A Phase 1b/2a, Open-Label Study to Evaluate the Safety, Tolerability and Immunogenicity of VTP-300 With or Without Nivolumab in Participants With Chronic Hepatitis B Infection
Phase: PHASE1
Conditions: Hepatitis B
Sponsor: Barinthus Biotherapeutics

C over p a ge c o nt ai ni n g N C T N u m ber  f or t he p ur p os e of Cli ni c al Tri als. g ov 
C LI NI C A L S T U D Y P R O T O C O L  
 
A P h ase 1 b / 2 a, O p e n-L a b el St u d y t o E v al u at e t h e S af et y, 
T oler a bilit y a n d I m m u n o g e nicit y of V T P -3 0 0  Wit h o r 
W it h o ut Ni v ol u m a b  i n P a rtici p a nts wit h C h r o nic 
He p atitis B Inf ecti o n  
St u d y C o d e: H B V 0 0 2  
 
E U D R A C T N u m b er: 2 0 2 0 -0 0 0 1 9 0 -2 5  
N C T N u m b er: N C T 0 4 7 7 8 9 0 4  
 
V e rsi o n: 6. 0  
0 9 D e c e m be r  2 0 2 1  
 
 

 
 
 
  
 
C LI NI C A L S T U D Y P R O T O C O L  
 
A P h ase 1 b / 2 a, O pe n- L a bel St u d y t o E v al u ate t he S afet y, 
T oler a bilit y a n d I m m u n o ge nicit y of V T P- 3 0 0 W it h or 
Wit h o ut Ni v ol u m a b i n P artici p a nts wit h C hr o nic 
He p atitis B I nfecti o n 
St u d y C o de: H B V 0 0 2  
E U D R A C T N u m ber: 2 0 2 0- 0 0 0 1 9 0- 2 5 
 
Versi o n: 6 . 0 
0 9 Dece m ber  2 0 2 1 
 
 
 
S p o ns or's A ut h orise d Re prese nt ati ve:    
 
 
  
  
  
  
  
  
 
 
 
 
Si g nat ure   
  
  
  
  
  
 
Date  
 
 
Pri nte d Na me  
 
 
I nf or mati o n i n t his pr ot oc ol is c o nfi de ntial a n d s h o ul d n ot be discl ose d, ot her t ha n t o t h ose 
directl y i n v ol ve d i n t he e xec uti o n or t he et hical/re g ulat or y re vie w of t he st u d y, wit h o ut writte n 
a ut h orisati o n fr o m Vaccitec h Lt d   
 
 
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 3 of 1 0 9  
I N V E S TI G A T O R A G R E E M E N T 
I, t he u n dersi g ne d, a gree t o c o n d uct t his st u d y i n acc or da nce wit h t his pr ot oc ol, I nter nati o nal 
C o u ncil o n Har m o nisati o n G o o d Cli nical Practice (I C H G C P), t he et hical pri nci ples set f ort h 
i n t he Declarati o n of Helsi n ki, a n d wit h l ocal re g ulat or y re q uire me nts.   
 
Si g nat ure & Date ( D D -M M -Y Y Y Y)  
 
 
Pri nte d Na me  
 
 
 
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 4 of 1 0 9  
T A B L E O F C O N T E N T S  
A D MI NI S T R A TI V E A N D C O N T A C T I N F O R M A TI O N  ............................................................................. 2 
I N V E S TI G A T O R A G R E E M E N T .................................................................................................................. 3 
T A B L E O F C O N T E N T S  ................................................................................................................................ 4 
LI S T O F T A B L E S  ........................................................................................................................................... 8 
LI S T O F FI G U R E S  ......................................................................................................................................... 8 
P R O T O C O L A M E N D M E N T C H A N G E HI S T O R Y ...................................................................................... 9 
P R O T O C O L S Y N O P SI S  .............................................................................................................................. 1 5  
A B B R E VI A TI O N S A N D D E FI NI TI O N S O F T E R M S  ............................................................................... 2 1  
List of A b bre viati o ns  .......................................................................................................................... 2 1  
1  
B A C K G R O U N D  ................................................................................................................................ 2 3  
1. 1  
Disease Re vie w  ....................................................................................................................... 2 3  
1. 2  
Treat me nt Re vie w  ................................................................................................................... 2 3  
1. 3  
S u m mar y of N o n -cli nical St u dies ........................................................................................... 2 4  
1. 4  
S u m mar y of Cli nical E x perie nce  ............................................................................................ 2 5  
1. 5  
St u d y Rati o nale  ....................................................................................................................... 2 6  
2  
S T U D Y O BJ E C TI V E S A N D E N D P OI N T S  ..................................................................................... 2 8  
3  
S T U D Y O V E R VI E W  ........................................................................................................................ 3 0  
3. 1  
O verall St u d y Desi g n a n d Met h o d ol o g y  ................................................................................. 3 0  
3. 1. 1  St u d y O ver vie w  ........................................................................................................... 3 0  
3. 1. 2  D urati o n of St u d y ......................................................................................................... 3 1  
3. 1. 2. 1  
D urati o n f or eac h Partici pa nt  ...................................................................... 3 1  
3. 1. 2. 2  
D urati o n of W h ole St u d y  ............................................................................ 3 1  
3. 1. 3  St o p pi n g Criteria/ H ol di n g Criteria ............................................................................... 3 1  
3. 1. 4  I n di vi d ual St o p pi n g R ules ( All Vacci nate d St u d y Partici pa nts) .................................. 3 2  
3. 2  
Disc ussi o n of St u d y Desi g n, I ncl u di n g t he C h oice of C o ntr ol Gr o u ps  ................................... 3 3  
3. 3  
Be nefit Ris k Assess me nt  ......................................................................................................... 3 4  
4  
S T U D Y P O P U L A TI O N  ..................................................................................................................... 3 5  
4. 1  
N u m ber of Partici pa nts  ........................................................................................................... 3 5  
4. 2  
I ncl usi o n Criteria ..................................................................................................................... 3 5  
4. 3  
E xcl usi o n Criteria  ................................................................................................................... 3 6  
4. 3. 1  Re m o val of Partici pa nts fr o m T hera p y or Assess me nt  ................................................ 3 7  
4. 3. 1. 1  
C o ntrai n dicati o ns t o Vacci nati o n  ................................................................ 3 7  
4. 3. 1. 2  
St u d y Disc o nti n uati o n  ................................................................................. 3 7  
4. 3. 2  St u d y Ter mi nati o n  ....................................................................................................... 3 8  
5  
I n vesti gati o nal Me dici nal Pr o d ucts .................................................................................................... 3 9  
5. 1  
I de ntit y of I n vesti gati o nal Me dici nal Pr o d ucts ....................................................................... 3 9  
5. 1. 1  St u d y Vacci nes  ............................................................................................................ 3 9  
5. 1. 2  Ni v ol u ma b  ................................................................................................................... 3 9  
5. 2  
I n vesti gati o nal Pr o d ucts A d mi nistere d ................................................................................... 4 0  
5. 2. 1  St u d y Vacci nes  ............................................................................................................ 4 0  
5. 2. 2  Ni v ol u ma b  ................................................................................................................... 4 0  
5. 3  
La belli n g, Pac ka gi n g a n d S hi p pi n g  ......................................................................................... 4 0  
5. 4  
St ora ge  .................................................................................................................................... 4 1  
5. 5  
Acc o u nta bilit y  ......................................................................................................................... 4 1  
5. 6  
Destr ucti o n or Dis p osal  ........................................................................................................... 4 1  
5. 7  
Met h o d of Assi g ni n g Partici pa nts t o Treat me nt Gr o u ps  ......................................................... 4 1  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 5 of 1 0 9  
5. 8  
Selecti o n of D oses, D osi n g Sc he d ule a n d A d mi nistrati o n  ...................................................... 4 2  
5. 8. 1  Selecti o n of D oses i n t he St u d y  ................................................................................... 4 2  
5. 8. 2  Selecti o n a n d Ti mi n g of D ose f or eac h Partici pa nt  ...................................................... 4 2  
5. 8. 2. 1  
D osi n g Sc he d ule  ......................................................................................... 4 2  
5. 8. 2. 2  
St u d y Vacci ne Pre parati o n a n d A d mi nistrati o n  .......................................... 4 2  
5. 8. 2. 3  
Ni v ol u ma b Pre parati o n a n d A d mi nistrati o n  ............................................... 4 3  
5. 8. 2. 4  
D ose a n d Sc he d ule M o dificati o ns  ............................................................... 4 3  
5. 9  
Bli n di n g  ................................................................................................................................... 4 3  
5. 1 0  Pri or a n d C o nc o mita nt Vacci nes a n d Me dicati o ns  ................................................................. 4 3  
5. 1 1  Treat me nt C o m plia nce  ............................................................................................................ 4 4  
5. 1 2  P ost- st u d y Treat me nt .............................................................................................................. 4 4  
6  
S T U D Y P R O C E D U R E S A T E A C H VI SI T/ S C H E D U L E O F A S S E S S M E N T S  .............................. 4 5  
6. 1  
Scree ni n g a n d Baseli ne Assess me nts  ...................................................................................... 4 5  
6. 2  
Treat me nt Da y Assess me nts ( Da y 0, Da y 2 8 a n d M o nt h  3 [ M V A -H B V B o ost ( U K 
partici pa nts o nl y)])  ....................................................................................................... 4 7  
6. 3  
F oll o w -u p Peri o d Assess me nts  ............................................................................................... 4 8  
6. 3. 1  Tele p h o ne Calls: Da y 1, Da y 2 9 a n d M o nt h  3 + 1 Da y ( M V A -H B V B o ost [ U K 
partici pa nts o nl y])  ........................................................................................................ 4 8  
6. 3. 2  Cli nic Visits: Da y  7, Da y 3 5 a n d M o nt h  3 + 7 Da ys ( M V A -H B V B o ost [ U K 
partici pa nts o nl y])  ........................................................................................................ 4 8  
6. 3. 3  Cli nic Visit: M o nt hs  3 a n d 6  ........................................................................................ 4 8  
6. 3. 4  Cli nic Visit: M o nt h  9 ( E n d of St u d y Visit)  .................................................................. 4 8  
6. 4  
Assess me nts at U nsc he d ule d Visits  ........................................................................................ 4 8  
6. 5  
Partici pa nt Disc o nti n uati o n  ..................................................................................................... 4 9  
7  
D E T AI L O F S T U D Y A S S E S S M E N T S  ............................................................................................ 5 0  
7. 1  
De m o gra p hic a n d Baseli ne Assess me nts  ................................................................................ 5 0  
7. 1. 1  De m o gra p hic Data a n d Baseli ne Varia bles .................................................................. 5 0  
7. 1. 2  Me dical a n d Disease Hist or y  ....................................................................................... 5 0  
7. 1. 3  Pri or Me dicati o ns a n d T hera pies  ................................................................................. 5 0  
7. 1. 4  La b orat or y Eli gi bilit y/ Safet y Tests  .............................................................................. 5 0  
7. 1. 4. 1  
Hae mat ol o g y  ............................................................................................... 5 0  
7. 1. 4. 2  
Bi oc he mistr y  ............................................................................................... 5 1  
7. 1. 4. 3  
H u ma n I m m u n o deficie nc y Vir us, He patitis B Vir us, He patitis C Vir us 
a n d He patitis D Vir us Dia g n ostic Testi n g  ............................................. 5 1  
7. 1. 4. 4  
Uri nal ysis  .................................................................................................... 5 1  
7. 1. 5  Uri ne Pre g na nc y Test  ................................................................................................... 5 1  
7. 2  
I m m u n o ge nicit y Assess me nts ................................................................................................. 5 1  
7. 2. 1  E x pl orat or y A nal ysis  ................................................................................................... 5 1  
7. 3  
Efficac y Assess me nts  .............................................................................................................. 5 2  
7. 4  
Safet y Assess me nts  ................................................................................................................. 5 2  
7. 4. 1  A d verse E ve nts  ............................................................................................................ 5 2  
7. 4. 1. 1  
S olicite d A d verse E ve nts  ............................................................................ 5 2  
7. 4. 1. 2  
U ns olicite d A d verse E ve nts  ........................................................................ 5 2  
7. 4. 2  La b orat or y Safet y Tests  ............................................................................................... 5 2  
7. 4. 3  Vital Si g ns  ................................................................................................................... 5 3  
7. 4. 4  P h ysical E xa mi nati o n  .................................................................................................. 5 3  
8  
S A F E T Y M A N A G E M E N T  ............................................................................................................... 5 4  
8. 1  
Res p o nsi bilities f or E ns uri n g t he Safet y of St u d y Partici pa nts  ............................................... 5 4  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 6 of 1 0 9  
8. 1. 1  I n vesti gat or .................................................................................................................. 5 4  
8. 1. 2  St u d y S p o ns or  .............................................................................................................. 5 4  
8. 1. 3  L ocal Me dical M o nit or  ................................................................................................ 5 4  
8. 1. 4  Safet y M o nit ori n g C o m mittee  ..................................................................................... 5 4  
8. 1. 5  Data M o nit ori n g C o m mittee  ........................................................................................ 5 5  
8. 1. 6  I nstit uti o nal Re vie w B oar ds a n d Et hics C o m mittees ................................................... 5 5  
8. 1. 7  Nati o nal Re g ulat or y A ut h orit y  .................................................................................... 5 5  
8. 2  
A d verse E ve nts  ....................................................................................................................... 5 5  
8. 2. 1  Defi niti o ns  ................................................................................................................... 5 5  
8. 2. 1. 1  
A d verse E ve nt  ............................................................................................. 5 5  
8. 2. 1. 2  
A d verse Reacti o n  ........................................................................................ 5 6  
8. 2. 1. 3  
Seri o us A d verse E ve nt  ................................................................................ 5 6  
8. 2. 1. 4  
S us pecte d U ne x pecte d Seri o us A d verse Reacti o n  ...................................... 5 7  
8. 2. 2  St u d y Re p orti n g Peri o d f or A d verse E ve nts  ................................................................ 5 7  
8. 2. 3  Re p orti n g E xe m pti o ns  ................................................................................................. 5 7  
8. 2. 4  Rec or di n g a n d Assess me nt of A d verse E ve nts b y t he I n vesti gat or  ............................. 5 7  
8. 2. 4. 1  
Assess me nt of Se verit y  ............................................................................... 5 8  
8. 2. 4. 2  
Assess me nt of Relati o ns hi p  ........................................................................ 5 8  
8. 2. 4. 3  
Acti o n Ta ke n wit h St u d y Vacci ne  .............................................................. 5 9  
8. 2. 4. 4  
Assess me nt of O utc o me  .............................................................................. 5 9  
8. 2. 5  Re p orti n g Re q uire me nts a n d Pr oce d ures f or S A Es  ..................................................... 5 9  
8. 2. 5. 1  
F oll o w -u p I nf or mati o n o n a n S A E  .............................................................. 6 0  
8. 2. 5. 2  
Re q uire d F oll o w -u p f or S A Es  ..................................................................... 6 0  
8. 2. 5. 3  
Me dical Re vie w a n d Re p orti n g b y t he S p o ns or  .......................................... 6 0  
8. 2. 5. 4  
S p o ns or Res p o nsi bilit y f or E x pe dite d Safet y Re p orts  ................................ 6 1  
8. 2. 6  F oll o w -u p of Partici pa nts after A d verse  E ve nts  .......................................................... 6 1  
8. 2. 6. 1  
I n vesti gat or F oll o w-u p  ................................................................................ 6 1  
8. 2. 7  P ost- St u d y A d verse E ve nts  .......................................................................................... 6 2  
8. 3  
E ve nts of S pecial I nterest  ........................................................................................................ 6 2  
8. 4  
Ot her E ve nts Re q uiri n g I m me diate Re p orti n g  ........................................................................ 6 2  
8. 5  
O ver d ose or I nc orrect A d mi nistrati o n  ..................................................................................... 6 2  
8. 6  
Ma na ge me nt of Pre g na nc y  ...................................................................................................... 6 3  
8. 6. 1  N otificati o n a n d F oll o w -u p  .......................................................................................... 6 3  
8. 6. 1. 1  
Pre g na ncies i n Fe male Partici pa nts  ............................................................. 6 3  
8. 6. 2  O utc o me  ....................................................................................................................... 6 3  
9  
D A T A Q U A LI T Y A S S U R A N C E A N D Q U A LI T Y C O N T R O L  ...................................................... 6 4  
9. 1  
Pr ot oc ol De viati o ns  ................................................................................................................. 6 4  
9. 2  
M o nit ori n g a n d S o urce D oc u me nt Verificati o n  ...................................................................... 6 4  
9. 3  
Data Ma na ge me nt a n d C o di n g  ................................................................................................ 6 4  
1 0  
S T A TI S TI C A L C O N SI D E R A TI O N S A N D A N A L Y SI S P L A N  ...................................................... 6 6  
1 0. 1  Sa m ple Size Deter mi nati o n  ..................................................................................................... 6 6  
1 0. 2  Statistical a n d A nal ytical Pla ns  ............................................................................................... 6 6  
1 0. 2. 1  A nal ysis Sets  ................................................................................................................ 6 6  
1 0. 2. 2  St u d y A nal yses  ............................................................................................................ 6 6  
1 0. 2. 2. 1  Ge neral Pri nci ples  ....................................................................................... 6 6  
1 0. 2. 2. 2  Dis p ositi o n  .................................................................................................. 6 6  
1 0. 2. 2. 3  Pr ot oc ol De viati o ns  ..................................................................................... 6 7  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 7 of 1 0 9  
1 0. 2. 2. 4  De m o gra p hics a n d Baseli ne Data  ............................................................... 6 7  
1 0. 2. 2. 5  I m m u n o ge nicit y A nal yses ........................................................................... 6 7  
1 0. 2. 2. 6  Safet y Data  .................................................................................................. 6 7  
1 0. 2. 2. 6. 1  
A d verse E ve nts  ..................................................................... 6 7  
1 0. 2. 2. 6. 2  
La b orat or y Safet y Tests  ........................................................ 6 8  
1 0. 2. 2. 6. 3  
Vital Si g ns  ............................................................................ 6 8  
1 0. 2. 2. 6. 4  
P h ysical E xa mi nati o n  ........................................................... 6 8  
1 0. 2. 3  I nteri m A nal yses .......................................................................................................... 6 8  
1 0. 2. 4  Ha n dli n g Missi n g, U n use d or S p uri o us Data  ............................................................... 6 8  
1 1  
S T U D Y D O C U M E N T A TI O N, I N S P E C TI O N S A N D R E C O R D K E E PI N G  ................................... 6 9  
1 1. 1  St u d y D oc u me ntati o n  .............................................................................................................. 6 9  
1 1. 2  A u dits a n d St u d y Ce ntre I ns pecti o ns  ...................................................................................... 6 9  
1 1. 3  Rete nti o n of Rec or ds  ............................................................................................................... 6 9  
1 2  
FI N A N C E A N D I N S U R A N C E  ......................................................................................................... 7 0  
1 3  
E T HI C A L A N D R E G U L A T O R Y C O N SI D E R A TI O N S  .................................................................. 7 1  
1 3. 1  L ocal Re g ulati o ns/ Declarati o n of Helsi n ki  ............................................................................. 7 1  
1 3. 2  Re g ulat or y A ut h orit y A p pr o val  .............................................................................................. 7 1  
1 3. 3  Et hics C o m mittee/I nstit uti o nal Re vie w B oar d A p pr o val  ........................................................ 7 1  
1 3. 4  I nf or me d C o nse nt .................................................................................................................... 7 1  
1 3. 5  Pr ot oc ol A me n d me nts  ............................................................................................................. 7 2  
1 3. 6  C o nfi de ntialit y of St u d y D oc u me nts a n d Partici pa nt Rec or ds  ................................................ 7 2  
1 4  
S T U D Y C O M P L E TI O N  .................................................................................................................... 7 4  
1 5  
P U B LI C A TI O N O F D A T A  ............................................................................................................... 7 5  
1 6  
R E F E R E N C E S  ................................................................................................................................... 7 6  
A P P E N DI C E S  ............................................................................................................................................... 7 9  
A p pe n di x  1 T o xicit y Ta ble f or Cli nical a n d La b orat or y A b n or malities .......................................... 7 9  
A p pe n di x 2  T o xicit y  Ma na ge me nt  G ui deli nes  f or  I m m u ne -Relate d  A d verse  E ve nts  
Ass ociate d wit h Ni v ol u ma b  ......................................................................................... 8 9  
A p pe n di x  3 Details  of  C ha n ges  Ma de  i n  Pr ot oc ol  A me n d me nt  2  ( Pr ot oc ol  Versi o n  3. 0,  
1 8  A pril  2 0 2 0)  .............................................................................................................. 9 4  
A p pe n di x  4 Details  of  C ha n ges  Ma de  i n  Pr ot oc ol  A me n d me nt  3  ( Pr ot oc ol  Versi o n  4. 0,  
2 1  J ul y 2 0 2 0)  9 5  
A p pe n di x  5 Details  of  C ha n ges  Ma de  i n  Pr ot oc ol  A me n d me nt  4  ( Pr ot oc ol  Versi o n  5. 0,  
0 4  Ma y  2 0 2 1)  1 0 2  
A p pe n di x  6 Details  of  C ha n ges  Ma de  i n  Pr ot oc ol  A me n d me nt  5  ( Pr ot oc ol  Versi o n  6. 0,  
0 9  Dec  2 0 2 1)  1 0 6  
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 8 of 1 0 9  
LI S T O F T A B L E S  
Ta ble  1 
St u d y Vacci ne Treat me nt Gr o u ps i n H B V 0 0 2  ........................................................................ 4 0  
Ta ble  2 
O verall Sc he d ule of Assess me nts at Eac h St u d y Visit  ............................................................ 4 6  
Ta ble  3 
Se verit y Gra di n g of A d verse E ve nts n ot liste d i n t he T o xicit y Ta ble f or Cli nical a n d 
La b orat or y A b n or malities  ....................................................................................................... 5 8  
LI S T O F FI G U R E S  
Fi g ure 1  
Sc he matic of He patitis B Vir us I m m u n o ge ns  ......................................................................... 2 5  
Fi g ure  2 
O verall St u d y Desi g n  .............................................................................................................. 3 0  
 
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 9 of 1 0 9  
P R O T O C O L A M E N D M E N T  C H A N G E HI S T O R Y  
T his  is  Versi o n  6 . 0  of  t he  pr ot oc ol.  T he  p ur p ose  of  t his  a me n d me nt  is  t o  u p date  t he 
ra n d o misati o n sc he me f oll o wi n g a re vie w of i nteri m data,  w hic h s h o we d s urface a nti ge n 
res p o nses i n Gr o u ps 2 a n d 3. Gr o u ps 1 a n d 4 will be cl ose d a n d patie nts will be ra n d o mise d t o 
Gr o u ps 2 a n d 3 o nl y.  
T he  ori gi nal  pr ot oc ol  ( Versi o n  1. 0)  was  iss ue d  o n  0 7 Fe br uar y 2 0 2 0 a n d  a me n de d  t o  
Versi o n  2. 0 o n 2 4  Marc h  2 0 2 0, t o Versi o n 3. 0 o n 1 8 A pril  2 0 2 0 t o Versi o n 4. 0 o n 2 1  J ul y 2 0 2 0 
a n d Versi o n 5. 0 o n 0 4 Ma y 2 0 2 1. 
F or detaile d pr ot oc ol a me n d me nt c ha n ges refer t o A p pe n di x 6 .  
S U M M A R Y O F M AI N C H A N G E S 
Versi o n 6. 0, 0 9 Dec  2 0 2 1 
S u m m ar y a n d J ustific ati o n of C h a n ge  
Secti o n C h a n ge d  
Cl osi n g e nr ol me nt of G r o u ps 1 a n d 4 d ue t o 
i nteri m data accr ue d o n t he first 2 7 patie nts 
t o t he 3-m o nt h ti me p oi nt  
3. 1. 1 St u d y O ver vie w  
4. 1 N u m ber of Partici pa nts  
5. 2 I n vesti gati o nal Pr o d ucts A d mi nistere d  
5. 7 Met h o d  of  Assi g ni n g  Partici pa nts  t o  
Treat me nt Gr o u ps  
C ha n ge t o o verall recr uit me nt n u m ber d ue t o 
cl osi n g of Gr o u ps 1 a n d 4 
3. 1. 1 St u d y O ver vie w  
4. 1 N u m ber of Partici pa nts  
J ustificati o n  f or  pr ot oc ol  c ha n ges  a n d  
s u p p orti n g i nf or mati o n a d de d  
3. 2 Disc ussi o n of St u d y Desi g n, I ncl u di n g 
t he C h oice of C o ntr ol Gr o u ps  
Clarificati o n  o n  ti mi n gs  f or  Da y  3 5  visit  
f oll o wi n g sec o n d vacci nati o n ( Da y 2 8)  
6. 3. 2 Cli nic Visits: Da y 7, Da y 3 5 a n d M o nt h 
3 + 7 da ys  
 
Mi n or e dit orial c ha n ges ha ve als o bee n ma de t o e ns ure c o nsiste nc y wit hi n t he pr ot oc ol. T he 
s y n o psis has bee n u p date d t o reflect all c ha n ges as a p pr o priate. 
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 1 0  of 1 0 9  
 
 
Versi o n 5. 0, 0 4 M a y 2 0 2 1 
S u m m ar y a n d J ustific ati o n of C h a n ge  
Secti o n C h a n ge d  
A d de d clarificati o n f or e xcl usi o n criteri o n # 5 
o n  e xcl usi o n  le vels  f or  cirr h osis  a n d  
a d va nce d fi br osis.  
4. 3 E xcl usi o n Criteria  
A d de d clarificati o n t hat e xcl usi o n criteri o n 
# 1 3  t hat  c o ntr olle d  t h yr oi d  disease  is  n ot  
e xcl usi o nar y  
4. 3 E xcl usi o n Criteria  
U p date d  w or di n g  o n  t he  use  of  n o n -oral 
a de n o viral vacci nes si nce t he de vel o p me nt 
a n d  a p pr o val  of  t he  Astra Ze neca/ O xf or d  
U ni versit y C O VI D -1 9 Vacci ne  
4. 3 E xcl usi o n Criteria  
5. 1 0  Pri or  a n d  C o nc o mita nt  Vacci nes  a n d  
Me dicati o ns  
A d de d
 w or di n g
 o n
 re -scree ni n g
 of
 
partici pa nts  t o  descri be  w he n  a n d  h o w  
re-scree ns s h o ul d occ ur 
6. 1 Scree ni n g a n d Baseli ne Assess me nts  
U p date d  w or di n g  t o  all o w  sites  t o  ta ke  
te m perat ure acc or di n g  t o  t heir  sta n dar d  
practice.  
7. 4. 3 Vital S i g ns 
U p date d w or di n g f or c o nsiste nc y wit h I C H 
S A E re p orti n g g ui deli nes. 
8. 2. 5
 Re p orti n g
 Re q uire me nts
 a n d
 
Pr oce d ures f or S A Es  
D ue  t o  sl o wer  t ha n  a ntici pate d  e nr ol me nt,  
w or di n g  has  b ee n u p date d  t o all o w  f or  
e n o u g h 
partici pa nts
 t o
 recei ve
 st u d y
 
vacci ne(s)  t o  pr o vi de  s ufficie nt data  f or  a  
mea ni n gf ul re vie w . 
1 0. 2. 3 I nteri m A nal yses  
C orrecti o n of t y p o g ra p hical err ors –  f o oters 
c orrecte d  t o  V 5. 0  a n d  S m P C  refere nce  t o  
c urre nt versi o n 3 0 N o ve m ber 2 0 2 0  
A p pe n di x 2  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 1 1  of 1 0 9  
S pecifie d t hat M o nt h 3 b o oster d ose is o nl y 
a p plica ble t o U K partici pa nts  
1. 5 St u d y Rati o nale  
3. 1. 1 St u d y O ver vie w 
3. 2 Disc ussi o n of St u d y Desi g n, I ncl u di n g 
t he C h oice of C o ntr ol Gr o u ps 
5. 2 I n vesti gati o nal Pr o d ucts A d mi nistere d  
5. 2. 1 St u d y Vacci nes  
5. 8. 2. 1 D osi n g Sc he d ule 
6 St u d y Pr oce d ures at Eac h Visit/ Sc he d ule of 
Assess me nts  
6. 2 Treat me nt Da y Assess me nts ( Da y 0, a n d 
Da y 2 8 a n d M o nt h 3 [ B o oster]) 
6. 3. 1 Tele p h o ne Calls: Da y 1, a n d Da y 2 9 
a n d M o nt h 3 + 1 Da y ( M V A- H B V B o ost) 
6. 3. 2 Cli nic Visits: Da y 7, a n d Da y 3 5 a n d 
M o nt h 3 + 7 Da ys ( M V A- H B V B o ost)  
6. 3. 3 Cli nic Visit: M o nt hs 3 a n d 6 
 
 
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 1 2  of 1 0 9  
Versi o n 4. 0, 2 1 J ul y  2 0 2 0 
S u m m ar y of C h a n ge s 
Secti o n C h a n ge d  
T he d ose of C h A d O x 1 -H B V  t o be use d i n 
t his
 st u d y
 has
 bee n
 c o nfir me d
 as
 
2. 5 x 1 0 1 0  v p.  A  s u m mar y  of  t he  c urre nt  
a vaila ble data fr o m St u d y H B V 0 0 1 has bee n 
pr o vi de d a n d  clarificati o n of w hic h data fr o m 
t hat st u d y has bee n  re vie we d t o c o nfir m t he 
c urre nt d ose has bee n a d de d  
1. 4 S u m mar y of Cli nical E x perie nce  
3. 2  Disc ussi o n  of  St u d y  Desi g n,  I ncl u di n g 
t he C h oice of C o ntr ol Gr o u ps 
5. 2. 1 St u d y Vacci nes 
5. 8. 1 Selecti o n of D oses i n t he St u d y 
T he  p ote ntial  of  a  b o oster  d ose  of  
M V A -H B V t o be gi ve n at M o nt h 3 (as part 
of pla n ne d cli nic visit) if t here is a 0. 5 l o g or 
greater  dr o p  i n  t he  h e patitis B 
surface 
a nti ge n, at t he I n vesti gat or’s discreti o n  a n d 
after disc ussi o n wit h t he S p o ns or 
1. 5 St u d y Rati o nale  
3. 1. 1 St u d y O ver vie w 
3. 2 Disc ussi o n  of  St u d y  Desi g n,  I ncl u di n g 
t he C h oice of C o ntr ol Gr o u ps 
5. 2 I n vesti gati o nal Pr o d ucts A d mi nistere d  
5. 2. 1 St u d y Vacci nes 
5. 8. 2. 1 D osi n g Sc he d ule 
6 St u d y Pr oce d ures at Eac h Visit/ Sc he d ule of 
Assess me nts  
6. 2 Treat me nt Da y Assess me nts ( Da y 0, a n d 
Da y 2 8 a n d M o nt h 3 [ B o oster]) 
6. 3. 1 Tele p h o ne Calls: Da y 1, a n d Da y 2 9 
a n d M o nt h 3 + 1 Da y ( M V A- H B V B o ost) 
6. 3. 2 Cli nic Visits: Da y 7, a n d Da y 3 5 a n d 
M o nt h 3 + 7 Da ys ( M V A- H B V B o ost)  
6. 3. 3 Cli nic Visit: M o nt hs 3 a n d 6 
7. 4. 4 P h ysical E xa mi nati o n 
Clarificati o n s ha ve  bee n a d de d t hat : 
•  t he  st u d y  will  be  st o p pe d  f or  a  deat h  
relate d t o st u d y vacci ne  
•  a n  a p pr o priate  s u bsta ntial  a me n d me nt  
will be file d if t he D M C rec o m me n ds 
res u m pti o n of t he st u d y, f oll o wi n g a halt 
i n e nr ol me nt 
3. 1. 3 St o p pi n g Criteria/ H ol di n g Criteria  
T he  H B V  D N A  t hres h ol d  f or  partici pa nt  
i ncl usi o n i n t he st u d y was ma de c o nsiste nt 
wit h
 p u blis he d
 defi niti o ns
 of
 viral
 
s u p pressi o n a n d St u d y H B V 0 0 1 ( 4 0 I U/ m L) 
4. 2 I ncl usi o n Criteria  
T he defi niti o n of p ost -me n o pa usal stat us has 
bee n  clarifie d  i n  t he  rele va nt  i ncl usi o n  
criteri o n  t o  s pecif y  t hat  t he  a me n orr h oea  
4. 2 I ncl usi o n Criteria  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 1 3  of 1 0 9  
Versi o n 4. 0, 2 1 J ul y  2 0 2 0 
S u m m ar y of C h a n ge s 
Secti o n C h a n ge d  
m ust be at least 1 2 m o nt hs a n d wit h o ut a n 
alter nati ve me dical ca use  
T he d urati o n of c o ntrace pti o n re q uire me nts 
has bee n clarifie d t o a d dress t he re q uire me nts 
f or ni v ol u ma b ( 5 m o nt hs p ost d ose) 
4. 2 I ncl usi o n Criteria  
E xcl usi o n criteria were a d de d a n d re vise d t o 
a d dress  a p pr o priate  ris k  miti gati o n  f or  
ni v ol u ma b 
4. 3 E xcl usi o n Criteria  
Clarificati o n t hat t he partici pa nts i n Gr o u ps 3 
a n d  4  will  be  i nitiate d  after  e val uati o n  of  
safet y data 7 da ys after t he first 6  partici pa nts 
i n  Gr o u p  2  ha ve  recei ve d  C h A d O x 1- H B V 
a n d n ot b ot h st u d y vacci nes 
5. 7 Met h o d  of  Assi g ni n g  Partici pa nts  t o  
Treat me nt Gr o u ps 
8. 1. 4 Safet y M o nit ori n g C o m mittee  
A d diti o nal  g ui da nce  o n  t he  ti mi n g  of  
ni v ol u ma b f oll o wi n g vacci nati o n a n d criteria 
t o c o nfir m t hat i nf usi o n ma y pr ocee d ha ve 
bee n pr o vi de d 
5. 8. 2. 3
 Ni v ol u ma b
 Pre parati o n
 a n d
 
A d mi nistrati o n  
6 St u d y Pr oce d ures at Eac h Visit/ Sc he d ule of 
Assess me nts  
6. 2 Treat me nt Da y Assess me nts ( Da y  0 a n d 
Da y 2 8) 
Clarificati o n re gar di n g t he use of o n -g oi n g 
me dicati o ns f or He patitis B i nfecti o n i n t hat 
patie nts s h o ul d re mai n o n t he sa me d ose as 
w he n t he y e ntere d t he st u d y a n d t hat a nti viral 
me dicati o n s h o ul d n ot be wit h dra w n 
Oral a nti viral me dicati o ns i ncl u de: e nteca vir, 
te n of o vir (te n of o vir alafe na mi de f u marate or 
te n of o vir dis o pr o xil f u marate), or besif o vir 
5. 1 0  Pri or  a n d  C o nc o mita nt  Vacci nes  a n d  
Me dicati o ns 
D ue  t o  t he  C O VI D -1 9 p a n de mic a n d t o 
e ns ure t he safet y of partici pa nts a n d ce ntre 
staff,  clarificati o n  t hat  st u d y  ce ntres will 
f oll o w  a n y  l ocal  pr oce d ures  i n  li ne  wit h  
testi n g has bee n a d de d  
6 St u d y Pr oce d ures at Eac h Visit/ Sc he d ule of 
Assess me nts  
Clarificati o n t hat t he scree ni n g tests f or H B V 
at scree ni n g are q ua ntitati ve H B V D N A a n d 
q ua ntitati ve H Bs A g has bee n a d de d 
6 St u d y Pr oce d ures at Eac h Visit/ Sc he d ule of 
Assess me nts  
6. 1 Scree ni n g a n d Baseli ne Assess me nts  
D ue  t o  t he  p ote ntial  terat o ge nic  effects  of  
ni v ol u ma b  a n d  c o ntrace pti o n  re q uire me nts  
f or 5 m o nt hs p ost d ose, a d diti o nal pre g na nc y 
6 St u d y Pr oce d ures at Eac h Visit/ Sc he d ule of 
Assess me nts  
6. 3. 3 Cli nic Visit: M o nt hs 3 a n d 6 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 1 4  of 1 0 9  
Versi o n 4. 0, 2 1 J ul y  2 0 2 0 
S u m m ar y of C h a n ge s 
Secti o n C h a n ge d  
testi n g  at  t he  3- a n d  6-m o nt h  visits  f or  
patie nts i n Gr o u ps 3 a n d 4 has bee n i ncl u de d  
Clarificati o n  t hat  i nter nati o nal  n or malize d  
rati o  will  be  meas ur e d  at  scree ni n g  o nl y,  
pr ot hr o m bi n  ti me  will  be  mea s ure d  at  
scree ni n g a n d M o nt h 9 a n d acti vate d partial 
t hr o m b o plasti n ti me  will  n ot  be  meas ur e d 
was a d de d  
6. 1 Scree ni n g a n d Baseli ne Assess me nts  
6. 3. 3 Cli nic Visit: M o nt hs 3 a n d 6 
6. 3. 4 Cli nic  Visit:  M o nt h  9  ( E n d  of  St u d y  
Visit)  
Clarificati o n  t hat  urea  nitr o ge n  a n d  direct  
bilir u bi n 
( n ot  t otal  bilir u bi n)  will 
be 
meas ure d as part of t he bi oc he mistr y pa nel 
a n d t hat bilir u bi n will be meas ure d as part of 
t he uri nal ysis was a d de d 
7. 1. 4. 2 Bi oc he mistr y  
7. 1. 4. 4 Uri nal ysis 
T he pr ot oc ol has bee n u p date d t o i ncl u de a 
refere nce t o Secti o n 4. 8 of t he S u m mar y of 
Pr o d uct 
C haracteristics
 ( S m P C)
 f or
 
ni v ol u ma b t o deter mi ne e x pecte d ness of a n y 
seri o us a d verse reacti o ns 
8. 2. 5. 3 Me dical Re vie w a n d Re p orti n g b y t he 
S p o ns or 
T o be c o nsiste nt wit h t he Statistical A nal ysis 
Pla n,
 se parate
 defi niti o ns
 f or
 t he
 
i nte nt-t o-treat a n d safet y a nal ysis sets ha ve 
bee n i ncl u de d 
1 0. 2. 1 A nal ysis Sets  
T o hel p wit h t he pla n ni n g of f ut ure st u dies,  
a n i nteri m a nal ysis of all a vaila ble data t o  be 
perf or me d i n J u ne  2 0 2 1 has bee n a d de d 
1 0. 2. 3 I nteri m A nal yses  
T o xicit y
 ma na ge me nt
 g ui deli nes
 f or
 
ni v ol u ma b ha ve bee n a d de d 
A p pe n di x
 2
 T o xicit y
 Ma na ge me nt
 
G ui deli nes  f or  I m m u ne -Relate d  A d verse  
E ve nts Ass ociate d wit h Ni v ol u ma b  
 
Versi o n 3. 0, 1 8 A pril  2 0 2 0 
S u m m ar y a n d J ustific ati o n of C h a n ge  
Secti o n C h a n ge d  
T he s t ora ge te m perat ure ha s bee n c orrect e d 
t o ≤- 7 0oC t o all o w f or t he safe st ora ge of 
b ot h vacci ne s. 
5. 4  St ora ge  
 
Mi n or e dit orial c ha n ges ha ve als o bee n ma de. T he s y n o psis has bee n u p date d t o reflect all 
c ha n ges as a p pr o priate.  
 
