1 4] t hat will be use d t o 
e val uate P F usi n g q uesti o ns 3a t hr o u g h 3j .
Secti o n 1 0. 6. 2. 4 .     E Q-5 D q uesti o n n aire
T he E Q -5 D q uesti o n naire is a ge neric meas ure of healt h stat us t hat pr o vi des a si m ple 
descri pti ve pr ofile a n d a si n gle i n de x val ue (refer t o A P P E N DI X B or t he we bsite a d dress 
htt p:// w w w.e ur o q ol. or g/filea d mi n/ user _ u pl oa d/ D oc u me nte n/ P D F/ Pr o d ucts/ Sa m ple _ U K _
_ E n glis h _f or a sa m ple of t he q uesti o n naire [ Ki n d, 1 9 9 6; E Q - 5 D, 2 0 1 4; E Q -5 D sa m ple , 
2 0 1 4 ]. T he E Q-5 D defi nes healt h i n ter ms of m o bilit y , self-care, us ual acti vities, 
pai n/ disc o mf ort a n d a n xiet y / de pressi o n. T he 5 ite ms are c o m bi ne d t o ge nerate healt h
pr ofiles, i.e., a res p o n de nt w h o res p o n ds 1 ( n o pr o ble m\ n o sy m pt o m) t o all 5 ite ms has a 
pr ofile “ 1 1 1 1 1” a n d si milarl y  a s u bject w h o res p o n ds wit h t he hi g hest le vel of diffic ult y 
or s y m pt o m t o all ite ms has a pr ofile “ 3 3 3 3 3”. T hese pr ofiles are s u bse q ue ntl y  c o n verted 
t o a c o nti n u o us si n gle i n de x utilit y sc ore usi n g a o ne t o o ne matc hi n g, e. g., 
“ 1 1 1 1 1” = 1. 0 0, “ 2 2 2 2 2” = 0. 5 2 a n d “ 3 3 3 3 3” = - 0. 5 9, usi n g val ue sets (i.e., matc hi n g 
pr ofiles t o si n gle i n de x utilit y  sc ores usi n g c o u ntr y s pecific val ue sets). A f ull list of val ue
sets is a vaila ble o n t he desi g ner’s we bsite [E Q - 5 D, 2 0 1 4]. N ote, hi g her sc ores re prese nt a 
better Q o L , a n d refer t o Secti o n 1 0. 5 f or h o w t he c alc ul ati o n of t he Q A L Y will be b ase d 
o n t he E Q -5 D q uesti o n n aire . T he E Q - 5 D als o i ncl u des a Vis u al A n al o g ue Sc ale ( V A S) 
r a n gi n g fr o m 0 t o 1 0 0, wit h 1 0 0 re prese nti n g t he best i m a gi n a ble he alt h st ate a n d 0 
re prese nti n g t he w orst i m a gi n a ble he alt h st ate. F urt her det ails will be pr ovi de d i n t he 
S A P .
T he E Q -5 D q uesti o n naires will be c o m plete d b y all s u bjects at eac h st u d y visits (i.e., 
Visit 1 Da y  -7, Visit 2 M o nt h 0 ( bef ore t he vacci nati o n), Visit 3 Da y  7, Visit 4 M o nt h 2 
( bef ore t he vacci nati o n) a n d Visit 5 Da y 6 7). A d diti o nall y, after eac h vacci nati o n, t he 
s u bjects will be gi ve n t he E Q - 5 D q uesti o n naires t o ta ke h o me a n d as ke d t o c o m plete t he 
e ntire E Q-5 D q uesti o n naire s o n a dail y basis o n Da ys 1 t o 6.
R E F E R E N C E S
E M A G ui deli ne o n t he e x p os ure t o me dici nal pr o d ucts d uri n g pre g na nc y : nee d f or p ost-
a ut h orizati o n data ( D oc. Ref. E M E A/ C H M P/ 3 1 3 6 6 6/ 2 0 0 5 ) ‘a d o pte d at C o m m u nit y  le vel 
i n Ma y 2 0 0 6);
htt p:// w w w.e m a.e ur o p a.e u/ d ocs/e n _ G B/ d oc u me nt _li br ary/ Re g ul at ory _ a n d _ pr oce d ur al _ g
ui deli ne/ 2 0 0 9/ 1 1/ W C 5 0 0 0 1 1 3 0 3. p df . Accesse d 2 4 Oct o ber 2 0 1 6.
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 0 8
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R-0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 0 9
E Q - 5 D. htt p:// w w w.e ur o q ol. or g/. Accesse d 9 Oct o ber 2 0 1 4.
E Q -5 D sa m ple: 
htt p:// w w w.e ur o q ol. or g/filea d mi n/ user _ u pl oa d/ D oc u me nte n/ P D F/ Pr o d ucts/ Sa m ple _ U K _
_ E n glis h _ _ E Q - 5 D-3 L _ Pa per _ Self _c o m plete _ v 1. 0 _ _I D _ 2 3 9 6 3 _. p df Accesse d 9 Oct o ber 
2 0 1 4.