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 1 5  of 1 0 9  
P R O T O C O L S Y N O P SI S  
Ti tle of St u d y: 
A P hase 1 b / 2a, O pe n-La bel St u d y t o E val uate t he Safet y, T olera bilit y a n d I m m u n o ge nicit y 
of V T P -3 0 0 Wit h or Wit h o ut Ni v ol u ma b  i n Partici pa nts wit h C hr o nic He patitis B I nfecti o n 
S h ort Title:  
First i n h u ma n st u d y of V T P -3 0 0  
S p o ns or:  
Vaccitec h Lt d.  
Pr ot oc ol N u m ber:  
H B V 0 0 2  
C hief I n vesti g at or:  
Pr ofess or Elea n or Bar nes  
Pr ofess or of He pat ol o g y a n d  E x peri me ntal Me dici ne  
N uffiel d De part me nt of  Me dici ne  
U ni versit y of O xf or d  
O xf or d, O X 3 7 B N  
U K  
St u d y Ce ntres:  
U p t o 1 5 ce ntres i n Asia ( S o ut h K orea a n d Tai wa n) a n d E ur o pe ( U K)  
O bjecti ves:  
Pri m ary O bjectives  
•  
Deter mi ne  t he  safet y  a n d  react o ge nicit y  of  t he  
f oll o wi n g i n partici pa nts wit h c hr o nic H B V (C H B ) 
i nfecti o n a n d virall y s u p presse d wit h oral a nti viral 
me dicati o n:  
− 
M V A -H B V vacci ne  
− 
C h A d O x 1 -H B V pl us M V A vacci nes  
− 
C h A d O x 1 -H B V  pl us  M V A  vacci nes  a n d  
ni v ol u ma b  
E n d p oi nts:  
Pri m ary E n d p oi nts  
•  
Safet y  a n d  react o ge nicit y  of  t he  vacci ne(s):  
i nci de nce of a d verse e ve nts, seri o us a d verse e ve nts 
( S A Es), ≥Gra de  3  st u d y  vacci ne -relate d  a d verse  
e ve nts wit hi n 4 wee ks of vacci nati o n  
•  
Safet y of t he vacci nes wit h ni v ol u ma b : i nci de nce of 
a d verse  e ve nts,  S A Es,  ≥Gra de  3  a d verse  e ve nts  
wit hi n 4 wee ks of d osi n g  
•  
I nci de nce of a d verse e ve nts of s pecial i nterest 
•  
N u m ber  a n d  pr o p orti o n  of  partici pa nt s re p orti n g 
treat me nt-e mer ge nt  a d verse  e ve nts  wit hi n  eac h  
treat me nt gr o u p 
•  
N u m ber a n d pr o p orti o n of partici pa nt s wit hi n eac h 
treat me nt
 gr o u p
 wit h
 p ote ntiall y
 cli nicall y
 
si g nifica nt la b orat or y val ues a n d vital si g ns wit hi n 
eac h treat me nt gr o u p  
•  
C ha n ge fr o m baseli ne i n la b orat or y tests a n d vital 
si g n meas ure me nts t o eac h ti me p oi nt of c ollecti o n  
Sec o n d ary O bjectives  
•  
Deter mi ne t he i m m u n o ge nicit y of t he f oll o wi n g i n 
partici pa nts  wit h  C H B  i nfecti o n  a n d  virall y  
s u p presse d wit h oral a nti viral me dicati o n: 
− 
M V A -H B V vacci ne  
− 
C h A d O x 1 -H B V pl us M V A -H B V vacci nes  
− 
C h A d O x 1 -H B V  pl us  M V A -H B V  vacci nes  
a d mi nistere d wit h ni v ol u ma b  
•  
Deter mi ne  t he  i m pact  of  P D -1  bl oc ka de  ti mi n g  
relati ve  t o  vacci nati o n  o n  i m m u n o ge nicit y i n 
partici pa nts 
wit h  C H B  i nfecti o n  a n d  virall y  
s u p presse d wit h oral a nti viral me dicati o n 
•  
Deter mi ne t he effect of t he f oll o wi n g o n t he le vel of 
he patitis  B  mar kers  i n  partici pa nts  wit h  C H B  
i nfecti o n a n d virall y s u p presse d wit h oral a nti viral 
me dicati o n : 
Sec o n d ary E n d p oi nts  
•  
Ma g nit u de a n d a vi dit y of H B V s pecific C D 4 + a n d 
C D 8 + T cells i n d uce d b y eac h re gi me n  
•  
Effect  o n  t he  fre q ue nc y  a n d  ma g nit u de  of  H B V 
i nfecti o n mar kers  ( H Bs A g,  h e patitis  B surface 
anti b o d y  ser oc o n versi o n, he patitis B D N A, H Be A g ) 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 1 7  of 1 0 9  
carrie d o ut b y a Safet y M o nit ori n g C o m mittee c o nsisti n g of t he S p o ns or Me dical M o nit or, 
t he C o u ntr y Lea d I n vesti gat ors f or S o ut h K orea, Tai wa n,  a n d t he U K a n d t he Me dical 
M o nit or . If a partici pa nt has a 0. 5 l o g or greater dr o p i n he patitis B s urface a nti ge n at 
Da y  3 5, t he y ma y recei ve a b o oster d ose of M V A - H BV, at t he I n vesti gat or’s discreti o n a n d 
after disc ussi o n wit h t he S p o ns or  ( U K partici pa nts o nl y). 
A Data M o nit ori n g C o m mittee will be a p p oi nte d t o perf or m u nsc he d ule d re vie ws of t he 
a vaila ble safet y a n d t olera bilit y st u d y data a n d ma ke rec o m me n dati o ns c o ncer ni n g t he 
c o nti n uati o n, m o dificati o n or ter mi nati o n of t he st u d y if o ne of t he st u d y st o p pi n g or h ol di n g 
r ules is met. 
D ur ati o n of St u d y:  
D ur ati o n f or e ac h P artici p a nt : U p t o 1 0 . 5 m o nt hs ( u p t o 1. 5 m o nt hs f or scree ni n g a n d 
9 m o nt hs o n t he st u d y wit h st u d y vacci ne gi ve n o n Da y  0).  
D ur ati o n of w h ole St u dy : It is pla n ne d t hat t he st u d y will ta ke 1 7  m o nt hs t o i m ple me nt, 
e nr ol a n d rea d o ut.  
P artici p a nt N u m bers:  
It is pla n ne d t hat a p pr o xi matle y  5 2 partici pa nts wit h C H B i nfecti o n a n d virall y s u p presse d 
wit h oral a nti viral me dicati o n will be e nr olle d i n t he st u d y.  
I ncl usi o n a n d E xcl usi o n 
Criteri a:  
I ncl usi o n Criteri a 
1.  
A d ult  males  or  fe males  a ge d  ≥1 8 t o  ≤6 5  years  at  scree ni n g (acc or di n g  t o  
c o u ntr y/l ocal re g ulati o ns)  
2.  
B MI ≤3 2 k g/ m 2 
3.  
A ble t o pr o vi de i nf or me d c o nse nt i n dicati n g t he y u n dersta n d t he p ur p ose of, a n d 
pr oce d ures re q uire d, f or t he st u d y a n d are willi n g t o partici pate  
4.  
If fe male, willi n g n ot t o bec o me pre g na nt u p t o 8 wee ks after last d ose of st u d y 
vacci ne  a n d u p t o 5 m o nt hs after t he last d ose of ni v ol u ma b  
5.  
If fe male: N ot pre g na nt or breast fee di n g a n d o ne of t he f oll o wi n g: 
•  
Of n o n -c hil d beari n g p ote ntial (i.e. w o me n w h o ha ve ha d a h ysterect o m y or 
t u bal li gati o n or are p ost-me n o pa usal, as defi ne d b y n o me nses i n ≥1 year  a n d 
wit h o ut a n alter nati ve me dical ca use ) 
•  
Of c hil d beari n g p ote ntial b ut a grees t o practice hi g hl y effecti ve c o ntrace pti o n 
f or 4 wee ks pri or t o st u d y vacci ne a n d 8 wee ks after st u d y vacci ne  a n d 5 m o nt hs 
after t he last d ose of ni v ol u ma b . Hi g hl y effecti ve met h o ds of c o ntrace pti o n 
i ncl u de o ne or m ore of t he f oll o wi n g: 
− Male part ner w h o is sterile ( me dicall y effecti ve vasect o m y) pri or t o t he 
fe male partici pa nt’s e ntr y i nt o t he st u d y a n d is t he s ole se x ual part ner f or 
t he fe male partici pa nt 
− C o m bi ne d
 ( o estr o ge n
 a n d
 pr o gest o ge n -c o ntai ni n g)
 h or m o nal
 
c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n:  
− oral  
− i ntra va gi nal 
− tra ns der mal 
− Pr o gest o ge n -o nl y  h or m o nal  c o ntrace pti o n  ass ociate d  wit h  i n hi biti o n  of  
o v ulati o n:  
− oral  
− i njecta ble 
− i m pla nta ble 
− A n i ntra uteri ne de vice  
− Bilateral t u bal occl usi o n  
6.  
D oc u me nte d e vi de nce of c hr o nic H B V i nfecti o n (e. g. H Bs A g p ositi ve ≥6 m o nt hs 
wit h detecta ble H Bs A g le vels at scree ni n g)  
7.  
Recei pt  of  o nl y  eit her  e nteca vir , te n of o vir  (te n of o vir alafe na mi de  f u marate  or 
te n of o vir dis o pr o xil f u marate), or besif o vir f or at least 1 2 m o nt hs bef ore scree ni n g  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 1 8  of 1 0 9  
8.  
Virall y s u p presse d ( H B V -D N A viral l oa d < 4 0  I U/ m L f or ≥ 1 year)  
9.  
H Bs A g le vels < 4 0 0 0  I U/ m L 
E xcl usi o n Criteri a  
1.  
Prese nce  of  a n y  si g nifica nt  ac ute  or  c hr o nic,  u nc o ntr olle d  me dical/ ps yc hiatric  
ill ness 
2.  
He patitis C vir us ( H C V) a nti b o d y p ositi ve.  
3.  
HI V a nti b o d y p ositi ve  
4.  
C o -i nfecti o n wit h he patitis D vir us  
5.  
D oc u me nte d  cirr h osis  or  a d va nce d  fi br osis  i n dicate d  b y  a  li ver  bi o ps y  wit hi n  
6 m o nt hs pri or t o scree ni n g (Meta vir acti vit y gra de A 3 a n d sta ges F 3 a n d F 4; Is ha k 
sta ges 4 – 6) .  
I n t he a bse nce of a d oc u me nte d li ver bi o ps y, eit her 1 of t he f oll o wi n g ( n ot b ot h):  
•  
Scree ni n g Fi br osca n wit h a res ult > 9 kil o pascals ( k Pa) ( or t he e q ui vale nt) 
wit hi n ≤ 6 m o nt hs of scree ni n g , O R  
•  
Scree ni n g Fi br o Test > 0. 4 8 a n d as partate a mi n otra nsferase ( A S T) t o platelet 
rati o i n de x ( A P RI) of > 1.  
6.  
A L T > 3 x u p per li mit of n or mal ( U L N ), i nter nati o nal n or malize d rati o (I N R) > 1. 5 
u nless  t he  p artici pant  was  sta ble  o n  a n  a ntic oa g ula nt  re gi me n  affecti n g  I N R,  
al b u mi n < 3. 5 g/ d L, direct  bilir u bi n > 1. 5  x U L N , platelet c o u nt < 1 0 0, 0 0 0/µ L. 
7.  
A  hist or y  of  li ver  dec o m pe nsati o n  (e. g.  ascites,  e nce p hal o pat h y  or  variceal  
hae m orr ha ge)  
8.  
Pri or he pat ocell ular carci n o ma  
9.  
C hr o nic li ver disease of a n o n -H B V aeti ol o g y  
1 0.  
Hist or y or e vi de nce of a ut oi m m u ne disease or k n o w n i m m u n o deficie nc y of a n y 
ca use 
1 1.  
Prese nce of acti ve i nfecti o n  
1 2.  
E vi de nce of i nterstitial l u n g disease, acti ve p ne u m o nitis, m y ocar ditis, or a hist or y 
of m y ocar ditis  
1 3.  
Past h ist or y of t h yr oi d dis or der or a b n or mal t h yr oi d f u ncti o n at scree ni n g that is still 
acti ve a n d u nc o ntr olle d  
1 4.  
Pr ol o n ge d t hera p y wit h i m m u n o m o d ulat ors (e. g . c ortic oster oi ds  s uc h as pre d nis o ne 
> 1 0  m g/ da y ) or bi ol o gics (e. g. m o n ocl o nal a nti b o dies, I F N) wit hi n 3 m o nt hs of 
scree ni n g 
1 5.  
Recei pt  of  i m m u n o gl o b uli n  or  ot her  bl o o d  pr o d ucts  wit hi n  3  m o nt hs  pri or  t o  
e nr ol me nt 
1 6.  
Recei pt of a n y i n vesti gati o nal dr u g or vacci ne wit hi n 3  m o nt hs pri or t o scree ni n g  
1 7.  
Recei pt of a n y a de n o viral -base d vacci ne wit hi n 3 m o nt hs pri or t o a d mi nistrati o n of 
C h A d O x 1 - H BV o n Da y 0, or pla n t o recei ve a n a de n o viral -base d vacci ne wit hi n 
3 m o nt hs after Da y 0.  
1 8.  
Recei pt of a n y li ve vacci nes wit hi n 3 0 da ys pri or t o scree ni n g  
1 9.  
Recei pt of a n y i nacti vate d vacci nes wit hi n 1 4  da ys pri or t o scree ni n g,  
2 0.  
Hist or y of  se vere h y perse nsiti vit y or a na p h ylactic reacti o ns li kel y t o be e xacer bate d 
b y a n y c o m p o ne nt of t he vacci ne  or ni v ol u ma b  
2 1.  
Mali g na nc y wit hi n 5 years pri or t o scree ni n g wit h t he e xce pti o n of s pecific ca ncers 
t hat are c ure d b y s ur gical resecti o n (e. g. e xce pt basal cell s ki n carci n o ma of t he s ki n 
a n d cer vical carci n o ma). Partici pa nts u n der e val uati o n f or p ossi ble mali g na nc y are 
n ot eli gi ble  
2 2.  
C urre nt alc o h ol or s u bsta nce a b use j u d ge d b y t he I n vesti gat or t o p ote ntiall y i nterfere 
wit h partici pa nt safet y a n d c o m plia nce  
2 3.  
Si g nifica nt car diac disease or u nsta ble u nc o ntr olle d car diac disease  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 2 0  of 1 0 9  
M o nt h  3 f or t h ose ha vi n g t he M V A -H B V b o ost  ( U K partici pa nts o nl y) , a n d b y e Diar y 
f or 7 da ys p ost -vacci nati o n  
•  
U ns olicite d a d verse e ve nts will be rec or de d i n t he e C R F fr o m t he date t he i nf or me d 
c o nse nt is si g ne d, at all cli nic visits t o c o ver t he peri o d si nce t he pre vi o us visit a n d 
d uri n g t he visit  
•  
Seri o us a d verse e ve nts a n d a d verse e ve nts of s pecial i nterest will be rec or de d fr o m t he 
date t he i nf or me d c o nse nt is si g ne d u ntil t he e n d of t he st u d y or res ol ve d or u ntil 
partici pa nt c o ntact disc o nti n ues  
•  
Cell ular i m m u ne res p o nses will be meas ure d i n peri p heral bl o o d m o n o n uclear cells 
sa m ples ta ke n o n pre-vacci nati o n o n Da ys  0 a n d 2 8, o n Da ys 7 a n d 3 5, a n d  o n  M o nt hs  3 
( pre-vacci nati o n  f or  U K  partici pa nts  ha vi n g t he  M V A- H BV b o ost  o nl y ), 6 a n d 9 . 
Sa m ples will be a nal yse d b y  E LI SP O T  a n d i ntracell ular c yt o ki ne stai ni n g 
St atistic al Met h o ds a n d 
A n al ysis:  
All data will be s u m marise d usi n g descri pti ve statistics. I m m u n o ge nicit y a n d efficac y data 
ma y be s u bjecte d t o a d diti o nal statistical a nal ysis.  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 2 1  of 1 0 9  
A B B R E VI A TI O N S A N D D E FI NI TI O N S O F T E R M S  
List of A b bre vi ati o ns  
A B B R E VI A TI O N  
D E FI NI TI O N  
A E SI  
A d verse E ve nt of S pecial I nterest  
A L T  
Ala ni ne A mi n otra nsferase  
A S T  
As partate A mi n otra nsferase  
ccc D N A  
C o vale ntl y C l ose d C irc ular D N A 
C h A d O x 1  
C hi m pa nzee A de n o vir us O xf or d 1  
C H B  
C hr o nic He patitis B  Vir us  
C R F  
Case R e p ort F or m  
D M C  
Data M o nit ori n g C o m mittee  
D N A  
De o x yri b o n ucleic Aci d  
e C R F  
Electr o nic C ase R e p ort F or m  
E LI S P O T  
E nz y me -li n ke d I m m u n os p ot 
e T M F 
Electr o nic Trial Master File  
E U  
E ur o pea n U ni o n  
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
G C P  
G o o d C li nical P ractice 
G M  
Ge neticall y M o difie d  
G M O  
Ge neticall y M o difie d Or ga nis m  
H Bcr A g  
He patitis B C ore -relate d A nti ge n 
H Be A g  
He patitis B e-A nti ge n  
H B p g R N A  
He patitis B Pre ge n o mic R N A  
H Bs A b  
He patitis B S urface A nti b o d y  
H Bs A g  
H e patitis B S urface A nti ge n  
H B V  
He patitis B Vir us  
H C C  
He pat ocell ular Carci n o ma  
H C V  
He patitis C Vir us  
H D V  
He patitis D Vir us  
HI V  
H u ma n I m m u n o deficie nc y Vir us  
I C H 
I nter nati o nal C ou ncil  o n Har m o nisati o n  of Tec h nical Re q uire me nts 
f or Re gistrati o n of P har mace uticals f or H u ma n Use 
I E C 
I n de pe n de nt E t hics C o m mittee  
I F N 
I nterfer o n 
I N R 
I nter nati o nal N or malise d Rati o  
I R B 
I nstit uti o nal R e vie w B oar d  
L F Ts  
Li ver F u ncti o n Tests  
Me d D R A  
Me dical Dicti o nar y f or Re g ulat or y Acti vities  
M E R S  
Mi d dle East Res pirat or y S y n dr o me  
M V A  
M o difie d V acci nia V ir us A n kara 
N A  
N ucle oti de A nal o g ue  
P B M C  
Peri p heral Bl o o d M o n o n uclear Cell  
P D -1  
P r o gra m me d C ell D eat h P r otei n 1 
P D L -1  
P r o gra m me d D eat h-li ga n d 1 
pf u  
Pla q ue F or mi n g U nits  
P T  
Pr ot hr o m bi n T i me 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 2 2  of 1 0 9  
A B B R E VI A TI O N  
D E FI NI TI O N  
R N A  
Ri b o n ucleic Aci d  
S A E  
Seri o us A d verse E ve nt  
S A S  
Statistical A nal ysis S oft ware  
SI  
Sta n dar d I nter nati o nal  
S M C  
Safet y M o nit ori n g C o m mittee  
S U S A R  
S us pecte d U ne x pecte d S eri o us A d verse R eacti o n 
T B  
T u berc ul osis  
T E A E  
Treat me nt E mer ge nt A d verse E ve nt  
U L N  
U p per Li mit of N or mal  
v p  
Viral Particles  
 
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 2 3  of 1 0 9  
1  
B A C K G R O U N D  
1. 1  
Dise ase Re vie w  
He patitis B vir us ( H B V) is a c o m ple x, s mall de o x yri b o n ucleic aci d ( D N A) vir us t hat g oes 
t hr o u g h a ri b o n ucleic aci d ( R N A) i nter me diate life c ycle re q uiri n g re verse tra nscri pti o n. After 
tra ns missi o n t hr o u g h i nfecte d bl o o d, c o nta mi nate d b o d y fl ui ds or t hr o u g h peri natal tra nsfer, 
t he vir us i nfects t he li ver a n d ca n t he n eit her i nte grate i nt o t he he pat oc yte ge n o me or ca n e xist 
as a sta ble c hr o m os o mal cl ose d circ ular D N A. O nce i nfecti o n ta kes place, H B V i nfecti o n 
res ults i n c hr o nic li ver disease i n 5-1 0 % of i nfec te d a d ults, w hereas t he rate f or peri natal 
tra ns missi o n is t he o p p osite, wit h greater t ha n 9 0 % of i nfecte d ne o nates pr o gressi n g t o c hr o nic 
disease [1 ]. After a c hr o nic H B V ( C H B) i nfecti o n is esta blis he d, t he rate of nat ural cleara nce 
is mi ni mal. S uc h C H B i nfecti o n fre q ue ntl y pr o gresses t o necr otic i nfla m mati o n a n d o n g oi n g 
li ver da ma ge, w hic h ma y lea d t o cirr h osis a n d he pat ocell ular carci n o ma ( H C C) [1 ]. 
1. 2  
Tre at me nt Re vie w  
Hi g hl y effecti ve pr o p h ylactic vacci nes were i m ple me nte d i n t he earl y 1 9 8 0's; h o we ver, t hese 
vacci nes are i neffecti ve o nce i nfecti o n is esta blis he d [ 2 ]. Des pite t he wi de use of pr o p h ylactic 
vacci nes, t here are a n esti mate d 2 4 0 milli o n C H B carriers a n d o ver 6 8 6, 0 0 0 relate d deat hs per 
year w orl d wi de [ 3 ].  
T w o classes of a nti viral t hera pies ha ve bee n a p pr o ve d a n d rec o m me n de d f or treat me nt of 
he patitis B: i nterfer o ns (I F Ns) a n d n ucle oti de a nal o g ues ( N As). T he use of I F N res ults i n hi g her 
rates of he patitis B e-a nti ge n ( H Be A g) a n d he patitis B s urface a nti ge n ( H Bs A g) l oss c o m pare d 
t o N As. 
Pe g ylate d I F N a d mi nistere d f or u p t o 5 2 wee ks res ults i n H Bs A g l oss i n 3 -7 % of patie nts 
c o m pare d t o 0 -3 % H Bs A g l oss after t he sa me d urati o n of N A t hera p y. Res p o nse t o I F N is als o 
m ore d ura ble, a n d H Bs A g l oss ma y occ ur after cessati o n of treat me nt, w hile vir ol o gical rela pse 
is fre q ue nt after cessati o n of N A. H o we ver, I F N is less effecti ve at s u p pressi n g viral re plicati o n 
c o m pare d t o N As, re q uires pare nteral a d mi nistrati o n, is ass ociate d wit h si g nifica nt si de effects, 
a n d is c o ntrai n dicate d i n patie nts wit h d ec o m pe nsate d cirr h osis or se vere e xacer bati o ns of 
he patitis a n d t h ose wit h a ut oi m m u ne or ps yc hiatric ill nesses.  
N ucle oti de  a nal o g ues  are  a d mi nistere d  orall y  a n d  ha ve  ne gli gi ble  a d verse  effects.  T he  
rec o m me n de d  first-li ne  N As,  e nteca vir  a n d  te n of o vir  (te n of o vir  alafe na mi de  f u marate  or  
te n of o vir  dis o pr o xil  f u marate;  hereafter  referre d  t o  as  te nof o vir), ha ve  l o w  ris k  of  dr u g  
resista nce;  b ut  t he  re q uire me nt  f or  i n defi nite  t hera p y  i ncreases  t he  c ost  a n d  t he  ris k  of  
n o n- a d here nce.  [4 ] 
Vari o us c o m bi nati o ns of I F N a n d N A ha ve bee n e val uate d, b ut m ost st u dies ha ve n ot s h o w n 
a n a d de d be nefit c o m pare d t o m o n ot hera p y [ 5 ,6 ,7 ]. A rece nt st u d y s h o we d t hat c o m bi nati o n of 
pe g ylate d I F N a n d te n of o vir i ncrease d t he rate of H Bs A g l oss t o 9. 1 % at Wee k 7 2, b ut t he 
be nefit was mai nl y o bser ve d wit h t h ose i nfecte d wit h H B V ge n ot y pe A [ 8 ].  
Ma n y researc h pr o gra ms are o n g oi n g t o de vel o p ne w treat me nt c o nce pts t hat f oc us o n t he 
cleara nce  of  H Bs A g  i n  a  si g nifica nt  pr o p orti o n  of  patie nts,  wit h  t he  pri nci p al ai ms  of:  
1) st o p pi n g treat me nt wit h n o ris k of vir ol o gical rela pse a n d n o ris k of li ver disease pr o gressi o n 
a n d, 2) t o f urt her decrease t he ris k of H C C. Se veral p ote ntial tar get mec ha nis ms f or i m m u ne 
m o d ulati o n t o rest ore H B V s pecific i m m u ne res p o nses i n c o nj u ncti o n wit h pr of o u n d i n hi biti o n 
of H B V re plicati o n a n d H Bs A g pr o d ucti o n t o attai n i m m u n ol o gical c o ntr ol are bei n g e val uate d  
[3 ]. 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 2 4  of 1 0 9  
T he i m m u ne cleara nce of C H B is li kel y t o de pe n d o n t he use of m o dalities t hat i n d uce effecti ve 
C D 8 + T cells [ 9 ,1 0 ]. F or o ver t w o deca des vacci nati o n strate gies t o i n d uce t hese C D 8 + T cells 
t o c o u nter s uc h i nfecti o ns as t u berc ul osis ( T B), h u ma n i m m u n o deficie nc y vir us ( HI V) a n d 
malaria ha ve bee n i n vesti gate d [ 1 1 ,1 2 ,1 3 ]. O ne platf or m a p pr oac h t hat has i n d uce d re mar ka bl y 
hi g h le vels of T cells i n ma n has bee n t o use a n o n -re plicati n g a de n o vir us " pri me" f oll o we d b y 
a heter ol o g o us viral vect or " b o ost" utilisi n g a n o n -re plicati n g p o x vir us ( m o difie d vacci nia 
vir us A n kara [ M V A]) [ 1 4 ,1 5 ,1 6 ]. N o n-re plicati n g c hi m pa nzee a de n o vir uses are ofte n use d 
rat her t ha n h u ma n a de n o vir uses, as t here is mi ni mal pri or i m m u nit y t o t he vect or itself [1 7 ,1 8 ]. 
T he c o m bi nati o n of c hi m pa nzee a de n o vir uses ( use d i n t h o usa n ds of partici pa nts) pl us M V A 
(a d mi nistere d t o o ver 1 3 0, 0 0 0 pe o ple) has bee n s h o w n t o i n d uce lar ge i m m u ne res p o nses i n 
ma n i n malaria, T B, HI V, i nfl ue nz a, he patitis C vir us ( H C V)  a n d res pirat or y s y nc ytial vir us  
[1 3 ,1 6 ,1 9 -2 2 ].  T he  c hi m pa nzee  a de n o vir us  vect or  pr o p ose d  i n  t his  st u d y  (chi m pa nzee 
ade n o vir us O xf or d 1 ; C h A d O x 1), a ser o gr o u p E a de n o vir us, has bee n a d mi nistere d t o o ver 
3 0 0 partici pa nt s i n  trials  of  Mi d dle  East  Res pirat or y  S y n dr o me  ( M E R S),  i nfl ue nza,  T B,  
c hi k u n g u n ya, a n d pr ostate  ca ncer, a n d has bee n safe a n d i m m u n o ge nic. It  has als o bee n 
m o difie d t o e n ha nce i m m u n o ge nicit y t hr o u g h t he a d diti o n of a s h ort s har k i n varia nt c hai n 
se q ue nce a nd use of t he tiss ue plas mi n o ge n pr o m oter.  
He patitis B vir us circ ulates i n t he w orl d as a n u m ber of ge n ot y pes ( A -I), of w hic h t he m ost 
pre vale nt (es peciall y i n Asia) is ge n ot y pe C [ 2 3 ]. T he pr otei ns e x presse d b y C h A d O x 1 i n t his 
st u d y i ncl u de m ost of t he H B V ge n o me fr o m a ge n ot y pe C c o nse ns us, i ncl u di n g H Bs A g, 
p ol y merase a n d c ore. I n vitr o e x peri me nts ha ve de m o nstrate d t hat t he H B V p ol y merase was 
s uccessf ull y i nacti vate d t hr o u g h t he i nserti o n of p oi nt m utati o ns at critical sites . I n or der t o 
st o p a g gre gati o n of s urface a nti ge n, t his pr otei n was s plit i nt o t w o se parate c o di n g re gi o ns i n 
t he viral vect ors.  
T he ge netic H B V i nsert was t he n cl o ne d i nt o b ot h t he C h A d O x 1 (c hi m pa nzee  a de n o vir us 
vect ore d h e patitis B v ir us v acci ne; C h A d O x 1 -H B V) a n d t he m o difie d vacci nia vir us A n kara 
( M V A; M V A-H B V ) vect ors. 
T his  st u d y  is  desi g ne d  t o  assess  t he  safet y  a n d  i m m u n o ge nicit y  of  C h A d O x 1 -H B V   a n d 
M V A -H B V, gi ve n eit her al o ne or wit h l o w d oses of a n a nti-pr o gra m me d cell deat h pr otei n 1 
(a nti-P D - 1)  c o m p o u n d  ( ni v ol u ma b), a n d t o assess t he brea dt h of res p o nses t o t he pr otei ns 
e nc o de d b y t he se c o m bi nati o ns. T he T cell cr oss-reacti vit y t o ot her ge n ot y pes will als o be 
assesse d. D oses of C h A d O x 1 vacci nes i n pre vi o us st u dies ha ve varie d fr o m 1 0 8 t o o ver 5 x 1 0 1 0 
viral particles ( v p) per d ose a n d a d ose of 2. 5 x 1 0 1 0 v p will be e val uate d i n t his st u d y t o pre pare 
f or a f urt her C h A d O x 1/ M V A heter ol o g o us pri me -b o ost re gi me n.  T he d ose of M V A of 1 x 1 0 8 
pf u  has bee n assesse d safel y i n t h o usa n ds of partici pa nts.  
1. 3  
S u m m ar y of N o n- cli nic al St u dies  
I m m u n o ge n  desi g n:  1, 4 4 7  H B V  ge n ot y pe  C  n ucle oti de  se q ue nces  ( H B V  data base)  were  
ali g ne d, a n d a n H B V ge n ot y pe C c o nse ns us se q ue nce was ge nerate d. T he n, a patie nt’s H B V 
ge n ot y pe C se q ue nce (accessi o n n u m ber: K P 0 1 7 2 6 9. 1 H B V is olate J P- 0 2) t hat ha d ma xi m u m 
si milarit y t o t he c o nse ns us was c h ose n f or use i n t he H B V i m m u n o ge n desi g n. T he H B V 
i m m u n o ge n  e nc o m passes  t hree  f ull  le n gt h  H B V -a nti ge ns  ( pre-c ore/c ore,  p ol y merase  a n d  
pre S 1/ pre S 2/s urface)  al o n g  wit h  tr u ncate d  s har k  i n varia nt  c hai n  a n d  tiss ue  plas mi n o ge n  
acti vat or  ge netic  a dj u va nts  a n d  is  e nc o de d  i n  t he  c hi m pa nzee  a de n o viral  vect or.  P oi nt  
m utati o ns were i ntr o d uce d wit hi n t he p o l y merase pr otei n e nc o de d i n t he i m m u n o ge n i n or der 
t o a b olis h its f u ncti o n a n d t o e ns ure n o re plicati o n-c o m pete nt H B V ge n o me c o ul d arise fr o m 
t he i m m u n o ge n se q ue nces. A n H B V-p ol y merase assa y perf or me d b y t he la b orat or y of Pr of. 
Mic hael  Nassal  at  U ni versit y  H os pital  Frei b ur g,  Ger ma n y,  c o nfir me d  t he  a bse nce  of  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 2 5  of 1 0 9  
p ol y merase acti vit y of t he p ol y merase c o ntai ne d i n t he H B V i m m u n o ge n. A  sc he matic of t he 
H B V i m m u n o ge n i n b ot h C h A d O x 1 a n d i n M V A is s h o w n i n Fi g ure 1 . 
Fi g ure 1 
Sc he m atic of He p atitis B Vir us I m m u n o ge n s 
A. C h A d O x 1 i nsert  
 
B. M V A i nsert  
 
T he H B V i m m u n o ge n was cl o ne d a n d rec o vere d i nt o t he C h A d O x 1 vect or ge n o me t o ge nerate 
C h A d O x 1 -H B V   a n d  i nt o M V A  t o  ge nerate  M V A - H B V. Researc h  st oc ks  of  t he  
C h A d O x 1 -H B V vect or were ge nerate d at t he viral vect or c ore facilit y of t he Je n ner I nstit ute, 
U ni versit y of O xf or d.  
Precli nical i m m u n o ge nicit y testi n g: C h A d O x 1 -H B V f oll o we d b y M V A-H B V was f o u n d t o be 
hi g hl y  i m m u n o ge nic  w he n  teste d  i n  m o use  i m m u n o ge nicit y  e x peri me nts  i n  b ot h  i n bre d  
( C 5 7 B L/ 6)  a n d  o ut bre d  ( C D-1)  mice,  meas ure d  usi n g  i nterfer o n -ga m ma  (I F N -γ) 
e nz y me-li n ke d i m m u n os p ot ( E LI S P O T) a n d i ntracell ular c yt o ki ne stai ni n g assa ys. E xcelle nt 
T cell res p o nses were als o o bser ve d t o c ore, p ol y merase a n d s urface H B V a nti ge ns i n H L A -A 2 
tra ns ge nic mice recei vi n g t he pri me- b o ost re gi me n.  
A  G o o d  La b orat or y  Practice  t o xic ol o g y  st u d y  of  C h A d O x 1- H B V  a n d  a  se parate  G o o d  
La b orat or y Practice t o xic ol o g y st u d y of M V A -H B V w ere c o n d ucte d at C o va nce ( U K), a n d 
s h o we d mi ni mal t o xicit y ot her t ha n e x pecte d l ocal site effects (see I n vesti gat or’s Br oc h ures 
f or f urt her st u d y details a n d res ults). 
1. 4  
S u m m ar y of Cli nic al E x perie nce  
O ne  cli nical  st u d y  ( H B V 0 0 1)  t o  i n vesti gate  react o ge nicit y  a n d  e x pl ore  t he  safet y  of  
C h A d O x 1 -H B V  i n  healt h y  a n d  C H B  partici pa nts  is  o n g oi n g  at  d oses  of  2. 5 x  1 0 9 a n d 
2. 5 x 1 0 1 0 vp. At t he hi g her  d ose, o nl y l ocalise d s welli n g at t he vacci nati o n site a n d mi n or 
a d verse e ve nts, w hic h all res ol ve d q uic kl y, ha ve bee n re p orte d. T here ha ve bee n n o re p orts of 
se vere or seri o us a d verse e ve nts ( S A Es) or ot her safet y c o ncer ns. T here ha ve bee n a lar ge 
n u m ber of cli nical st u dies usi n g rec o m bi na nt re plicati o n -i nc o m pete nt ade n o vir uses f oll o we d 
b y M V A t o a d dress a variet y of diseases, s uc h as HI V, H C V, T B , malaria, i nfl ue nza a n d 
pr ostate ca ncer [ 2 4 ]. C h A d O x 1 has bee n a d mi nistere d t o o ver 3 0 0 partici pa nt s (c hi k u n g u n ya, 
M E R S , malaria, i nfl ue nza a n d pr ostate ca ncer) a n d as t he pri me f or a n M V A b o ost i n t he 
malaria, i nfl ue nza, t u berc ul osis a n d pr ostate ca ncer st u dies ( N C T 0 3 2 0 3 4 2 1, N C T 0 1 8 1 8 3 6 2, 
N C T 0 1 6 2 3 5 1 8, N C T 0 1 8 2 9 4 9 0, N C T 0 3 8 1 5 9 4 2 a n d  N C T 0 2 3 9 0 0 6 3) . I n all of t h ose st u dies, 
e xtre mel y hi g h le vels of tra ns ge ne -s pecific C D 4 + a n d C D 8 + T cells ha ve bee n i n d uce d a n d 
t here ha ve bee n n o vacci ne-ass ociate d S A Es  or e vi de nce of a ut oi m m u nit y . T his is t he first 
cli nical st u d y f or t he c o m bi nati o n of t he C h A d O x 1 -H B V  a n d M V A-H B V  vacci nes.  
F urt her  i nf or mati o n   o n C h A d O x 1 - H B V a n d  M V A- H B V are  c o ntai ne d  i n  t he  res pecti ve  
I n vesti gat or’s Br oc h ures; t hese s h o ul d be re vie we d pri or t o st u d y i nitiati o n. 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 2 6  of 1 0 9  
1. 5  
St u d y R ati o n ale  
C hr o nic he patitis B vir us i nfecti o n is a gl o bal p u blic healt h c halle n ge o n t he sa me scale as HI V 
a n d malaria. T he c urre nt pr o p h ylactic vacci ne has n o effect o n esta blis he d c hr o nic i nfecti o n. 
A vaila ble treat me nts s u p press viral re plicati o n, b ut t he y are n ot  c urati ve, lar gel y d ue t o t he 
persiste nce of t he viral c o vale ntl y cl ose d circ ular D N A (ccc D N A), a tra nscri pti o nal te m plate 
i n i nfecte d he pat oc ytes. C hr o nicall y i nfecte d patie nts fail t o m o u nt a cell ular i m m u ne res p o nse 
t hat is s ufficie ntl y r o b ust, f u ncti o nal, a n d s ustai ne d t o clear t he i nfecti o n. T h us, i n m ost cases, 
treat me nt m ust c o nti n ue f or life. H o we ver, e ve n s uccessf ull y virall y s u p presse d patie nts ma y 
still de vel o p li ver ca ncer. 
Ma n y researc h pr o gra ms are o n g oi n g t o de vel o p ne w treat me nt c o nce pts t hat f oc us o n t he 
cleara nce  of  H Bs A g  i n  a  si g nifica nt  pr o p orti o n  of  patie nts,  wit h  t he  pri nci ple  ai ms  of:  
1) st o p pi n g treat me nt wit h n o ris k of rela pse a n d n o ris k of li ver disease pr o gressi o n a n d 2) t o 
f urt her decrease t he ris k of H C C. 
Pre -cli nical m o dels still ha ve c o nsi dera ble li mitati o ns i n t his i n dicati o n, a n d i m p orta nt ga ps i n 
o ur  u n dersta n di n g  of  t he  H B V  re plicati o n  c ycle  a n d  t he  h ost  i m m u ne  res p o nse  m ust  be  
a d dresse d t o e x pa n d t he e x pl oita ble v ul nera bilities i n t he re plicati o n c ycle t hat ca n be tar gete d 
t hera pe uticall y t o c ure t he i nfecti o n. A maj or eff ort has bee n ma de t o c o m pare t he efficie nt 
i nte grate d res p o nse res ulti n g i n H B V cleara nce of ac ute i nfecti o n t o t he d ysre g ulate d res p o nse 
o bser ve d i n patie nts wit h c hr o nic he patitis B. A c o m ple x i nter pla y of i n nate a n d a da pti ve 
i m m u ne res p o nses is esse ntial f or viral cleara nce a n d a fail ure of t hese res p o nses ca n res ult i n 
li ver pat h o ge nesis. C D 8 + T cells are t he mai n effect or cells t hat eli mi nate t he vir us b y c yt ol ytic 
a n d n o n-c yt ol ytic effect or f u ncti o ns [2 5 ,2 6 ]. S ufficie nt C D 4 T cell acti vit y a n d t he pr o d ucti o n 
of ne utralisi n g a nti -H B V e n vel o pe a nti b o dies ma y als o be re q uire d f or pr otecti ve i m m u nit y 
[2 7 ].  
Vaccitec h is de vel o pi n g a pri me b o ost vacci nati o n strate g y usi n g t w o n o n -re plicati n g viral 
vect ors t o deli ver i m m u n o ge ns i n vari o us i n dicati o ns: C h A d O x 1 f oll o we d b y b o osti n g wit h a 
heter ol o g o us  vect or,  M V A,  c o ntai ni n g  t he  sa me  i m m u n o ge n.  T hese  vect ors  are  use d  t o  
ge nerate  hi g h  ma g nit u de  C D 4 +  a n d  C D 8 +  T -cell  res p o nses  a n d  als o  ge nerate  lasti n g  
cell-me diate d  i m m u nit y.  
A de n o viral vect ors re prese nt e xce pti o nal pri mi n g vacci nes b ut are diffic ult t o re use i n t he first 
fe w m o nt hs after a d mi nistrati o n d ue t o i nitial a nti-vect or i m m u nit y. F or t his reas o n, vacci ne 
de vel o pers ofte n use a differe nt vect or ( k n o w n as a heter ol o g o us  pri me -b o ost) t o a u g me nt t he 
le vels of t he i n d uce d T cells [2 8 ,1 5 ].   
M V A b o osts a n d pr ol o n gs t he C D 4 + a n d C D 8 + T cells i n d uce d b y C h A d O x 1. T his t w o - d ose 
heter ol o g o us vacci ne re gi me n has bee n safe a n d i m m u n o ge nic. C h A d O x 1 a n d M V A i ncl u di n g 
d oses u p t o 5  x 1 01 0 v p wit h C h A d O x 1 a n d d oses u p t o 2. 5  x 1 08 pla q ue f or mi n g u nits ( pf u) 
wit h M V A were e val uate d i n vari o us i n dicati o ns.  
C hr o nic he patitis B i nfecti o n is als o ass ociate d wit h u pre g ulati o n of t he P D - 1/ pr o gra m me d 
deat h -li ga n d 1 (P D L - 1) i n hibit or a xis  [2 9 -3 2 ], a n d t he use of c hec k p oi nt i n hi bit ors has s h o w n 
a t hera pe utic effect i n s o me a ni mal m o dels  [3 3 ]. Ni v ol u ma b a n d pe m br oliz u ma b ha ve bee n 
a d mi nistere d t o h u n dre ds of he pat ocell ular carci n o ma patie nts, ma n y of w h o m were i nfecte d 
wit h he patitis B, wit h n o i ncrease i n li ver t o xicit y a n d s o me effect o n H B sA g re d ucti o n. I n 
a d diti o n, a st u d y of ni v ol u ma b, use d at o ne te nt h t he lice nse d d ose f or o nc ol o g y, c o m bi ne d 
wit h a partiall y i m m u n o ge nic H B V vacci ne was s h o w n t o be safe a n d t o i n d uce s o me H B sA g 
re d ucti o n [3 4 ]. T he d ose use d was selecte d base d o n rece pt or occ u pa nc y st u dies w hic h s h o we d 
near ma xi mal peri p heral T cell rece pt or occ u pa nc y at 0. 3 m g/ k g. F urt her st u dies of a nti -P D - 1 
a n d a nti- P D L 1 i n c hr o nic he patitis B are u n der wa y. 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 2 7  of 1 0 9  
St u dies  e xa mi ni n g  t he  effect  of  c hec k p oi nt  i n hi bit ors  a n d  ma n y  ot her  i nter ve nti o ns  ha ve  
f oc use d o n patie nts wit h l o w le vels of ser u m he patitis B D N A a n d le vels of H B sA g meas ure d 
at < 1 0 4 I U/ m L, a n d i n patie nts w h o ha ve well c o ntr olle d C H B w hile o n a nti viral a ge nts, w hic h 
at prese nt is d o mi nate d b y t he use of te n of o vir ( or its pr o dr u g, te n of o vir alafe na mi de f u marate) 
or e nteca vir. M ost f u ncti o nal c ures eit her o n t hera p y or at t hera p y disc o nti n uati o n ha ve bee n 
o bser ve d i n s uc h patie nts. 
T h us, a  pri me -b o ost strate g y usi n g C h A d O x 1 vect or ( C h A d O x 1 -H B V) a n d a n M V A vect or 
( M V A-H B V), wit h a n d wit h o ut ni v ol u ma b will be e val uate d i n t his st u d y. I n or der t o decrease 
p ote ntial safet y iss ues, o nl y partici pa nt s wit h sta ble a nti viral t hera p y i n t he pre vi o us o ne year 
wit h res ulta nt l o w H B V D N A a n d H Bs A g  will be e nr olle d.  As t he T cell res p o nses ma y wa ne 
wit h ti me, a n d a b o ost t o t he hi g hest le vels ma y be nee de d t o s us tain a n o n g oi n g res p o nse (as 
e vi de nce d b y s o me l o weri n g of t he H Bs A g le vels ), a b o ost usi n g t he M V A vacci ne is per mitte d 
at M o nt h  3,  at  t he  discreti o n  of  t he  I n vesti gat or a n d  c o nc urre nce  of  t he  S p o ns or  ( U K 
partici pa nts  o nl y). 
C o m pre he nsi ve re vie w s of C h A d O x 1 - H BV a n d M V A - H B V are c o ntai ne d i n t he res pecti ve 
I n vesti gat or’s Br oc h ures; t hese a n d t he Pac ka ge I nsert f or ni v ol u ma b  s h o ul d be re vie we d pri or 
t o st u d y i nitiati o n. 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 2 8  of 1 0 9  
2  
S T U D Y O B J E C TI V E S  A N D E N D P OI N T S  
O bjecti ves  
E n d p oi nts  
Pri mar y  O bjecti ves  
•  
Deter mi ne t he safet y  a n d react o ge nicit y of  
t he f oll o wi n g i n  partici pa nts  wit h  C H B  
i nfecti o n  a n d  virall y  s u p presse d  wit h  oral  
a nti viral me dicati o n : 
− M V A -H B V vacci ne  
− C h A d O x 1 -H B V  pl us M V A vacci nes  
− C h A d O x 1- H B V pl us M V A vacci nes a n d 
ni v ol u ma b 
Pri mar y  E n d p oi nts  
•  
Safet y a n d react o ge nicit y of t he vacci ne(s): 
i nci de nce  of  a d verse  e ve nts,  S A Es,  
≥Gra de  3  st u d y  vacci ne -relate d  a d verse  
e ve nts wit hi n 4 wee ks of vacci nati o n  
•  
Safet y  of  t he  vacci nes  wit h  ni v ol u ma b : 
i nci de nce  of  a d verse  e ve nts,  S A Es,  
≥Gra de  3 a d verse e ve nts wit hi n 4  wee ks of 
d osi n g  
•  
I nci de nce of  a d verse  e ve nts  of  s pecial  
i nterest ( A E SIs) 
•  
N u m ber  a n d  pr o p orti o n  of  partici pa nt s 
re p orti n g
 treat me nt-e mer ge nt
 a d verse
 
e ve nts wit hi n eac h treat me nt gr o u p  
•  
N u m ber  a n d  pr o p orti o n  of  partici pa nt s 
wit hi n
 eac h
 treat me nt
 gr o u p
 wit h
 
p ote ntiall y cli nicall y si g nifica nt la b orat or y 
val ues  a n d  vital  si g ns  wit hi n  eac h  
treat me nt gr o u p  
•  
C ha n ge fr o m baseli ne i n la b orat or y tests 
a n d vital si g n meas ure me nts t o eac h ti me 
p oi nt of c ollecti o n  
Sec o n dar y O bjecti ves  
•  
Deter mi ne  t he  i m m u n o ge nicit y  of  t he  
f oll o wi n g  i n  partici pa nts  wit h  C H B  
i nfecti o n a n d virall y s u p presse d wit h oral 
a nti viral me dicati o n:  
− M V A -H B V vacci ne  
− C h A d O x 1 -H B V pl us M V A -H B V vacci nes  
− C h A d O x 1 -H B V pl us M V A -H B V vacci ne 
a d mi nistere d wit h ni v ol u ma b 
•  
Deter mi ne  t he  i m pact  of  P D - 1  bl oc ka de 
ti mi n g
 relati ve
 t o
 vacci nati o n
 o n
 
i m m u n o ge nicit y i n partici pa nts wit h C H B 
i nfecti o n a n d virall y s u p presse d wit h oral 
a nti viral me dicati o n  
•  
Deter mi ne t he effect of C  t he f oll o wi n g o n 
t he le vel of he patitis B mar kers: 
− C h A d O x 1- H B V pl us M V A -H B V vacci nes 
wit h o ut ni v ol u ma b 
Sec o n dar y E n d p oi nts  
•  
Ma g nit u de  a n d  a vi dit y  of  H B V  s pecific  
C D 4 + a n d C D 8 + T cells i n d uce d b y eac h 
re gi me n 
•  
Effect o n t he f re q ue nc y a n d ma g nit u de of 
H B V i nfecti o n mar kers ( H Bs A g, He patitis 
B 
surface 
a nti b o d y  
[ H Bs A b ] 
ser oc o n versi o n, he patitis B D N A, H Be A g) 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 2 9  of 1 0 9  
− C h A d O x 1 -H B V pl us M V A -H B V vacci nes 
wit h ni v ol u ma b  
E x pl orat or y  O bjecti ves  
•  
Assess t he H B V s pecific cell ular i m m u ne 
res p o nse  ge nerate d  b y  C h A d O x 1-H B V 
pl us M V A- H B V vacci nes  
•  
Deter mi ne  t he  effect  of  C h A d O x 1 -H B V 
pl us M V A -H B V o n he patitis B bi o mar kers  
E x pl orat or y  E n d p oi nts  
E x pl orat or y e n d p oi nts ma y i ncl u de, b ut ma y n ot 
be li mite d t o:  
•  
Effect  o n  he patitis  B  c ore -relate d A g 
( H Bcr A g) 
•  
Effect  o n  he patitis  B  pre ge n o mic  R N A  
( H B p g R N A) 
•  
I n d ucti o n of i n di vi d ual p he n ot y pic s u bsets 
of  C D 4 +  a n d  C D 8 +  T cells  i n d uce d  b y  
vacci nati o n 
•  
T he T cell brea dt h of res p o nse t o t he H B V  
pr otei ns e nc o de d b y  t he C h A d O x 1 -H B V 
pl us M V A- H B V vacci nes  
•  
Fre q ue nc y of re g ulat or y T c ells res p o nses 
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 3 1  of 1 0 9  
A Data M o nit ori n g C o m mittee ( D M C ) c o m p ose d of t hree i n de pe n de nt e x perts (t w o cli nicia ns 
a n d o ne statisticia n) will be a p p oi nte d t o perf or m u nsc he d ule d re vie ws of t he a vaila ble safet y  
a n d t olera bilit y  st u d y  data  a n d  ma ke  rec o m me n dati o ns  c o ncer ni n g  t he  c o nti n uati o n,  
m o dificati o n or ter mi nati o n of t he st u d y if o ne of t he st u d y st o p pi n g or h ol di n g r ules defi ne d 
i n Secti o n  3. 1. 3  is met. 
3. 1. 2  D ur ati o n of St u d y  
3. 1. 2. 1  D ur ati o n f or e ac h P artici p a nt 
U p t o  1 0. 5 m o nt hs ( u p t o 1. 5  m o nt h s f or scree ni n g a n d 9 m o nt hs o n t he st u d y wit h st u d y 
vacci ne gi ve n o n Da y 0). 
3. 1. 2. 2  D ur ati o n of W h ole St u dy 
It is pla n ne d t hat t he st u d y will ta ke 1 7 m o nt hs t o i m ple me nt, e nr ol a n d rea d o ut. 
T he e n d of t he st u d y is defi ne d as t he date of data base l oc k.  
3. 1. 3  St o p pi n g Criteri a/ H ol di n g Criteri a  
T here will be a re vie w of t he st u d y data b y t he D M C w he n t here is a reas o na ble p ossi bilit y t hat 
t he i n vesti gati o nal vacci ne ca use d a n y of t he S A Es or se vere a d verse e ve nts liste d bel o w,  base d 
o n t he assess me nt of t he I n vesti gat or , i n o ne or m ore partici pa nts at a n y d ose. Vacci nati o ns 
will be p ut o n h ol d pe n di n g t his re vie w: 
•  
Deat h  relate d t o st u d y vacci ne 
•  
Life -t hreate ni n g a d verse e ve nt or life-t hreate ni n g s us pecte d reacti o n 
•  
Seri o us s us pecte d a d verse reacti o n  
•  
S us pecte d u ne x pecte d seri o us a d verse reacti o n ( S U S A R)  
•  
Ac ute aller gic reacti o n or a na p h ylactic s h oc k f oll o wi n g t he a d mi nistrati o n of vacci ne 
i n vesti gati o nal pr o d uct  
•  
A na p h yla xis or br o nc h os pas m, i n dicati ve of a n i m me diate h y perse nsiti vit y reacti o n t o 
st u d y vacci ne 
•  
If a n y partici pa nt has a n y of t he f oll o wi n g d uri n g t he st u d y: 
− Ala ni ne a mi n otra nsferase ( A L T ) or as partate a mi n otra nsferase ( A S T ) > 3 x u p per li mit 
of n or mal ( U L N ) a n d t otal bilir u bi n > 2 x U L N or I nter nati o nal N or malise d Rati o (I N R) 
> 1. 5 
− A L T or A S T > 3 x U L N wit h t he a p peara nce of fati g ue, na usea, v o miti n g, ri g ht u p per 
q ua dra nt pai n or te n der ness, fe ver, ras h, a n d/ or e osi n o p hilia ( > 5 %)  
− Gra de  4  diarr h oea,  h y p ot h yr oi dis m,  h y pert h yr oi dis m,  h y p o p h ysitis,  a dre nal  
i ns ufficie nc y, ras h, t o xic e pi der mal necr ol ysis, Ste ve ns-J o h ns o n s y n dr o me, dia betes, 
ot her i m m u ne -relate d a d verse reacti o n, or creati ni ne ele vati o n   
− Gra de 3 m y ocar ditis or p ne u m o nitis  
− S olicite d l ocal a d verse e ve nts: If t hree o ut of t he first 2 0 partici pa nts d ose d wit h a st u d y  
vacci ne, or > 1 0 % of partici pa nts,  t hereafter, are f oll o we d b y t he sa me Gra de 3 s olicite d 
l ocal a d verse e ve nt 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 3 2  of 1 0 9  
− S olicite d s yste mic a d verse e ve nts: If t hree o ut of t he first 2 0 partici pa nts d ose d wit h a  
st u d y vacci ne, or > 1 0 % of partici pa nts,  t hereafter, are f oll o we d b y t he sa me Gra de 3 
s olicite d s yste mic a d verse e ve nt 
− U ns olicite d a d verse e ve nts: If t hree partici pa nts of t he first 2 0 partici pa nts d ose d, or  
> 1 0 % of partici pa nts,  t hereafter, de vel o p a Gra de 3 u ns olicite d a d verse e ve nt of t he 
sa me t y pe t hat is c o nsi dere d relate d t o st u d y vacci ne 
Ot her  p ote ntial  reas o ns f or  disc o nti n uati o n of  t he sec o n d pla n ne d d ose of  ni v ol u ma b f or 
Gr o u p 4 are f o u n d i n A p pe n di x 2  – T o xicit y Ma na ge me nt G ui deli nes  f or Ni v ol u ma b. 
If, f oll o wi n g re vie w of data, a rec o m me n dati o n is ma de b y t he D M C t o res u me st u d y e nr ol me nt 
a n d vacci ne a d mi nistrati o n, t he D M C will rec or d t heir j u d g me nt i n a me m ora n d u m t o t he st u d y 
file a n d n otif y t he S p o ns or. T he D M C me m ora n d u m will be f or war de d t o t he l ocal Me dical 
M o nit or a n d I n vesti gat ors  a n d a n a p pr o priate s u bsta ntial a me n d me nt file d .  
If t he st u d y is ter mi nate d earl y, the Re g ulat or y A ut h orit ies, I E C/I R Bs a n d st u d y ce ntres will 
be n otifie d wit hi n 1 5 da ys acc or di n g t o l ocal re q uire me nts.  
3. 1. 4  I n di vi d u al St o p pi n g R ules ( All V acci n ate d St u d y P artici p a nts ) 
I n a d diti o n t o t he a b o ve state d gr o u p h ol di n g r ules, st o p pi n g r ules f or i n di vi d ual partici pa nt s 
will a p pl y (i.e. i n a d diti o n t o wit h dra w al of i n di vi d uals fr o m a sec o n d vacci nati o n). St u d y 
partici pa nts w h o prese nt wit h at least o ne of t he f oll o wi n g st o p pi n g r u les will be wit h dra w n 
fr o m f urt her vacci nati o n i n t he st u d y: 
•  
L oc al re acti o ns:  i njecti o n site ulcerati o n, a bscess or necr osis 
•  
L a b or at or y A Es : 
− T he partici pa nt  de vel o ps  a  Gra de  3  la b orat or y  a d verse  e ve nt  c o nsi dere d  p ossi bl y,  
pr o ba bl y  or  defi nitel y  relate d  wit hi n  7  da ys  after  vacci nati o n  a n d  persisti n g  
c o nti n u o usl y at Gra de 3 f or > 7 2 h o urs 
•  
S yste mic  s olicite d a d verse e ve nts: 
− T he partici pa nt de vel o ps  a  Gra de  3  s yste mic  s olicite d  a d verse  e ve nt  c o nsi dere d  
p ossi bl y,  pr o ba bl y  or  defi nitel y  relate d  wit hi n  2  da ys  after  vacci nati o n  ( da y  of  
vacci nati o n a n d o ne s u bse q ue nt da y) a n d persisti n g c o nti n u o usl y at Gra de 3 f or > 7 2 
h o urs 
•  
U ns olicite d a d verse e ve nts:  
− T he partici pa nt  has  a n y  Gra de  3  a d verse  e ve nt  c o nsi dere d  p ossi bl y,  pr o ba bl y  or  
defi nitel y relate d t o vacci nati o n, persisti n g c o nti n u o usl y at Gra de 3 f or > 7 2 h o urs 
− T he partici pa nt  has  a n S A E  c o nsi dere d  p ossi bl y,  pr o ba bl y or  defi nitel y  relate d t o 
vacci nati o n 
− T he partici pa nt  has a n ac ute aller gic reacti o n or a na p h ylactic s h oc k f oll o wi n g t he 
a d mi nistrati o n of vacci ne i n vesti gati o nal pr o d uct  
If t he partici pa nt has a n ac ute ill ness ( m o derate or se vere ill ness wit h or wit h o ut fe ver) or a 
fe ver ( oral te m perat ure > 3 7. 5° C) at t he sc he d ule d ti me of a d mi nistrati o n of i n vesti gati o nal 
pr o d uct,  t he  partici pa nt  will  n ot  recei ve  t he  vacci ne  at  t hat  ti me.  T he  vacci ne  ma y  be  
a d mi nistere d t o t hat partici pa nt  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 
or t he partici pa nt ma y be wit h dra w n fr o m t he st u d y at t he discreti o n of t he I n vesti gat or. 
All vacci nate d partici pa nt s will be f oll o we d f or safet y u ntil res ol uti o n or sta bilisati o n (if 
deter mi ne d t o be c hr o nic se q uelae) of t heir S A Es.  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 3 3  of 1 0 9  
3. 2  
Disc ussi o n of  St u d y Desi g n, I ncl u di n g t he C h oice of C o ntr ol Gr o u ps  
T his is a first i n h u ma n st u d y of t he c o m bi nati o n of C h A d O x 1 -H B V f oll o we d b y M V A -H B V  
vacci ne s ( V T P- 3 0 0) a n d is desi g ne d t o assess t he safet y a n d react o ge nicit y of t hese vacci nes 
gi ve n wit h a n d wit h o ut ni v ol u ma b i n t he tar get C H B p o p ulati o n.  
Sta n dar d cli nical st u d y safet y assess me nts are use d i ncl u di n g a d verse e ve nts, la b orat or y tests, 
vital si g ns a n d p h ysical e xa mi nati o ns. F oreseea ble a d verse e ve nts f oll o wi n g vacci nati o n are 
s olicite d fr o m partici pa nts dail y f or t he first 7 da ys p ost -vacci nati o n usi n g a n electr o nic diar y 
(e Diar y; pl us a n assess me nt at t he st u d y ce ntre o n eac h vacci nati o n da y). S pecific gra di n g 
scales are  defi ne d  f or  se verit y  of  s olicite d  a n d  u ns olicite d  a d verse  e ve nts  a n d  a b n or mal  
la b orat or y res ults f or partici pa nts i n t he lea d-i n p hase (Secti o n  8. 2. 4. 1 ). St u d y st o p pi n g/ h ol di n g 
criteria ha ve bee n defi ne d, wit h a D M C re vie w ma n date d if o ne of t hese is met ( Secti o n  3. 1. 3 ). 
T he C h A d O x 1- H B V  d ose is 2. 5 x 1 01 0 v p, base d o n t he re vie w of t he t w o d oses st u die d i n 
H B V 0 0 1  (2. 5 x 1 0 9 v p a n d 2. 5 x 1 0 1 0 v p). Safet y data fr o m all healt h y v ol u nteers was re vie we d 
fr o m H B V 0 01 b y t he S M C, a n d t he hi g her d ose was c h ose n t o use i n t his st u d y. T o f urt her 
mi ni mi se the  ris k  t hat  i m m u ne  res p o nses  ge nerate d b y  vacci nati o n  d o  n ot  res ult  i n  li ver  
t o xicity , o nl y t h ose partici pa nt s w h ose D N A le vels are well c o ntr olle d o n a nti virals will be 
i ncl u de d i n t he st u d y, a n d t h ose wit h a d va nce d  li ver fi br osis or cirr h osis will be e xcl u de d. T he 
safet y of M V A -H B V will be e val uate d  b y t he S M C  after t he first 6 pa rtici pants  ha ve recei ve d 
t he first d ose, t o i ncl u de at least 7 da ys safet y data, pri or t o i nitiati o n of t he pri me-b o ost re gi me n 
of C h A d O x 1 f oll o we d b y M V A wit h a n d wit h o ut ni v ol u ma b.  
D oses of C h A d O x 1 vacci nes i n pre vi o us st u dies ha ve varie d fr o m 1 x 1 0 8 t o o ver 5 x 1 0 1 0  v p 
per d ose  wit h 2. 5 x 1 0 1 0 v p a p peari n g t o be nearl y o pti mal. A p hase 1 st u d y is e xa mi ni n g t he 
safet y a n d i m m u n o ge nicit y of t w o C h A d O x 1-H B V d oses, 2. 5 x 1 0 9 v p a n d 2. 5 x 1 0 1 0  v p, wit h 
t he e x pectati o n t hat t he latter d ose will be safe a n d c h ose n f or f urt her de vel o p me nt. M V A has 
bee n use d i n ma n y trial s at d oses t hat ra n ge fr o m 1 x 1 0 7 t o 2. 5 x 1 0 8 pf u, a n d i n m ost st u dies 
t he d ose of 1-2 x 1 0 8 pf u is st u die d. T his d ose has bee n s h o w n t o be safe a n d i m m u n o ge nic i n 
t h o usa n ds of partici pa nts t o date. T h us, pe n di n g ne w i nf or mati o n, t he d oses c h ose n f or t his 
st u d y are 2. 5  x  1 0 1 0 v p of C h A d O x 1 -H B V a n d 1 x 1 0 8  pf u  of M V A-H B V . As t he T cell 
res p o nses ma y wa ne wit h ti me, a n d a b o ost t o t he hi g hest le vels ma y be nee de d t o s ustai n a n 
o n g oi n g res p o nse (as e vi de nce d b y s o me l o weri n g of t he H Bs A g le vels ), a b o ost usi n g t he 
M V A vacci ne is per mitte d at M o nt h 3, at t he discreti o n of t he In vesti gat or a n d c o nc urre nce of 
t he S p o ns or ( U K partici pa nts o nl y). 
As a n o pe n -la bel st u d y, data o n t he first 2 7 patie nts fr o m t his c urre nt st u d y t hr o u g h 3 m o nt hs 
f oll o w- u p has bee n re vie we d ( Gr o u p 1, N = 9, f or eac h of Gr o u ps 2, 3, a n d 4, N = 6).  
T here is a differe nce bet wee n G r o u p 3 a n d t he ot her gr o u ps at t he 3-m o nt h ti me p oi nt ( p < 0. 0 1), 
wit h t he mea n l o g 1 0 s urface a nti ge n re d ucti o ns fr o m t he a vera ge of t he scree ni n g a n d baseli ne 
val ues f or Gr o u ps 1, 2, 3, a n d 4 of - 0. 0 9, - 0. 3 5, -1. 0 4 a n d -0. 1 3, res pecti vel y. I n G r o u p 3 t he 
M o nt h  3,  l o g
1 0-tra nsf or me d  c ha n ge fr o m  baseli ne val ues  ra n ge  fr o m  -0. 3 2  t o  - 1. 6 4 
( u n detecta ble), a n d o nl y G r o u p 2 has i n di vi d uals wit h m ore t ha n a 0. 5 l o g dr o p ( 2/ 6, b ot h wit h 
a baseli ne < 1 0 0 I U/ m L ).  
Alt h o u g h t hese n u m bers are s mall, t he hi g hl y si g nifica nt tre n d lea ds t o t he c o ncl usi o n t hat 
a d mi nistrati o n of l o w d ose ni v ol u ma b at t he ti me of t he M V A -H B V b o ost is li kel y be neficial, 
a n d a d mi nistrati o n at t he ti me of C h A d O X 1 -H B V pri me a blates t hese i m pr o v e me nts. T h us, t o 
i ncrease t he li keli h o o d of patie nt be nefit, t he s p o ns or will cl ose Gr o u ps 1 a n d 4, a n d c o nti n ue 
wit h t he pla n ne d N = 1 6 f or Gr o u ps 2 a n d 3.  
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 3 4  of 1 0 9  
T he  prese nt  sta n dar d  meas ure  t o  assess  t he  li keli h o o d  of  f u ncti o nal  c ure  is  t he  le vel  of  
circ ulati n g H Bs A g , alt h o u g h t he e xact c o ntri b uti o ns of e pis o mal ccc D N A or i nte grate d D N A 
are n ot e ntirel y clear. Ot her meas ures u n der i n vesti gati o n t o assess vir ol o gic effects i ncl u de 
meas ure me nt of he patitis  B D N A  a n d effect o n he patitis e A g ser oc o n versi o n. Ot her meas ure 
of vir ol o gic acti vit y u n der st u d y a n d wit h o ut f ull lice ns ure i ncl u de meas ure me nt of he patitis B 
c ore-relate d a nti ge n, a n d meas ure me nt of circ ulati n g h e patitis B f ull le n gt h pre- ge n o mic R N A.  
3. 3  
Be nefit Ris k  Asses s me nt 
T here are p ote ntial k n o w n a n d u n k n o w n ris ks ass ociate d wit h vacci nati o n. Wit h a n y vacci ne, 
i ncl u di n g t h ose  t hat  are lice nse d,  t here  is  a  rare  ris k  of  a na p h yla xis  w hic h  ca n  be  fatal.  
Partici pa nts will t heref ore be o bser ve d i n t he cli nic f or at least 3 0 mi n utes p ost - vacci nati o n a n d 
p ost- ni v ol u ma b  i nf usi o n.  
I ntra m usc ular  i njecti o n  of vacci nes  fre q ue ntl y  ca uses  t he  l ocal  a n d  s yste mic  si g ns  a n d  
s y m pt o ms  t hat  are  bei n g  c ollecte d  as  a d verse  e ve nts.  T hese  will  be  s olicite d  fr o m  t he  
partici pa nt  f or t he first 7 da ys after eac h vacci nati o n t o e ns ure t he y are n o t occ urri n g m ore 
fre q ue ntl y or are m ore se vere t ha n e x pecte d base d o n pre vi o us e x perie nce wit h t he sa me or 
si milar viral vect ors. After t his ti me, u n s olicite d a d verse e ve nts will be c ollecte d at eac h cli nic 
visit t hr o u g h o ut t he st u d y.  
Wit h a n y ne w treat me nt t here is al wa ys a p ossi bilit y of u ne x pecte d a d verse e ve nts. H ol d i n g 
a n d  st o p pi n g r ules ha ve bee n defi ne d f or t he st u d y (see Secti o n  3. 1. 3 ) a n d t he D M C will 
perf or m a re vie w of safet y data if o ne of t hese is met. T here are als o r o uti nel y sc he d ule d 
re vie ws of safet y d uri n g  t he lea d-i n p hase b y t he S M C. F urt her detail is pr o vi de d i n t he 
I n vesti gat or’s Br oc h ure. 
T he C h A d O x 1 a n d M V A vect ors ha ve bee n wi del y a d mi nistere d f or ma n y pat h ol o gies wit h o ut 
si g nifica nt safet y c o ncer ns (see Secti o n  1. 4 ). F urt her detail is pr o vi de d i n t he I n vesti gat or’s 
Br oc h ure.  
As t his is a n earl y de vel o p me nt  st u d y wit h little cli nical data , t here ma y be n o be nefit t o st u d y 
partici pa nts . T he partici pa nts will  h o we ver recei ve a d diti o nal m o nit ori n g of t heir H B V  stat us 
c o m pare d t o t he sta n dar d of care.  
Ni v ol u ma b, at f ull d ose , is ass ociate d wit h a variet y of a d verse effect, i ncl u di n g p ote ntial deat h. 
C o m m o n a d verse effects i ncl u de t h yr oi ditis, c olitis, p ne u m o nitis, he patitis, m y ocar ditis, a n d 
ot her a d verse i m m u ne relate d effects . I n t he p u blis he d data usi n g ni v ol u ma b at 0. 3 m g/ k g t he 
m ost c o m m o n a d verse e ve nts were fati g ue, hea dac he a n d c o u g h, wit h n o i m m u ne -relate d 
a d verse e ve nts o bser ve d [3 5 ].   

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 3 5  of 1 0 9  
4  
S T U D Y P O P U L A TI O N  
4. 1  
N u m ber of P artici p a nts  
It  is  pla n ne d  t hat u p  t o   a p pr o xi matel y  5 2 partici pa nts  wit h  C H B  i nfecti o n  a n d  virall y  
s u p presse d  wit h  oral  a nti viral  me dicati o n  will  be  e nr olle d  i n  t he  st u d y.  C hr o nic  H B V  
partici pa nts will be recr uite d/ dee me d eli gi ble b y he pat ol o gists, i nfecti o us disease s pecialists or 
p h ysicia ns  e x perie nce d  i n  treati n g  C H B  p artici pa nts.  Ce ntres  n ot  meeti n g  t he  e nr ol me nt  
e x pectati o ns  will  be  c o nsi dere d  f or  re place me nt  wit h  t he a d diti o n  of  a  ne w  ce ntre.  If  
partici pa nts lea ve t he st u d y bef ore all f oll o w -u p visits are c o m plete d (f or a n y reas o n), t he y ma y 
be re place d at t he discre ti o n of t he st u d y tea m. A l o g of all partici pa nts e nr olle d i nt o t he st u d y 
(i.e. ha vi n g gi ve n i nf or me d c o nse nt) will be mai ntai ne d i n t he I n vesti gat or’s Site File (I S F) at 
t he st u d y ce ntre irres pecti ve of w het her t he y ha ve bee n treate d wit h vacci ne or n ot. 
Versi o n 6. 0 of t he pr ot oc ol has cl ose d Gr o u ps 1 a n d 4 t o f urt her ra n d o misati o n f oll o wi n g 
a nalysis of o n -g oi n g data;  Gr o u ps 2 a n d 3 will c o nti n ue t o recr uit a p pr o xi matel y 1 6 partici pa nts 
i n a 1: 1 rati o. 
T he n u m ber of partici pa nts is base d o n feasi bilit y c o nsi derati o ns rat her t ha n f or mal sa m ple size 
calc ulati o ns. A t otal of u p t o a p pr o xi matel y 5 2 partici pa nts  wit h C H B i nfecti o n is c o nsi dere d 
s ufficie nt t o c o nfir m t he safet y, t olera bilit y a n d i m m u n o ge nicit y of C h A d O x 1-H B V f oll o we d 
b y M V A -H B V, C h A d O x 1 -H B V pl us M V A vacci nes wit h or wit h o ut ni v ol u ma b, a n d t o a ns wer 
t he o bjecti ves of t he st u d y. 
T he  statistical  c o nsi derati o ns  use d  t o  deter mi ne  t he  n u m ber  of   partici pa nts pla n ne d  a n d  
e val ua ble are prese nte d i n Secti o n  1 0. 1 . 
4. 2  
I ncl usi o n Criteri a 
Partici pa nts  m ust meet all t he f oll o wi n g criteria t o be eli gi ble f or t he st u d y: 
1.  A d ult m ales or fe males a ge d ≥1 8 t o ≤6 5 years at scree ni n g (acc or di n g t o c o u ntr y/l ocal 
re g ulati o ns) 
2.  B MI ≤3 2 k g/ m 2 
3.  A ble  t o  pr o vi de  i nf or me d  c o nse nt  i n dicati n g  t he y  u n dersta n d  t he  p ur p ose  of,  a n d  
pr oce d ures re q uire d, f or t he st u d y a n d are willi n g t o partici pate 
4.  If fe male, willi n g n ot t o bec o me pre g na nt u p t o 8 wee ks after last d ose of st u d y vacci ne  
a n d u p t o 5 m o nt hs after t he last d ose of ni v ol u ma b 
5.  If fe male: N ot pre g na nt or breast fee di n g a n d o ne of t he f oll o wi n g: 
•  
Of n o n -c hil d beari n g p ote ntial (i.e. w o me n w h o ha ve ha d a h ysterect o m y or t u bal 
li gati o n or are p ost-me n o pa usal, as defi ne d b y n o me nses i n ≥1 year  a n d wit h o ut 
a n alter nati ve me dical ca use ) 
•  
Of c hil d beari n g p ote ntial b ut a grees t o practice hi g hl y effecti ve c o ntrace pti o n f or 
4 wee ks pri or t o st u d y vacci ne a n d 8 wee ks after st u d y vacci ne a n d 5 m o nt hs after 
t he last d ose of ni v ol u ma b. Hi g hl y effecti ve met h o ds of c o ntrace pti o n i ncl u de o ne 
or m ore of t he f oll o wi n g:  
− M ale part ner w h o is sterile ( me dicall y effecti ve vasect o m y) pri or t o t he fe male 
partici pa nt’s e ntr y i nt o t he st u d y a n d is t he s ole se x ual part ner f or t he fe male 
partici pa nt  
− C o m bi ne d  ( o estr o ge n  a n d  pr o gest o ge n  c o ntai ni n g)  h or m o nal  c o ntrace pti o n  
ass ociate d wit h i n hi biti o n of o v ulati o n:  

 
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− oral 
− i ntra va gi nal 
− tra ns der mal 
− Pr o gest o ge n- o nl y  h or m o nal  c o ntrace pti o n  ass ociate d  wit h  i n hi biti o n  of  
o v ulati o n: 
− oral 
− i njecta ble 
− i m pla nta ble 
− A n i ntra uteri ne de vice  
− Bilateral t u bal occl usi o n  
6.  D oc u me nte d e vi de nce of c hr o nic H B V i nfecti o n (e. g. H Bs A g p ositi ve ≥6 m o nt hs wit h 
detecta ble H Bs A g le vels at scree ni n g)  
7.  Recei pt of o nl y eit her e nteca vir, te n of o vir (te n of o vir alafe na mi de f u marate or te n of o vir 
dis o pr o xil f u marate), or besif o vir f or at least 1 2  m o nt hs bef ore scree ni n g  
8.  Virall y s u p presse d ( H B V -D N A viral l oa d bel o w 4 0 I U/ m L f or ≥ 1 year)  
9.  H Bs A g le vels < 4 0 0 0 I U/ m L 
4. 3  
E xcl usi o n Criteri a  
Partici pa nts  w h o meet a ny  of t he f oll o wi n g criteria are n ot eli gi ble f or t he st u d y: 
1.  Prese nce of a n y si g nifica nt ac ute or c hr o nic, u nc o ntr olle d me dical / ps yc hiatric ill ness 
2.  He patitis C vir us a nti b o d y p ositi ve.  
3.  HI V a nti b o d y p ositi ve 
4.  C o -i nfecti o n wit h he patitis D vir us ( H D V)  
5.  D oc u me nte d cirr h osis or a d va nce d fi br osis i n dicate d b y a li ver bi o ps y wit hi n 6 m o nt hs 
pri or t o scree ni n g  (Meta vir acti vit y gra de A 3 a n d sta ges F 3 a n d F 4; Is ha k sta ges 4 – 6) .  
I n t he a bse nce of a d oc u me nte d li ver bi o ps y, eit her 1 of t he f oll o wi n g ( n ot b ot h):  
•  Scree ni n g Fi br osca n wit h a res ult > 9 kil o pascals ( k Pa) ( or t he e q ui vale nt) wit hi n 
≤ 6 m o nt hs of scree ni n g, O R  
•  Scree ni n g Fi br o Test > 0. 4 8 a n d A S T t o platelet rati o i n de x ( A P RI) of > 1.  
6.  A L T > 3 x U L N, i nter nati o nal n or malize d rati o (I N R) > 1. 5 u nless t he pa rtici pant was 
sta ble o n a n a ntic oa g ula nt re gi me n affecti n g I N R, al b u mi n < 3. 5 g/ d L, direct bilir u bi n 
> 1. 5 U L N , platelet c o u nt < 1 0 0, 0 0 0/µ L.  
7.  A hist or y of li ver dec o m pe nsati o n (e. g. ascites, e nce p hal o pat h y or variceal hae m orr ha ge)  
8.  Pri or h e pat ocell ular carci n o ma 
9.  C hr o nic li ver disease of a n o n- H B V aeti ol o g y  
1 0.  Hist or y or e vi de nce of a ut oi m m u ne disease or k n o w n i m m u n o deficie nc y of a n y ca use 
1 1.  Prese nce of acti ve i nfecti o n  
1 2.  E vi de nce of i nterstitial l u n g disease, acti ve p ne u m o nitis, m y ocar ditis, or a hist or y of 
m y ocar ditis  
1 3.  Past h ist or y of t h yr oi d dis or der or a b n or mal t h yr oi d f u ncti o n at scree ni n g t hat is still 
acti ve a n d u nc o ntr olle d  

 
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1 4.  Pr ol o n ge d t hera p y wit h i m m u n o m o d ulat ors (e. g .  c ortic oster oi ds s uc h as pre d nis o ne 
> 1 0 m g/ da y )  or  bi ol o gics  (e. g.  m o n ocl o nal  a nti b o dies,  I F N)  wit hi n  3  m o nt hs  of  
scree ni n g 
1 5.  Recei pt of i m m u n o gl o b uli n or ot her bl o o d pr o d ucts wit hi n 3 m o nt hs pri or t o e nr ol me nt 
1 6.  Recei pt of a n y i n vesti gati o nal dr u g or vacci ne wit hi n 3 m o nt hs pri or t o scree ni n g  
1 7.  Recei pt of a n y a de n o viral -base d vacci ne wit hi n 3 m o nt hs pri or t o a d mi nistrati o n of 
C h A d O x 1 -H B V  o n  Da y  0,  or  pla n  t o  recei ve  a n  a de n o viral -base d  vacci ne  wit hi n  
3 m o nt hs after Da y 0 
1 8.  Recei pt of a n y li ve vacci nes wit hi n 3 0 da ys pri or t o scree ni n g  
1 9.  Recei pt of a n y i nacti vate d vacci nes wit hi n 1 4  da ys pri or t o scree ni n g 
2 0.  Hist or y of se vere h y perse nsiti vit y or a na p h ylactic reacti o ns li kel y t o be e xacer bate d b y 
a n y c o m p o ne nt of t he vacci ne or ni v ol u ma b  
2 1.  Mali g na nc y wit hi n 5 years pri or t o scree ni n g wit h t he e xce pti o n of s pecific ca ncers t hat 
are c ure d b y s ur gical resecti o n (e. g. e xce pt basal cell s ki n carci n o ma of t he s ki n a n d 
cer vical  carci n o ma).  Partici pa nts  u n der  e val uati o n  f or  p ossi ble  mali g na nc y  are  n ot 
eli gi ble 
2 2.  C urre nt alc o h ol or s u bsta nce a b use j u d ge d b y t he I n vesti gat or t o p ote ntiall y i nterfere 
wit h partici pa nt safet y a n d c o m plia nce  
2 3.  Si g nifica nt car diac disease or u nsta ble u nc o ntr olle d car diac disease  
2 4.  A n y la b orat or y test w hic h is a b n or mal, a n d w hic h is dee me d b y t he I n vesti gat or t o be 
cli nicall y si g nifica nt.  
2 5.  C yt ot o xic a ge nts, ot her a nti H B V or tra diti o nal her bal me dici nes w hic h, i n t he o pi ni o n 
of t he In vesti gat or, ma y ha ve acti vit y a gai nst H B V wit hi n t he pre vi o us 6 m o nt hs pri or 
t o ra n d o mizati o n 
2 6.  A n y  ot her  fi n di n g  t hat,  i n  t he  o pi ni o n  of  t he  I n vesti gat or,  dee ms  t he  partici pa nt  
u ns uita ble f or t he st u d y 
4. 3. 1  Re m o v al of P artici p a nts  fr o m T her a p y or Assess me nt  
4. 3. 1. 1  C o ntr ai n dic ati o ns t o V acci n ati o n 
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 st u d y vacci ne  at t hat 
p oi nt i n ti me; if a n y o ne of t hese e ve nts occ urs at t he ti me sc he d ule d f or vacci nati o n, t he 
partici pa nt ma y be vacci nate d wit hi n 2 8 da ys  of t he sc he d ule d ti me, or wit h dra w n fr o m t he 
st u d y at t he discreti o n of t he I n vesti gat or.  
•  
Ac ute disease at t he ti me of vacci nati o n. Ac ute disease is defi ne d as t he prese nce of a 
m o derate or se vere ill ness wit h or wit h o ut fe ver. All st u d y vacci nes ca n be a d mi nistere d 
t o partici pa nts wit h a mi n or ill ness s uc h as diarr h oea, mil d u p per res pirat or y i nfecti o n 
wit h or wit h o ut l o w -gra de fe brile ill ness  
•  
Te m perat ure of > 3 7. 5° C ( 1 0 0. 4° F) at t he ti me of vacci nati o n  
4. 3. 1. 2  St u dy Disc o nti n u ati o n 
Partici pa nts ma y c h o ose t o disc o nti n ue b ot h treat me nt a n d st u d y assess me nts. I n t his case, t he 
In vesti gat or or  researc h w or ker  s h o ul d atte m pt t o ascertai n t he reas o n f or a p artici pant’s 
disc o nti n uati o n of safet y f oll o w -u p assess me nts, wit h o ut c o m pr o misi n g t heir ri g ht t o wit h dra w 
at a n y ti me wit h o ut gi vi n g a reas o n, a n d rec or d t his i n t he electr o nic Case Re p ort F or m  (eC R F ). 
N ote t hat, u nless t he pa rtici pant s pecificall y re v o kes t heir earlier c o nse nt f or i nf or mati o n a b o ut 

 
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t heir pr o gress, cli nical i nf or mati o n will c o nti n ue t o be c ollecte d a n d partici pa nt i nf or mati o n 
will be retai ne d i n t he trial data base a n d use d f or i nte nti o n- t o-treat a nal yses of st u d y o utc o me. 
Partici pa nts m a y  be wit h dra w n fr o m t he st u d y i n t he e ve nt of: 
•  
A se vere a d verse e ve nt  or S A E  
•  
Diffic ulties i n o btai ni n g bl o o d or ot her sa m ples  
•  
Fail ure of t he partici pa nt t o c o m pl y wit h t he pr ot oc ol re q uire me nts or t o c o o perate wit h 
t he I n vesti gat or 
Partici pa nts m ust  be wit h dra w n fr o m t he st u d y i n t he e ve nt of: 
•  
Wit h dra wal of c o nse nt  
Partici pa nts will be wit h dra w n fr o m st u d y vacci nati o n (if it has n ot yet bee n a d mi nistere d) i n 
t he e ve nt of: 
•  
F or  safet y  reas o ns,  it  bei n g  i n  t he  best  i nterest  of  t he  partici pa nt  t hat  he/s he  be  
wit h dra w n, i n t he I n vesti gat or’s o pi ni o n 
•  
A p ositi ve pre g na nc y test or if t he partici pa nt is n o n -c o m plia nt wit h t he c o ntrace pti o n 
re q uire me nts (see Secti o n  4. 2 ) 
•  
De vel o p me nt  of  a  me dical  c o n diti o n  t hat  re q uires  c o nc o mita nt  treat me nt  wit h  a  
p ote ntiall y t o xic t hera p y  
4. 3. 2  St u d y Ter mi n ati o n  
T he st u d y ma y be ter mi nate d, eit her at o ne ce ntre or all ce ntres  f or t he f oll o wi n g reas o ns: 
•  
T he disc o ver y of a n u ne x pecte d, seri o us or u nacce pta ble ris k t o partici pa nts  e nr olle d i n 
t he st u d y 
•  
T he decisi o n o n t he part of t he S p o ns or t o s us pe n d or disc o nti n ue testi n g, e val uati o n or 
de vel o p me nt  of  C h A d O x 1 -H B V a n d M V A -H B V  vacci nes. I n  t he  e ve nt  of  t he  
S p o ns or’s  decisi o n  t o  n o  l o n ger  s u p pl y  st u d y  vacci ne ,  a m ple  n otificati o n  will  be  
pr o vi de d s o t hat a p pr o priate a dj ust me nts t o treat me nt ca n be ma de. 
•  
Seri o us fail ure of t he I n vesti gat or t o c o m pl y wit h I C H G C P [3 6 ] or l ocal re g ulati o ns 
•  
S u b missi o n of k n o wi n gl y false i nf or mati o n fr o m t he st u d y ce ntre t o t he S p o ns or, t he 
i n de pe n de nt et hics c o m mittee  (I E C)/i nstit uti o nal re vie w b oar d (I R B) or re g ulat or y 
a ut h orities 
•  
Maj or, re peate d, n o n -a d here nce t o t he pr ot oc ol 
T he S p o ns or m ust be i nf or me d i m me diatel y i n t he e ve nt of a n y maj or pr ot oc ol vi olati o n or 
seri o us breac h of I C H G C P. 

 
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5  
IN V E S TI G A TI O N A L M E DI CI N A L P R O D U C T S  
T he I n vesti gat or m ust e ns ure t hat st u d y vacci nes a n d ni v ol u ma b are  ha n dle d o nl y b y st u d y 
tea m me m bers w h o ha ve bee n a p pr o priatel y trai ne d f or t he c o n d uct of t his cli nical st u d y a n d 
t hat d osi n g is o nl y perf or me d b y st u d y tea m me m bers w h o f ull y u n dersta n d t he pr oce d ures 
o utli ne d i n t his secti o n, t he I n vesti gat or's Br oc h ure a n d t he P har mac y  Ma n ual . A Dele gati o n 
of A ut h orit y L o g will be mai ntai ne d b y t he st u d y ce ntre a n d will i de ntif y t he i n di vi d ual(s) 
a ut h orise d t o pre pare a n d a d mi nister t he st u d y vacci ne. 
5. 1  
I de ntit y of I n vesti g ati o n al Me dici n al Pr o d ucts 
5. 1. 1  St u d y V acci nes  
C h A d O x 1 -H B V is a ge neticall y -m o difie d ( G M) n o n -re plicati n g c hi m pa nzee a de n o vir us vect or 
e nc o di n g H B V c o nse ns us se q ue nces fr o m a gr o u p  C ge n ot y pe. T he C h A d O x 1 vir us has bee n 
e n gi neere d t o be re plicati o n deficie nt. 
C h A d O x 1 - H BV is f or m ulate d i n is ot o nic b uffere d sali ne c o m prisi n g of 1 0  m M L- h isti di ne, 
3 5 m M  Na Cl,  7. 5 %  s ucr ose  ( w/ v),  1  m M  M g Cl 2. 6 H2O ,  0.1 %  ( w/ v)  P ol ys or bate 8 0, 
0. 1 m M  et h yle ne dia mi netetraacetic aci d, 0. 5 % et ha n ol ( v/ v), water f or i njecti o ns t o 1 m L , p H 
6. 6 t o a tar get c o nce ntrati o n of 1 x 1 0 1 1 v p/ m L. 
M V A -H B V  is a G M p o x vir us t hat is n o n- re plicati n g i n ma m malia n cells e nc o di n g t he sa me 
H B V c o nse ns us se q ue nces  as C h A d O x 1 -H B V . T he M V A vir us is n o l o n ger a ble t o re plicate 
i n h u ma ns a n d has safel y bee n a d mi nistere d t o o ver 1 3 0, 0 0 0  pe o ple. It b ot h b o osts a n d pr ol o n gs 
t he C D 4 + a n d C D 8 + T cells i n d uce d b y C h A d O x 1. 
M V A -H B V  is f or m ulate d i n sacc har ose 5 0  g/ L, 5 0  m M Na Cl, 1 0  m M  T RI S, 1 0  m M s o di u m 
gl uta mate, p H 8. 0 t o a tar get fi nal c o nce ntrati o n of 2. 0 x 1 0 8 pf u / m L.  
T he C h A d O x 1 - H BV a n d M V A- H BV vacci nes will be s u p plie d i n glass  vials. T he vials are 
st o p pere d  wit h  sterilise d  E ur o pea n P har mac o p oeial /U nite d  States  P har mac o p oeial  T y pe  1  
c hl or o b ut yl 
a n d
 br o m o b ut yl  
r u b ber
 st o p pers
 res pecti vel y 
a n d
 seale d
 wit h
 
al u mi ni u m/c o p ol y mer ca ps. 
T he st u d y vacci nes  are ma n ufact ure d t o G o o d Ma n ufact uri n g Practice  a n d release d b y a 
q ualifie d pers o n.  
5. 1. 2  Ni v ol u m a b 
Ni v ol u ma b is a p pr o ve d i n all of t he partici pati n g c o u ntries ( S o ut h K orea, Tai wa n a n d t he U K) 
f or o nc ol o gic i n dicati o ns. It is pr o vi de d as a 1 0 m g/ m L s ol uti o n i n a glass vial wit h a c oate d 
b ut yl r u b ber st o p per a n d seale d wit h a n al u mi ni u m ca p. 