S F -3 6. or g. A c o m m u nit y f or meas uri n g healt h o utc o mes usi n g S F -t o ols. http:// w w w.sf-
3 6. or g/t o ols/sf 3 6.s ht ml Accesse d 9 Oct o ber 2 0 1 4.
S F -3 6 sa m ple: htt p:// w w w.sf -3 6. or g/ de m os/ S F - 3 6. ht ml. Accesse d 9 Oct o ber 2 0 1 4.
A P P E N DI X A     S F -3 6 ( Versi o n 2. 0 S A M P L E)
S F - 3 6 v 2 ™ Healt h S ur ve y Sc ori n g De m o nstrati o n
T his s ur ve y  as ks f or yo ur vie ws a b o ut y o ur healt h. T his i nf or mati o n will hel p y o u kee p 
trac k of h o w y o u feel a n d h o w well y o u are a ble t o d o y o ur us ual acti vities.
A ns wer e ver y  q uesti o n b y selecti n g t he a ns wer as i n dicate d. If yo u are u ns ure a b o ut h o w 
t o a ns wer a q uesti o n, please gi ve t he best a ns wer y o u ca n. 
1.
I n ge neral, w o ul d y o u sa y y o ur healt h is:
E xcelle nt
Ver y  g o o d
G o o d
Fair
P o or
2.
C o m pare d t o o ne wee k a g o, h o w w o ul d y o u rate y o ur healt h i n ge neral n o w? 
M uc h better
n o w t ha n o ne
wee k a g o
S o me w hat better
n o w t ha n o ne
wee k a g o
A b o ut t he
sa me as o ne
wee k a g o
S o me w hat w orse
n o w t ha n o ne
wee k a g o
M uc h w orse
n o w t ha n o ne
wee k a g o
3.
T he f oll o wi n g q uesti o ns are a b o ut acti vities y o u mi g ht d o d uri n g a t y pical da y. D oes 
y o ur healt h n o w li mit y o u i n t hese acti vities? If s o, h o w m uc h?
Yes,
Yes,
N o, n ot 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 0 9
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R-0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 1 0
li mite d
a l ot
li mite d
a little
li mite d
at all
a
Vi g or o us acti vities, s uc h as r u n ni n g, lifti n g hea v y  o bjects, 
partici pati n g i n stre n u o us s p orts
b
M o derate acti vities, s uc h as m o vi n g a ta ble, p us hi n g a 
vac u u m clea ner, b o wli n g, or pla y i n g g olf
c
Lifti n g or carr y i n g gr oceries
d
Cli m bi n g se veral fli g hts of stairs
e
Cli m bi n g o ne fli g ht of stairs
f
Be n di n g, k neeli n g, or st o o pi n g
g
Wal ki n g m ore t ha n a mile
h
Wal ki n g se veral h u n dre d yar ds
i
Wal ki n g o ne h u n dre d ya r ds
j
Bat hi n g or dressi n g y o urself
4.
D uri n g t he past wee k, h o w m uc h of t he ti me ha ve y o u ha d a n y of t he f oll o wi n g 
pr o ble ms wit h y o ur w or k or ot her re g ular dail y acti vities as a res ult of y o ur p h y sical 
healt h?
All
of t he 
ti me
M ost
of t he 
ti me
S o me
of t he 
ti me
A little
of t he 
ti me
N o ne
of t he 
ti me
a
C ut d o w n o n t he a m o u nt of ti me y o u 
s pe nt o n w or k or ot her acti vities
b
Acc o m plis he d less t ha n y o u w o ul d li ke
c
Were li mite d i n t he
ki n d of w or k or 
ot her acti vities
d
Ha d diffic ult y perf or mi n g t he w or k or 
ot her acti vities (f or e xa m ple, it t o o k 
e xtra eff ort)
5.
D uri n g t he past wee k, h o w m uc h of t he ti me ha ve y o u ha d a n y of t he f oll o wi n g 
pr o ble ms wit h y o ur w or k or ot her re g ular dail y acti vities as a res ult of a n y e m oti o nal 
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 1 0
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R-0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 1 1
pr o ble ms (s uc h as feeli n g de presse d or a n xi o us)?
All
of t he 
ti me
M ost
of t he 
ti me
S o me
of t he 
ti me
A little
of t he 
ti me
N o ne
of t he 
ti me
a
C ut d o w n o n t he a m o u nt of ti me y o u 
s pe nt o n w or k or ot her acti vities
b
Acc o m plis he d less t ha n y o u w o ul d li ke
c
Di d w or k or acti vities less caref ull y  
t ha n us ual
6.
D uri n g t he past wee k, t o w hat e xte nt has yo ur p h ysical healt h or e m oti o nal pr o ble ms 
i nterfere d wit h yo ur n or mal s ocial acti vities wit h fa mil y , frie n ds, nei g h b ors, or 
gr o u ps?
N ot at all
Sli g htl y
M o deratel y
Q uite a bit
E xtre mel y
7.
H o w m uc h b o dil y  pai n ha ve yo u ha d d uri n g t he past wee k?