 
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m o nit ors s h o ul d be d o w nl oa de d acc or di n g t o t he acc o m pa n yi n g i nstr ucti o ns i n t he s hi p me nt. 
Te m perat ure  rec or ds  m ust  be  se nt  t o  t he  S p o ns or  a n d  t he  ce ntre  will  recei ve  writte n  
c o nfir mati o n t hat t he vials are cli nicall y release d bef ore t he y are use d. If t he t e m perat ure 
m o nit or has bee n o ut of ra n ge, t he n t he s hi p me nt s h o ul d be place d i nt o q uara nti ne a n d t he 
S p o ns or a n d St u d y M o nit or c o ntacte d i m me diatel y t o deter mi ne w het her t he st u d y vacci ne 
ma y be use d.  
At t he start of t he st u d y, a s ufficie nt n u m ber of  st u d y vacci ne vials will be s hi p pe d t o eac h 
st u d y ce ntre base d o n pr ojecte d recr uit me nt at eac h ce ntre wit h  a p pr o priate o vera ge i n case of 
s pilla ge or brea ka ge. F urt her st u d y vacci ne s u p plies ma y be re q ueste d f oll o wi n g t he re-s u p pl y 
pr ocess i n t he P har mac y  Ma n ual.  
5. 4  
St or a ge 
Vials of C h A d O x 1 -H B V a n d M V A -H B V m ust be st ore d i n a c o nti n u o usl y m o nit ore d ≤- 7 0oC 
freezer a n d ni v ol u ma b m ust be st ore d i n t he o uter cart o n (t o pr otect fr o m li g ht) bet wee n 
2 a n d 8 oC i n a c o nti n u o usl y m o nit ore d refri gerat or.  
All st u d y vacci ne a n d st u d y -la belle d ni v ol u ma b m ust be ke pt i n a sec ure d l ocati o n wit h n o 
access f or u na ut h orise d pers o n nel.   
5. 5  
Acc o u nt a bilit y  
T he p har macist or  desi g nee is re q uire d t o mai ntai n acc urate acc o u nta bilit y rec or ds f or t he st u d y 
vacci ne. I nstr ucti o ns a n d f or ms t o be c o m plete d a n d ke pt f or acc o u nta bilit y will be pr o vi de d 
t o t he p har macist or desi g nee. If t he p har macist or desi g nee wis hes t o use st u d y ce ntre-s pecific 
acc o u nta bilit y f or ms, t hese m ust be re vie we d a n d a p pr o ve d i n a d va nce b y t he S p o ns or. U p o n 
c o m pleti o n of t he st u d y, all acc o u nta bilit y rec or ds will be c o pie d a n d t he c o pies file d i n t he 
electr o nic Trial Master File ( e T M F). T he ori gi nals m ust be mai ntai ne d at t he st u d y ce ntre wit h 
t he rest of t he st u d y rec or ds. 
T he n u m ber of vials of st u d y vacci nes a n d ni v ol u ma b  recei ve d a n d dis pe nse d m ust be rec or de d 
o n a partici pa nt b y partici pa nt basis, i ncl u di n g t he a p plica ble batc h n u m ber.  
5. 6  
Destr ucti o n or Dis p os al  
T he S p o ns or will pr o vi de i nstr ucti o ns f or t he ret ur n of u n use d C h A d O x 1 -H B V a n d M V A -H B V  
vacci nes  a n d  st u d y -la belle d  ni v ol u ma b.  Ge neticall y  m o difie d  or ga nis m  ( G M O)  waste,  
i ncl u di n g e m pt y vials after f ull st u d y vacci ne acc o u nta bilit y has bee n c o n d ucte d, will be 
destr o ye d b y a p pr o priatel y lice nse d ve n d ors. T his destr ucti o n will be rec or de d wit h a n ori gi nal 
c o p y ke pt at t he ce ntre a n d a c o p y se nt t o t he e T M F. 
5. 7  
Met h o d of Assi g ni n g P artici p a nts  t o Tre at me nt Gr o u ps 
Partici pa nts ha ve s o far bee n ra n d o mise d t o all o pe n gr o u ps i n  a 1: 1: 1: 1 all ocati o n as eac h 
gr o u p is i nitiate d. Pr ot oc ol Versi o n 6. 0 cl oses Gr o u ps 1 a n d 4 t o f urt her ra n d o misati o n a n d all 
re mai ni n g partici pa nts will be ra n d o mise d t o Gr o u ps 2 a n d 3 o nl y i n a 1: 1 rati o.  
A se nti nel partici pa nt  will be d ose d i n c o h ort 1, a n d t he rest of t he c o h ort will o nl y be e nr olle d 
at least 4 8 h o urs later. F oll o wi n g t he 7 -da y safet y assess me nt of t he first 6 partici pa nts i n 
Gr o u p 1 b y t he S M C, Gr o u p  2 will be i nitiate d. Gr o u ps 3 a n d 4 will be i nitiate d after e val uati o n 
of safet y data 7  da ys after t he first 6 partici pa nts i n Gr o u p 2 ha ve recei ve d C h A d O x 1 -H B V . At  
t he scree ni n g visit, partici pa nts will be se q ue ntiall y all ocate d a scree ni n g n u m ber o nce writte n, 
i nf or me d c o nse nt has bee n o btai ne d . T he y will be i de ntifie d b y t his n u m ber u ntil e ntr y i nt o 
st u d y. 

 
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C O N FI D E N TI A L  
P a ge 4 2  of 1 0 9  
P artici pa nts f ulfilli n g e ntr y criteria will be all ocate d a n  e nr ol me nt  n u m ber a n d all ocate d t o 
treat me nt base d o n t he treat me nt sc he d ule pre pare d b y statisticia n.  
O nce scree ni n g a n d e nr ol me nt n u m bers ha ve bee n assi g ne d, n o atte m pt will be ma de t o use 
t hose n u m bers a gai n. If an e nr ol me nt n u m ber is all ocate d i nc orrectl y, n o atte m pt will be ma de 
t o re me d y t he err or o nce t he st u d y vacci ne has bee n dis pe nse d. A n y partici pa nts t hat are 
wit h dra w n pri or t o eit her  vacci nati o n will be re place d o n a case b y case basis f oll o wi n g 
disc ussi o n wit h t he S p o ns or. Disc o nti n ue d partici pa nts f oll o wi n g vacci nati o n w h o d o n ot 
c o m plete all f oll o w - u p visits will be re place d f oll o wi n g disc ussi o n wit h t he S p o ns or. 
A n y re place me nt partici pa nts will be gi ve n t he ne xt se q ue ntial partici pa nt n u m ber. 
T he treat me nt sc he d ule list will be hel d b y t he statisticia n d uri n g t he st u d y. 
5. 8  
Selecti o n of D oses, D osi n g Sc he d ule a n d A d mi nistr ati o n  
5. 8. 1  Selecti o n of D oses i n t he St u d y  
T he C h A d O x 1- H B V d ose is 2. 5 x 1 0 1 0 v p, base d o n t he re vie w of t he t w o d oses st u die d i n 
st u d y H B V 0 0 1 ( 2. 5 x 1 0 9 v p a n d 2. 5 x 1 0 1 0 v p ). Safet y data fr o m all healt h y v ol u nteers was  
re vie we d fr o m H B V 0 01 b y t he S M C, a n d t he hi g her d ose was c h ose n t o use i n t his st u d y . T his 
d ose, or hi g her , of C h A d O x 1 -base d vacci nes has bee n safel y use d i n h u n dre ds of partici pa nts 
(see I n vesti gat or’s Br oc h ure), a n d t h o usa n ds of pe o ple ha ve bee n i m m u nise d wit h a C h A d O x 1 
C O VI D -1 9 vacci ne at a d ose of 5  x 1 01 0 v p. T he d ose of M V A - H BV will be fi xe d at 1 x 1 0 8 
pf u as ta ke n fr o m hist orical data of pre vi o us st u dies . A 1. 5  x 1 08 pf u M V A d ose was use d i n 
nearl y 2, 0 0 0  healt h y partici pa nts i n i nfl ue nza st u dies c o n d ucte d b y O xf or d U ni versit y a n d 
Vaccitec h.  
T he d ose of ni v ol u ma b will be fi xe d at 0. 3 m g/ k g t o be gi ve n i ntra ve n o usl y o ver 3 0 mi n utes. 
5. 8. 2  Selecti o n  a n d Ti mi n g of D ose f or e ac h P artici p a nt  
5. 8. 2. 1  D osi n g Sc he d ule 
T he partici pa nts will be all ocate d t o d osi n g gr o u p de pe n di n g o n t he treat me nt sc he d ule  a n d 
g r o u ps o pe n at t he ti me of ra n d o misati o n. Vacci nati o n will be perf or me d o n Da y 0, after 
eli gi bilit y has bee n rec o nfir me d, a n d o n Da y 2 8. 
If a partici pa nt has a 0. 5 l o g or greater dr o p i n he patitis B s urface a nti ge n at Da y 3 5, t he y ma y 
recei ve a b o oster d ose of M V A- H BV at M o nt h  3, at t he I n vesti gat or’s discreti o n a n d after 
disc ussi o n wit h t he S p o ns or ( U K partici pa nts o nl y). 
T here are n o restricti o ns i n t he ti me of da y t hat t he vacci nati o n s h o ul d be a d mi nistere d or i n 
ti mi n g of vacci nati o n i n relati o n t o meals. 
5. 8. 2. 2  St u dy V acci ne Pre p ar ati o n a n d A d mi nistr ati o n  
C h A d O x 1 -H B V a n d M V A -H B V  vials s h o ul d  be all o we d t o reac h r o o m te m perat ure bef ore 
use.  
T he st u d y vacci nes will be pr o vi de d at 1 x 1 0 1 1 v p/ ml C h A d O x 1 -H B V a n d 2 x 1 0 8 pf u/ ml f or 
M V A -H B V.  T he a p pr o priate d oses will be pre pare d b y dil uti o n of i n di vi d ual vials o n a per 
partici pa nt basis b y st u d y staff acc or di n g t o t he pr oce d ure i n t he P har mac y Ma n ual. D ose 
Pre parati o n  kits i ncl u di n g e q ui p me nt will be pr o vi de d b y t he S p o ns or. 
B ot h vacci nati o ns will be gi ve n b y i ntra m usc ular i njecti o n i nt o t he delt oi d m uscle, t o t he sa me, 
n o n- d o mi na nt ar m i n a partici pa nt, w here p ossi ble.  All vacci nati o ns will be ma de b y a s uita bl y 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 4 3  of 1 0 9  
q ualifie d healt h pr ofessi o nal. A sec o n d st u d y tea m me m ber will p erf or m a c hec k of t he vacci ne 
dil uti o n t o e ns ure t he ri g ht dil uti o n is perf or me d . 
T he s uita bl y q ualifie d healt hcare pr ofessi o nal will wear gl o ves, e ye pr otecti o n a n d a n a pr o n or 
la b orat or y c oat/ g o w n d uri n g t he pr oce d ure. T he vacci nati o n site will be c o vere d wit h a sterile 
dressi n g t o mi ni mise disse mi nati o n of t he rec o m bi na nt vir us i nt o t he e n vir o n me nt. T his s h o ul d 
a bs or b a n y vir us t hat ma y lea k o ut t hr o u g h t he nee dle trac k. T he sterile dressi n g will be 
re m o ve d a p pr o xi matel y 1 0 mi n utes after vacci nati o n. T he dressi n g will be discar de d as G M O 
waste. N o f urt her dressi n g c o vera ge is nee de d.  
Aller gic  reacti o ns  t o  vacci nati o n  are  p ossi ble,  t heref ore,  a p pr o priate  dr u gs  a n d  me dical  
e q ui p me nt t o treat ac ute a na p h ylactic reacti o ns m ust be i m me diatel y a vaila ble a n d a me dicall y 
q ualifie d st u d y tea m me m ber trai ne d t o rec o g nise a n d treat a na p h yla xis m u st be prese nt i n t he 
cli nic d uri n g t he e ntire vacci nati o n pr oce d ure a n d p ost- vacci nati o n o bser vati o n peri o d. 
5. 8. 2. 3  Niv ol u m a b Pre p ar ati o n a n d A d mi nistr ati o n 
Ni v ol u ma b will be pre pare d acc or di n g t o t he P har mac y Ma n ual. 
I n Gr o u ps 3 a n d 4, t he patie nts will be o bser ve d f or 3 0 mi n utes after vacci nati o n. If t here are 
n o safet y c o ncer ns ( vital si g ns a n d react o ge nicit y), ni v ol u ma b will be i nf use d o ver 3 0  mi n utes 
a n d t he patie nts will be o bser ve d i n t he st u d y ce ntre f or a f urt h er 3 0 mi n utes p ost-i nf usi o n. 
5. 8. 2. 4  D ose a n d Sc he d ule M o dific ati o ns  
E ver y eff ort will be ma de t o a d mi nister t he pla n ne d d oses of st u d y vacci ne s a n d ni v ol u ma b. 
5. 9  
Bli n di n g  
T his is a n o pe n la bel st u d y; t heref ore, n o pr oce d ures f or bli n di n g are necessar y.  T he st u d y tea m 
me m bers  a n d partici pa nt  will k n o w t he treat me nt t he  partici pa nt  is recei vi n g. 
5. 1 0  Pri or a n d C o nc o mit a nt V acci nes  a n d Me dic ati o ns  
Patie nts  will  ha ve  bee n  ta ki n g  a nti virals  f or  at  least  1 2  m o nt hs  bef ore  scree ni n g.  O nce  
ra n d o mise d t o t he st u d y, oral a nti viral me dicati o n s h o ul d n ot be wit h dra w n. Patie nts s h o ul d 
re mai n o n t he sa me d ose of a nti virals t hat t he y were o n w he n t he y e ntere d t he st u d y f or t he 
d urati o n of t he st u d y. 
All o we d a nti viral me dicati o ns i ncl u de: e nteca vir, te n of o vir (te n of o vir alafe na mi de f u marate or 
te n of o vir dis o pr o xil f u marate), or besif o vir. 
Pri or a n d c o nc o mita nt me dicati o n s i ncl u de prescri pti o n a n d n o n -prescri pti o n dr u gs or ot her 
treat me nts, a n d a n y vacci nes ot her t ha n t he st u d y vacci ne.  
Rece ntl y use d a n d o n g oi n g me dicati o ns will be re vie we d a n d rec or de d d uri n g scree ni n g. 
C o nc o mita nt  me dicati o ns  use d  b y  partici pa nts  p ost -vacci nati o n  will  c oi nci de  wit h  t he  
c ollecti o n  peri o d  of  a d verse  e ve nts.  All  me dicati o ns  ta ke n  t o  treat s olicite d  A Es  will  be  
rec or de d i n t he e Diar y a n d will be disc usse d wit h t he partici pa nt at t he sc he d ule d cli nic visits 
d uri n g t he st u d y. All me dicati o ns ta ke n t o treat u ns olicite d A Es a n d S A Es will be rec or de d i n 
t he e C R F b y q uesti o ni n g t he partici pa nt at eac h visit w het her t he y t o o k a n y c o nc o mita nt 
me dicati o ns si nce t he pre vi o us visit . 
T he na me of t he me dicati o n, treat me nt start a n d st o p dates ( or ‘ o n g oi n g’), a n d i n dicati o n m ust 
be rec or de d o n t he c o nc o mita nt me dicati o n  e C R F. T he i n dicati o n rec or de d o n t he c o nc o mita nt 
me dicati o n e C R F m ust c orres p o n d t o a me dical ter m/ dia g n osis rec or de d o n t he a d verse e ve nt 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 4 4  of 1 0 9  
e C R F, or t o a pre -e xisti n g c o n diti o n n ote d i n t he partici pa nt’s me dical hist or y, or be n ote d as 
pr o p h yla xis, e. g. dietar y s u p ple me nt .  
Als o, partici pa nts s h o ul d n ot recei ve a n y a de n o viral-base d va cci ne wit hi n 3 m o nt hs pri or t o or 
3 m o nt hs after a d mi nistrati o n of C h A d O x 1- H B V o n Da y 0. 
5. 1 1  Tre at me nt C o m pli a nce  
Vac ci ne a d mi nistrati o n will ta ke place at t he st u d y ce ntre a n d will be perf or me d b y a s uita bl y 
q ualifie d healt hcare pr ofessi o nal. T he precise date a n d ti me of vacci nati o n s hall be d oc u me nte d 
i n t he s o urce d oc u me nts a n d e C R F. T he st u d y will be m o nit ore d b y a St u d y M o nit or a p pr o ve d 
b y t he S p o ns or. D uri n g m o nit ori n g visits, all pr oce d ures will be m o nit ore d f or c o m plia nce wit h 
t he pr ot oc ol. S o urce d oc u me nts will be re vie we d a n d c o m pare d wit h t he data e ntries i n t he 
e C R Fs t o e ns ure c o nsiste nc y.  
5. 1 2  P ost -st u d y Tre at me nt  
T he S p o ns or d oes n ot i nte n d t o pr o vi de  C h A d O x 1 -H B V n or M V A -H B V  after t he e n d of t he 
st u d y or after a n y earl y partici pa nt wit h dra wal , as t here is c urre ntl y n o cli nical data s u p p orti n g 
t heir efficac y. T hese partici pa nts will re mai n u n der t he care of t heir healt hcare pr ofessi o nals 
a n d treate d acc or di n g t o sta n dar d care.  If ne w i nf or mati o n bec o mes a vaila ble t hat w o ul d i nf or m 
t he be nefit of re peat d osi n g, t his will be c o nsi dere d as a pr ot oc ol a me n d me nt at a later ti me. 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 4 5  of 1 0 9  
6  
S T U D Y  P R O C E D U R E S A T E A C H VI SI T / SC H E D U L E O F A S S E S S M E N T S  
T he st u d y c o nsists of t he f oll o wi n g: 
•  A 4 2- da y scree ni n g peri o d bef ore t he start of st u d y treat me nt  
•  A st u d y peri o d of 9 m o nt hs 
•  A n e n d of st u d y visit 
T he sc he d ule of assess me nts at eac h visit is s h o w n i n Ta ble  2 a n d liste d i n Secti o n  6. 1   t o 
Secti o n  6. 3. 1 . T he st u d y assess me nts are descri be d i n Secti o n  7 . 
N ote:  a n y  a d diti o n al  visits  or  assess me nts  perf or me d  d uri n g  t he  st u d y  e. g.  t o  assess  
a d verse e ve nts m ust als o be rec or de d o n t he u nsc he d ule d pr oce d ures or u nsc he d ule d 
visits i n t he e C R F.  
U ns olicite d a d verse e ve nts will be rec or de d fr o m t he date t he i nf or me d c o nse nt is si g ne d a n d  
at all cli nic visits, b y q uesti o ni n g t he partici pa nt at eac h visit w het her t he y ha d a n y a d verse 
e ve nts si nce t he pre vi o us visit a n d b y o bser vi n g t he partici pa nt d uri n g cli nic visits. 
Seri o us a d verse e ve nts a n d A E SIs will be rec or de d fr o m t he date t he i nf or me d c o nse nt is si g ne d 
u ntil t he e n d of t he st u d y a n d/ or res ol ve d or u ntil partici pa nt c o ntact disc o nti n ues. 
S olicite d A Es  a n d me dicati o n ta ke n t o treat s olicite d A Es will be c ollecte d dail y i n t he e Diar y 
f or 7 da ys p ost- vacci nati o n. 
All me dicati o ns ta ke n t o treat u ns olicite d A Es a n d S A Es will be rec or de d i n t he  e C R F b y 
q uesti o ni n g t he partici pa nt at eac h visit w het her t he y t o o k a n y c o nc o mita nt me dicati o ns si nce 
t he pre vi o us visit. 
D ue t o t he C O VI D -1 9 pa n de mic, st u d y ce ntres will f oll o w a n y l ocal pr oce d ures i n li ne wit h 
testi n g t o e ns ure t he safet y of partici pa nts a n d staff. 
6. 1  
Scree ni n g a n d B aseli ne  Assess me nts 
Writte n i nf or me d c o nse nt f or partici pati o n i n t he st u d y m ust be o btai ne d bef ore perf or mi n g 
a n y st u d y s pecific scree ni n g tests or e val uati o ns acc or di n g t o t he pr ocess i n Secti o n  1 3. 4 . 
T he f oll o wi n g will be perf or me d at scree ni n g:  
•  De m o gra p hic data will be c ollecte d  
•  Hei g ht a n d wei g ht will be meas ure d  
•  A me dical a n d disease  hist or y will be rec or de d, i ncl u di n g a n y me dicati o ns bei n g ta ke n 
•  A  bl o o d  sa m ple  will  be  ta ke n  f or  HI V,  H C V,  H B V  ( q ua ntitati ve  H B V  D N A  a n d  
q ua ntitati ve H Bs A g) , H D V  dia g n ostic testi n g    
•  A uri nal ysis di pstic k test will be perf or me d  
•  A uri ne dr u g scree n will be perf or me d  
•  A  uri ne  pre g na nc y  test  will  be  perf or me d,  c hil d beari n g  stat us  rec or de d  a n d  if  of  
c hil d beari n g p ote ntial, assess me nt of c o ntrace pti ve meas ures perf or me d  
•  Bl o o d sa m ples will be ta ke n f or hae mat ol o g y (i ncl u di n g pr ot hr o m bi n ti me [ P T] a n d 
I N R), bi oc he mistr y a n d li ver f u ncti o n tests (L F Ts ) 
•  A f ull p h ysical e xa mi nati o n will be perf or me d  
•  Vital si g ns ( p ulse rate, bl o o d press ure a n d te m perat ure) will be meas ure d  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 4 6  of 1 0 9  
T a ble  2 
O ver all Sc he d ule of Assess me nts at E ac h St u d y Visit  
Visit/ C all 
Scree n  V acci n ati o n 
Cli nic 
Tele p h o ne 
C all  
Cli nic 
V acci n ati o n 
Cli nic 
Tele p h o ne 
C all 
Cli nic  
E n d of St u d y  / 
E arl y 
Disc o nti n u ati o n  
Cli nic  
Ti me p oi nt ( wi n d o w) 
D a y 
M o nt h  
-4 2 t o - 1 
0 
1 ( + 1 d) 
7 ( ±1 d ) 
2 8  (+ 2 d ) 
2 9 ( + 1 d) 
3 5 ( ±1 d ) 3 ( ±7 d )  6 ( ±7 d ) 
9 ( ± 7 d )  
I nf or me d c o nse nt 
X 
 
 
 
 
 
 
 
 
 
B aseli ne/eli gi bilit y v ari a bles  
 
 
 
 
 
 
 
 
 
 
De m o gra p hics 
X 
 
 
 
 
 
 
 
 
 
I ncl usi o n
 a n d
 e xcl usi o n
 
criteria 
X 
 
 
 
 
 
 
 
 
 
Hei g ht a n d wei g ht  
X 
 
 
 
 
 
 
 
 
 
Me dical a n d diseas e hist or y  
X 
 
 
 
 
 
 
 
 
 
HI V, H C V, H B V  ( q ua ntitati ve 
H B V D N A a n d q ua ntitati ve 
H Bs A g) , H D V ser ol o g y 
X 
 
 
 
 
 
 
 
 
 
Uri nal ysis  
X 
 
 
 
 
 
 
 
 
 
Uri ne dr u g scree n  
X 
 
 
 
 
 
 
 
 
 
Uri ne pre g na nc y test ( β -h C G)  
X 
X [a ]  
 
 
X [a ]  
 
 
X [f] 
X [f] 
X 
L a b or at or y 
eli gi bilit y  a n d  
s afet y tests  
 
 
 
 
 
 
 
 
 
 
Hae mat ol o g y 
X 
X [a ]  
 
X 
X [a ] 
 
X 
X 
X 
X 
Bi oc he mistr y 
X 
X [a ] 
 
X 
X [a ] 
 
X 
X 
X 
X 
Li ver f u ncti o n tests  
X 
X [a ] 
 
X 
X [a ] 
 
X 
X 
X 
X 
St u d y v acci n ati o n  
 
 
 
 
 
 
 
 
 
 
Vacci nati o n d ose  
 
X 
 
 
X 
 
 
X [g ] 
 
 
P ost- d ose o bser vati o n  
 
X 
 
 
X 
 
 
X [g ] 
 
 
Ni v ol u ma b d ose ( Gr o u p  3 
o nl y ) [b ] 
 
 
 
 
X 
 
 
 
 
 
Ot her s afet y assess me nts  
 
 
 
 
 
 
 
 
 
 
F ull p h ysical e xa mi nati o n  
X 
X [a ] 
 
 
X [a ] 
 
 
X [a ]  
 
X 
S y m pt o m - directe d p h ysical 
e xa mi nati o n 
 
 
 
X 
 
 
X 
X 
X 
 
Vital si g ns   
X 
X 
 
X 
X 
 
X 
X 
X 
X 
L ocal/s yste mic 
react o ge nicit y 
 
X [c ] 
X 
X 
X [c ] 
X 
X 
X [c ] 
 
 
U ns olicite d a d verse e ve nts [ d] 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Seri o us a d verse e v e nts a n d 
a d verse e ve nts of s pecial 
i nterest  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pri or a n d c o nc o mit a nt 
me dicati o ns 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Bl o o d f or H B V dise ase 
m ar kers [e ] 
 
X [a ] 
 
X 
X [a ] 
 
X 
X 
X 
X 
I m m u n o ge nicit y assess me nts 
 
 
 
 
 
 
 
 
 
 
Bl o o d f or cell ular 
i m m u n o ge nicit y assess me nts 
 
X [a ] 
 
X 
X [a ] 
 
X 
X [a ] 
X 
X 
[a] 
Pre- vacci nati o n o n Da y  0, Da y  2 8 , a n d M o nt h 3 (f or U K  partici pants ha vi n g a n M V A - H BV b o ost ) 
[ b] 
Pa rtici pants i n Gr o u p 3 will recei ve ni v ol u ma b o n Da y  2 8.Gr o u p 4 is n o w cl ose d. T he patie nts will be o bser ve d f or 3 0 mi n utes after 
vacci nati o n. If t here are n o safet y c o ncer ns ( vital si g ns a n d react o ge nicit y), ni v ol u ma b will be i nf use d o ver 3 0 mi n utes a n d t he patie nts 
will be o bser ve d i n t he st u d y ce ntre f or a f urt her 3 0 mi n utes p ost -i nf usi o n. 
[c] 
Ca pt ure d pre -vacci nati o n a n d p ost -vacci nati o n o n Da ys 0 a n d 2 8, a n d M o nt h  3 (f or U K partici pa nts ha vi n g a n M V A - H BV b o ost ) , 
via e Diaries f or 7 da ys p ost -vacci nati o n a n d t he n at t he cli nic assess me nt 7 da ys p ost -vacci nati o n ( Da y 7 or 3 5)   
[ d] 
Rec or de d i n t he e C R F fr o m t he date t he i nf or me d c o nse nt is si g ne d, at all cli nic visits t o c o ver t he peri o d si nce t he pre vi o u s visit a n d 
d uri n g t he visit  
[e] 
I n di vi d ual disease mar kers teste d acc or di n g t o t he St u d y La b orat or y Ma n ual  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 4 7  of 1 0 9  
[f] 
Pre g na nc y testi n g at M o nt h 3 i n Gr o u ps 1 a n d 2 if a n M V A- H BV b o ost is gi ve n, a n d at  M o nt hs 3 a n d 6 i n Gr o u ps 3 a n d 4  
[ g] 
If a partici pa nt has a 0. 5 l o g or greater dr o p i n he patitis B s urface a nti ge n at Da y 3 5, t he y ma y recei ve a b o oster d ose of M V A- H BV 
at M o nt h 3, at t he I n vesti gat or’s discreti o n a n d after disc ussi o n wit h t he S p o ns or  ( U K partici pa nts o nl y). T hese patie nts will als o ha ve 
a tele p h o ne call t he da y after t he b o ost vacci nati o n a n d a cli nic visit 7 da ys p ost- b o ost, as per Da y  1 a n d Da y  7.  
 
All scree ni n g e val uati o ns m ust be c o m plete d a n d re vie we d t o c o nfir m t hat partici pa nts meet 
all eli gi bilit y criteria bef ore t he first d ose of st u d y vacci ne . T he I n vesti gat or will mai ntai n a 
scree ni n g l o g t o rec or d details of all partici pa nts scree ne d a n d t o c o nfir m eli gi bilit y or rec or d 
reas o ns f or scree ni n g fail ure, as a p plica ble. 
Partici pa nts w h o d o n ot meet eli gi bilit y criteria ma y be rescree ne d at  t he discreti o n of t he 
I n vesti gat or. O nl y  a b n or mal /  o ut  of  wi n d o w  tests  are  re q uire d  t o  deter mi ne  eli gi bilit y.  
Re -scree ni n g ca n occ ur at a n y p oi nt wit h t he all o we d o verall scree ni n g wi n d o w ( u p t o 4 2 da ys).  
6. 2  
Tre at me nt D a y Assess me nts ( D a y 0 , D a y 2 8  a n d M o nt h  3 [ M V A - H BV B o ost 
( U K p artici p a nts o nl y)]) 
T he f oll o wi n g will be perf or me d pre - vacci nati o n: 
•  
Re -c hec k of eli gi bilit y criteria  ( Da y 0 o nl y) 
•  
A uri ne pre g na nc y test will be perf or me d  
•  
Bl o o d sa m ples will be ta ke n f or hae mat ol o g y , bi oc he mistr y a n d L F Ts  
•  
A f ull p h ysical e xa mi nati o n will be perf or me d  
•  
Vital si g ns ( p ulse rate, bl o o d press ure a n d te m perat ure) will be meas ure d   
•  
A baseli ne assess me nt of l ocal a n d s yste mic react o ge nicit y will be perf or me d  (see 
A p pe n di x 1 ) 
•  
Bl o o d sa m ples will be ta ke n f or i m m u n o ge nicit y assess me nts  a n d H B V disease mar kers  
Partici pa nts will t he n recei ve st u d y vacci ne b y i ntra m usc ular i njecti o n  i n t he n o n-d o mi na nt 
ar m, a n d will be o bser ve d f or 3 0 mi n utes p ost vacci nati o n f or safet y c o ncer ns. Ni v ol u ma b will 
t he n be a d mi nistere d via a n i nf usi o n, if a p plica ble, acc or di n g t o Ta ble  1. All partici pa nts will 
be assesse d i n t he cli nic f or at least 3 0  mi n utes p ost - vacci nati o n a n d p ost-ni v ol u ma b i nf usi o n  
i n case of i m me diate a d verse e ve nts. T he first partici pa nt i n eac h c o h ort will be o bser ve d f or 
1 h o ur. I n t he first c o h ort, t he sec o n d partici pa nt  will n ot be d ose d u ntil 4 8 h o urs after t he first 
se nti nel partici pa nt .  
T he f oll o wi n g will be perf or me d p ost- vacci nati o n: 
•  
T he vacci nati o n site will be c o vere d wit h a sterile dressi n g d uri n g t he o bser vati o n 
peri o d; it will t he n be re m o ve d a n d dis p ose d of as G M O waste 
•  
Vital si g ns ( p ulse rate, bl o o d press ure a n d te m perat ure) will be meas ure d  at t he e n d of 
t he o bser vati o n peri o d 
•  
L ocal a n d s yste mic react o ge nicit y will be assesse d at t he e n d of t he o bser vati o n peri o d  
•  
O n Da y 0, a n e Diar y, ta pe meas ure a n d t her m o meter  will be pr o vi de d t o perf or m 
self-assess me nt of l ocal a n d s yste mic react o ge nicit y f or 7 da ys after t he vacci nati o n s. 
P artici pa nts will be re mi n de d t o d o t he f oll o wi n g dail y f or t he 7 da ys  after eac h  
vacci nati o n: 
− 
Ta ke a n d rec or d t heir te m perat ure  
− 
Meas ure a n d rec or d t he size of vacci nati o n site re d ness  
− 
Assess t he ot her s olicite d a d verse e ve nts  liste d i n t he e Diar y 

 
Pr ot oc ol H B V 0 0 2  
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V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 4 8  of 1 0 9  
6. 3  
F oll o w- u p  Peri o d Assess me nts  
6. 3. 1  Tele p h o ne C alls : D a y 1, D a y 2 9 a n d M o nt h  3 + 1 D a y (M V A - H B V B o ost [U K 
p artici p a nts o nl y ]) 
•  
Re mi n der t o c o m plete e Diar y f or c ollecti o n of l ocal a n d s yste mic reacti o ns d uri n g 
7 c o nsec uti ve da ys p ost - vacci nati o n 
6. 3. 2  Cli nic Visit s: D a y  7, D a y 3 5  a n d M o nt h  3 + 7 D a ys ( M V A - H BV B o ost   [U K  
p artici p a nts  o nl y ]) 
•  
Bl o o d sa m ples will be ta ke n f or hae mat ol o g y, bi oc he mistr y a n d L F Ts  
•  
A s y m pt o m-directe d  p h ysical e xa mi nati o n will be perf or me d  if re q uire d 
•  
Vital si g ns ( p ulse rate, bl o o d press ure a n d te m perat ure) will be meas ure d  
•  
L ocal a n d s yste mic react o ge nicit y  
•  
Bl o o d sa m ples will be ta ke n f or i m m u n o ge nicit y assess me nts a n d H B V disease mar kers  
T hese visits s h o ul d be a nc h ore d t o t he date of Vacci nati o n a n d sc he d ule d t o occ ur 7 ± 1 da y 
after vacci nati o n. If vacci nati o n is a d mi nistere d o n a n y da y ot her t ha n Da y 2 8, t he f oll o w u p 
visit s h o ul d be sc he d ule d 6 -8 da ys after t he date of act ual vacci nati o n. All ot her st u d y visits 
after Da y 0 (e xce pt da y 3 5) are a nc h ore d t o Da y 0.  
6. 3. 3  Cli nic Visit:  M o nt h s 3 a n d 6  
•  
F or partici pa nts e nr olle d at U K sites , chec k he patitis B s urface a nti ge n Da y 3 5  res ult 
( M o nt h 3 o nl y) 
− 
If a partici pa nt has a 0. 5 l o g or greater dr o p i n he patitis B s urface a nti ge n, t he y ma y 
recei ve a b o oster d ose of M V A- H BV, at t he I n vesti gat or’s discreti o n a n d after 
disc ussi o n wit h t he S p o ns or. Please see Secti o n  6. 2  f or t he assess me nts t o be 
perf or me d. 
•  
A uri ne pre g na nc y test will be perf or me d ( M o nt hs 3 a n d 6 i n Gr o u ps 3 a n d 4 o nl y) 
•  
Bl o o d sa m ples will be ta ke n f or hae mat ol o g y, bi oc he mistr y a n d L F Ts 
•  
A s y m pt o m-directe d  p h ysical e xa mi nati o n will be perf or me d  if re q uire d 
•  
Vital si g ns ( p ulse rate, bl o o d press ure a n d te m perat ure) will be meas ure d  
•  
Bl o o d sa m ples will be ta ke n f or i m m u n o ge nicit y assess me nts a n d H B V disease mar kers  
6. 3. 4  Cli nic Visit:  Mo nt h  9 ( E n d of St u d y Visit) 
•  
A uri ne pre g na nc y test will be perf or me d  
•  
Bl o o d sa m ples will be ta ke n f or hae mat ol o g y (i ncl u di n g P T ), bi oc he mistr y a n d L F Ts 
•  
A f ull p h ysical e xa mi nati o n will be perf or me d  
•  
Vital si g ns ( p ulse rate, bl o o d press ure a n d te m perat ure) will be meas ure d  
•  
Bl o o d sa m ples will be ta ke n f or i m m u n o ge nicit y assess me nts a n d H B V disease mar kers  
6. 4  
Assess me nts at U nsc he d ule d Visits  
U nsc he d ule d visits ma y be re q uire d acc or di n g t o b y t he partici pa nt’s  c o n diti o n, assess me nts 
perf or me d will be  rec or de d i n t he e C R F.  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 4 9  of 1 0 9  
6. 5  
P artici p a nt Disc o nti n u ati o n  
Partici pa nts ha ve t he ri g ht t o wit h dra w c o nse nt fr o m t he st u d y at a n y ti me f or a n y reas o n, 
i ncl u di n g t heir f ut ure care. T he I n vesti gat or s h o ul d h o we ver tr y t o fi n d o ut w h y a partici pa nt 
wit h dra ws fr o m t he st u d y a n d d oc u me nt t he reas o n f or wit h dra wal i n t he s o urce d oc u me nts 
a n d e C R F.  
If t here is a me dical reas o n f or wit h dra wal, t he partici pa nt will re mai n u n der t he s u per visi o n of 
t he I n vesti gat or u ntil satisfact or y healt h has ret ur ne d. 
Partici pa nts w h o are wit h dra w n fr o m t he st u d y pri or t o c o m pleti o n of t he sc he d ule d st u d y 
pr oce d ures f or a n y reas o n s h o ul d c o m plete t he e n d of st u d y visit assess me nts as far as p ossi ble. 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 5 0  of 1 0 9  
7  
D E T AI L O F S T U D Y A S S E S S M E N T S  
7. 1  
De m o gr a p hic a n d B aseli ne Assess me nts  
T he f oll o wi n g will be c ollecte d at scree ni n g t o deter mi ne eli gi bilit y a n d baseli ne stat us of t he 
partici pa nt . Baseli ne safet y assess me nts will als o be perf or me d as detaile d i n Secti o n  7. 4 . 
7. 1. 1  De m o gr a p hic D at a a n d B aseli ne V ari a bles  
De m o gra p hic data will i ncl u de a ge, ge n der a n d race/et h nicit y, s m o ki n g hist or y, use of alc o h ol 
a n d dr u gs of a b use. 
7. 1. 2  Me dic al a n d Dise ase Hist or y  
Disease  hist or y (i ncl u di n g date of dia g n osis) a n d a n y  aller gies or  ot her cli nicall y si g nifica nt 
diseases  a n d s ur geries will be rec or de d.  
7. 1. 3  Pri or Me dic ati o ns a n d T her a pies  
All pri or t hera pies a n d pr oce d ures will be rec or de d.  
All
 ot her
 pri or
 me dicati o ns
 ( e. g. prescri pti o n
 dr u gs,
 o ver  t he c o u nter
 dr u gs,
 
her bal/ h o me o pat hic re me dies, n utriti o nal s u p ple me nts) use d b y t he partici pa nt  i n t he 2 8 da ys 
bef o re t he scree ni n g visit will als o be rec or de d (see Secti o n  5. 1 0 ). 
7. 1. 4  L a b or at or y Eli gi bilit y/ S afet y Tests  
Hae mat ol o g y,  bi oc he mistr y ,  L F Ts a n d  viral  ser ol o g y  bl o o d  tests  a n d  uri nal ysis  will  be  
perf or me d at scree ni n g f or all partici pa nts. Sa m ples will be a nal yse d at t he ce ntral la b orat or y.  
Res ults fr o m tests m ust be re vie we d b y t he I n vesti gat or ( or a desi g nee w h o is a me dicall y 
q ualifie d st u d y tea m me m ber) a n d ma na ge d i n acc or da nce wit h t he st u d y ce ntre pr oce d ures. 
T he cli nical si g nifica nce of all res ults o utsi de of t he n or mal ra n ge will be  deter mi ne d b y t he 
I n vesti gat or t o deter mi ne eli gi bilit y a n d ma y be re p orte d as a n a d verse e ve nt at t he d iscreti o n 
of t he I n vesti gat or . 
A d diti o nal la b orat or y safet y tests ma y be perf or me d if t he I n vesti gat or dee ms t he m t o be 
necessar y t o f ull y e val uate a n a d verse e ve nt. I n t he e ve nt t hat t he I n vesti gat or elects t o or der 
n o n- pr ot oc ol- s pecifie d la b orat or y tests, t he I n vesti gat or m ust rec or d t he rati o nale f or t he tests 
a n d  a  deter mi nati o n  of  cli nical  si g nifica nce  of  t he  res ult  i n  t he  s o urce  d oc u me nts.  T he  
I n vesti gat or m ust  kee p t he l ocal  Me dical M o nit or i nf or me d of a d verse e ve nts of cli nical 
si g nifica nce. 
A b n or mal res ults a n d fi n di n gs will be disc usse d as a p plica ble wit h t he partici pa nt a n d t he 
partici pa nt will be referre d f or f oll o w -u p wit h t heir healt hcare pr o vi der if necessar y.  
7. 1. 4. 1  
H ae m at ol o gy 
A sa m ple of ve n o us bl o o d will be c ollecte d acc or di n g t o t he ce ntral la b orat or y pr oce d ures.  
T he f oll o wi n g will be meas ure d: f ull bl o o d c o u nt, hae m o gl o bi n, hae mat ocrit, er yt hr oc ytes, 
mea n  cell  v ol u me,  mea n  c or p usc ular  hae m o gl o bi n,  mea n  c or p usc ular  hae m o gl o bi n  
c o nce ntrati o n, le u k oc ytes, ne utr o p hils, l y m p h oc ytes, m o n oc ytes, e osi n o p hils, bas o p hils, P T  
a n d platelets. 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 5 1  of 1 0 9  
7. 1. 4. 2  Bi oc he mistry  
A sa m ple of ve n o us bl o o d will be c ollecte d acc or di n g t o t he ce ntral la b orat or y pr oce d ures. 
T he f oll o wi n g bi oc he mistr y para meters will be meas ure d: s o di u m, p otassi u m, urea  nitr o ge n , 
creati ni ne a n d al b u mi n a n d L F Ts ( al kali ne p h os p hatase , ga m ma -gl uta m yl tra ns pe pti dase , A L T 
A S T a n d direct  bilir u bi n).  
7. 1. 4. 3  H u m a n I m m u n o deficie ncy Vir us, He p atitis B Vir us, He p atitis C Vir us a n d 
He p atitis D Vir us Di a g n ostic Testi n g  
Bl o o d sa m ples will be teste d f or: HI V a nti b o dies, H C V a nti b o dies, H Bs A g, H Be A g, H Bc rA g,  
H Bs A b , H Be A b , he patitis B c ore a nti b o d y, H B V D N A, H B p g R N A , H D V ser ol o g y 
7. 1. 4. 4  Uri n alysis  
A uri ne sa m ple will be o btai ne d t o scree n  f or dr u gs of a b use. 
A uri ne sa m ple will be c ollecte d i n a sterile c o ntai ner f or di pstic k uri nal ysis. T he f oll o wi n g 
will be teste d: bl o o d, bilir u bi n, gl uc ose, ket o nes, le uc oc ytes, nitrite, p H, pr otei n, s pecific 
gra vit y a n d ur o bili n o ge n. T he I n vesti gat or ma y or der a d diti o nal uri ne tests t o be perf or me d. 
7. 1. 5  Uri ne  Pre g n a nc y Test  
A uri ne pre g na nc y test will be perf or me d i n fe male partici pa nts  of c hil d beari n g p ote ntial at 
scree ni n g a n d c o nfir me d t o be ne gati ve pre-vacci nati o n o n Da y  0 a n d 2 8 a n d at M o nt h 3 if a 
b o oster d ose of M V A -H B V is gi ve n ( U K partici pa nts o nl y), a n d at M o nt h 3 a n d 6 f or t h ose i n 
Gr o u p 3  a n d 4, as per l ocal sta n dar d pr oce d ures a n d at eac h of t he ti me p oi nts acc or di n g t o 
Ta ble  2.  
7. 2  
I m m u n o ge nicit y Assess me nts  
I m m u n o ge nicit y sa m ples ( peri p heral bl o o d m o n o n uclear cells; P B M Cs) will be ta ke n f or 
pla n ne d a n d p ote ntial e x pl orat or y a nal yses at eac h of t he ti me p oi nts acc or di n g t o Ta ble  2. 
I m m u n o ge nicit y st u dies will i ncl u de ( b ut are n ot li mite d t o) a nal ysis of sa m ples e x vi v o b y 
m ulti para meter fl o w c yt o metr y (i ncl u di n g Mea n Fl u oresce nce I nte nsit y meas ure me nts) a n d 
e x vi v o I F N -γ E LI S P O T assa ys. T he latter will be use d f or e pit o pe ma p pi n g. I n nate i m m u ne 
res p o nses ma y  be meas ure d pri maril y b y R N A se q ue nci n g of sa m ples a n d ma y be assesse d i n 
ot her  assa ys  if  cell  n u m bers  per mit.  A d diti o nal  i m m u n o ge nicit y  assess me nts  ma y  be  
perf or me d. 
7. 2. 1  E x pl or at or y A n al ysis 
H B V- s pecific  C D 4 +, C D 8 +   a n d T  cell  s u bsets  wit hi n  P B M C  will  be  f urt her  defi ne d  b y  
p he n ot y pic mar kers of acti vati o n, differe ntiati o n a n d me m or y. P eri p heral bl o o d m o n o n uclear 
cells will als o be use d i n I F N -γ E LI S P O T assa ys t o deter mi ne t he brea dt h of H B V- s pecific 
T cell res p o nses ( defi ne d b y n u m ber of pe pti de p o ols or i n di vi d ual pe pti des rec o g nise d). T hese 
data ma y be use d t o b uil d i m m u n ol o gic m o dels of t he i m m u ne s yste m. 
Bl o o d or P B M C sa m ples ma y be use d f or e xtracti o n of R N A a n d s u bse q ue nt u n biase d a nal ysis 
of i n nate i m m u ne res p o nses bef ore a n d after vacci nati o n b y R N A se que nci n g. 
Ser u m  bl o o d sa m ples will be use d f or a nal ysis of H B p g R N A a n d H Bcr A g . 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 5 2  of 1 0 9  
7. 3  
Effic ac y Assess me nts  
F or mal e fficac y will n ot be assesse d i n t he st u d y, alt h o u g h c ha n ges i n H Bs A g will be f oll o we d. 
7. 4  
S afet y Assess me nts  
7. 4. 1  A d verse E ve nts  
Rec or di n g a n d re p orti n g of a d verse e ve nts is  descri be d i n detail i n Secti o n  8. 2 . 
7. 4. 1. 1  S olicite d A dverse Eve nts  
S olicite d a d verse e ve nts are e ve nts t he partici pa nt is s pecificall y as ke d a b o ut. T hese a d verse 
e ve nts are c o m m o nl y o bser ve d s o o n after recei pt of vacci nes a n d relate t o l ocal a n d s yste mic 
si g ns a n d s y m pt o ms. S olicite d a d verse e ve nts will be c ollecte d dail y i n t he e Diar y f or 7 da ys 
p ost- vacci nati o n. 
F or t his st u d y, s olicite d a d verse e ve nts t o be c ollecte d i ncl u de:  
•  
Vacci nati o n site reacti o ns: pai n, i n d urati o n, war mt h , er yt he ma (re d ness) 
•  
S yste mic  a d verse  e ve nts:  fe veris h ness,  c hills,  m yal gia,  fati g ue,  hea dac he,  na usea,  
art hral gia, malaise  
Partici pa nts will be as ke d t o rec or d t he prese nce of t hese s y m pt o ms a n d gra de t he se verit y as 
descri be d  i n  Secti o n  8. 2. 4. 1 .  Oral  te m perat ure  will  be  meas ure d  usi n g  t he  t her m o meter  
pr o vi de d a n d t he dia meter of i n d urati o n will be meas ure d wit h t he ta pe meas ure pr o vi de d.  
7. 4. 1. 2  U ns olicite d A dverse Eve nts  
U ns olicite d  a d verse  e ve nts  are  ot her  e ve nts  meeti n g  t he  criteria  f or  a d verse  e ve nts  (see  
Secti o n  8. 2. 1 ) a part fr o m t h ose t he partici pa nt is s pecificall y as ke d a b o ut. U ns olicite d a d verse 
e ve nts, h os pitalisati o ns, ot her S A Es a n d A E SIs will be c ollecte d f or t he d urati o n of t he st u d y. 
Partici pa nts will c ollect u ns olicite d a d verse e ve nts i n t he e Diar y a n d t hese will be re vie we d 
d uri n g tele p h o ne calls wit h t he partici pa nt a n d rele va nt i nf or mati o n (e ve nt ter m, start a n d e n d 
date, se verit y, ca usalit y, o utc o me a n d seri o us ness) c ollecte d a n d e ntere d i nt o t he e C R F as 
descri be d i n Secti o n  8. 2. 4 . 
7. 4. 2  L a b or at or y S afet y Tests  
L a b orat or y safet y tests will be perf or me d  at eac h of t he ti me p oi nts acc or di n g t o Ta ble  2, as per 
Secti o ns 7. 1. 4. 1  a n d 7. 1. 4. 2 . E xtra la b orat or y safet y tests ma y be perf or me d if t he I n vesti gat or 
dee ms t he m t o be necessar y t o f ull y e val uate a n a d verse e ve nt. I n t he e ve nt t hat t he I n vesti gat or 
elects  t o  or der  n o n -pr ot oc ol -s pecifie d  la b orat or y  tests,  t he  I n vesti gat or  m ust  rec or d  t he  
rati o nale f or t he tests a n d a deter mi nati o n of cli nical si g nifica nce of t he res ult i n t he s o urce 
d oc u me nts. T he I n vesti gat or m ust kee p t he l ocal Me dical M o nit or i nf or me d of a d verse e ve nts 
of cli n ical si g nifica nce. 
A b n or mal res ults a n d fi n di n gs will be disc usse d as a p plica ble wit h t he partici pa nt, a n d t he 
partici pa nt will be referre d f or f oll o w -u p wit h t heir healt hcare pr o vi der if necessar y.  
Res ults fr o m t he L F Ts o btai ne d o n t he st u d y m ust be re vie we d b y t he I n vesti gat or ( or a 
desi g nee w h o is a me dicall y q ualifie d st u d y tea m me m ber) a n d ma na ge d i n acc or da nce wit h 
t he st u d y ce ntre pr oce d ures. T he cli nical si g nifica nce of all res ults o utsi de of t he n or mal ra n ge 
will be deter mi ne d b y t he I n vesti gat or a n d ma y be re p orte d as a n a d verse e ve nt at t he discreti o n 
of t he I n vesti gat or.  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 5 3  of 1 0 9  
7. 4. 3  Vit al S i g ns 
Vital si g ns will be perf or me d at scree ni n g, pre - vacci nati o n a n d p ost- vacci nati o n (at t he e n d of 
t he o bser vati o n peri o d) at t he vacci nati o n visit , at all visits d uri n g t he f oll o w- u p a n d t he e n d of 
st u d y visit. At eac h ti me p oi nt bl o o d press ure, p ulse rate a n d te m perat ure, will be meas ure d 
after t he partici pa nt has bee n i n a sitti n g p ositi o n f or 5  mi n utes.  
7. 4. 4  P h ysic al E x a mi n ati o n   
A s ki n, res pirat or y, car di o vasc ular, a b d o mi nal a n d l y m p hatic s yste m e xa mi nati o n will be 
perf or me d at scree ni n g , pre- vacci nati o n o n Da y  0, Da y 2 8 a n d M o nt h 3 ( f or U K partici pa nts  
ha vi n g t he M V A - H BV b o ost  o nl y) a n d o n M o nt h  9. A s y m pt o m-directe d p h ysical e xa mi nati o n 
will be perf or me d at all ot her cli nic visits  if re q uire d. Res ults  will be rec or de d as n or mal, 
a b n or mal a n d n ot cli nicall y si g nifica nt or a b n or mal a n d cli nicall y si g nifica nt.  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 5 4  of 1 0 9  
8  
S A F E T Y  M A N A G E M E N T  
8. 1  
Res p o nsi bilities f or E ns uri n g t he S afet y of St u d y P artici p a nts  
T he nati o nal Re g ulat or y A ut h orit ies, t he st u d y S p o ns or, t he I nstit uti o ns t hr o u g h w hic h t he 
researc h is perf or me d a n d all me m bers of t he I n vesti gat or’s st u d y tea m s hare res p o nsi bilit y f or 
e ns uri n g t hat partici pa nts i n t his st u d y are e x p ose d t o t he least p ossi ble ris k of a d verse e ve nts 
t hat ma y res ult fr o m partici pati o n i n t his pr ot oc ol.  
8. 1. 1  I n vesti g at or 
T he I n vesti gat or has a pers o nal res p o nsi bilit y t o cl osel y m o nit or st u d y partici pa nts a n d a n 
i n here nt a ut h orit y t o ta ke w hate ver meas ures necessar y t o e ns ure t heir safet y. T he I n vesti gat or 
ma y dela y a partici pa nt’s  st u d y vacci ne a d mi nistrati o n or pa use st u d y vacci ne a d mi nistrati o n 
i n t he w h ole st u d y if t he y ha ve s o me s us pici o n t hat t he st u d y vacci ne mi g ht place a partici pa nt 
at si g nifica nt ris k. T he  In vesti gat or deter mi nes se verit y a n d ca usalit y f or eac h a d verse e ve nt.  
Res p o nsi bilities of t he I n vesti gat or ma y be assi g ne d t o a desi g nee w h o is a me dicall y q ualifie d 
st u d y tea m  me m ber,  h o we ver  t he  acc o u nta bilit y  f or  t he  s pecific  tas k  re mai ns  wit h  t he  
I n vesti gat or. 
8. 1. 2  St u d y S p o ns or  
T he  S p o ns or  als o  has  a n  i nstit uti o nal  res p o nsi bilit y  t o  e ns ure  partici pa nt  safet y.  T his  
res p o nsi bilit y is veste d i n t he l ocal Me dical M o nit or, S M C a n d D M C. 
8. 1. 3  L oc al Me dic al M o nit or 
T he l ocal Me dical M o nit or is t he S p o ns or’s re prese ntati ve a n d is a cre de ntiale d p h ysicia n or 
s ur ge o n i n t heir c o u ntr y of resi de nce wit h t he necessar y e x pertise t o act i n s uc h ca pacit y. T he 
l ocal Me dical M o nit or re vie ws t he safet y of t he pr o d uct f or pr ot oc ols i n a s pecific re gi o n a n d 
ca n a d d a n ot her ca usalit y assess me nt t o t he In vesti gat or’s ca usalit y assess me nt. T he ca usalit y 
assess me nt gi ve n b y t he I n vesti gat or m ust n ot be d o w n gra de d b y t he l ocal Me dical M o nit or. If 
t he Me dical M o nit or disa grees wit h t he In vesti gat or’s ca usalit y assess me nt, t he o pi ni o n of b ot h 
t he I n vesti gat or a n d Sp o ns or s h o ul d be pr o vi de d wit h t he re p ort .  
8. 1. 4  S afet y M o nit ori n g C o m mittee  
A S M C , c o nsisti n g  of  t he  S p o ns or  Me dical  M o nit or,  t he  C o u ntr y  Lea d  I n vesti gat ors  f or 
S o ut h K orea , Tai wa n  a n d t he U K, a n d t he trial Me dical M o nit or, will be a p p oi nte d t o re vie w 
t he st u d y data t hr o u g h o ut t he st u d y a n d at s pecific ti me p oi nts, a n d ma ke rec o m me n dati o ns 
c o ncer ni n g t he c o nti n uati o n, m o dificati o n, or ter mi nati o n of t he st u d y. T he S M C will perf or m 
t he f oll o wi n g: 
•  
Sc he d ule d e val uati o n of st u d y c o n d uct a n d pr o gress , a n d re vie w of t he c u m ulati ve 
safet y a n d efficac y data. Sc he d ule d meeti n gs will ta ke place as f oll o ws: 
- 
Kic k off meeti n g bef ore t he first partici pa nt is e nr olle d  
- 
7 da ys after t he first 6 partici pa nts i n Gr o u p 1 ha ve recei ve d t he first d ose of M V A -H B V  
- 
7 da ys  after  t he  first  6 partici pa nts  i n  Gr o u p  2  ha ve  recei ve d  C h A d O x -H B V  a n d  
M V A -H B V  
- 
7 da ys after t he first 6 partici pa nts i n Gr o u ps 3 a n d 4 ha ve recei ve d C h A d O x 1 -H B V , 
wit h or wit h o ut ni v ol u ma b  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 5 5  of 1 0 9  
•  
A d h oc e val uati o n of A L T or A S T res ults > 1 0 x U L N , or A L T or A S T > 5 x U L N f or 
m ore t ha n 3 wee ks, a n d if c o nsi dere d of c o ncer n, refer t o t he D M C . 
8. 1. 5  D at a M o nit ori n g C o m mittee  
A D M C , c o m p ose d of t hree i n de pe n de nt e x perts (t w o cli nicia ns a n d o ne statisticia n), will be 
a p p oi nte d t o re vie w t he st u d y data a n d  ma ke rec o m me n dati o ns c o ncer ni n g t he c o nti n uati o n, 
m o dificati o n, or ter mi nati o n of t he st u d y. T he D M C will perf or m t he f oll o wi n g:  
•  
E val uati o n of st u d y c o n d uct a n d pr o gress a n d re vie w of t he c u m ulati ve safet y a n d 
efficac y data. M eeti n gs will ta ke place as f oll o ws:  
- 
Kic k off meeti n g bef ore t he first partici pa nt is e nr olle d  
- 
Perf or m u nsc he d ule d re vie w of data if o ne of t he st u d y st o p pi n g or h ol di n g r ules 
is met, see  Secti o n  3. 1. 3 . 
- 
Meet  if re q ueste d b y t he S M C  
T he D M C will o perate i n acc or da nce wit h t he st u d y -s pecific D M C C harter, w hic h will be 
a gree d pri or t o t he start of e nr ol me nt.    
T he c hair of t he D M C ma y be c o ntacte d f or a d vice a n d i n de pe n de nt re vie w b y t he I n vesti gat or 
or S p o ns or i n a n y ot her sit uati o n w here t he I n vesti gat or or S p o ns or feels i n de pe n de nt a d vice 
or re vie w is i m p orta nt.  
T he D M C will als o be n otifie d wit hi n 2 4  h o urs of t he I n vesti gat ors’ bei n g a ware of a n y st u d y  
vacci ne -relate d S A Es. T he D M C has t he p o wer t o place t he st u d y o n h ol d if dee me d necessar y.  
F oll o wi n g re vie w of data b y t he D M C, a rec o m me n dati o n t o res u me , m o dif y or halt st u d y 
e nr ol me nt a n d vacci ne a d mi nistrati o n will be ma de, a n d t he D M C will rec or d t heir j u d g me nt 
i n  a  me m ora n d u m  t o  t he  st u d y  file  a n d  n otif y  t he  S p o ns or. I n  t he  e ve nt  of  halti n g  or  
m o dificati o n of t he pr ot oc ol, t he  D M C me m ora n d u m will be f or war de d t o t he l ocal Me dical 
M o nit or a n d I n vesti gat ors.  
8. 1. 6  I nstit uti o n al Re vie w B o ar ds a n d Et hics C o m mittees 
T he I E C /I R B has i nstit uti o nal res p o nsi bilit y f or t he safet y of partici pa nts i n cli nical st u dies. 
T he I E C /I R B has t he a ut h orit y t o ter mi nate, s us pe n d or re q uire c ha n ges t o a cli nical st u d y. 
8. 1. 7  N ati o n al Re g ul at or y A ut h orit y 
Si nce t he nati o nal re g ulat or y a ut h orit y recei ves all e x pe dite d safet y re p orts f or t he st u d y it als o 
has t he a ut h orit y t o ter mi nate, s us pe n d or re q uire c ha n ges t o a cli nical st u d y. 
8. 2  
A d verse E ve nt s  
8. 2. 1  Defi niti o ns   
8. 2. 1. 1  A dverse Eve nt  
A n a d verse e ve nt is:  
•  A n y  u nt o war d  me dical  occ urre nce  i n  a  partici pa nt or  cli nical  i n vesti gati o n  s u bject 
a d mi nistere d a p har mace utical pr o d uct a n d w hic h d oes n ot necessaril y ha ve t o ha ve a 
ca usal relati o ns hi p wit h t his treat me nt  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 5 6  of 1 0 9  
•  A n a d verse e ve nt 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 m al la b orat or y fi n di n g), s y m pt o m or disease te m p orall y ass ociate d wit h t he use 
of st u d y vacci ne, w het her or n ot c o nsi dere d relate d t o t he i n vesti gati o nal pr o d uct 
A n a d verse e ve nt i ncl u des b ut is n ot li mite d t o:  
•  A n y cli nicall y si g nifica nt w orse ni n g of a pre-e xisti n g c o n diti o n 
•  A n a d verse e ve nt occ urri n g fr o m o ver d ose ( i.e. a d osa ge hi g her t ha n t hat prescri be d b y a 
healt hcare pr ofessi o nal f or cli nical reas o ns, or a d osa ge hi g her t ha n t hat descri be d i n 
t he I n vesti gat or’s Br oc h ure or o n t he mar kete d pr o d uct la bel) of a n i n vesti gati o nal or 
mar kete d pr o d uct, w het her acci de ntal or i nte nti o nal 
•  A n  a d verse  e ve nt  occ urri n g  fr o m  a b use  ( e. g. use  f or  n o n -cli nical  reas o ns)  of  a n  
i n vesti gati o nal or mar kete d pr o d uct 
•  A n e ve nt relate d t o a me dical pr oce d ure or ass ociate d wit h t he disc o nti n uati o n of t he 
pre vi o us use of a n i n vesti gati o nal or mar kete d pr o d uct re q uire d b y pr ot oc ol ( pr ot oc ol  
relate d a d verse e ve nt) 
•  N ot all vital si g n or la b orat or y a b n or malities will be c o nsi dere d a n a d verse e ve nt. Us uall y 
t hese will be c o nsi dere d as a n a d verse e ve nt: 
− If Gra de 3 (se vere) or greater  i n se verit y 
− If j u d ge d t o be cli nicall y si g nifica nt b y t he I n vesti gat or 
− If acc o m pa nie d b y cli nical s y m pt o ms 
− If meeti n g t he defi niti o n of a S A E 
− If res ulti n g i n d ose m o dificati o n, i nterr u pti o n or disc o nti n uati o n of st u d y vacci ne  
− If re q uiri n g s pecific treat me nt 
8. 2. 1. 2  A dverse Re acti o n  
A n a d verse reacti o n is defi ne d as a n y u nt o war d a n d u ni nte n de d res p o nse t o st u d y vacci ne  
relate d t o a n y d ose a d mi nistere d. 
A n u ne x pecte d a d verse reacti o n is a n a d verse reacti o n i n w hic h t he nat ure or se verit y of w hic h 
is n ot c o nsiste nt wit h t he I n vesti gat or’s Br oc h ure or Prescri bi n g I nf or mati o n. 
8. 2. 1. 3  S eri o us A dverse Eve nt  
S A Es are a d verse e ve nts meeti n g at least o ne of t he f oll o wi n g criteria:  
•  It res ults i n de at h  (i.e. t he a d verse e ve nt ca use d or le d t o t he fatalit y). Seri o us d oes n ot 
descri be a n e ve nt w hic h h y p ot heticall y mi g ht ha ve ca use d deat h if it were m ore se vere  
•  It  was  i m me diatel y  life-t hreate ni n g (i.e.  t he  a d verse  e ve nt  place d  t he  partici pa nt  at  
i m me diate ris k of d yi n g. It d oes n ot refer t o a n e ve nt w hic h h y p ot heticall y ma y ha ve 
le d t o deat h if it were m ore se vere) 
•  It re q uire d i n patie nt h os pit alis ati o n  or pr ol o n ge d h os pitalisati o n be y o n d t he e x pecte d 
le n gt h of sta y. H os pitalisati o ns f or sc he d ule d treat me nts a n d electi ve me dical/s ur gical 
pr oce d ures  relate d  t o  a  pre -e xisti n g  c o n diti o n  t hat  di d  n ot  i ncrease  i n  se verit y  or  
fre q ue nc y  f oll o wi n g  recei pt  of  st u dy  vacci ne,  are  n ot seri o us  b y  t his  criteri o n.  
H os pitalisati o n is defi ne d as a h os pital a d missi o n or a n e mer ge nc y r o o m visit f or a 
peri o d greater t ha n 2 4 h o urs 
•  It res ulte d i n a persiste nt or si g nifica nt dis a bilit y/i nc a p acit y  (i.e. s u bsta ntial re d ucti o n 
of t he partici pa nt’s a bilit y t o carr y o ut acti vities of dail y li vi n g)  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 5 7  of 1 0 9  
•  It res ulte d i n a c o n ge nit al a n o m al y or birt h defect  (i.e. a n a d verse fi n di n g i n a c hil d or 
f oet us of a partici pa nt e x p ose d t o t he st u d y vacci ne pri or t o c o nce pti o n or d uri n g 
pre g na nc y) 
•  Ot her me dic all y i m p ort a nt c o n diti o ns  t hat ma y n ot res ult i n deat h, t hreate n life or 
re q uire h os pitalisati o n (i.e. t he a d verse e ve nt d oes n ot meet a n y of t he a b o ve seri o us 
criteria) ma y be c o nsi dere d a n S A E w he n, base d o n a p pr o priate me dical j u d g me nt , t he y 
ma y je o par dise t he partici pa nt a n d 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 seri o us o utc o mes liste d i n t hese criteria (e. g. aller gic br o nc h os pas m re q uiri n g 
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; bl o o d d yscrasias or c o n v ulsi o ns 
t hat d o n ot res ult i n h os pitalisati o n, or t he de vel o p me nt of dr u g de pe n de nc y or dr u g 
a b use) 
A n  S A E  is  a n  a d verse  e ve nt  meeti n g  t he  o utc o me  criteria  f or  seri o us ness  re gar dless  of  
relati o ns hi p t o t he st u d y vacci ne. T he f oll o wi n g are n ot (a n d s h o ul d n ot be re p orte d as) S A Es: 
h os pitalisati o n f or sc he d ule d treat me nts a n d electi ve me dical/s ur gical  pr oce d ures relate d t o a 
pre- e xisti n g c o n diti o n t hat di d n ot i ncrease i n se verit y or  fre q ue nc y f oll o wi n g recei pt of st u d y 
vacci ne, a n d a d missi o ns f or s ocial reas o ns . 
8. 2. 1. 4  S us pecte d U nex pecte d S eri o us A dverse Re acti o n 
A S U S A R is a n y s us pecte d a d verse reacti o n relate d t o t he st u d y vacci ne  t hat is b ot h u ne x pecte d 
a n d seri o us. 
8. 2. 2  St u d y Re p orti n g Peri o d f or A d verse E ve nts  
T he re p orti n g peri o d f or all a d verse e ve nts be gi ns o n t he date t he i nf or me d c o nse nt is si g ne d . 
S olicite d a d verse e ve nts are rec or de d i n t he e Diar y u p t o 7 da ys p ost -vacci nati o n. All ot her 
e ve nts are rec or de d i n t he e C R F at all cli nic visits t hr o u g h o ut t he st u d y . All S A Es a n d/or A E SIs  
are rec or de d  u ntil t he fi nal st u d y visit a n d f or all seri o us or st u d y vacci ne -relate d a d verse e ve nts 
u ntil t hese are res ol ve d or u ntil partici pa nt  c o ntact disc o nti n ues.  Se vere a d verse e ve nts or S A Es 
t hat c o nti n ue at t he e n d of t he st u d y will be atte m pte d t o be f oll o we d u ntil res ol ve d or sta bilise d. 
A d verse e ve nt i nf or mati o n will be c ollecte d at st u d y visits a n d partici pa nt will be i nstr ucte d t o 
call st u d y tea m me m bers t o re p ort a n y a b n or malities d uri n g t he i nter vals bet wee n st u d y visits 
a n d t o c o me t o t he st u d y ce ntre if me dical e val uati o n is nee de d a n d t he ur ge nc y of t he sit uati o n 
per mits.  
8. 2. 3  Re p orti n g E xe m pti o ns  
N o re p orti n g e xe m pti o ns ha ve bee n i de ntifie d f or t his st u d y. 
8. 2. 4  Rec or di n g a n d Assess me nt of A d verse E ve nts b y t he I n vesti g at or  
S olicite d a d verse e ve nts are rec or de d i n t he e Diar y u p t o 7 da ys p ost -vacci nati o n. All ot her 
a d verse e ve nts are rec or de d i n t he e C R F at all cli nic visits t hr o u g h o ut t he st u d y . All a d verse 
e ve nts, b ot h t h ose o bser ve d b y st u d y tea m me m bers a n d t h ose s p o nta ne o usl y re p orte d b y t he 
partici pa nt, will  be rec or de d i n  t he e C R F. S olicite d a d verse e ve nts will be re p orte d usi n g 
pre- defi ne d ter ms. U ns olicite d a d verse e ve nts will be re p orte d usi n g a rec o g nise d me dical ter m 
or dia g n osis t hat acc uratel y reflects t he e ve nt.  
A d verse e ve nts will be assesse d b y t he I n vesti gat or ,  or a me dicall y q ualifie d st u d y tea m 
me m ber , f or se verit y, relati o ns hi p t o st u d y vacci ne , acti o n ta ke n, o utc o me a n d w het her t he 
e ve nt meets criteria as a n S A E acc or di n g t o t he f oll o wi n g g ui deli nes: 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 5 8  of 1 0 9  
8. 2. 4. 1  Assess me nt of Severity  
W he ne ver p ossi ble, t he  se verit y of ad verse eve nts will be gra de d acc or di n g t o t he t o xicit y ta ble 
i n A p pe n di x 1 . T he scale s h o w n i n Ta ble  3 will be use d t o assess se verit y  of a d verse e ve nts n ot 
liste d i n A p pe n di x 1 . 
T a ble  3 
Se verit y Gr a di n g of A d verse E ve nts n ot liste d i n t he T o xicit y T a ble f or 
Cli nic al a n d L a b or at or y A b n or m alities 
Gr a de  
Se verit y  
1 
Mil d  
As y m pt o matic or mil d s y m pt o ms; cli nical or dia g n ostic o bser vati o ns o nl y; 
or i nter ve nti o n n ot i n dicate d; n o disr u pti o n of n or mal dail y acti vit y.  
2 
M o derate  
Mi ni mal,  l ocal,  or  n o n -i n vasi ve  i nter ve nti o n  i n dicate d;  disc o mf ort  
s ufficie nt t o re d uce or affect dail y acti vit y. 
3 
Se vere  
Se vere  or  me dicall y  si g nifica nt,  b ut  n ot  i m me diatel y  life -t hreate ni n g; 
h os pitali sati o n  or  pr ol o n gati o n  of  h os pitali sati o n  i n dicate d;  i na bilit y  t o  
w or k or perf or m n or mal dail y acti vit y.  
4 
Life -threate ni n g  
Re prese nts a n i m me diate t hreat t o life. 
5 
Fatal  
Deat h as a res ult of t his a d verse e ve nt  
A c ha n ge i n se verit y of a n a d verse e ve nt will n ot be rec or de d as a ne w a d verse e ve nt. O nl y t he 
hi g hest se verit y le vel t hat occ urs d uri n g t he e ntire peri o d of t he a d verse e ve nt will be rec or de d 
o n t he e C R F  wit h t he o nset a n d res ol uti o n dates e nc o m passi n g t he e ntire d urati o n of t he e ve nt.  
N ote: I t is i m p orta nt t o disti n g uis h bet wee n seri o us a n d se vere a d verse e ve nt s. Se verit y is a 
meas ure of i nte nsit y w hereas seri o us ness is defi ne d b y t he criteria i n Secti o n  8. 2. 1. 3 . 
8. 2. 4. 2  Assess me nt of Rel ati o ns hi p  
S olicite d a d verse e ve nts of vacci nati o n site reacti o ns will be c o nsi dere d ca usall y relate d t o 
st u d y treat me nt. 
F or all ot her a d verse e ve nts, t he I n vesti gat or will deter mi ne a  c a us al rel ati o ns hi p t o t he st u d y 
vacci ne. A n u m ber of fact ors will be c o nsi dere d i n ma ki n g t his assess me nt, i ncl u di n g: 1) t he 
te m p oral relati o ns hi p of t he e ve nt t o t he a d mi nistrati o n of t he st u d y vacci ne 2) w het her a n 
alter nati ve aeti ol o g y has bee n i de ntifie d a n d 3) bi ol o gica l pla usi bilit y.  
Ca usalit y of all a d verse e ve nts 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 dverse eve nt m ay h ave bee n c a use d by t he st u dy 
v acci ne ? ” 
•  
Y E S (rel ate d): T here is a reas o na ble p ossi bilit y t hat t he st u d y vacci ne c o ntri b ute d t o 
t he a d verse e ve nt 
•  
N O ( n ot rel ate d):  T here is n o reas o na ble p ossi bilit y t hat t he a d verse e ve nt 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. 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 is n ot s us pecte d t o ha ve c o ntri b ute d t o t he 
a d verse e ve nt  
T he I n vesti gat or is re q uire d t o pr o vi de a n assess me nt of relati o ns hi p of A Es t o t he vacci ne or 
st u d y pr oce d ures  a n d deter mi nes ca usalit y. T he S p o ns or a n d l ocal me dical m o nit or ca n a d d 
a n ot her ca usalit y assess me nt t o t he In vesti gat or’s ca usalit y. H o we ver, t he ca usalit y gi ve n b y 
t he In vesti gat or m ust n ot be d o w n gra de d b y t he S p o ns or or t he l ocal me dical m o nit or. If t he 

 
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S p o ns or or t he l ocal me dical m o nit or disa grees wit h t he In vesti gat or’s ca usalit y assess me nt, 
t he o pi ni o n of b ot h t he In vesti gat or, t he S p o ns or a n d t he l ocal me dical m o nit or s h o ul d be 
pr o vi de d wit h t he re p ort. 
E ver y eff ort s h o ul d be ma de b y t he I n vesti gat or t o deter mi ne t he e xiste nce of a n y pre -e xisti n g 
c o n diti o ns (e. g.  hea dac he i n a d ults or ras hes i n i nfa nts o n st u d y Da y 0 wit h o nset pri or t o st u d y 
vacci nati o n) t hat m ust be ta ke n i nt o c o nsi derati o n w he n assessi n g ca usal relati o ns hi p of a n 
a d verse e ve nt. Pre -e xisti n g c o n diti o ns s h o ul d be rec or de d i n t he e C R F as baseli ne hist or y a n d 
s u bsta ntiate d b y a p pr o priate s o urce d oc u me ntati o n. I nter mitte nt c o n diti o ns s uc h as hea dac hes 
ma y n ot be prese nt o n st u d y Da y 0 b ut ma y re prese nt a n a d verse e ve nt if t he i nte nsit y or 
d urati o n of t he e ve nt is w orse t ha n us ual f oll o wi n g st u d y vacci ne. 
8. 2. 4. 3  Acti o n T ake n wit h St u dy V acci ne  
T he acti o n ta ke n wit h t he st u d y vacci ne will be rec or de d as N o ne, as o nl y o ne d ose is gi ve n. 
8. 2. 4. 4  Assess me nt of O utc o me  
T he o utc o me of t he a d verse e ve nt will be assesse d as:  
•  
Rec o vere d/res ol ve d  
•  
Rec o vere d/ res ol ve d wit h se q uelae 
•  
N ot rec o vere d/res ol ve d  
•  
U n k n o w n 
•  
Fatal  
8. 2. 5  Re p orti n g Re q uire me nts  a n d Pr oce d ures  f or S A Es  
All S A Es are re p orte d t o t he S p o ns or f or t he e ntire st u d y peri o d. S us pecte d u ne x pecte d seri o us 
a d verse reacti o n s are re p orte d e ve n after t he st u d y is o ver, if t he S p o ns or, l ocal Me dical 
M o nit or or Pri nci pal I n vesti gat or bec o mes a ware of t he m. T he st u d y ce ntre will be pr o vi de d 
wit h  s pecific  re p orti n g  pr oce d ures  i ncl u di n g  t he  S A E  pa per  f or m  a n d  a n y  s u p ple me ntal  
re p orti n g f or ms t o be use d. S A Es will be re p orte d o n t he S A E pa per f or m a n d t he a d verse e ve nt 
e C R F usi n g a rec o g nise d me dical ter m or dia g n osis t hat a cc uratel y reflects t he e ve nt.  
S A Es will be assesse d f or se verit y, ca usal relati o ns hi p t o t he st u d y vacci ne  or alter nati ve 
aeti ol o g y b y t he S p o ns or a n d I n vesti gat or. T he o nset a n d res ol uti o n dates of t he e ve nt a n d 
me dical care ta ke n i n res p o nse t o t he e ve nt will be d oc u me nte d. If t he e ve nt has n ot res ol ve d 
b y t he e n d of t he st u d y, it will be d oc u me nte d as “ o n g oi n g” o n t he e C R F, h o we ver, f oll o w -u p 
of t he S A E m ust c o nti n ue u ntil res ol ve d or t he c o n diti o n has sta bilise d. I nf or mati o n rec or de d 
o n t he e C R F m ust be s u bsta ntiate d i n t he s o urce d oc u me nts. 
T he S A E pa per f or m s h o ul d be c o m plete d wit h all i nf or mati o n k n o w n at t he ti me a n d sca n ne d 
a n d e maile d t o t he l ocal Me dical M o nit or a n d t o M H G Safet y @ pra hs.c o m .  If e mail ser vice is 
n ot a vaila ble d ue t o tec h nical reas o ns, t he t oll -free fa x n u m bers will be use d f or S A E re p orti n g. 
Li ke wise, fatal or life -t hreate ni n g S A Es will ha ve t o be re p orte d via M H G Safet y @ pra hs.c o m  
or t he t oll -free fa x n u m bers. If t he l ocal Me dical M o nit or is re q uire d b y t he pr ot oc ol or c h o oses 
t o s us pe n d e nr ol me nt s/ he s hall i m me diatel y create a writte n me m ora n d u m f or rec or d t o t he 
st u d y file a n d tele p h o nicall y n otif y t he S p o ns or of t his act. 
C o ntact i nf or mati o n f or all safet y pers o n nel are c o ntai ne d i n t he Tea m C o ntact List, w hic h will 
be st ore d at t he st u d y ce ntre i n t he I S F a n d mai ntai ne d b y t he st u d y S p o ns or. 

 
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I n vesti gat ors m ust n ot wait  t o c ollect a d diti o nal i nf or mati o n t o f ull y d oc u me nt t he e ve nt bef ore 
n otif yi n g t he l ocal Me dical M o nit or of a n S A E. T he i nitial n otificati o n s h o ul d i ncl u de t he 
f oll o wi n g (at a mi ni m u m):  
•  
Pr ot oc ol n u m ber a n d na me a n d c o ntact n u m ber of t he I n vesti gat or  
•  
Partici pa nt i de ntificati o n  
•  
I n vesti gati o nal pr o d uct 
•  
E ve nt ter m 
T he S p o ns or  will n otif y t he D M C of all S U S A Rs wit hi n 2 4 h o urs of bec o mi n g a ware of a n 
e ve nt a n d will pr o vi de all f oll o w- u p i nf or mati o n i n a ti mel y ma n ner.  
8. 2. 5. 1  F oll o w- u p I nf or m ati o n o n an S A E 
A p pr o priate dia g n ostic tests s h o ul d be perf or me d a n d t hera pe utic meas ures, as me dicall y  
i n dicate d, s h o ul d be i nstit ute d. A p pro priate c o ns ultati o n a n d f oll o w- u p e val uati o ns s h o ul d be  
carrie d o ut u ntil t he e ve nt has res ol ve d or is ot her wise e x plai ne d b y t he I n vesti gat or. F or all  
S A Es, t he I n vesti gat or is o bli gate d t o p urs ue a n d pr o vi de i nf or mati o n t o t he S p o ns or. I n 
a d diti o n, a n I n vesti gat or ma y be re q ueste d b y t he S p o ns or t o o btai n s pecific i nf or mati o n i n a n 
e x pe dite d ma n ner.  T his i nf or mati o n ma y be m ore detaile d t ha n t hat ca pt ure d o n t he S A E  f or m. 
I n ge neral, t his will i ncl u de a descri pti o n of t he a d verse e ve nt  i n s ufficie nt detail t o all o w f or a 
c o m plete me dical assess me nt of  t he case a n d i n de pe n de nt deter mi nati o n of p ossi ble ca usalit y. 
I nf or mati o n o n ot her p ossi ble ca uses s uc h as c o nc o mita nt me dicati o n a n d ill nesses m ust be 
pr o vi de d. 
After t he i nitial S A E re p ort, t he In vesti gat or is re q uire d t o f oll o w eac h partici pa nt  pr oacti vel y  
a n d t o re p ort ne w si g nifica nt f oll o w- u p b y s u b mitti n g a n u p date d S A E re p ort f or m t o t he 
S p o ns or ( or  desi g nee).  Ne w  si g nifica nt  i nf or mati o n  i ncl u des,  b ut  is  n ot  li mite d  t o,  t he 
f oll o wi n g: 
•  Ne w si g ns or s y m pt o ms or a c ha n ge i n t he dia g n osis 
•  Si g nifica nt ne w dia g n ostic test res ults  
•  C ha n ge i n ca usalit y base d o n ne w i nf or mati o n 
•  C ha n ge i n t he e ve nt’s o utc o me, i ncl u di n g rec o ver y 
•  A d diti o nal narrati ve i nf or mati o n o n t he cli nical c o urse of t he e ve nt  
8. 2. 5. 2  Re q uire d F oll o w - u p f or S A Es  
T here s h o ul d be atte m pte d f oll o w-u p u ntil t he e n d of t he st u d y  i n all partici pa nts. If a n S A E 
c o nti n ues after t his peri o d, t he n t he partici pa nt  m ust be f oll o we d u p u ntil t he e ve nt res ol ves or 
sta bilises. T he l ocal Me dical M o nit or ma y s pecif y a l o n ger peri o d of ti me, if re q uire d t o ass ure 
t he safet y of t he partici pa nt . 
8. 2. 5. 3  Me dic al Revie w a n d Re p orti n g by t he S p o ns or  
T he S p o ns or  (or desi g nee ) will deter mi ne e x pe dite d re p orti n g re q uire me nts f or eac h re p orte d 
S A E acc or di n g t o l ocal re q uire me nts base d u p o n: 
•  I n vesti gat or's assess me nt of ca usalit y a n d seri o us ness 
•  E x pecte d ness  
T he e x pecte d ness of a n S A E is assesse d b y t he S p o ns or i n t he o verall classificati o n of S A Es 
f or  e x pe dite d re p orta bilit y.  T he  c urre nt I n vesti gat or's Br oc h ure secti o n “Refere nce Safet y 

 
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I nf or mati o n”  will  be  use d  as  t he  refere nce  f or  deter mi nati o n  of  e x pecte d ness a n d  ris k  
assess me nt  of vacci ne-relate d a d verse e ve nts  a n d Secti o n 4. 8 of t he Ni v ol u ma b S m P C will be 
use d t o assess t he e x pecte d ness f or ni v ol u ma b relate d e ve nts .  
8. 2. 5. 4  S p o ns or Res p o nsi bility f or Ex pe dite d S afety Re p orts 
T he S p o ns or ( or desi g nee) will n otif y In vesti gat ors of all re p orta ble S A Es. T his n otificati o n 
will be i n t he f or m of  a n e x pe dite d safet y re p ort. U p o n recei vi n g s uc h n otices, t he I n vesti gat or 
m ust re vie w a n d retai n  t he n otice wit h ot her st u d y relate d d oc u me ntati o n.  
T he I n vesti gat or  sh o ul d als o c o m pl y wit h t he I E C/I R B pr oce d ures f or re p orti n g a n y ot her 
safet y i nf or mati o n. 
T he S p o ns or will e ns ure t hat S A Es are re p orte d t o t he I E Cs/I R Bs a n d re g ulat or y a ut h orit y(ies) 
acc or di n g t o l ocal re q uire me nts.  
S U S A Rs  a n d ot her si g nifica nt safet y iss ues re p orte d fr o m t he  de vel o p me nt pr o gra m me  s hall 
be re p orte d t o t he rele va nt re g ulat or y a ut h orities i n all c o ncer ne d c o u ntries acc or di n g t o l ocal 
re g ulati o ns (eit her as e x pe dite d safet y re p orts a n d/ or i n a g gre gate re p orts), b y t he S p o ns or ( or 
desi g nee). 
8. 2. 6  F oll o w- u p  of P artici p a nts after A d verse  E ve nts  
8. 2. 6. 1  I nvesti g at or F oll o w- u p 
Treat me nt of a n y a d verse e ve nts will be deter mi ne d b y t he I n vesti gat or usi n g his/ her best 
me dical j u d g me nt a n d acc or di n g t o c urre nt cli nical practice g ui deli nes. F or ma na ge me nt of 
ni v ol u ma b t o xicities, please see t he Safet y Ma na ge me nt Pla n w hic h i ncl u des i nf or mati o n o n 
ni v ol u ma b a n d p ote ntial ni v ol u ma b i nteracti o ns. All a p plie d meas ures as well as f oll o w -u p will 
be rec or de d i n t he a p pr o priate e C R F. 
T he I n vesti gat or will c o nti n ue f oll o w -u p o n a d verse e ve nts, i ncl u di n g la b orat or y a b n or malities 
a n d s olicite d a d verse e ve nts, u ntil t he e ve nt has res ol ve d, is ot her wise satisfact oril y e x plai ne d , 
or t he partici pa nt c o m pletes t he st u d y. T he res ol uti o n date will be rec or de d o n t he e C R F as t he 
last date o n w hic h t he partici pa nt e x perie nce d t he a d verse e ve nt. If a n a d verse e ve nt res ol uti o n 
date  is  u ncertai n  t he  I n vesti gat or  s h o ul d  esti mate  t he  c o m pleti o n  date  base d  o n  me dical  
j u d g me nt a n d i nter vie w of t he partici pa nt. A p pr o xi mate dates of res ol uti o n fr o m p h o ne or ot her 
c o m m u nicati o ns ma y be ta ke n as a d verse e ve nt res ol uti o n dates. S o me e xa m ples of esti mati o n 
of a d verse e ve nt res ol uti o n are: 1) a n as y m pt o matic la b orat or y a b n or malit y o n o ne visit t hat 
has n ot bee n f oll o we d  u p bet wee n visits b ut has res ol ve d b y t he ne xt visit ma y be ass u me d t o 
ha ve res ol ve d b y t he mi d p oi nt of t he i nter -visit i nter val; 2) A res ol ve d a d verse e ve nt t hat was 
treate d ma y be ass u me d t o ha ve bee n res ol ve d b y t he e n d of treat me nt.  
A d verse e ve nts t hat are still prese nt at t he e n d of t he st u d y s h o ul d be rec or de d as o n g oi n g.  
I nf or mati o n rec or de d o n t he e C R F m ust be s u bsta ntiate d i n t he s o urce d oc u me nts. If a n a d verse 
e ve nt e v ol ves i nt o a c o n diti o n t hat bec o mes “seri o us,” it will be desi g nate d as seri o us o n t he 
a d verse e ve nt e C R F a n d a s u p ple me ntal S A E re p ort f or m will be c o m plete d.  
F oll o w- u p f or S A Es m ust c o nti n ue u ntil res ol uti o n or sta bili sati o n a n d t he o utc o me re p orte d t o 
t he S p o ns or, e ve n if t his e xte n ds be y o n d t he S A E re p orti n g peri o d. 