N o ne
Ver y  mil d
Mil d
M o derate
Se vere
Ver y  se vere
8.
D uri n g t he past wee k, h o w m uc h di d pai n i nterfere wit h y o ur n or mal w or k 
(i ncl u di n g b ot h w or k o utsi de t he h o me a n d h o use w or k)?
N ot at all
A little bit
M o deratel y
Q uite a bit
E xtre mel y
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 1 1
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R-0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 1 2
9.
T hese q uesti o ns are a b o ut h o w y o u feel a n d h o w t hi n gs ha ve bee n wit h y o u d uri n g 
t he past wee k. F or eac h q uesti o n, please gi ve t he o ne a ns wer t hat c o mes cl osest t o 
t he wa y yo u ha ve bee n feeli n g.
H o w m uc h of t he ti me d uri n g t he past wee k...
All
of t he 
ti me
M ost
of t he 
ti me
S o me
of t he 
ti me
A little
of t he 
ti me
N o ne
of t he 
ti me
a
Di d y o u feel f ull of life?
b
Ha ve y o u bee n ver y  ner v o us?
c
Ha ve y o u felt s o d o w n i n t he d u m ps t hat 
n ot hi n g c o ul d c heer y o u u p?
d
Ha ve y o u felt cal m a n d peacef ul?
e
Di d y o u ha ve a l ot of e ner g y ?
f
Ha ve y o u felt d o w n hearte d a n d 
de presse d?
g
Di d y o u feel w or n o ut?
h
Ha ve y o u bee n ha p p y?
i
Di d y o u feel tire d?
1 0. D uri n g t he past wee k, h o w m uc h of t he ti me has y o ur p h ysical healt h or e m oti o nal 
pr o ble ms i nterfere d wit h y o ur s ocial acti vities (li ke visiti n g frie n ds, relati ves, etc.)?
All
of t he ti me
M ost
of t he ti me
S o me
of t he ti me
A little
of t he ti me
N o ne
of t he ti me
1 1. H o w T R U E or F A L S E is eac h of t he f oll o wi n g state me nts f or y o u?
Defi nitel y
tr ue
M ostl y
tr ue
D o n't
k n o w
M ostl y
false
Defi nitel y
false
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 1 2
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R-0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 1 3
A
I see m t o get sic k a little easier t ha n 
ot her pe o ple
B
I a m as healt h y as a n yb o d y  I k n o w
C
I e x pect m y healt h t o get w orse
D
M y  healt h is e xcelle nt
T ha n k y o u f or c o m pleti n g t hese q uesti o ns!
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 1 3
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R-0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 1 4
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 1 4
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R-0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 1 5
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 1 5
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R-0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 1 6
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 1 6
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R-0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 1 7
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 1 7
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R-0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 1 8
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 1 8
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R-0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 1 9
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 1 9
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R-0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 2 0
A P P E N DI X B      E Q -5 D ( E n glis h Versi o n U S S A M P L E)
B y  placi n g a c hec k mar k i n o ne b o x i n eac h gr o u p bel o w, please i n dicate w hic h 
state me nts best descri be y o ur o w n healt h state t o da y .
M o bilit y
I ha ve n o pr o ble ms i n wal ki n g a b o ut 
I ha ve s o me pr o ble ms i n wal ki n g a b o ut 
I a m c o nfi ne d t o be d 
Self -C are
I ha ve n o pr o ble ms wit h self-care 
I ha ve s o me pr o ble ms was hi n g or dressi n g mys elf 
I a m u na ble t o was h or dress m y self 
Us u al Acti vities (e. g., w ork, st u dy, h o use w ork, f a mily or leis ure activities)
I ha ve n o pr o ble ms wit h perf or mi n g my us ual acti vities 
I ha ve s o me pr o ble ms wit h perf or mi n g m y us ual acti vities 
I a m u na ble t o perf or m m y us ual acti vities 
P ai n/ Disc o mf ort
I ha ve n o pai n or disc o mf ort 
I ha ve m o derate pai n or disc o mf ort 
I ha ve e xtre me pai n or disc o mf ort 
A n xiet y/ De pressi o n
I a m n ot a n xi o us or de presse d 
I a m m o deratel y a n xi o us or de presse d 
I a m e xtre mel y a n xi o us or de presse d 
© 1 9 9 0 E ur o Q ol Gr o u p. E Q -5 D ™ is a tr a de m ark of t he E ur o Q ol Gr o u p
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 2 0
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R-0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 2 1
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 2 1
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R-0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 2 2
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 2 2
1 6- N O V- 2 0 1 6

C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R-0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
1 6 -N O V -2 0 1 6
1 2 3
 
C O N FI D E N TI A L
2 0 4 9 2 8 ( Z O S T E R- 0 6 3)
Pr ot o c ol A m e n d m e nt 2 Fi n al
6 7 d 8 3 9 1f a ef 6 4 e 9 d 0 5f d 1 c 8f 3 a 9 b 9 3 8 7 3 2f d d 1 8 a
1 2 3
1 6- N O V- 2 0 1 6

P P D