 
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8. 2. 7  P ost -St u d y A d verse E ve nts  
At  t he  fi nal  st u d y  visit,  t he  I n vesti gat or  s h o ul d  i nstr uct  eac h  partici pa nt  t o  re p ort  t o  t he  
I n vesti gat or a n y s u bse q ue nt a d verse e ve nts t hat t he partici pa nt’s pers o nal p h ysicia n belie ves 
c o ul d be relate d t o st u d y vacci ne or st u d y pr oce d ures.   
T he I n vesti gat or s h o ul d n otif y t he S p o ns or ( or desi g nee) of a n y deat h, S A E or ot her a d verse 
e ve nt of c o ncer n occ urri n g at a n y ti me after a partici pa nt has disc o nti n ue d st u d y vacci ne if t he 
e ve nt is belie ve d t o be relate d t o st u d y vacci ne or st u d y pr oce d ures. T he S p o ns or ( or desi g nee) 
s h o ul d als o be n otifie d if t he I n vesti gat or bec o mes a ware of t he de vel o p me nt of ca ncer or a 
c o n ge nital a n o mal y/ birt h defect i n a s u bse q ue ntl y c o ncei ve d offs pri n g of a partici pa nt t hat 
partici pate d i n t his st u d y.  
T he I n vesti gat or s h o ul d rec or d t he e ve nt i n t he e C R F; if t he e C R F is n o l o n ger a vaila ble, t he 
I n vesti gat or s h o ul d re p ort t he e ve nt directl y t o t he S p o ns or ( or desi g nee). 
8. 3  
E ve nts of S peci al I nterest  
A d verse e ve nts of s pecial i nterest  i n t his st u d y are t h ose pre vi o usl y re p orte d wit h ni v ol u ma b  
i n o nc ol o g y i n dicati o ns re q uiri n g d ose m o dificati o n or ter mi nati o n (see S m P C), a n d pri or 
st u dies i n C H B patie nts, i ncl u di n g t he o nset of a n y a ut oi m m u ne dis or der a n d he patitis flares. 
T hese i ncl u de p ne u m o nitis, gra de 3 or 4 diarr h o ea, dia betes, t h yr oi d diseases, c olitis, ne p hritis, 
i m m u ne-relate d  e n d ocri n o pat hies,  m y ocar ditis,  i m m u ne-relate d  s ki n  c o n diti o ns,  or  ot her  
u ns pecifie d i m m u ne-relate d a d ver se reacti o ns.  
T hese e ve nts will be re p orte d t o t he S p o ns or as f or S A Es (see Secti o n  8. 2. 5 ). 
8. 4  
Ot her E ve nts Re q uiri n g I m me di ate Re p orti n g  
T he I n vesti gat or m ust re p ort t he f oll o wi n g e ve nts t o t he S p o ns or or t o t he trial Me dical M o nit or  
wit hi n 2 4 h o urs of bec o mi n g a ware of t he e ve nt: 
•  
Wit h dra wal of c o nse nt d uri n g t he st u d y f or safet y reas o ns  
•  
Pr ot oc ol de viati o n affecti n g t he safet y of a partici pa nt or i n v ol vi n g t he vacci nati o n 
pr ocess  
•  
Gra de 3, or a b o ve a d verse e ve nt t h o u g ht t o be a n aller gic reacti o n t o t he st u d y vacci ne 
•  
A n y e ve nt t hat, i n t he o pi ni o n of t he I n vesti gat or, precl u des f urt her a d mi nistrati o n of 
t he st u d y vacci ne  
•  
Pre g na nc y (see Secti o n  8. 6 ) 
8. 5  
O ver d ose  or I nc orrect A d mi nistr ati o n  
St u d y vacci ne o ver d ose is t he acci de n tal or i nte nti o nal use of t he st u d y vacci ne  i n a n a m o u nt 
hi g her t ha n t he d ose bei n g st u die d. A n o ver d ose or i nc orrect a d mi nistrati o n of st u d y  vacci ne is 
n ot a n a d verse e ve nt u nless it res ults i n u nt o war d me dical effects : 
•  A n y st u d y vacci ne  o ver d ose or i nc orrect a d mi nistrati o n of st u d y vacci ne s h o ul d be 
rec or de d i n t he e C R F as part of t he st u d y vacci ne  a d mi nistrati o n i nf or mati o n   
•  A n y u nt o war d me dical effects  ass ociate d wit h a n o ver d ose or i nc orrect a d mi nistrati o n of 
st u d y vacci ne s h o ul d be rec or de d i n t he e C R F  as a n a d verse e ve nt . If t he ass ociate d 
a d verse e ve nt f ulfils seri o us criteria, t he e ve nt s h o ul d be re p orte d t o t he S p o ns or  ( or 
desi g nee) wit hi n 2 4 h o urs of k n o wle d ge of t he e ve nt 

 
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8. 6  
M a n a ge me nt of Pre g n a nc y  
8. 6. 1  N otific ati o n a n d F oll o w- u p   
8. 6. 1. 1  Pre g n a ncies i n Fe m ale P artici p a nts 
A n y pre g na ncies occ urri n g d uri n g t he st u d y or wit hi n 6 m o nt hs after t he last d ose of st u d y 
vacci ne  m ust be re p orte d t o t he S p o ns or ( or desi g nee) wit hi n 2 4  h o urs of k n o wle d ge of t he 
e ve nt. T he pa per pre g na nc y f or m s h o ul d be c o m plete d wit h all i nf or mati o n k n o w n at t he ti me 
a n d sca n ne d a n d e maile d t o M H G Safet y @ pra hs .c o m or fa xe d t o t he t oll -free fa x n u m bers. 
Fe male  partici pa nt s of c hil d beari n g p ote ntial will be i nstr ucte d t o i m me diatel y i nf or m t he 
I n vesti gat or if t he y bec o me pre g na nt d uri n g t he re p orti n g wi n d o w a n d m ust be i m me diatel y 
disc o nti n ue d fr o m st u d y vacci ne.  T he I n vesti gat or s h o ul d c o u nsel t he partici pa nt , disc ussi n g 
t he ris ks of t he pre g na nc y a n d t he u n k n o w n effects o n t he f o et us. M o nit ori n g of t he  partici pa nt  
s h o ul d c o nti n ue u ntil c o ncl usi o n of t he pre g na nc y. 
Male partici pa nts will be i nstr ucte d t o i m me diatel y i nf or m t he I n vesti gat or if t heir part ner 
bec o mes pre g na nt d uri n g t he re p orti n g wi n d o w. Atte m pts s h o ul d be ma de t o c ollect a n d re p ort 
details of t he c o urse a n d o utc o me of a n y pre g na nc y i n t he part ner of a male  partici pa nt  e x p ose d 
t o st u d y vacci ne . T he pre g na nt part ner will nee d t o si g n a n a ut h orisati o n f or use a n d discl os ure 
of pre g na nc y healt h i nf or mati o n  t o all o w f or f oll o w- u p o n her pre g na nc y. T he I n vesti gat or ma y 
pr o vi de i nf or mati o n o n t he ris ks of t he pre g na nc y a n d t he u n k n o w n effects o n t he f oet us, t o 
s u p p ort a n i nf or me d decisi o n i n c o o perati o n wit h t he treati n g p h ysicia n a n d/ or o bstetricia n. 
8. 6. 2  O utc o me  
A d diti o nal i nf or mati o n o n t he c o urse a n d o utc o me of t he pre g na nc y s h o ul d be pr o vi de d t o t he 
S p o ns or ( or desi g nee ) w he n a vaila ble usi n g t he pre g na nc y re p ort f or m. 
T he f oll o wi n g pre g na nc y o utc o mes will be c o nsi dere d t o be S A Es a n d s h o ul d be re p orte d 
acc or di n g t o t he pr oce d ure i n Secti o n  8. 2. 5 . Pre g na nc y is n ot c o nsi dere d a n a d verse e ve nt 
u nless o ne of t he se criteria is met: 
•  S p o nta ne o us a b orti o n (as  t he S p o ns or c o nsi ders s p o nta ne o us a b orti o ns t o be me dicall y 
si g nifica nt e ve nts) 
•  A n y c o n ge nital a n o mal y/ birt h defect i n a c hil d b or n t o a fe male partici pa nt or fe male 
part ner of a male partici pa nt  

 
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9  
D A T A  Q U A LI T Y A S S U R A N C E A N D Q U A LI T Y C O N T R O L  
9. 1  
Pr ot oc ol De vi ati o ns 
Maj or pr ot oc ol de viati o ns are defi ne d as t h ose t hat res ult i n har m t o t he st u d y partici pa nts or 
si g nifica ntl y affect t he scie ntific val ue of t he re p orte d res ults of t he st u d y. Ot her de viati o ns will 
be c o nsi dere d mi n or.  
Pr ot oc ol de viati o ns will be rec or de d o n t he s o urce d oc u me nts a n d wit h a n e x pla nati o n f or t he 
de viati o n. All  pr ot oc ol de viati o ns will als o be rec or de d  as s pecifie d i n t he m o nit ori n g pla n a n d 
statistical a nal ysis pla n. 
Maj or pr ot oc ol de viati o ns t hat meet t he criteria f or a seri o us breac h of I C H G C P [3 6 ] s h o ul d 
be re p orte d t o t he S p o ns or i m me diatel y. N o de viati o n fr o m t he i ncl usi o n /e xcl usi o n criteria will 
be per mitte d.  
9. 2  
M o nit ori n g a n d  S o urce D oc u me nt  Verific ati o n  
T he S p o ns or will arra n ge f or t he st u d y t o be m o nit ore d i n acc or da nce wit h t he pri nci ples of 
I C H G C P [3 6 ]. T he fre q ue nc y of m o nit ori n g visits will be deter mi ne d b y t he rate of partici pa nt  
recr uit me nt. 
T he f oll o wi n g are e xa m ples of ite ms t hat will be re vie we d at t hese visits:  
•  C o m plia nce wit h t he pr ot oc ol 
•  C o nse nt pr oce d ure 
•  S o urce d oc u me nts 
•  A d verse e ve nt pr oce d ures 
•  St ora ge a n d acc o u nta bilit y of st u d y vacci ne  
T he m o nit ori n g visits als o pr o vi de t he S p o ns or wit h t he o p p ort u nit y t o e ns ure t hat ti mel y 
partici pa nt  accr ual a n d t he ot her I n vesti gat or’s o bli gati o ns a n d all a p plica ble re q uire me nts are 
bei n g f ulfille d.  
T he I n vesti gat or m ust per mit t he St u d y M o nit or , t he I E C/I R B, t he S p o ns or’s a u dit ors a n d 
re prese ntati ves  fr o m  re g ulat or y  a ut h orities  direct  access  t o  all  s o urce  d oc u me nts  (see 
Secti o n  1 1. 1 ) f or c o nfir mati o n of t he acc urac y a n d relia bilit y of data c o ntai ne d wit hi n t he e C R F  
(s o urce d oc u me nt verificati o n). P artici pa nt  c o nfi de ntialit y will be pr otecte d at all ti mes.  T he 
St u d y  M o nit or will carr y o ut s o urce d oc u me nt verificati o n at re g ular i nter vals. T his is a n 
esse ntial ele me nt of q ualit y c o ntr ol, as it all o ws t he rectificati o n of tra nscri pti o n err ors a n d 
o missi o ns. 
9. 3  
D at a M a n a ge me nt a n d C o di n g 
Data f or eac h partici pa nt will be rec or de d o n a n e C R F. Data c ollecti o n m ust be c o m plete d f or 
eac h partici pa nt  w h o si g ns a n i nf or me d c o nse nt f or m a n d recei ves at least o ne d ose of st u d y 
vacci ne.  
Electr o nic C R Fs will be desi g ne d a n d pr o d uce d b y t he S p o ns or (or desi g nee ) a n d s h o ul d be 
c o m plete d i n acc or da nce wit h i nstr ucti o ns. T he I n vesti gat or is res p o nsi ble f or mai ntai ni n g 
a de q uate a n d acc urate me dical rec or ds fr o m w hic h acc urate i nf or mati o n will be tra nscri be d 
directl y i nt o t he e C R Fs usi n g a sec ure i nter net c o n necti o n. T he e C R Fs s h o ul d be fille d o ut 
c o m pletel y b y t he I n vesti gat or ( or desi g nee)  as state d o n t he d ele gati o n of res p o nsi bilities for m. 
T he e C R F s yste m will be F o o d a n d Dr u g A d mi nistrati o n  ( F D A) C o de of Fe deral Re g ulati o ns 
2 1 Part 1 1 c o m plia nt. 

 
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T he e C R Fs m ust be re vie we d  a n d a p pr o ve d b y t he I n vesti gat or. 
Data e ntere d i nt o t he e C R F will be vali date d as defi ne d i n t he data vali dati o n s pecificati o ns. 
Vali dati o n i ncl u des, b ut is n ot li mite d t o, vali dit y c hec ks ( e. g. ra n ge c hec ks), c o nsiste nc y 
c hec ks a n d c ust o mi se d c hec ks (l o gical c hec ks bet wee n varia bles t o e ns ure t hat st u d y data are 
acc uratel y re p orte d) f or e C R F data a n d e xter nal data ( e. g. la b orat or y data). A maj orit y of e dit 
c hec ks will be tri g gere d d uri n g data e ntr y a n d will t heref ore facilitate efficie nt ‘ p oi nt of e ntr y’ 
data clea ni n g.  
Data ma na ge me nt pers o n nel will perf or m b ot h ma n ual e C R F re vie w a n d re vie w of electr o nic 
e dit c hec ks t o e ns ure t hat t he data are c o m plete, c o nsiste nt a n d reas o na ble. T he electr o nic e dit 
c hec ks will r u n c o nti n uall y t hr o u g h o ut t he c o urse of t he st u d y a n d t he iss ues will be re vie we d 
ma n uall y o nli ne t o deter mi ne w hat acti o n nee ds t o be ta ke n. 
Ma n ual q ueries ma y be a d de d t o t he s yste m b y cli nical data ma na ge me nt , l ocal Me dical 
M o nit or or St u d y M o nit or . Cli nical D ata Ma na gers a n d St u d y M o nit ors are a ble t o re m otel y 
a n d pr oacti vel y m o nit or t he e C R Fs t o i m pr o ve data q ualit y.  
E xter nal data will be tra nsferre d electr o nicall y i nt o t he st u d y data base. Discre pa ncies will be 
q uerie d t o t he st u d y ce ntre a n d/ or t he la b orat or y u ntil t he electr o nic data a n d t he data base are 
rec o ncile d.  
All u p dates t o q uerie d data will be ma de b y a ut h ori se d st u d y tea m me m bers o nl y a n d all 
m o dificati o ns t o t he data base will be rec or de d i n a n a u dit trail. O nce all t he q ueries ha ve bee n 
res ol ve d, e C R Fs will  be l oc ke d. A n y c ha n ges t o l oc ke d e C R Fs will  be a p pr o ve d b y t he 
I n vesti gat or. 
O nce t he f ull set of e C R Fs ha s bee n c o m plete d a n d l oc ke d, a n d S A E rec o nciliati o n has bee n 
c o m plete d, t he S p o ns or  will a ut h ori se data base l oc k a n d all electr o nic data will be se nt t o t he 
desi g n ate d statisticia n f or a nal ysis.  S u bse q ue nt c ha n ges t o t he data base will t he n o nl y be ma de 
o nl y b y writte n a gree me nt of t he S p o ns or . T he I n vesti gat or will be pr o vi de d wit h a c o p y of t he 
e C R Fs i n a n o n- e dita ble f or mat. 
A d verse e ve nts a n d me dical/ca ncer hist or y ter ms will be c o de d fr o m t he ver bati m descri pti o n 
(I n vesti gat or  ter m)  usi n g  t he  Me dical  Dicti o nar y  f or  Re g ulat or y  Acti vities  ( Me d D R A)  
(Versi o n  2 2. 0  or later).  Pri or  a n d  c o nc o mita nt  me dicati o ns  a n d  t hera pies  will  be  c o de d  
acc or di n g  t o  t he  W orl d  H ealt h  Or ga nis ati o n  dr u g  dicti o nar y   ( Versi o n Dr u g  B 3  Gl o bal  
Se pte m ber 2 0 1 9  or later ). C o di n g re vie w will be perf or me d b y t he S p o ns or ( or desi g nee) pri or 
t o data base l oc k. 
T he cli nical data (i n S A S ®  dataset  f or mat) will be tra nsferre d t o t he S p o ns or at t he e n d of t he 
st u d y. 

 
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1 0  S T A TI S TI C A L C O N SI D E R A TI O N S A N D A N A L Y SI S P L A N  
1 0. 1  S a m ple Size Deter mi n ati o n  
T he  sa m ple  size  of  1 6  partici pa nts  per  gr o u p  is  c h ose n  t o  assess  t he  varia bilit y  i n  b ot h  
i m m u n ol o gic res p o nses, as well as t he p ote ntial c ha n ge i n H Bs A g . Wit h 1 6 partici pa nt s, t he 
trial als o has an 8 0 % c ha nce  t o detect a n y se vere or seri o us a d verse e ve nt t hat w o ul d occ ur at 
a 1 0 % i nci de nce. 
1 0. 2  St atistic al a n d A n al ytic al Pl a ns  
T his secti o n prese nts a s u m mar y of t he pla n ne d statistical a nal yses. F ull details of t he a nal ysis 
will be descri be d i n t he statistical a nal ysis pla n t hat will be a p pr o ve d bef ore data base l oc k . A n y 
a nal ysis t hat de viates fr o m t he statistical a nal ysis pla n will be d oc u me nte d a n d j ustifie d i n t he 
cli nical st u d y re p ort.    
T he c o m p uter pr o gra m pac ka ge S A S ®  E nter prise G ui de ®  (Versi o n  9. 4 or later) will be use d  f or 
statistical a nal ysis.  
1 0. 2. 1  
A n al ysis S ets 
•  
T he i nte nt-t o-treat set will c o nsist of all partici pa nts w h o are ra n d o mise d 
•  
T he  safet y  a nal ysis  set  will  c o nsist  of  all  partici pa nts  w h o  recei ve d  at  least  o ne  
vacci nati o n ( data will be s u m marise d acc or di n g t o t he vacci nati o n act uall y recei ve d)  
•  
T he per -pr ot oc ol a nal ysis set will c o nsist of all partici pa nts i n t he safet y a nal ysis set 
w h o recei ve d t he c orrect st u d y vacci ne a n d w h o ha d n o maj or pr ot oc ol de viati o ns 
•  
T he i m m u n o ge nicit y a nal ysis set will c o nsist of all partici pa nts i n t he per - pr ot oc ol set 
a n d ha ve a vaila ble i m m u n o ge nicit y data t o e val uate t he i m m u n o ge nicit y e n d p oi nts a n d 
di d n ot ha ve a n y maj or pr ot oc ol de viati o ns t hat w o ul d i m pact o n t he res ults of t he 
i m m u n ol o gical a nal ysis 
All ocati o n of partici pa nt s t o t he a nal ysis sets (a n d w het her a n y partici pa nt  or s pecific data fr o m 
a  partici pa nt  will be e xcl u de d) will be deter mi ne d at t he pre -data base l oc k Data Re vie w 
meeti n g . 
1 0. 2. 2  
St u d y A n al yses  
1 0. 2. 2. 1  Ge ner al Pri nci ples  
T he maj orit y of t he a nal ysis will be descri pti ve i n nat ure. U nless state d ot her wise, c o nti n u o us 
varia bles  will  be  s u m marised  usi n g  descri pti ve  statistics  ( n u m ber  of  partici pa nt s,  mea n,  
sta n dar d de viati o n, me dia n, mi ni m u m a n d ma xi m u m val ues) a n d t he n u m ber a n d perce nta ge 
of partici pa nt s will be use d f or cate g orical  varia bles.  
Data will be s u m marise d  b y st u d y vacci ne, partici pa nt gr o u p a n d w here a p pr o priate, o verall. 
I m m u n o ge nicit y a n d efficac y data ma y be s u bject t o a d diti o nal statistical a nal ysis , w hic h will 
be detaile d i n t he S A P. 
1 0. 2. 2. 2  Dis p ositi o n 
P artici pa nt  dis p ositi o n,  i ncl u di n g  reas o ns  f or  st u d y  wit h dra wal  if  a p plica ble,  will  be  
s u m marised descri pti vel y.  

 
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1 0. 2. 2. 3  Pr ot oc ol Devi ati o ns 
Pr ot oc ol  de viati o ns  will  be  liste d  i ncl u di n g:  nat ure  ( misse d  pr oce d ure(s),  earl y  or  late  
pr oce d ure(s) ,  misse d  visits,  visit  perf or me d  o ut  of  pr ot oc ol  defi ne d  wi n d o w,  pr o hi bite d 
me dicati o n  ta k e n,  st u d y  vacci ne  d osi n g  de viati o n,  i ncl usi o n/e xcl usi o n  criteria  vi olati o n , 
partici pa nt s n ot wit h dra w n b ut meeti n g wit h dra wal criteria , bi ol o gical sa m ple ha n dli n g err or, 
o t her) o verall a n d cate g orise d b y maj or a n d mi n or. 
1 0. 2. 2. 4  De m o gr a p hics a n d B aseli ne D at a 
T he safet y a nal ysis set will be use d f or t he a nal ysis of de m o gra p hic a n d baseli ne data.  
De m o gra p hics  a n d  baseli ne  c haracteristics  will  be  liste d  a n d  s u m marised descri pti vel y . 
Me dicati o ns a n d  t hera pies will be s u m marised b y a nat o mic t hera pe utic c he mical classificati o n.  
1 0. 2. 2. 5  I m m u n o ge nicity A n alyses 
T he f oll o wi n g e n d p oi nts will be prese nte d b y st u d y vacci ne a n d partici pa nt gr o u p: 
•  
A  m ulti -para meter  i n de x  ma de  of  C D 4 +  ma g nit u de ,  C D 4 +  a vi dit y,  a n d 
C D 8 +  ma g nit u de 
•  
Re d ucti o n i n H Bs A g titre at M o nt hs 3 a n d 9 ( e n d of st u d y visit) ; s pecificall y t h ose wit h 
l oss of > 0. 5 l o g1 0 a n d > 1. 0 l o g 1 0 fr o m baseli ne 
•  
Pr o p orti o n of partici pa nt s wit h H BeA g a n d H Bs A g l oss  
•  
Pr o p orti o n of H B eA g  a n d H Bs A g ser oc o n versi o n (a nti b o d y p ositi vit y) 
•  
Re d ucti o n of he patitis B D N A le vel 
•  
Effect o n H Bc rA g  
•  
Effect of H B p g R N A  
1 0. 2. 2. 6  S afety D at a 
Safet y data will be s u m marise d descri pti vel y.  
Treat me nt e mer ge nt e ve nts are defi ne d as t h ose occ urri n g after st u d y vacci ne a d mi nistrati o n . 
1 0. 2. 2. 6. 1  A d verse E ve nts 
All a d verse e ve nts will be liste d, i ncl u di n g t he ver bati m descri pti o n a n d Me d D R A preferre d 
ter ms a n d s yste m or ga n class ( S O C).  
T E A Es  will be s u m marised b y S O C  a n d b y preferre d ter m. T he i nci de nce of T E A Es will be 
base d o n t he n u m bers a n d perce nta ges of partici pa nts  wit h e ve nts  a n d n u m ber of e ve nts . 
T E A E s will be f urt her s u m marised b y se verit y a n d relati o ns hi p t o st u d y vacci ne.   
A n o verall s u m mar y of a d verse e ve nt i nci de nce will als o be prese nte d b y st u d y  vacci ne d ose 
a n d o verall  t o i ncl u de t he n u m ber a n d perce nta ge of partici pa nts  wit h at least o ne: T E A E , 
vacci ne -relate d T E A E , Gra de  3 t o Gra de 5  T E A E,  deat h, S AE , vacci ne-relate d S A E, A E SI, 
vacci ne -relate d A E SI, T E A E lea di n g t o st u d y vacci ne disc o nti n uati o n a n d T E A E lea di n g t o 
st u d y disc o nti n uati o n. 
Narrati ves will be writte n f or a n y deat hs, ot her S A Es , A E SI s, T E A Es lea di n g t o st u d y vacci ne  
disc o nti n uati o n a n d T E A Es lea di n g t o st u d y disc o nti n uati o n. 

 
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1 0. 2. 2. 6. 2  La b orat or y Safet y Tests  
Se verit y gra di n g  usi n g t he t o xicit y ta ble i n A p pe n di x 1  will be  assi g ne d t o la b orat or y safet y 
val ues w here a p plica ble. La b orat or y res ults i n re p orte d u nits a n d sta n dar d i nter nati o nal (SI ) 
u nits  w ill  be liste d,  i ncl u di n g  hi g h  a n d  l o w  fla gs,  se verit y gra des  w here  a p plica ble,  t he  
c orres p o n di n g n or mal ra n ge a n d cli nical si g nifica nce. 
La b orat or y safet y tests s u m maries w ill be base d o n res ults i n SI u nits. A bs ol ute a n d c ha n ge 
fr om baseli ne res ults , i ncl u di n g t he w orst c ha n ge f or eac h varia ble f or eac h partici pa nt  w ill be 
s u m marise d usi n g descri pti ve statistics.  
Treat me nt e mer ge nt o ut of ra n ge res ults wit h t he c orres p o n di n g se verit y gra de, n or mal ra n ges, 
baseli ne res ults a n d cli nical si g nifica nce will be se paratel y liste d. S hift ta bles will be use d t o 
s h o w c ha n ges fr o m baseli ne at eac h ti me p oi nt a n d t he w orst c ha nge i n eac h partici pa nt a n d 
scatter pl ots of t he w orst c ha n ge will be pr o d uce d. T he n u m ber of partici pa nts  s h o wi n g s hifts 
of at least t w o se verit y gra des will be s u m marise d.  
T he n u m ber of partici pa nt s wit h treat me nt e mer ge nt cli nicall y si g nifica nt la b orat or y safet y test 
res ults a n d la b orat or y safet y test res ults of Gra de 3 or 4 will be s u m marise d. 
1 0. 2. 2. 6. 3  Vital Si g ns  
A bs ol ute a n d c ha n ge fr o m baseli ne vital si g n res ults, i ncl u di n g t he w orst c ha n ge f or eac h 
varia ble  f or  eac h  partici pa nt  w ill  be s u m marise d  usi n g  descri pti ve  statistics.  Treat me nt  
e mer ge nt o ut of ra n ge res ults wit h t he c orres p o n di n g n or mal ra n ges , baseli ne res ults a n d 
cli nical si g nifica nce will be se paratel y liste d. S hift ta bles will be use d t o s h o w c ha n ges fr o m 
baseli ne at eac h ti me p oi nt a n d t he w orst c ha n ge i n eac h partici pa nt a n d scatter pl ots of t he w orst 
c ha n ge  will  be  pr o d uce d.  T he  n u m ber  of  partici pa nt s  wit h  treat me nt e mer ge nt  cli nicall y  
si g nifica nt res ults will be s u m marise d. 
1 0. 2. 2. 6. 4  P h ysical E xa mi nati o n  
Treat me nt  e mer ge nt  a b n or mal  p h ysical  e xa mi nati o n  wit h  t he  c orres p o n di n g  cli nical  
si g nifica nce will be are liste d. S hift ta bles will be use d t o s h o w c ha n ges i n p h ysical e xa mi nati o n 
stat us fr o m baseli ne at eac h ti me p oi nt a n d t he w orst s hift i n eac h partici pa nt  will be i ncl u de d . 
1 0. 2. 3  
I nteri m A n al yses 
T o hel p wit h t he pla n ni n g of f ut ure st u dies,  a n i nteri m a nal ysis of all a vaila ble data will be 
perf or me d w he n at least 2 0 partici pa nts ha ve bee n e nr olle d a n d after t heir sec o n d d ose  of 
st u d y vacci ne. 
 
U n bli n de d listi n gs a n d s u m maries will be s u b mitte d t o t he D M C, as nee de d. T he ti mi n g of t he 
D M C s u b missi o ns will be s pecifie d i n t he D M C C harter . 
1 0. 2. 4  
H a n dli n g Missi n g, U n use d or S p uri o us D at a  
T he S A P will descri be a n d acc o u nt f or t he occ urre nce of a n d e xte nt of missi n g data, a n d its 
p ossi ble i m pact o n t he st u d y a nal ysis. 

 
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1 1  S T U D Y D O C U M E N T A TI O N, I N S P E C TI O N S A N D R E C O R D K E E PI N G  
1 1. 1  St u d y D oc u me nt ati o n  
T he I n vesti gat or m ust mai ntai n a de q uate a n d acc urate rec or ds t o e na ble t he c o n d uct of t he 
st u d y t o be f ull y d oc u me nte d a n d t he st u d y data t o be s u bse q ue ntl y verifie d. T hese d oc u me nts 
s h o ul d c o ntai n all esse ntial d oc u me nts re q uire d b y I C H G C P [3 6 ] a n d i ncl u de: 
1.  
I n vesti gat or’s S ite File (e. g. pr ot oc ol a n d a me n d me nts, I E C/I R B a n d re g ulat or y a ut h orit y 
a p pr o val wit h c orres p o n de nce, sa m ple i nf or me d c o nse nt, st u d y vacci ne  acc o u nta bilit y  
rec or ds, staff c urric ul um vitae a n d a ut h orisati o n f or ms, c orres p o n de nce) 
2.  
Partici pa nt  s o urce d oc u me nts 
S o urce d oc u me nts are defi ne d as t he res ults of ori gi nal o bser vati o ns a n d acti vities of a 
cli nical i n vesti gati o n, i ncl u di n g me dical n otes. All s o urce d oc u me nts pr o d uce d i n t his 
st u d y will be mai ntai ne d b y t he I n vesti gat or a n d ma de a vaila ble f or i ns pecti o n. S o urce 
data i ncl u de, b ut is n ot li mite d t o, t he f oll o wi n g a n d will be i de ntifie d i n a s o urce data 
l ocati o n l o g: 
•  
Scree ni n g/e nr ol me nt l o g  
•  
Me dical n otes - w hic h s h o ul d be u p date d after eac h visit t o i ncl u de visit dates, 
me dical hist or y a n d ca ncer hist or y, c o nc o mita nt me dicati o n, a n y cli nicall y rele va nt 
fi n di n gs of cli nical e xa mi nati o ns or cli nicall y rele va nt a d verse e ve nts/ me dicati o n 
c ha n ges, S A Es a n d i nf or mati o n o n partici pa nt  wit h dra wal  
•  
I nf or me d c o nse nt f or m 
•  
Safet y la b orat or y re p orts  
•  
Visit dates  
•  
St u d y vacci ne  acc o u nta bilit y a n d i n ve nt or y f or ms 
3.  
Partici pa nt  e C R F data (w hic h i ncl u des a n a u dit trail c o ntai ni n g a c o m plet e rec or d of all 
c ha n ges t o data) will be se nt t o t he I n vesti gat or at t he e n d of t he st u d y 
1 1. 2  A u dits a n d St u d y Ce ntre  I ns pecti o ns 
A ut h oris e d pers o n nel fr o m re g ulat or y a ut h orities a n d t he S p o ns or q ualit y ass ura nce f u ncti o n  
ma y carr y o ut i ns pecti o ns a n d a u dits res pecti vel y. T he p ur p ose of a n a u dit  or i ns pecti o n is t o 
e ns ure t hat et hical, re g ulat or y a n d q ualit y re q uire me nts are f ulfille d i n S p o ns or st u dies. 
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 ti me a n d t he ti me 
of his staff t o t he a u dit or 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. 3  Rete nti o n of Rec or ds  
Rec or ds a n d d oc u me nts pertai ni n g t o t he c o n d uct of t his st u d y a n d t he distri b uti o n of st u d y 
vacci ne , i ncl u di n g e C R Fs,  inf or me d c o nse nt  for ms, la b orat or y safet y test res ults a n d st u d y 
vacci ne  i n ve nt or y a n d acc o u nta bilit y rec or ds, m ust be retai ne d b y t he I n vesti gat or f or at least 
1 5 years after c o m pleti o n or disc o nti n uati o n of t he st u d y, or acc or di n g t o l ocal re q uire me nts,  
w hic he ver is l o n ger. After t hat peri o d of ti me, t he d oc u me nts ma y be destr o ye d, s u bject t o l ocal 
re g ulati o ns.   
N o  rec or ds  ma y  be  dis p ose d  of  wit h o ut  t he  writte n  a p pr o val  of  t he  S p o ns or. Writte n 
n otificati o n s h o ul d be pr o vi de d t o t he S p o ns or pri or t o tra nsferri n g a n y rec or ds t o a n ot her part y 
or m o vi n g t he m t o a n ot her l ocati o n. 

 
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1 2  FI N A N C E A N D I N S U R A N C E  
Fi na ncial arra n ge me nts are detaile d i n t he I n vesti gat or A gree me nt bet wee n t he S p o ns or a n d 
I n vesti gat or. 
Details of t he S p o ns or ’s arra n ge me nt f or  cli nical st u d y i ns ura nce t o pr o vi de f or c o m pe nsati o n 
t o partici pa nt  f or a n y clai m f or b o dil y i nj ur y or deat h arisi n g fr o m partici pati o n i n t he cli nical 
st u d y are pr o vi de d i n t he i nf or me d c o nse nt f or m.  

 
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1 3  E T HI C A L A N D R E G U L A T O R Y C O N SI D E R A TI O N S  
1 3. 1  L oc al Re g ul ati o ns/ Decl ar ati o n of Helsi n ki  
T he I n vesti gat or will e ns ure t hat t his st u d y is c o n d ucte d i n f ull c o nf or ma nce wit h t he pr ot oc ol 
a n d t he pri nci ples of t he “ Declarati o n of Helsi n ki” [3 7 ] or wit h t he la ws a n d re g ulati o ns of t he 
c o u ntr y i n w hic h t he researc h is c o n d ucte d, w hic he ver aff or ds t he greater pr otecti o n t o t he 
i n di vi d ual.  
T h e st u d y m ust f ull y a d here t o  I C H G C P [3 6 ] or wit h l ocal re g ulati o ns if t he y aff or d greater 
pr otecti o n t o t he partici pa nt . 
1 3. 2  Re g ul at or y A ut h orit y A p pr o v al  
T he st u d y will n ot c o m me nce bef ore a p pr o val fr o m t he nati o nal re g ulat or y a ut h orit y bee n 
gra nte d acc or di n g t o l ocal re q uire me nts.  T he S p o ns or (or desi g nee ) will be res p o nsi ble f or t he 
pre parati o n, s u b missi o n a n d c o nfir mati o n of recei pt of a n y re g ulat or y a ut h orit y a p pr o vals 
re q uire d pri or t o release of st u d y vacci ne f or s hi p me nt t o t he st u d y ce ntre. 
D uri n g t he st u d y, t he S p o ns or ( or desi g nee) is als o res p o nsi ble f or s u b mitti n g s u bse q ue nt 
a me n d me nts a n d n otificati o ns t o t he  re g ulat or y a ut h orit y acc or di n g t o l ocal re q uire me nts.  
1 3. 3  Et hics C o m mittee/I nstit uti o n al Re vie w B o ar d  A p pr o v al 
T he I n vesti gat or will be res p o nsi ble f or s u b mitti n g all d oc u me nts re q uire d b y t he I E C/I R B 
e. g. t his pr ot oc ol, t he i nf or me d c o nse nt f or m rele va nt s u p p orti n g i nf or mati o n a n d all t y pes of 
st u d y s pecific partici pa nt recr uit me nt i nf or mati o n (i ncl u di n g a d vertise me nts) a n d a n y ot her 
writte n i nf or mati o n t o be pr o vi de d t o partici pa nts, t o t he I E C/I R B f or re vie w. T he I n vesti gat or 
or S p o ns or s h o ul d als o pr o vi de t he I E C/I R B wit h a c o p y of t he I n vesti gat or’s Br oc h ure or 
pr o d uct la belli n g, i nf or mati o n t o be pr o vi de d t o partici pa nts a n d a n y u p dates. If t he I E C/I R B 
re q uires  m o dificati o n  of  t he  s u b mitte d  i nf or mati o n,  t he  d oc u me ntati o n  s u p p orti n g  t his  
re q uire me nt m ust be pr o vi de d t o t he S p o ns or ( or desi g nee). 
T he st u d y m ust ha ve t he i nitial a n d at least a n n ual ( w he n re q uire d) a p pr o val of a n I E C/I R B. 
T he  si g ne d  a p pr o val  letter  m ust  i de ntif y  t he  e xact  pr ot oc ol  title  a n d  n u m ber,   d oc u me nts 
a p pr o ve d a n d t he date of a p pr o val of t he pr ot oc ol a n d t he i nf or me d c o nse nt d oc u me nt. T he 
S p o ns or will n ot s hi p cli nical s u p plies u ntil a si g ne d a p pr o val letter has bee n recei ve d a n d a 
Cli nical Trial A gree me nt has bee n si g ne d b y t he S p o ns or a n d t he st u d y ce ntre. 
A list of I E C/I R B me m bers m ust be pr o vi de d t o t he S p o ns or ( or desi g nee). 
T he I n vesti gat or  or  S p o ns or s h o ul d pr o vi de t he I E C/I R B wit h re p orts, u p dates a n d ot her 
i nf or mati o n (e. g. e x pe dite d safet y re p orts, a me n d me nts a n d a d mi nistrati ve letters) acc or di n g 
t o re g ulat or y re q uire me nts or st u d y ce ntre pr oce d ures. 
T he S p o ns or ( or desi g nee) will e ns ure t he I E C/I R B is n otifie d of a n y a d verse e ve nts meeti n g 
t he criteria f or e x pe dite d re p orti n g, a n n ual u p date s a n d w he n t he st u d y has bee n c o m plete d  
acc or di n g t o l ocal re q uire me nts . T he S p o ns or ( or desi g nee) will pr o vi de i nf or mati o n t o t he 
I n vesti gat or w h o will be res p o nsi ble f or f or war di n g t his t o t he I E C/I R B. 
1 3. 4  I nf or me d C o nse nt 
It is t he res p o nsi bilit y of t he I n vesti gat or t o o btai n writte n i nf or me d c o nse nt fr o m partici pa nts  
pri or  t o  c o n d ucti n g  a n y  st u d y  relate d  pr oce d ures. All  c o nse nt  d oc u me ntati o n  m ust  be  i n  
acc or da nce wit h a p plica ble re g ulati o ns a n d  I C H G C P  [3 6 ]. Eac h partici pa nt  is re q ueste d t o 
si g n a n d date t he i nf or me d c o nse nt f or m after (s) he has recei ve d a n d rea d t he partici pa nt  

 
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i nf or mati o n s heet a n d recei ve d a n e x pla nati o n of w hat t he st u d y i n v ol ves, i ncl u di n g b ut n ot 
li mite d t o: t he o bjecti ves, p ote ntial be nefits a n d ris k, i nc o n ve nie nces a n d t he partici pa n t’s 
ri g hts a n d res p o nsi bilities. partici pa n ts will be gi ve n a de q uate ti me t o e val uate t he i nf or mati o n 
gi ve n t o t he m bef ore si g ni n g a n d dati n g t he i nf or me d c o nse nt f or m. T he i nf or me d c o nse nt f or m 
als o be si g ne d a n d date d b y t he pers o n o btai ni n g c o nse nt.  T he ori gi nal si g ne d i nf or me d c o nse nt 
f or m f or eac h partici pa nt  will be retai n e d o n file  b y t he I n vesti gat or a n d t he sec o n d si g ne d 
ori gi nal gi ve n t o t he partici pa nt. 
I nf or me d c o nse nt f or ms m ust be retai ne d f or e nr olle d partici pa nt s a n d f or partici pa nt s w h o are 
n ot s u bse q ue ntl y e nr olle d a n d m ust be a vaila ble f or verificati o n b y t he St u d y M o nit or at a n y 
ti me.  
I n t he e ve nt of c ha n ges t o t he i nf or me d c o nse nt f or m d uri n g t he st u d y, the I n vesti gat or m ust 
al wa ys  use  t he  m ost  c urre nt I E C/I R B a p pr o ve d  f or m  f or  d oc u me nti n g  writte n  i nf or me d  
c o nse nt. 
1 3. 5  Pr ot oc ol A me n d me nts  
T he pr ot oc ol (a n d ot her s u p p orti n g d oc u me nts t hat ha ve recei ve d a p pr o val bef ore t he start of 
t he st u d y e. g. i nf or me d c o nse nt f or m) ma y n ot be m o difie d wit h o ut writte n a p pr o val fr o m t he 
S p o ns or . I n t he e ve nt t hat a n a me n d me nt t o t he  pr ot oc ol (a n d/ or s u p p orti n g d oc u me nts) is 
re q uire d, it will be classifie d i nt o o ne of t he f oll o wi n g cate g ories b y t he S p o ns or : 
•  S u bsta ntial a me n d me nts are t h ose c o nsi dere d ‘s u bsta ntial’ t o t he c o n d uct of t he cli nical 
st u d y a n d are li kel y t o ha ve a si g nifica nt i m pact o n e. g.  t he safet y or p h ysical or me ntal 
i nte grit y  of  t he  partici pa nts ,  t he  scie ntific  val ue  of  t he  st u d y,  t he  c o n d uct  or  
ma na ge me nt of t he  st u d y or t he q ualit y or safet y of t he st u d y vacci ne  use d i n t he st u d y 
•  N o n -su bsta ntial ame n d me nts  o nl y  i n v ol ve  a d mi nistrati ve  or  l o gistical  c ha n ges,  
t y p o gra p hical err ors 
T he S p o ns or will deter mi ne if re g ulat or y a ut h orit y a n d/ or I E C/I R B re vie w is re q uire d pri or t o 
t he i m ple me ntati o n of t he a me n d me nt acc or di n g t o l ocal re g ulati o ns. I n ge neral, s u bsta ntial 
a me n d me nts  ma y  n ot  be  i nitiate d  wit h o ut  a p pr o val  e xce pt  w he n  necessar y  t o  eli mi nate  
i m me diate  hazar ds  t o  t he  partici pa nt s or  w he n  t he  c ha n ge(s)  i n v ol ves.  N o n -s u bsta ntial 
a me n d me nts d o n ot re q uire a p pr o val. 
T he S p o ns or (or desi g nee ) is res p o nsi ble f or o btai ni n g a p pr o val f or s u bsta ntial a me n d me nts 
fr o m t he re g ulat or y a ut h orit y. T he I n vesti gat or is res p o nsi ble f or pr o m ptl y i nf or mi n g t he 
I E C/I R B of a n y s u bsta ntial a me n d me nts a n d pr o vi di n g d oc u me ntati o n of fa v o ura ble o pi ni o n 
t o t he S p o ns or ( or desi g nee). 
1 3. 6  C o nfi de nti alit y of St u d y  D oc u me nts a n d P artici p a nt  Rec or ds  
T he I n vesti gat or m ust e ns ure t hat partici pa nt ’s a n o n y mit y will be mai ntai ne d a n d t hat t heir 
i de ntities are pr otecte d fr o m u na ut h orise d parties. T he S p o ns or   (or desi g nee ) will mai ntai n 
c o nfi de ntialit y sta n dar ds b y assi g ni n g a u ni q ue c o de d i de ntificati o n n u m ber t o eac h partici pa nt  
i ncl u de d i n t he st u d y. Partici pa nt  na mes will ne ver be i ncl u de d i n data sets t hat are tra ns mitte d 
t o t he S p o ns or or t heir re prese ntati ves or t o t hir d parties as per mitte d b y t he i nf or me d c o nse nt 
f or m.  
P artici pa nt s s h o ul d be i de ntifie d b y a n i de ntificati o n c o de rat her t ha n  b y t heir na mes  o n e C R Fs 
or ot her d oc u me nts s u b mitte d t o t he S p o ns or. T he I n vesti gat or s h o ul d kee p a partici pa nt  
e nr ol me nt l o g relati n g c o des t o t he na mes of partici pa nt s. T he I n vesti gat or s h o ul d mai ntai n 
d oc u me nts n ot f or s u b missi o n t o t he S p o ns or e. g. i nf or me d c o nse nt f or ms, i n strict c o nfi de nce. 

 
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Rec or ds  will  n ot  be  destr o ye d  wit h o ut  gi vi n g  t he  S p o ns or  pri or  writte n  n otice  a n d  t he  
o p p ort u nit y t o f urt her st ore s uc h rec or ds, at t he S p o ns or’s c ost a n d e x pe nse. 
P artici pa nt  me dical  i nf or mati o n  o btai ne d  b y  t his  st u d y  is  c o nfi de ntial  a n d  ma y  o nl y  be  
discl ose d t o t hir d parties as per mitte d b y t he i nf or me d c o nse nt for m si g ne d b y t he partici pa nt , 
u nless per mitte d or re q uire d b y la w. 

 
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1 4  S T U D Y C O M P L E TI O N  
All materials or s u p plies pr o vi de d b y t he S p o ns or will be ret ur ne d t o t he S p o ns or u p o n st u d y 
c o m pleti o n. T he I n vesti gat or will n otif y t he I E C/I R B w he n t he st u d y has bee n c o m plete d. T he 
st u d y will be c o nsi dere d c o m plete w he n t he last partici pa nt  c o m pletes t heir fi nal f oll o w- u p 
visit a n d all t he data clarificati o n f or ms ha ve bee n res ol ve d. T his re p ort  s h o ul d be ma de wit hi n 
3 m o nt hs of t he c o m pleti o n or ter mi nati o n of t he st u d y. T he fi nal re p ort se nt t o t he I E C/I R B 
s h o ul d als o be se nt t o t he S p o ns or a n d, al o n g wit h t he c o m plete d e C R Fs, c o nstit utes t he fi nal 
s u m mar y t o t he S p o ns or, t here b y f ulfilli n g t he I n vesti gat or’s re g ulat or y res p o nsi bilit y.  

 
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1 5  P U B LI C A TI O N O F D A T A  
T he fi nal st u d y re p ort will be ma de a vaila ble t o t he I n vesti gat or f or p ur p oses of p u blicati o ns. 
T he I n vesti gat or a n d st u d y  tea m m ust se n d all ma n uscri pts, a bstracts, a n d prese ntati o ns usi n g 
data fr o m t his st u d y t o t he S p o ns or f or re vie w pri or t o t heir s u b missi o n. The S p o ns or  reser ves 
t he ri g ht t o delete a n y part or parts of s uc h materials dee me d t o be c o nfi de ntial or pr o prietar y. 

 
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1 6  R E F E R E N C E S  
1.  
W orl d Healt h Or ga nizati o n. G ui deli nes f or t he pre ve nti o n, care a n d treat me nt of pers o ns 
wit h
 c hr o nic
 he patitis
 B
 i nfecti o n.
 Marc h
 2 0 1 5.
 A vaila ble
 
at: htt ps:// w w w. w h o.i nt/ he patitis/t o pics/ he patitis - b/e n/. Last accesse d o n 1 1 J ul y 2 0 1 9. 
2.  
Cesar A g uilar J, L o bia na Y. I m m u n ot hera p y f or c hr o nic he patitis B usi n g H Bs A g -base d 
v acci ne for m ulati o ns: fr o m p re ve nti ve co m mercial v acci nes t o t hera pe utic  a p pr oac h. 
E ur oasia n J He pat o - Gastr oe nter ol. 2 0 1 4; 4( 2): 9 2-9 7 . 
3.  
E ur o pea n  Ass ociati o n  f or  t he  St u d y  of  t he  Li ver.  E A S L  2 0 1 7  Cli nical  Practice  
G ui deli nes  o n  t he  ma na ge me nt  of  he patitis  B  vir us  i nfecti o n.  J  He pat ol.  
2 0 1 7; 6 7: 3 7 0- 3 9 8. 
4.  
Vi ga n ò M, Gr ossi G, L o gli o A, La m pertic o P. Treat me nt of he patitis B: Is t here still a 
r ole f or i nterfer o n? Li ver I nt. 2 0 1 8; 3 8( S u p pl. 1): 7 9 – 8 3. 
5.  
La u G K, Pirat vis ut h T, L u o K X, et al. Pe gi nterfer o n Alfa -2a, la mi v u di ne, a n d t he 
c o m bi nati o n  f or  H Be A g -p ositi ve  c hr o nic  he patitis  B.  N  E n gl  J  Me d.  
2 0 0 5; 3 5 2: 2 6 8 2- 2 6 9 5. 
6.  
Marcelli n P, La u G K, B o ni n o F, et al. Pe gi nterfer o n alfa -2a al o ne, la mi v u di ne al o ne, 
a n d t he t w o i n c o m bi nati o n i n patie nts wit h H Be A g -ne gati ve c hr o nic he patitis B. N E n gl 
J Me d. 2 0 0 4; 3 5 1: 1 2 0 6- 1 2 1 7. 
7.  
Xie Q, Z h o u H, Bai X, et al. A ra n d o mize d, o pe n -la bel cli nical st u d y of c o m bi ne d 
pe g ylate d i nterfer o n alfa -2a ( 4 0 k D) a n d e nteca vir treat me nt f or he patitis B “e” a nti ge n -
p ositi ve c hr o nic He patitis B. Cli n I nfect Dis. 2 0 1 4; 5 9: 1 7 1 4- 1 7 2 3. 
8.  
Marcelli n P, A h n S H, Ma X, et al. C o m bi nati o n of te n of o vir dis o pr o xil f u marate a n d 
pe gi nterfer o n α -2a i ncreases l oss of he patitis B s urface a nti ge n i n patie nts wit h c hr o nic 
he patitis B. Gastr oe nter ol. 2 0 1 6; 1 5 0: 1 3 4- 1 4 4. 
9.  
Z ha n g  Y,  W u  Y,  De n g  M , et  al.  C D 8 +  T -cell res p o nse-ass ociate d ev ol uti o n  of  
h e patitis B v ir us core pr otei n a n d d isease pr o gress. J Vir ol. 2 0 1 8; 9 2( 1 7):e 0 2 1 2 0- 1 7. 
1 0.  
K n olle P A, T hi m me R. He patic i m m u ne re g ulati o n a n d its i n v ol ve me nt i n viral he patitis 
i nfecti o n. Gastr oe nter ol . 2 0 1 4; 1 4 6: 1 1 9 3 – 1 2 0 7. 
1 1.  
Se der R A, Dara h P A, R oe derer M. T -cell q ualit y i n me m or y a n d pr otecti o n: i m plicati o ns 
f or vacci ne desi g n. Nat ure Re v I m m u n ol. 2 0 0 8; 8: 2 4 7- 2 5 8. 
1 2.  
M o y o N, B ort h wic k N, Wee E G et al. L o n g- ter m f oll o w u p of h u ma n T-cell res p o nses 
t o  c o nser ve d  HI V-1  re gi o ns  elicite d  b y  D N A/si mia n  a de n o vir us/ M V A  vacci ne  
re gi me ns. P L o S O ne 2 0 1 7; 1 2( 7): e 0 1 8 1 3 8 2. 
1 3.  
Ra m pli n g T, E wer KJ, B o w yer G et al. Safet y a n d hi g h le vel efficac y of t he c o m bi nati o n 
malaria vacci ne re gi me n of R T S, S/ A S 0 1 B  wit h c hi m pa nzee a de n o vir us 6 3 a n d m o difie d 
vacci nia  A n kara  vect ore d  vacci nes  e x pressi n g  M E -T R A P.  J  I nfect  Dis.  
2 0 1 6; 2 1 4: 7 7 2- 7 8 1. 
1 4.  
L u S. Heter ol o g o us pri me -b o ost vacci nati o n. C urr O pi n I m m u n ol. 2 0 0 9; 2 1( 3): 3 4 6 - 3 5 1. 
1 5.  
Sc h nei der J, Gil bert S C, Ha n na n C M et al. I n d ucti o n of C D 8 + T cells usi n g heter ol o g o us 
pri me‐ b o ost i m m u nisati o n  strate gies. I m m u n ol Re v. 1 9 9 9; 1 7 0: 2 9- 3 8. 
1 6.  
C o u g hla n L, Sri d har S, Pa y ne R et al. Heter ol o g o us t w o -d ose vacci nati o n wit h si mia n 
a de n o vir us  a n d  p o x vir us  vect ors  elicits  l o n g -lasti n g  cell ular  i m m u nit y  t o  i nfl ue nza  
vir us A i n healt h y a d ults. E Bi o Me dici ne. 2 0 1 8; 2 9: 1 4 6- 1 5 4. 
1 7.  
E wer  K,  Se bastia n  S,  S pe ncer  AJ,  Gil bert  S,  Hill  A V S,  La m be  T.  C hi m pa nzee  
a de n o viral  vect ors  as  vacci nes  f or  o ut brea k  pat h o ge ns.  H u m  Vacci n  I m m u n ot her.  
2 0 1 7; 1 3( 1 2): 3 0 2 0 – 3 0 3 2. 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 7 7  of 1 0 9  
1 8.  
M orris SJ, Se bastia n S, S pe ncer AJ, Gil bert S C. Si mia n a de n o vir uses as vacci ne vect ors. 
F ut ure Vir ol. 2 0 1 6; 1 1( 9): 6 4 9 – 6 5 9. 
1 9.  
S hee ha n S, Harris S A, Satti I, et al. A P hase I, o pe n -la bel trial, e val uati n g t he safet y a n d 
i m m u n o ge nicit y  of  ca n di date  t u berc ul osis  vacci nes  A E R A S-4 0 2  a n d  M V A 8 5 A,  
a d mi nistere d b y pri me -b o ost re gi me i n B C G -vacci nate d healt h y a d ults. P L o S O ne. 
2 0 1 5; 1 0( 1 1):e 0 1 4 1 6 8 7. 
2 0.  
H o d gs o n S H, E wer KJ, Bliss C M, et al. E val uati o n of t he efficac y of C h A d 6 3 -M V A 
vect ore d  vacci nes  e x pressi n g  circ u ms p or oz oite  pr otei n  a n d  M E -T R A P  a gai nst  
c o ntr olle d  h u ma n  malaria  i nfecti o n  i n  malaria -nai ve  i n di vi d uals.  J  I nfect  Dis.  
2 0 1 5; 2 1 1: 1 0 7 6- 1 0 8 6. 
2 1.  
M ot he B, Ma nzar d o C, Sa nc hez -Ber na be uet A, et al. T hera pe utic vacci nati o n ref oc uses 
T- cell  res p o nses  t o war ds  c o nser ve d  re gi o ns  of  HI V -1  i n  earl y  treate d  i n di vi d uals  
( B C N 0 1 st u d y). E Cli nical Me dici ne 2 0 1 9; 1 1: 6 5 – 8 0. 
2 2.  
Gree n  C A,  Sa n de  CJ,  Scarselli  E,  et  al.  N o vel  ge neticall y -m o difie d  c hi m pa nzee  
a de n o vir us a n d M V A -vect ore d res pirat or y s y nc ytial vir us vacci ne safel y b o osts h u m oral 
a n d cell ular i m m u nit y i n healt h y ol der a d ults. J I nfect. 2 0 1 9; 7 8( 5): 3 8 2- 3 9 2. 
2 3.  
Vel k o v S, Ott  JJ, Pr otzer U, Mic hler  T. T he gl o bal h e patitis B v ir us ge n ot y pe d istri b uti o n 
a p pr o xi mate d fr o m a vaila ble ge n ot y pi n g data. Ge nes ( Basel) 2 0 1 8; 9( 1 0): 4 9 5. 
2 4.  
Dra per, S.J. a n d J. L. Hee ne y. 2 0 1 0. Vir uses as vacci ne vect ors f or i nfecti o us diseases 
a n d ca ncer. Nat Re v Micr o bi ol, 2 0 1 0. 8( 1): 6 2- 7 3.  
2 5.  
T hi m me R, Wiela n d S, Stei ger C, et al. C D 8 +  T cells me diate viral cleara nce a n d disease 
pat h o ge nesis d uri n g ac ute he patitis B vir us i nfecti o n. J Vir ol. 2 0 0 3; 7 7( 1): 6 8 – 7 6. 
2 6.  
G ui d otti L G, R oc hf or d R, C h u n g J, S ha pir o M, P urcell R, C hisari F V. Viral cleara nce 
wit h o ut  destr ucti o n  of  i nfecte d  cells  d uri n g  ac ute  H B V  i nfecti o n.  Scie nce  
1 9 9 9; 2 8 4: 8 2 5 8 2 9. 
2 7.  
Asa be S, Wiela n d S F, C hatt o pa d h ya y P K, et al. T he size of t he viral i n oc ul u m c o ntri b utes 
t o t he o utc o me of he patitis B vir us i nfecti o n. J Vir ol. 2 0 0 9; 8 3: 9 6 5 2- 9 6 6 2. 
2 8.  
L u S. Heter ol o g o us pri me- b o ost vacci nati o n. 2 0 0 9. C urr O pi n I m m u n ol 2 1( 3): 3 4 6- 5 1. 
2 9.  
B o ni C, Fisicar o P, Val datta C, A ma dei B, Di Vi nce nz o P, Gi u berti T, Lacca b ue D, 
Zer bi ni A, Ca valli A, Missale G, Bert oletti A, Ferrari C. 2 0 0 7. C haracterizati o n of 
he patitis B vir us ( H B V) -s pecific T-cell d ysf u ncti o n i n c hr o nic H B V i nfecti o n. J Vir ol 
8 1: 4 2 1 5- 2 5. 
3 0.  
C he n J, Wa n g X M, W u XJ, Wa n g Y, Z ha o H, S he n B, Wa n g G Q. 2 0 1 1. I ntra he patic 
le vels of P D-1/ P D -L c orrelate wit h li ver i nfla m mati o n i n c hr o nic he patitis B. I nfla m m 
Res 6 0: 4 7- 5 3.  
3 1.  
Fisicar o P, Val datta C, Massari M, L o g gi E, Ra va netti L, Ur ba ni S, Gi u berti T, Ca valli 
A,  Va n delli  C,  A n dre o ne  P,  Missale  G,  Ferrari  C.  2 0 1 2.  C o m bi ne d  bl oc ka de  of  
pr o gra m me d deat h -1 a n d acti vati o n of C D 1 3 7 i ncrease res p o nses of h u ma n li ver T cells 
a gai nst H B V, b ut n ot H C V. Gastr oe nter ol o g y 1 4 3: 1 5 7 6- 1 5 8 5 e 4. 
3 2.  
Z ha n g E, Z ha n g X, Li u J, Wa n g B, Tia n Y, K osi ns ka A D, Ma Z, X u Y, Ditt mer U, 
R o g ge n d orf  M,  Ya n g  D,  L u  M.  2 0 1 1.  T he  e x pressi o n  of  P D -1  li ga n ds  a n d  t heir  
i n v ol ve me nt i n re g ulati o n of T cell f u ncti o ns i n ac ute a n d c hr o nic w o o dc h uc k he patitis 
vir us i nfecti o n. P L o S O ne 6:e 2 6 1 9 6. 
3 3.  
Balsitis S, Gali V, Mas o n PJ, C ha nie ws ki S, Le vi ne S M, Wic hr os ki MJ, Fe ul ner M, S o n g 
Y, Gra nal di K, L o y J K, T h o m ps o n C M, Les nia k J A, Br oc k us C, Kis h na ni N, Me n ne S, 
C oc kett MI, I yer R, Mas o n S W, Te n ne y DJ. 2 0 1 8. Safet y a n d efficac y of a nti -P D -L 1 
t hera p y i n t he w o o dc h uc k m o del of H B V i nfecti o n. P L o S O ne 1 3:e 0 1 9 0 0 5 8. 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 7 8  of 1 0 9  
3 4.  
Ga ne E, Ver d o n DJ, Br o o ks A E, Ga g gar A, N g u ye n A H, S u bra ma nia n G M, Sc h wa be C, 
D u n bar P R. 2 0 1 9. A nti -P D -1 bl oc ka de wit h ni v ol u ma b wit h a n d wit h o ut t hera pe utic 
vacci nati o n f or virall y s u p presse d c hr o nic he patitis B: A pil ot st u d y. J He pat ol 7 1: 9 0 0 -
9 0 7. 
3 5.  
Y o o S H, Kea m B, Ki m M, et al: L o w- d ose ni v ol u ma b ca n be effecti ve i n n o n- s mall cell 
l u n g ca ncer: Alter nati ve o pti o n f or fi na ncial t o xicit y. E S M O O pe n 3:e 0 0 0 3 3 2, 2 0 1 8 
3 6.  
I nter nati o nal C o nfere nce o n Har m o nisati o n. I C H Har m o nise d Tri partite G ui deli ne. G o o d 
Cli nical Practice. C P M P/I C H/ 1 3 5/ 9 5. J ul y 2 0 0 2. 
3 7.  
W orl d Me dical Ass ociati o n, Declarati o n of Helsi n ki. Et hical Pri nci ples f or Me dical 
Researc h I n v ol vi n g H u ma n S u bjects as a me n de d b y t he 5 9t h W orl d Me dical Ass ociati o n 
Ge neral Asse m bl y, Se o ul, K orea, Oct o ber 2 0 0 8. 
 
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 7 9  of 1 0 9  
A P P E N DI C E S  
A p pe n di x  1 T o xicit y T a ble f or Cli nic al a n d L a b or at or y A b n or m alities 
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 8 0  of 1 0 9  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 8 1  of 1 0 9  
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 8 2  of 1 0 9  
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 8 3  of 1 0 9  
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 8 4  of 1 0 9  
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 8 5  of 1 0 9  
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 8 6  of 1 0 9  
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 8 7  of 1 0 9  
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 8 8  of 1 0 9  
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 8 9  of 1 0 9  
A p pe n di x 2  T o xicit y  M a n a ge me nt G ui deli nes for I m m u ne -Rel ate d A d verse E ve nt s Ass oci ate d w it h Ni v ol u m a b 
D ose m o dific ati o n a n d t o xicit y m a n a ge me nt of i nf usi o n -re acti o ns rel ate d t o ni v ol u m a b 
Ni v ol u ma b ma y ca use se vere or life -t hreate ni n g i nf usi o n-reacti o ns i ncl u di n g se vere h y perse nsiti vit y or a na p h yla xis. Si g ns a n d s y m pt o ms us uall y 
de vel o p d uri n g or s h ortl y after dr u g i nf usi o n a n d ge nerall y res ol ve c o m pletel y wit hi n 2 4 h o urs of c o m pleti o n of i nf usi o n. D ose m o dificati o n a n d 
t o xicit y ma na ge me nt g ui deli nes o n ni v ol u ma b ass ociate d i nf usi o n reacti o n are pr o vi de d.  
N CI C T C A E Gr a de  
Tre at me nt  
Pre me dic ati o n at S u bse q ue nt D osi n g  
Gr a de 1  
Mil d reacti o n; i nf usi o n 
i nterr u pti o n n ot i n dicate d; 
i nter ve nti o n n ot i n dicate d 
 
 
I ncrease m o nit ori n g of vital si g ns as me dicall y i n dicate d 
u ntil t he partici pa nt  is dee me d me dicall y sta ble i n t he 
o pi ni o n of t he In vesti gat or.  
 
 
N o ne  
Gr a de 2  
Re q uires t hera p y or i nf usi o n 
i nterr u pti o n b ut res p o n ds 
pr o m ptl y t o s y m pt o matic 
treat me nt (e. g., a nti hista mi nes, 
N S AI Ds, narc otics, I V fl ui ds); 
pr o p h ylactic me dicati o ns 
i n dicate d f or ≤2 4 hrs. 
St o p I nf usi o n . 
A d diti o nal a p pr o priate me dical t hera p y ma y i ncl u de b ut is 
n ot li mite d t o:  
•  
I V fl ui ds 
•  
A nti hista mi nes  
•  
N S AI Ds  
•  
Aceta mi n o p he n  
•  
Narc otics  
I ncrease m o nit ori n g of vital si g ns as me dicall y i n dicate d 
u ntil t he partici pa nt  is dee me d me dicall y sta ble i n t he 
o pi ni o n of t he In vesti gat or.  
If s y m pt o ms res ol ve wit hi n 1 h o ur of st o p pi n g dr u g 
i nf usi o n, t he i nf usi o n ma y be restarte d at 5 0 % of t he 
ori gi nal i nf usi o n rate (e. g. fr o m 1 0 0 m L/ hr t o 5 0 m L/ hr).  
Ot her wise d osi n g will be hel d u ntil s y m pt o ms res ol ve a n d 
t he partici pa nt s h o ul d be pre me dicate d f or t he ne xt 
sc he d ule d d ose. 
 
Partici pa nt  ma y be pre me dicate d 1. 5 h ( ± 3 0 mi n utes) pri or t o 
i nf usi o n of ni v ol u ma b  wit h:  
•  
Di p he n h y dra mi ne 5 0 m g p o ( or e q ui vale nt d ose of 
a nti hista mi ne).  
•  
Aceta mi n o p he n 5 0 0 -1 0 0 0 m g p o ( or e q ui vale nt d ose 
of a nal gesic ). 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 9 0  of 1 0 9  
Partici pa nt s w h o de vel o p Gra de 2 t o xicit y des pite 
a de q uate pre me dicati o n s h o ul d be per ma ne ntl y 
disc o nti n ue d fr o m f urt her st u d y dr u g treat me nt  
Gr a des 3 or 4  
Gr a de 3:  
Pr ol o n ge d  (i.e.,  n ot  ra pi dl y  
res p o nsi ve
 t o
 s y m pt o matic
 
me dicati o n
 a n d/ or
 brief
 
i nterr u pti o n
 of
 i nf usi o n);
 
rec urre nce
 of
 s y m pt o ms
 
f oll o wi n g  i nitial  i m pr o ve me nt;  
h os pitalizati o n
 i n dicate d
 f or
 
ot her cli nical se q uelae (e. g., re nal 
i m pair me nt,
 p ul m o nar y
 
i nfiltrates) 
Gr a de 4:  
Life -t hreate ni n g; press or or 
ve ntilat or y s u p p ort i n dicate d  
St o p I nf usi o n.  
 
A d diti o nal a p pr o priate me dical t hera p y ma y i ncl u de b ut is 
n ot li mite d t o:  
•  
E pi ne p hri ne * *  
•  
I V fl ui ds 
•  
A nti hista mi nes  
•  
N S AI Ds  
•  
Aceta mi n o p he n  
•  
Narc otics  
•  
O x y ge n  
•  
Press ors  
•  
C ortic oster oi ds  
I ncrease m o nit ori n g of vital si g ns as me dicall y i n dicate d 
u ntil  t he  partici pa nt  is  dee me d  me dicall y  sta ble  i n  t he  
o pi ni o n of t he In vesti gat or.  
H os pitalizati o n ma y be i n dicate d.  
* *I n  cases  of  a na p h yla xis,  e pi ne p hri ne  s h o ul d  be  use d  
i m me diatel y. 
P artici p a nt  is per m a ne ntl y disc o nti n ue d fr o m f urt her 
st u d y dr u g tre at me nt. 
N o s u bse q ue nt d osi n g  
A p pr o priate res uscitati o n e q ui p me nt s h o ul d be a vaila ble at t he be dsi de a n d a p h ysicia n rea dil y a vaila ble d uri n g t he peri o d of dr u g a d mi nistrati o n.  
F or f urt her i nf or mati o n, please refer t o t he C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts v 5. 0  ( C T C A E) at htt p://cte p.ca ncer. g o v  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 9 1  of 1 0 9  
D ose M o dific ati o n Sc he m a a n d S u p p orti ve C are G ui deli nes f or Ni v ol u m a b  
A Es ass ociate d wit h ni v ol u ma b e x p os ure ma y re prese nt a n i m m u n ol o gic aeti ol o g y. T hese i m m u ne -relate d A Es (ir A Es) ma y occ ur s h ortl y after 
t he first d ose or se veral m o nt hs after t he last d ose of ni v ol u ma b  treat me nt a n d ma y affect m ore t ha n o ne b o d y s yste m si m ulta ne o usl y. T heref ore, 
earl y rec o g niti o n a n d i nitiati o n of treat me nt is critical t o re d uce c o m plicati o ns.   
Base d o n e xisti n g cli nical trial data, m ost ir A Es were re versi ble a n d c o ul d be ma na ge d wit h i nterr u pti o ns of ni v ol u ma b , a d mi nistrati o n of 
c ortic oster oi ds a n d/ or ot her s u p p orti ve care. F or s us pecte d ir A Es, e ns ure a de q uate e val uati o n t o c o nfir m aeti ol o g y or e xcl u de ot her ca uses. 
A d diti o nal pr oce d ures or tests s uc h as br o nc h osc o p y, e n d osc o p y, s ki n bi o ps y ma y be i ncl u de d as part of t he e val uati o n. Base d o n t he se verit y of 
ir A Es, wit h h ol d or per ma ne ntl y disc o nti n ue ni v ol u ma b a n d a d mi nister c ortic oster oi ds. D ose m o dificati o n a n d t o xicit y ma na ge me nt g ui deli nes f or 
ir A Es ass ociate d wit h ni v ol u ma b are pr o vi de d. 
I m m u ne-rel ate d a d verse re acti o n  
Se verit y  
Tre at me nt M o dific ati o n  
I m m u ne-relate d p ne u m o nitis 
Gra de 2 p ne u m o nitis  
Wit h h ol d d ose(s) u ntil s y m pt o ms res ol ve,  ra di o gra p hic 
a b n or malities i m pr o ve, a n d  ma na ge me nt wit h c ortic oster oi ds is  
c o m plete 
Gra de 3 or 4 p ne u m o nitis  
Per ma ne ntl y disc o nti n ue treat me nt  
I m m u ne-relate d c olitis 
Gra de 2 diarr h oea or c olitis  
Wit h h ol d d ose(s) u ntil s y m pt o ms res ol ve  a n d ma na ge me nt wit h 
c ortic oster oi ds, if  nee de d, is c o m plete  
Gra de 3 diarr h oea or c olitis  
Wit h h ol d d ose(s) u ntil s y m pt o ms res ol ve a n d ma na ge me nt wit h 
c ortic oster oi ds is  c o m plete 
Gra de 4 diarr h oea or c olitis  
Per ma ne ntl y disc o nti n ue treat me nt  
I m m u ne-relate d he patitis 
Gra de 2 ele vati o n i n as partate  a mi n otra nsferase ( A S T), 
ala ni ne a mi n otra nsferase ( A L T), or t otal bilir u bi n  
Wit h h ol d d ose(s) u ntil la b orat or y val ues  ret ur n t o baseli ne a n d 
ma na ge me nt wit h  c ortic oster oi ds, if nee de d, is c o m plete  
Gra de 3 or 4 ele vati o n i n A S T, A L T, or t otal  bilir u bi n  
Per ma ne ntl y disc o nti n ue treat me nt  
I m m u ne-relate d  ne p hritis  a n d  re nal 
d ysf u ncti o n  
Gra de 2 or 3 creati ni ne ele vati o n  
Wit h h ol d d ose(s) u ntil creati ni ne ret ur ns t o  baseli ne a n d 
ma na ge me nt wit h  c ortic oster oi ds is c o m plete  
Gra de 4 creati ni ne ele vati o n  
Per ma ne ntl y disc o nti n ue treat me nt  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 9 2  of 1 0 9  
I m m u ne-rel ate d a d verse re acti o n  
Se verit y  
Tre at me nt M o dific ati o n  
I m m u ne-relate d e n d ocri n o pat hies  
S y m pt o matic Gra de 2 or 3 h y p ot h yr oi dis m,  
h y pert h yr oi dis m, h y p o p h ysitis  
Gra de 2 a dre nal i ns ufficie nc y  
Gra de 3 dia betes  
Wit h h ol d d ose(s) u ntil s y m pt o ms res ol ve  a n d ma na ge me nt wit h 
c ortic oster oi ds (if  nee de d f or s y m pt o ms of ac ute  i nfla m mati o n) 
is c o m plete. Treat me nt s h o ul d be c o nti n ue d i n t he prese nce of 
h or m o ne re place me nt t hera p y as l o n g as  n o s y m pt o ms are 
prese nt  
Gra de 4 h y p ot h yr oi dis m  
Gra de 4  h y pert h yr oi dis m  
Gra de 4 h y p o p h ysitis  
Gra de 3 or 4 a dre nal i ns ufficie nc y  
Gra de 4 dia betes  
Per ma ne ntl y disc o nti n ue treat me nt  
I m m u ne-relate d s ki n a d verse reacti o ns 
Gra de 3 ras h  
Wit h h ol d d ose(s) u ntil s y m pt o ms res ol ve  a n d ma na ge me nt wit h 
c ortic oster oi ds is  c o m plete 
Gra de 4 ras h  
Per ma ne ntl y disc o nti n ue treat me nt  
Ste ve ns -J o h ns o n s y n dr o me ( SJ S) or t o xic e pi der mal 
necr ol ysis ( T E N)  
Per ma ne ntl y disc o nti n ue treat me nt  
I m m u ne-relate d m y ocar ditis  
Gra de 2 m y ocar ditis  
Wit h h ol d d ose(s) u ntil s y m pt o ms res ol ve  a n d ma na ge me nt wit h 
c ortic oster oi ds is  c o m plete 
Gra de 3 or 4 m y ocar ditis  
Per ma ne ntl y disc o nti n ue treat me nt  
Ot her i m m u ne -relate d a d verse 
reacti o ns 
Gra de 3 (first occ urre nce)  
Wit h h ol d d ose(s)  
Gra de 4 or rec urre nt Gra de 3; persiste nt  Gra de 2 or 3 des pite 
treat me nt m o dificati o n; i na bilit y t o re d uce c ortic oster oi d 
d ose t o 1 0  m g pre d nis o ne or e q ui vale nt per da y  
Per ma ne ntl y disc o nti n ue treat me nt  
N ote: T o xicit y gra des are i n acc or da nce wit h Nati o nal Ca ncer I nstit ute C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts Versi o n 5 . 0 ( N CI-C T C A E v 5. 0 ). 
a D uri n g a d mi nistrati o n of t he sec o n d p hase of treat me nt ( ni v ol u ma b m o n ot hera p y) f oll o wi n g c o m bi nati o n treat me nt, per ma ne ntl y disc o nti n ue treat me nt if Gra de 3 
diarr h oea or c olitis occ urs.  
A da pte d fr o m S u m mar y of Pr o d uct C haracteristics f or O P DI V O  1 0  m g/ m L c o nce ntrate f or s ol uti o n f or i nf usi o n, 3 0 N o ve m ber 2 0 2 0  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 9 3  of 1 0 9  
Ot her A ll o we d D ose Interr u pti o n f or Ni v ol u m a b 
D osi n g i nterr u pti o ns are per mitte d i n t he case of me dical/s ur gical e ve nts or l o gistical reas o ns n ot relate d t o st u d y t hera p y (e. g., electi ve s ur ger y, 
u nrelate d me dical e ve nts, partici pa nt  vacati o n, a n d/ or h oli da ys). Partici pa nt s s h o ul d be place d bac k o n st u d y t hera p y wit hi n 3 wee ks of t he 
sc he d ule d i nterr u pti o n, u nless ot her wise disc usse d wit h t he S p o ns or. T he reas o n f or i nterr u pti o n s h o ul d be d oc u me nte d i n t he pa rtici pant 's st u d y 
rec or d.

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 9 4  of 1 0 9  
A p pe n di x  3 Det ails of C h a n ges M a de  i n Pr ot oc ol A me n d me nt 2 ( Pr ot oc ol Versi o n 3. 0 , 
1 8 A pril  2 0 2 0) 
5. 4  
St or a ge 
Vials of C h A d O x 1 -H B V a n d  M V A-H B V m ust be st ore d i n a c o nti n u o usl y m o nit ore d ≤- 67 0 oC 
freezer a n d ni v ol u ma b m ust be st ore d i n t he o uter cart o n (t o pr otect fr o m li g ht) bet wee n 
2 a n d 8 oC i n a c o nti n u o usl y m o nit ore d refri gerat or.  
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 9 5  of 1 0 9  
A p pe n di x  4 Det ails of C h a n ges M a de  i n Pr ot oc ol A me n d me nt 3 ( Pr ot oc ol Versi o n 4. 0, 
2 1 J ul y  2 0 2 0) 
E dit orial  c ha n ges are n ot i ncl u de d bel o w. 
1. 2 
Tre at me nt Re vie w  
T his st u d y is desi g ne d t o assess t he safet y a n d i m m u n o ge nicit y of C h A d O x 1 -H B V a n d  M V A 
H B V,  gi ve n  eit her  al o ne  or  wit h  l o w  d oses  of  a n  a nti -pr o gra m me d  cell  deat h  pr otei n  1  
(a nti-P D -1) c o m p o u n d ( ni v ol u ma b), a n d t o assess t he brea dt h of res p o nses t o t he pr otei ns 
e nc o de d b y t hese c o m bi nati o ns. T he T cell cr oss reacti vit y t o ot her ge n ot y pes will als o be 
assesse d.  D oses  of  C h A d O x 1  vacci nes  i n  pre vi o us  st u dies  ha ve  varie d  fr o m  1 0 8 t o  o ver  
5 x 1 0 1 1 1 0 viral particles ( v p) per d ose a n d a d ose of 2. 5 x 1 0 1 0 v p will be  e val uate d i n t his st u d y 
t o pre pare f or a f urt her C h A d O x 1/ M V A heter ol o g o us pri me-b o ost re gi me n. T he d ose of M V A 
of 1 x 1 0 8 pf u has bee n assesse d safel y i n t h o usa n ds of partici pa nts.  
1. 4 
S u m m ar y of Cli nic al E x perie nce  
O ne  c li nical  st u d y  ( H B V 0 0 1)  t o  i n vesti gate  react o ge nicit y  a n d  e x pl ore  t he  safet y  of  
C h A d O x 1 -H B V  i n  healt h y  a n d  C H B  partici pa nts  is  o n g oi n g  at  d oses  of  2. 5  x  1 0 9 a n d 
2. 5 x 1 0 1 0 v p . T o date At t he hi g her d ose , o nl y l oc alise d s welli n g at t he v acci n ati o n site a n d 
mi n or a d verse e ve nts, w hic h h a ve all res ol ve d, h a ve bee n re p orte d. T here h a ve bee n  n o 
re p orts of  seri o us a d verse e ve nts ( S A Es) or ot her safet y c o ncer ns ha ve bee n re p orte d. 
1. 5 
St u d y R ati o n ale  
T h us, a pri me -b o ost strate g y usi n g C h A d O x 1 vect or ( C h A d O x 1 -H B V) a n d a n M V A vect or 
( M V A-H B V), wit h a n d wit h o ut ni v ol u ma b will be e val uate d i n t his st u d y. I n or der t o decrease 
p ote ntial safet y iss ues, o nl y partici pa nts wit h sta ble a nti viral t hera p y i n t he pr e vi o us o ne year 
wit h res ulta nt l o w H B V D N A a n d H Bs A g  will be e nr olle d. As t he T cell res p o nses m a y w a ne 
wit h ti me, a n d a b o ost t o t he hi g hest le vels m a y be nee de d t o s ust ai n a n o n g oi n g res p o nse 
( as e vi de nce d b y s o me l o weri n g of t he H Bs A g le vels, a b o ost usi n g t he M V A v acci ne is 
per mitte d  at  M o nt h  3,  at  t he  discreti o n  of  t he  I n vesti g at or  a n d  c o nc urre nce  of  t he  
S p o ns or.  
Secti o n 3. 1. 1 St u dy Overvie w  
All treat me nt gr o u ps will recei ve st u d y vacci ne o n Da y 0 a n d D a y 2 8. I n Gr o u p 1, M V A -H B V 
will be e val uate d 7  da ys after t he first d ose of st u d y vacci ne i n t he first 6 partici pa nts pri or t o 
i nitiati o n of t he pri me-b o ost re gi me n of C h A d O x 1 -H B V f oll o we d b y M V A -H B V ( Gr o u p 2). 
Partici pa nts i n Gr o u ps 3 a n d 4 will be d ose d i n parall el t o recei ve C h A d O x 1-H B V ( wit h a n d 
wit h o ut ni v ol u ma b) o n  Da y 0 f oll o we d b y M V A -H B V wit h ni v ol u ma b o n  Da y 2 8. Gr o u ps 3 
a n d 4 will be i nitiate d after e val uati o n of data 7  da ys after t he first 6  partici pa nts i n Gr o u p 2 
ha ve recei ve d b ot h st u d y vacci nes C h A d O x 1 -H B V . T he e val uati o ns will be carrie d o ut b y a 
Safet y M o nit ori n g C o m mittee ( S M C) c o nsisti n g of t he S p o ns or Me dical M o nit or, t he C o u ntr y 
Lea d I n vesti gat ors f or S o ut h K orea, Tai wa n a n d t he U K, a n d t he trial Me dical M o nit or. If a 
p artici p a nt h as a 0. 5  l o g or gre ater dr o p i n he p atitis B s urf ace a nti ge n at D a y 3 5, t he y 
m a y recei ve a b o oster d ose of M V A - H BV, at t he I n vesti g at or’s discreti o n a n d after 
disc ussi o n wit h t he S p o ns or.  
Secti o n 3. 1. 3 St o p p i n g Criteri a/ H ol di n g Criteri a 
T here will be a re vie w of t he st u d y data b y t he D M C w he n t here is a reas o na ble p ossi bilit y t hat 
t he i n vesti gati o nal vacci ne ca use d a n y of t he S A Es or se vere a d verse e ve nts liste d bel o w, base d 
o n t he assess me nt of t he I n vesti gat or, i n o ne or m ore partici pa n ts at a n y d ose. Vacci nati o ns 
will be p ut o n h ol d pe n di n g t his re vie w: 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 9 6  of 1 0 9  
•  
Deat h rel ate d t o st u d y v acci ne  
•  
Life -t hreate ni n g a d verse e ve nt or life-t hreate ni n g s us pecte d reacti o n 
 
If, f oll o wi n g re vie w of data, a rec o m me n dati o n is ma de b y t he D M C t o res u me st u d y e nr ol me nt 
a n d vacci ne a d mi nistrati o n, t he D M C will rec or d t heir j u d g me nt i n a me m ora n d u m t o t he st u d y 
file a n d n otif y t he S p o ns or. T he D M C me m ora n d u m will be f or war de d t o t he l ocal Me dical 
M o nit or a n d I n vesti gat ors  a n d a n a p pr o pri ate s u bst a nti al a me n d me nt file d . 
3. 2 
Disc ussi o n of St u d y Desi g n, I ncl u di n g t he C h oice of C o ntr ol Gr o u ps  
T he C h A d O x 1 -H B V d ose will be  is 2. 5 x 1 01 0 v p , base d o n t he res ultsre vie w of st u d y H B V
0 0 1; safet y a n d  t he i n d ucti o n of T cell acti vit y, as meas ure dt w o d oses st u die d i n H B V 0 0 1 
( 2. 5 x 1 0 9 v p a n d 2. 5 x 1 0 1 0 v p). S afet y d at a fr o m all he alt h y v ol u nteers w as  re vie we d fr o m 
H B V 0 0 1 b y b ot h ma g nit u de of res p o nse as well as f u ncti o nalit yt he S M C, a n d t he hi g her 
d ose w as c h ose n t o use i n t his st u d y . T o f urt her mi ni mi se the ris k t hat i m m u ne res p o nses 
ge nerate d b y vacci nati o n d o n ot  res ult i n li ver t o xicity, o nl y t h ose partici pa nt s w h ose D N A 
le vels are well c o ntr olle d o n a nti virals will be i ncl u de d i n t he st u d y, a n d t h ose wit h a d va nce d  
li ver fi br osis or cirr h osis will be e xcl u de d. T he safet y of M V A -H B V will be e val uate d  b y t he 
S M C  after t he first 6 pa rtici pants ha ve recei ve d t he first d ose, t o i ncl u de at least 7 da ys safet y 
data, pri or t o i nitiati o n of t he pri me-b o ost re gi me n of C h A d O x 1 f oll o we d b y M V A wit h a n d 
wit h o ut ni v ol u ma b.  
D oses  of  C h A d O x 1  vacci nes  i n  pre vi o us  st u dies  ha ve  varie d  fr o m  1  x  1 0 8 t o  o ver  
1 5 x 1 0 1 11 0 1 0  v p per d ose  wit h 2. 5 x 1 0 1 0 v p a p peari n g t o be nearl y o pti mal. A p hase 1 st u d y is 
e xa mi ni n g t he safet y a n d i m m u n o ge nicit y of t w o C h A d O x 1 -H B V d oses, 2. 5 x 1 0 9 v p a n d 2. 5 
x  1 0 1 0  v p,  wit h  t he  e x pectati o n  t hat  t he  latter  d ose  will  be  safe  a n d  c h ose n  f or  f urt her  
de vel o p me nt. M V A has bee n use d i n ma n y trials at d oses t hat ra n ge fr o m 1 x 1 0 7 t o 2. 5 x 1 08 
pf u, a n d i n m ost st u dies t he d ose of 1 -2 x 1 0 8 pf u are st u die d. T his d ose has bee n s h o w n t o be 
safe a n d i m m u n o ge nic i n t h o usa n ds of partici pa nts t o date. T h us, pe n di n g ne w i nf or mati o n, t he 
d oses c h ose npr o p ose d  f or t his st u d y are 2. 5 x 1 01 0 v p of C h A d O x 1 -H B V a n d 1 x 1 0 8 pf u of 
M V A -H B V. As t he T cell res p o nses m a y w a ne wit h ti me, a n d a b o ost t o t he hi g hest le vels 
m a y be nee de d t o s ust ai n a n o n g oi n g r es p o nse ( as e vi de nce d b y s o me l o weri n g of t he 
H Bs A g le vels, a b o ost usi n g t he M V A v acci ne is per mitte d at M o nt h 3, at t he discreti o n 
of t he I n vesti g at or a n d c o nc urre nce of t he S p o ns or.  
4. 2 
I ncl usi o n Criteri a 
4.  If fe male, willi n g n ot t o bec o me pre g na nt u p t o 8 wee ks after last d ose of st u d y vacci ne  
a n d u p t o 5 m o nt hs after t he l ast d ose of ni v ol u m a b  
5.  If fe male: N ot pre g na nt or breast fee di n g a n d o ne of t he f oll o wi n g: 
•  
Of n o n -c hil d beari n g p ote ntial (i.e. w o me n w h o ha ve ha d a h ysterect o m y or t u bal 
li gati o n or are p ost-me n o pa usal, as defi ne d b y n o me nses i n ≥1 year  a n d wit h o ut 
a n alter n ati ve me dic al c a use ) 
•  
Of c hil d beari n g p ote ntial b ut a grees t o practice hi g hl y effecti ve c o ntrace pti o n f or 
4 wee ks pri or t o st u d y vacci ne a n d 8  wee ks after st u d y vacci ne a n d 5 m o nt hs after 
t he l ast d ose of ni v ol u m a b. Hi g hl y effecti ve  met h o ds of c o ntrace pti o n i ncl u de o ne 
or m ore of t he f oll o wi n g:  
− M ale part ner w h o is sterile ( me dicall y effecti ve vasect o m y) pri or t o t he fe male 
partici pa nt’s e ntr y i nt o t he st u d y a n d is t he s ole se x ual part ner f or t he fe male 
partici pa nt  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 9 7  of 1 0 9  
− C o m bi ne d  ( oestr o ge n  a n d  pr o gest o ge n  c o ntai ni n g)  h or m o nal  c o ntrace pti o n  
ass ociate d wit h i n hi biti o n of o v ulati o n:  
− oral 
− i ntra va gi nal 
− tra ns der mal 
− Pr o gest o ge n- o nl y  h or m o nal  c o ntrace pti o n  ass ociate d  wit h  i n hi biti o n  of  
o v ulati o n: 
− oral 
− i njecta ble 
− i m pla nta ble 
− A n i ntra uteri ne de vice  
− Bilateral  t u bal occl usi o n 
8. Virall y s u p pres se d (H B V -D N A viral l oa d bel o w 4 0 0 4 0  I U/ m L f or ≥ 1 year) 
4. 3 
E x cl usi o n Criteri a 
5.  D oc u me nte d cirr h osis or a d va nce d fi br osis i n dicate d b y a li ver bi o ps y wit hi n 6 m o nt hs 
pri or t o scree ni n g.  
I n t he a bse nce of a d oc u me nte d li ver bi o ps y, eit her 1 of t he f oll o wi n g ( n ot b ot h):  
•  Scree ni n g Fi br osca n wit h a res ult > 9 kil o pascals ( k Pa) ( or t he e q ui vale nt) wit hi n 
≤ 6 m o nt hs of scree ni n g, orO R  
•  Scree ni n g Fi br o Test > 0. 4 8 a n d A S T t o platelet rati o i n de x ( A P RI) of > 1.  
I n t he e ve nt of disc or da nt res ults bet wee n n o n i n vasi ve met h o ds, t he Fi br osca n res ult 
will ta ke prece de nce.  
1 1. Prese nce of acti ve i nfecti o n  
1 2. E vi de nce of i nterstiti al l u n g dise ase, acti ve p ne u m o nitis, m y oc ar ditis, or a hist or y 
of m y oc ar ditis  
1 3. Hist or y of t h yr oi d dis or der or a b n or m al t h yr oi d f u ncti o n at scree ni n g  
 
2 0.  Hist or y of aller gic disease or se vere h y perse nsiti vit y or a n a p h yl actic reacti o ns li kel y 
t o be e xacer bate d b y a n y c o m p o ne nt of t he vacci ne or ni v ol u m a b 
Pre vi o us 2 0  A n y hist or y of a na p h yla xis i n reacti o n t o vacci nati o n 
5. 2 I n vesti g ati o n al Pr o d ucts A d mi nistere d  
If a p artici p a nt h as a 0. 5 l o g or gre ater dr o p i n he p atitis B s urf ace a nti ge n at D a y 3 5, t he y 
m a y recei ve a b o oster d ose of M V A - H BV, at t he I n vesti g at or’s discreti o n a n d after 
disc ussi o n wit h t he S p o ns or.  
5. 2. 1 
St u dy V acci nes  
All partici pa nts will recei ve t w o d oses of st u d y vacci ne, wit h or wit h o ut ni v ol u ma b, o n Da y  0 
a n d Da y 2 8. B ot h vacci nati o ns will be gi ve n b y i ntra m usc ular i njecti o n i nt o t he delt oi d m uscle, 
t o t he sa me, n o n-d o mi na nt ar m i n a partici pa nt, w here p ossi ble. If a p artici p a nt h as a 0. 5 l o g 
or gre ater dr o p i n he p atitis B s urf ace a nti ge n at D a y 3 5, t he y m a y recei ve a b o oster d ose 
of M V A - H BV at M o nt h  3, at t he I n vesti g at or’s discreti o n a n d after disc ussi o n wit h t he 
S p o ns or.  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 9 8  of 1 0 9  
T he C h A d O x 1- H B V d ose will be 2. 5 x 1 0 1 0 v p, a n d c o nfir me d base d o n t he re vie w of st u d y 
H B V - 0 0 1. is 2. 5 x 1 01 0 v p, b ase d o n t he re vie w of t he t w o d oses st u die d i n H B V 0 0 1. T his 
d ose , or  hi g her , of  C h A d O x 1 -b ase d  v acci nes  h as  bee n  s afel y  use d  i n  h u n dre ds  of  
p artici p a nts (see I n vesti g at or’s Br oc h ure), a n d t h o us a n ds of pe o ple h a ve bee n i m m u ni se d 
wit h a C h A d O x 1 C O VI D -1 9 v acci ne at a d ose of 5  x 1 01 0 v p.  T he d ose of M V A -H B V will 
be fi xe d at 1 x 1 0 8 pf u, as ta ke n fr o m hist orical data of pre vi o us st u dies. A 1. 5 x 1 0 8 pf u M V A 
d ose w as use d i n ne arl y 2, 0 0 0  he alt h y p artici p a nts i n i nfl ue nz a st u dies c o n d ucte d b y 
O xf or d U ni versit y a n d V accitec h.  
5. 7 
Met h o d of Assi g ni n g P artici p a nts t o Tre at me nt Gr o u ps  
Partic i pa nts will be ra n d o mise d t o all o pe n gr o u ps o n a 1: 1: 1: 1 all ocati o n as eac h gr o u p is 
i nitiated . A se nti nel partici pa nt will be d ose d i n c o h ort 1, a n d t he rest of t he c o h ort will o nl y 
be  e nr olle d  at  least  4 8  h o urs  later.  F oll o wi n g  t he  7 -da y  safet y  assess me nt  of  t he  first  
6 partici pa nts i n Gr o u p  1 b y t he S M C, Gr o u p  2 will be i nitiate d. Gr o u ps 3 a n d 4  will be i nitiate d 
after e val uati o n of safet y data 7  da ys after t he first 6  partici pa nts i n Gr o u p 2 ha ve recei ve d b ot h 
st u d y  vacci nesC h A d O x 1 -H B V .  At  t he scree ni n g  visit, partici pa nts will  be  se q ue ntiall y  
all ocate d a scree ni n g n u m ber o nce writte n, i nf or me d c o nse nt has bee n  o btai ne d. T he y will be 
i de ntifie d b y t his n u m ber u ntil e ntr y i nt o st u d y.  
5. 8. 1 
Selecti o n of D oses i n t he St u dy  
T he C h A d O x 1- H B V d ose  will be 2. 5 x 1 0 1 0 v p, a n d c o nfir me d base d o n t he re vie w of st u d y 
H B V 0 0 1  is 2. 5 x 1 01 0 v p a n d c o nfir me d b ase d o n t he re vie w of t he t w o d oses st u die d i n 
H B V 0 0 1  ( 2. 5 x 1 0 9 v p a n d 2. 5 x 1 0 1 0 v p). S afet y d at a fr o m all he alt h y v ol u nteers w as  
re vie we d fr o m H B V 0 0 1 b y t he S M C, a n d t he hi g her d ose w as c h ose n t o use i n t his st u d y . 
T his d ose or hi g her of C h A d O x 1 -b ase d v acci nes h as bee n s afel y use d i n h u n dre ds of 
p artici p a nts (see I n vesti g at or’s Br oc h ure), a n d t h o us a n ds of pe o ple h a ve bee n i m m u ni se d 
wit h a C h A d O x 1 C O VI D -1 9 v acci ne at a d ose of 5  x 1 01 0 v p.  T he d ose of M V A -H B V will 
be fi xe d at 1 x 1 0 8 pf u, as ta ke n fr o m hist orical data of pre vi o us st u dies. A 1. 5 x 1 0 8 M V A 
d ose w as use d i n ne arl y 2, 0 0 0  he alt h y p artici p a nts i n i nfl ue nz a st u dies c o n d ucte d b y 
O xf or d U ni versit y a n d V accitec h.  
5. 8. 2. 1 D osi n g Sc he d ule 
T he  part ici pa nts  will  be  all ocate d  t o  d osi n g  gr o u p  de pe n di n g  o n  t he  treat me nt  sc he d ule.  
Vacci nati o n will be perf or me d o n Da y 0, after eli gi bilit y has bee n rec o nfir me d, a n d o n Da y  2 8. 
If a p artici p a nt h as a 0. 5 l o g or gre ater dr o p i n he p atitis B s urf ace a nti ge n at D a y 3 5, t he y 
m a y recei ve a b o oster d ose of M V A - H BV at M o nt h  3, at t he I n vesti g at or’s discreti o n a n d 
after disc ussi o n wit h t he S p o ns or.  
5. 8. 2. 3 Niv ol u m a b Pre p ar ati o n a n d A d mi nistr ati o n 
I n Gr o u ps 3 a n d 4, t he p atie nts will be o bser ve d f or 3 0 mi n utes after v acci n ati o n. If t here 
are n o s af et y c o ncer ns ( vit al si g ns a n d re act o ge nicit y), ni v ol u m a b will be i nf use d o ver 
3 0 mi n utes a n d t he p atie nts will be o bser ve d i n t he st u d y ce ntre f or a f urt her 3 0 mi n utes 
p ost -i nf usi o n. Ni v ol u ma b will  be a d mi nistere d via i ntra ve n o us i nf usi o n o ver  3 0  mi n utes, 
f oll o wi n g vacci nati o n. 
5. 1 0 
Pri or a n d C o nc o mit a nt V acci nes a n d Me dic ati o ns  
P atie nts will h a ve bee n t a ki n g a nti vir als f or at le ast 1 2 m o nt hs bef ore scree ni n g. O nce 
r a n d o mise d t o t he st u d y, or al a nti vir al me dic ati o n s h o ul d n ot be wit h dr a w n.  P atie nts 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 9 9  of 1 0 9  
s h o ul d re m ai n o n t he s a me d ose of a nti vir als t h at t he y were o n w he n t he y e ntere d t he 
st u d y f or t he d ur ati o n of t he st u d y. 
All o we d  a nti vir al  me dic ati o ns  i ncl u de:  e ntec a vir,  te n of o vir  (te n of o vir  al afe n a mi de  
f u m ar ate or te n of o vir dis o pr o xil f u m ar ate), or besif o vir. 
Pri or a n d c o nc o mita nt me dicati o n s i ncl u de prescri pti o n a n d n o n -prescri pti o n dr u gs or ot her 
treat me nts, a n d a n y vacci nes ot her t ha n t he st u d y vacci ne.  
6 
S T U D Y P R O C E D U R E S A T E A C H VI SI T/ S C H E D U L E O F A S S E S S M E N T S  
All me dicati o ns ta ke n t o treat u ns olicite d A Es a n d S A Es will be rec or de d i n t he  e C R F b y 
q uesti o ni n g t he partici pa nt at eac h visit w het her t he y t o o k a n y c o nc o mita nt me dicati o ns si nce 
t he pre vi o us visit. 
D ue t o t he C O VI D -1 9 p a n de mic, st u d y ce ntres will f oll o w a n y l oc al pr oce d ures i n li ne 
wit h testi n g t o e ns ure t he s afet y of p artici p a nts a n d st aff.  
T a ble 2  
O ver all Sc he d ule of Assess me nts at E ac h St u d y Visit  
Visit/ C all 
Scree n  V acci n ati o n 
Cli nic 
Tele p h o ne 
C all  
Cli nic V acci n ati o n 
Cli nic 
Tele p h o ne 
C all 
Cli nic  
E n d of St u d y  / 
E arl y 
Disc o nti n u ati o n  
Cli nic  
Ti me p oi nt ( wi n d o w) 
D a y 
M o nt h  
-4 2 t o -1  
0 
1 ( + 1 d) 
7 ( ±1 d ) 
2 8  (+ 2 d ) 
2 9 ( + 1 d)  
3 5 
(± 1 d ) 
3 
(± 7 d )  
6 
(± 7 d ) 
9 ( ± 7 d )  
HI V, H C V, H B V  
( q u a ntit ati ve H B V D N A 
a n d q u a ntit ati ve H Bs A g) , 
H D V ser ol o g y  
X 
 
 
 
 
 
 
 
 
 
Uri ne pre g na nc y test ( β - h C G) 
X 
X [a ]  
 
 
X [a ]  
 
 
X [f] X [f] 
X 
Vacci nati o n d ose  
 
X 
 
 
X 
 
 
X [ g ] 
 
 
P ost- d ose o bser vati o n  
 
X 
 
 
X 
 
 
X [g ] 
 
 
F ull p h ysical e xa mi nati o n  
X 
X [a ] 
 
 
X [a ] 
 
 
X [a ]  
 
 
L ocal/s yste mic 
react o ge nicit y [c] 
 
X [c] 
X 
X 
X [c] 
X 
X 
X [c ] 
 
 
Bl o o d f or cell ular 
i m m u n o ge nicit y assess me nts 
 
X [a ] 
 
X 
X [a ] 
 
X 
X [a ] 
 
 
[a] Pre-vacci nati o n o nl y o n D a y  0, D a y  2 8 a n d at M o nt h  3 f or p atie nts h a vi n g a n M V A - H BV b o ost o nl y  
[ b] Partici pa nts i n Gr o u p 3 will recei ve ni v ol u ma b o n Da y  2 8 o nl y w hile Gr o u p 4 will recei ve ni v ol u m a b o n D a ys 1 a n d 
2 8. T he p atie nts will be o bser ve d f or 3 0 mi n utes after v acci n ati o n. If t here are n o s afet y c o ncer ns ( vit al si g ns a n d 
re act o ge nicit y), ni v ol u m a b will be i nf use d o ver 3 0 mi n utes a n d t he p atie nts will be o bse r ve d i n t he st u d y ce ntre f or a 
f urt her 3 0 mi n utes p ost-i nf usi o n. 
[c] Ca pt ure d pre -vacci nati o n a n d p ost -vacci nati o n o n Da ys 0 a n d 2 8 , a n d M o nt h 3 if a n M V A - H BV b o ost is gi ve n , via 
e Diaries f or 7 da ys p ost -vacci nati o n a n d t he n at t he tele p h o ne or  cli nic assess me nt 7 da ys p ost vacci nati o n ( Da y 7 or 3 5)  
[f] Pre g n a nc y testi n g at M o nt h 3 i n Gr o u ps 1 a n d 2 if a n M V A -H B V b o ost is gi ve n, a n d at M o nt hs 3 a n d 6 i n Gr o u ps  3 
a n d 4  
[ g] If a p artici p a nt h as a 0. 5 l o g or gre ater dr o p i n he p atitis B s urf ace a nti ge n at D a y 3 5, t he y m a y recei ve a b o oster 
d ose of M V A - H BV at M o nt h 3, at t he I n vesti g at or’s discreti o n a n d after disc ussi o n wit h t he S p o ns or . T hese p atie nts 
will als o h a ve a tele p h o ne c all t he d a y after t he b o ost v acci n ati o n a n d a cli nic visit 7 d a ys p ost -b o ost, as per D a y  1 a n d 
D a y  7. 
6. 1 
Scree ni n g a n d B aseli ne Assess me nts  
T he f oll o wi n g will be perf or me d at scree ni n g:  
•  
A bl o o d sa m ple will be ta ke n f or HI V, H C V, H B V  ( q u a ntit ati ve H B V D N A a n d 
q u a ntit ati ve H Bs A g) , H D V  dia g n ostic testi n g  
•  Bl o o d sa m ples will be ta ke n f or hae mat ol o g y (i ncl u di n g pr ot hr o m bi n ti me [ P T] a n d 
I N R), bi oc he mistr y a n d li ver f u ncti o n tests ( L FTs)  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 1 0 0  of 1 0 9  
6. 2 
Tre at me nt D a y Assess me nts ( D a y 0 , D a y 2 8 a n d  M o nt h 3  [M V A -H B V  B o ost]) 
Partici pa nts will t he n recei ve st u d y vacci ne b y i ntra m usc ular i njecti o n i n t he n o n -d o mi na nt 
ar m, f oll o we d b y ni v ol u ma ba n d will be o bser ve d f or 3 0 mi n utes p ost v acci n ati o n f or s afet y 
c o ncer ns. Ni v ol u m a b will t he n be a d mi nistere d vi a a n i nf usi o n, if a p plica ble, acc or di n g t o 
Ta ble 1 . 
•  
O n Da y 0, a n e Diar y, ta pe meas ure a n d t her m o meter  will be pr o vi de d t o perf or m 
self-assess me nt of l ocal a n d s yste mic react o ge nicit y f or 7 da ys after t he vacci nati o n s. 
O n Da y  0 pP artici pa nts will be re mi n de d t o d o t he f oll o wi n g dail y f or t he ne xt 7 da ys 
after e ac h v acci n ati o n : 
6. 3. 1  Tele p h o ne C alls: D ay 1, a n d D ay 2 9 a n d M o nt h 3 + 1 D ay ( M V A- H B V B o ost ) 
•  Re mi n der t o c o m plete e Diar y f or c ollecti o n of l ocal a n d s yste mic reacti o ns d uri n g 
7 c o nsec uti ve da ys p ost - vacci nati o n 
6. 3. 2 
Cli nic Visits: D ay 7, a n d D ay 3 5 a n d M o nt h 3 + 7 D ays ( M V A- H B V B o os t) 
• Bl o o d sa m ples will be ta ke n f or hae mat ol o g y, bi oc he mistr y a n d L F Ts 
6. 3. 3 
Cli nic Visit: M o nt hs  3 a n d 6 
•  
C hec k he p atitis B s urf ace a nti ge n D a y 3 5 res ult ( M o nt h 3 o nl y).  
− 
If a p artici p a nt h as a 0. 5 l o g or gre ater dr o p i n he p atitis B s urf ace a nti ge n, 
t he y m a y recei ve a b o oster d ose of M V A- H BV, at t he I n vesti g at or’s discreti o n 
a n d  after  disc ussi o n  wit h  t he  S p o ns or.  Ple ase  see  Secti o n  6. 2  f or  t he  
assess me nts t o be perf or me d.  
•  A uri ne pre g n a nc y test will be perf or me d ( M o nt hs 3 a n d 6 i n Gr o u ps 3 a n d 4)  
•  Bl o o d sa m ples will be ta ke n f or hae mat ol o g y  (i ncl u di n g pr ot hr o m bi n ti me [ P T]/I N R 
a n d acti vate d partial t hr o m b o plasti n ti me  [a P T T]), bi oc he mistr y a n d L F Ts 
6. 3. 3 
Cli nic Visit: M o nt hs  3 a n d 6 
•  
 
•  Bl o o d sa m ples  will  be  ta ke n  f or  hae mat ol o g y  (i ncl u di n g  P T/I N R  a n d  a P T T), 
bi oc he mistr y a n d L F Ts 
7. 1. 4. 2 Bi oc he mistry  
T he f oll o wi n g bi oc he mistr y para meters will be meas ure d: s o di u m, p otassi u m, urea  nitr o ge n, 
creati ni ne a n d al b u mi n a n d L F Ts ( al kali ne p h os p hatase , ga m ma -gl uta m yl tra ns pe pti dase , A L T 
A S T a n d t otal a n d direct  bilir u bi n).  
7. 1. 4. 4 Uri n alysis  
A uri ne sa m ple will be c ollecte d i n a sterile c o ntai ner f or di pstic k uri nal ysis. T he f oll o wi n g 
will  be teste d: bl o o d, t otal a n d direct bilir u bi n, gl uc ose, ket o nes, le uc oc ytes, nitrite, p H, pr otei n, 
s pecific gra vit y a n d ur o bili n o ge n. T he I n vesti gat or ma y or der a d diti o nal uri ne tests t o be 
perf or me d. 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 1 0 1  of 1 0 9  
7. 4. 4  P hysic al Ex a mi n ati o n 
A s ki n, res pirat or y, car di o vasc ular, a b d o mi nal a n d l y m p hatic s yste m e xa mi nati o n will be 
perf or me d at scree ni n g , a n d pre- vacci nati o n o n Da y  0, Da y 2 8 a n d M o nt h 3 (f or t h ose h a vi n g 
t he M V A-H B V b o ost o nl y) a n d o n M o nt h  9. A s y m pt o m-directe d p h ysical e xa mi nati o n will 
be perf or me d at all ot her cli nic visits  if re q uire d. Res ults  will be rec or de d as n or mal, a b n or mal 
a n d n ot cli nicall y si g nifica nt or a b n or mal a n d cli nicall y si g nifica nt. 
8. 1. 4 
S afety M o nit ori n g C o m mittee  
•  
Sc he d ule d e val uati o n of st u d y c o n d uct a n d pr o gress , a n d re vie w of t he c u m ulati ve 
safet y a n d efficac y data. Sc he d ule d meeti n gs will ta ke place as f oll o ws: 
- 
Kic k off meeti n g bef ore t he first partici pa nt is e nr olle d  
- 
7 da ys after t he first 6 partici pa nts i n Gr o u p 1 ha ve recei ve d t he first d ose of M V A -H B V  
- 
7 da ys  after  t he  first  6  partici pa nts  i n  Gr o u p  2  ha ve  recei ve d  C h A d O x -H B V  a n d  
M V A -H B V  
- 
7  da ys  after  t he  first  6  partici pa nts  i n  Gr o u ps  3  a n d  4  ha ve  recei ve d  b ot h  st u d y  
vacci nes C h A d O x 1 -H B V , wit h or wit h o ut ni v ol u ma b 
8. 2. 5. 3 Me dic al Revie w a n d Re p orti n g by t he S p o ns or 
T he e x pecte d ness of a n S A E is assesse d b y t he S p o ns or i n t he o verall classificati o n of S A Es 
f or  e x pe dite d re p orta bilit y.  T he  c urre nt I n vesti gat or's Br oc h ure secti o n “Refere nce Safet y 
I nf or mati o n”  will  be  use d  as  t he  refere nce  f or  deter mi nati o n  of  e x pecte d ness  a n d  ris k  
assess me nt  of vacci ne -relate d a d verse e ve nts a n d Secti o n 4. 8 of t he Ni v ol u m a b S m P C will 
be use d t o assess t he e x pecte d ness f or ni v ol u m a b rel ate d e ve nts . 
1 0. 2. 1 A n alys is Sets  
•  
T he i nte nt-t o-treat set will c o nsist of all p artici p a nts w h o are r a n d o mise d 
•  
T he   /safet y  a nal ysis  set  will  c o nsist  of  all  partici pa nts  w h o  recei ve d  at  least  o ne  
vacci nati o n ( data will be s u m marise d acc or di n g t o t he vacci nati o n act uall y recei ve d) 
1 0. 2. 3 I nteri m A n alyses 
N o f or mal i nteri m a nal yses are pla n ne d as t he st u d y is o pe n la bel. T o hel p wit h t he pl a n ni n g 
of f ut ure st u dies,  a n i nteri m a n al ysis of all a v ail a ble d at a will be perf or me d i n J u ne  2 0 2 1. 
U n bli n de d listi n gs a n d s u m maries will be s u b mitte d t o t he D M C, as nee de d. T he ti mi n g of t he 
D M C s u b missi o ns will be s pecifie d i n t he D M C C harter . 
A p pe n di x 2  T o xicit y  M a n a ge me nt  G ui deli nes  f or  I m m u ne -Rel ate d  A d verse  E ve nts  
Ass oci ate d wit h Ni v ol u m a b  
D ose M o dific ati o n Sc he m a a n d S u p p orti ve C are G ui deli nes f or Ni v ol u m a b  
T a ble re pl ace d wit h t he a p pr o pri ate i nf or m ati o n fr o m t he  S u m m ary of Pr o d uct C h ar acteristics 
f or O P DI V O 1 0 m g/ m L c o nce ntr ate f or s ol uti o n f or i nf usi o n, 2 4 J a n u ary 2 0 2 0 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 1 0 2  of 1 0 9  
A p pe n di x  5 Det ails of C h a n ges M a de i n Pr ot oc ol A me n d me nt 4 ( Pr ot oc ol Versi o n 5. 0, 
0 4 M a y 2 0 2 1) 
1. 5 
St u dy R ati o n ale  
T h us, a pri me -b o ost strate g y usi n g C h A d O x 1 vect or ( C h A d O x 1 -H B V) a n d a n M V A vect or 
( M V A-H B V), wit h a n d wit h o ut ni v ol u ma b will be e val uate d i n t his st u d y. I n or der t o decrease 
p ote ntial safet y iss ues, o nl y partici pa nts wit h sta ble a nti viral t hera p y i n t he pr e vi o us o ne year 
wit h res ulta nt l o w H B V D N A a n d H Bs A g  will be e nr olle d. As t he T cell res p o nses ma y wa ne 
wit h ti me, a n d a b o ost t o t he hi g hest le vels ma y be nee de d t o s ustai n a n o n g oi n g res p o nse (as 
e vi de nce d b y s o me l o weri n g of t he H Bs A g le vels ), a b o ost usi n g t he M V A vacci ne is per mitte d 
at M o nt h  3,  at  t he  discreti o n  of  t he  In vesti gat or  a n d  c o nc urre nce  of  t he  S p o ns or U K 
p artici p a nt s o nl y. 
3. 1. 1 St u dy Overvie w  
T his  is  a  P hase  1 b/ 2 a,  m ultice ntre  st u d y  of  C h A d O x 1 -H B V  a n d  M V A -H B V  vacci nes  
( V T P-3 0 0). T he st u d y is pla n ne d t o be c o n d ucte d at u p t o 1 4  1 5  ce ntres i n 6 4 partici pa nts 
c hr o nicall y i nfecte d wit h He patitis B I nfecti o n a n d virall y s u p presse d wit h a p pr o ve d oral a nti -
H B V t hera pies.  
T he e val uati o ns will be carrie d o ut b y a Safet y M o nit ori n g C o m mittee ( S M C) c o nsisti n g of t he 
S p o ns or M e dical M o nit or, t he C o u ntr y Lea d I n vesti gat ors f or S o ut h K orea, Tai wa n a n d t he 
U K, a n d t he trial Me dical M o nit or. If a partici pa nt has a 0. 5 l o g or greater dr o p i n he patitis B 
s urface a nti ge n at Da y 3 5, t he y ma y recei ve a b o oster d ose of M V A- H BV, at t he I n vesti gat or’s 
discreti o n a n d after disc ussi o n wit h t he S p o ns or ( U K p artici p a nts o nl y). 
3. 1. 4 
I n divi d u al St o p pi n g R ules ( All V acci n ate d St u dy P artici p a nts) 
All vacci nate d partici pa nt s will be f oll o we d f or safet y u ntil res ol uti o n or sta bilisati o n (if 
deter mi ne d t o be c hr o nic se q uelae) of t heir S A Es.  
3. 2  
Disc ussi o n of St u d y Desi g n, I ncl u di n g t he C h oice of C o ntr ol Gr o u ps  
As t he T cell res p o nses ma y wa ne wit h ti me, a n d a b o ost t o t he hi g hest le vels ma y be nee de d 
t o s ustai n a n o n g oi n g res p o nse (as e vi de nce d b y s o me l o weri n g of t he HBs A g le vels ), a b o ost 
usi n g t he M V A vacci ne is per mitte d at M o nt h 3, at t he discreti o n of t he In vesti gat or a n d 
c o nc urre nce of t he S p o ns or ( U K p artici p a nts o nl y). 
4. 3  
E xcl usi o n Criteri a  
5.  D oc u me nte d cirr h osis or a d va nce d fi br osis i n dicate d b y a li ver bi o ps y wit hi n 6 m o nt hs 
pri or t o scree ni n g (Met a vir acti vit y gr a de A 3 a n d st a ges F 3 a n d F 4; Is h a k st a ges 4 – 
6) .  
1 3.  P ast  Hhis t or y of t h yr oi d dis or der or a b n or mal t h yr oi d f u ncti o n at scree ni n g t h at is still 
acti ve a n d u nc o ntr olle d  
1 7.  A n y hist or y of recei pt of n o n oral a de n o viral vacci ne  Rece i pt of a n y a de n o vir al-b ase d 
v acci ne wit hi n 3 m o nt hs pri or t o a d mi nistr ati o n of C h A d O x 1 -H B V o n D a y 0, or 
pl a n t o recei ve a n a de n o vir al- b ase d v acci ne wit hi n 3 m o nt hs after D a y 0  
5. 2 
I n vesti g ati o n al Pr o d ucts A d mi nistere d 
If a partici pa nt has a 0. 5 l o g or greater dr o p i n he patitis B s urface a nti ge n at Da y 3 5, t he y ma y 
recei ve a b o oster d ose of M V A- H BV, at t he I n vesti gat or’s discreti o n a n d after disc ussi o n wit h 
t he S p o ns or ( U K p artici p a nts o nl y). 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 1 0 3  of 1 0 9  
5. 2. 1 
St u dy V acci nes  
All partici pa nts will recei ve t w o d oses of st u d y vacci ne, wit h or wit h o ut ni v ol u ma b, o n Da y 0 
a n d Da y 2 8. B ot h vacci nati o ns will be gi ve n b y i ntra m usc ular i njecti o n i nt o t he delt oi d m uscle, 
t o t he sa me, n o n d o mi na nt ar m i n a partici pa nt, w here p ossi ble. If a partici pa nt has a 0. 5 l o g or 
greater dr o p i n he patitis B s urface a nti ge n at Da y 3 5, t he y ma y recei ve a b o oster d ose of M V A 
H B V at M o nt h 3, at t he I n vesti gat or’s discreti o n a n d after disc ussi o n wit h t he S p o ns or ( U K 
p artici p a nts o nl y).  
5. 8. 2. 1 D osi n g Sc he d ule 
T he  partici pa nts  will  be  all ocate d  t o  d osi n g  gr o u p  de pe n di n g  o n  t he  treat me nt  sc he d ule.  
Vacci nati o n will be perf or me d o n Da y 0, after eli gi bilit y has bee n rec o nfir me d, a n d o n Da y 2 8.  
If a partici pa nt has a 0. 5 l o g or greater dr o p i n he patitis B s urface a nti ge n at Da y 3 5, t he y ma y 
recei ve a b o oster d ose of M V A-H B V at M o nt h 3, at t he I n vesti gat or’s discreti o n a n d after 
disc ussi o n wit h t he S p o ns or ( U K p artici p a nts o nl y). 
5. 1 0 
Pri or a n d C o nc o mit a nt V acci nes a n d Me dic ati o ns  
T he na me of t he me dicati o n, treat me nt start a n d st o p dates ( or ‘ o n g oi n g’), a n d i n dicati o n m ust 
be rec or de d o n t he c o nc o mita nt me dicati o n  e C R F. T he i n dicati o n rec or de d o n t he c o nc o mita nt 
me dicati o n e C R F m ust c orres p o n d t o a me dical ter m/ dia g n osis rec or de d o n t he a d verse e ve nt 
e C R F, or t o a pre -e xisti n g c o n diti o n n ote d i n t he partici pa nt’s me dical hist or y, or be n ote d as 
pr o p h yla xis, e. g. dietar y s u p ple me nt .  
Als o, p artici p a nts s h o ul d n ot recei ve a n y a de n o vir al-b ase d v acci ne wit hi n 3 m o nt hs pri or 
t o or 3 m o nt hs after a d mi nistr ati o n of C h A d O x 1 -H B V o n D a y 0. 
6. 1 
Scree ni n g a n d B aseli ne Assess me nts  
[a] Pre- vacci nati o n o n Da y  0, Da y  2 8,  a n d  at M o nt h 3 (f or U K p artici p a nts  ha vi n g a n M V A -H B V b o ost ) o nl y 
[ b] 
Partici pa nts i n Gr o u p 3 will recei ve ni v ol u ma b o n Da y  2 8 o nl y w hile Gr o u p 4 will recei ve ni v ol u ma b o n Da ys 1 a n d 2 8. 
T he  patie nts  will  be  o bser ve d  f or  3 0  mi n utes  after  vacci nati o n.  If  t here  are  n o  safet y  c o ncer ns  ( vital  si g ns  a n d  
react o ge nicit y), ni v ol u ma b will be i nf use d o ver 3 0 mi n utes a n d t he patie nts will be o bser ve d i n t he st u d y ce ntre f or a 
f urt her 3 0 mi n utes p ost-i nf usi o n. 
[c] 
Ca pt ure d pre -va cci nati o n a n d p ost -vacci nati o n o n Da ys 0 a n d 2 8, a n d M o nt h  3 (f or U K p artici p a nts h a vi n g a n M V A -
H B V b o ost ) is gi ve n, via e Diaries f or 7 da ys p ost -vacci nati o n a n d t he n at t he cli nic assess me nt 7 da ys p ost - vacci nati o n 
( Da y 7 or 3 5)  
[ d] 
Rec or de d i n t he e C R F fr o m t he date t he i nf or me d c o nse nt is si g ne d, at all cli nic visits t o c o ver t he peri o d si nce t he 
pre vi o us  visit a n d d uri n g t he visit 
[e] 
I n di vi d ual disease mar kers teste d acc or di n g t o t he St u d y La b orat or y Ma n ual  
[f] 
Pre g na nc y testi n g at M o nt h 3 i n Gr o u ps 1 a n d 2 if a n M V A- H BV b o ost is gi ve n , a n d at M o nt hs 3 a n d 6 i n Gr o u ps 3 a n d 
4 
[ g] 
If a partici pa nt has a 0. 5 l o g or greater dr o p i n he patitis B s urface a nti ge n at Da y 3 5, t he y ma y recei ve a b o oster d ose of 
M V A -H B V at M o nt h 3, at t he I n vesti gat or’s discreti o n a n d after disc ussi o n wit h t he S p o ns or ( U K p artici p a nts o nl y). 
T hese patie nts will als o ha ve a tele p h o ne call t he da y after t he b o ost vacci nati o n a n d a cli nic visit 7 da ys p ost -b o ost, as 
per Da y  1 a n d Da y  7. 
All scree ni n g e val uati o ns m ust be c o m plete d a n d re vie we d t o c o nfir m t hat partici pa nts meet 
all eli gi bilit y criteria bef ore t he first d ose of st u d y vacci ne . T he I n vesti gat or will mai ntai n a 
scree ni n g l o g t o rec or d details of all partici pa nts scree ne d a n d t o c o nfir m eli gi bilit y or rec or d 
reas o ns f or scree ni n g fail ure, as a p plica ble. 
P artici p a nts w h o d o n ot meet eli gi bilit y criteri a m a y be rescree ne d at t he discreti o n of t he 
I n vesti g at or. O nl y a b n or m al/ o ut of wi n d o w tests are re q uire d t o deter mi ne eli gi bilit y. 
Re -scree ni n g c a n occ ur at a n y p oi nt wit h t he all o we d o ver all wi n d o w ( u p t o 4 2 d a ys). 
6. 2 
Treat me nt Da y Assess me nts ( Da y 0, Da y 2 8 a n d M o nt h 3 (M V A -H B V B o ost [U K 
p artici p a nts o nl y])  

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 1 0 4  of 1 0 9  
6. 3. 1 
Tele p h o ne  Calls:  Da y  1,  Da y  2 9  a n d  M o nt h  3  +  1  Da y  ( M V A -H B V  B o ost  [ U K 
p artici p a nts o nl y])  
6. 3. 2 
Cli nic  Visits:  Da y  7,  Da y  3 5  a n d  M o nt h  3  +  7  Da ys  ( M V A -H B V  B o ost  [ U K 
p artici p a nts o nl y])  
6. 3. 3  Cli nic Visit: M o nt hs  3 a n d 6 
•  
F or p artici p a nts e nr olle d at U K sites , chec k he patitis B s urface a nti ge n Da y 3 5  res ult 
( M o nt h 3 o nl y) 
− 
If a partici pa nt has a 0. 5 l o g or greater dr o p i n he patitis B s urface a nti ge n, t he y ma y 
recei ve a b o oster d ose of M V A- H BV, at t he I n vesti gat or’s discreti o n a n d after 
disc ussi o n wit h t he S p o ns or. Please see Secti o n  6. 2  f or t he assess me nts t o be 
perf or me d. 
7. 1. 5 
Uri ne Pre g n a ncy Test  
A uri ne pre g na nc y test will be perf or me d i n fe male partici pa nts of c hil d beari n g p ote ntial at 
scree ni n g a n d c o nfir me d t o be ne gati ve pre-vacci nati o n o n Da y 0 a n d 2 8 a n d at M o nt h 3 if a 
b o oster d ose of M V A -H B V is gi ve n ( U K p artici p a nts o nl y), as per l ocal sta n dar d pr oce d ures 
a n d at eac h of t he ti me p oi nts acc or di n g t o Ta ble 2. 
7. 4. 3 
Vit al Si g ns  
Vital si g ns will be perf or me d at scree ni n g, pre - vacci nati o n a n d p ost- vacci nati o n (at t he e n d of 
t he o bser vati o n peri o d) at t he vacci nati o n visit , at all visits d uri n g t he f oll o w- u p a n d t he e n d of 
st u d y visit. At eac h ti me p oi nt bl o o d press ure, p ulse rate a n d oral  te m perat ure, will be meas ure d 
after t he partici pa nt has bee n i n a sitti n g p ositi o n f or 5  mi n utes.  
7. 4. 4 
P hysic al E x a mi n ati o n  
A s ki n, res pirat or y, car di o vasc ular, a b d o mi nal a n d l y m p hatic s yste m e xa mi nati o n will be 
perf or me d  at  scree ni n g,  pre -vacci nati o n  o n  Da y  0,  Da y  2 8  a n d  M o nt h  3  (f or  t h ose U K 
p artici p a nts  ha vi n g t he M V A -H B V b o ost o nl y) a n d o n M o nt h 9. A s y m pt o m directe d p h ysical 
e xa mi nati o n will be perf or me d at all ot her cli nic visits if re q uire d. Res ults will be rec or de d as 
n or mal, a b n or mal a n d n ot cli nicall y si g nifica nt or a b n or mal a n d cli nicall y si g nifi ca nt. 
8. 2. 2 
St u dy Re p orti n g Peri o d f or A dverse Eve nts  
T he r e p orti n g peri o d f or all a d verse e ve nts be gi ns o n t he date t he i nf or me d c o nse nt is si g ne d . 
S olicite d a d verse e ve nts are rec or de d i n t he e Diar y u p t o 7 da ys p ost -vacci nati o n. All ot her 
e ve nts are rec or de d i n t he e C R F at all cli nic visits t hr o u g h o ut t he st u d y. All S A Es a n d/ or A E SIs 
are rec or de d  u ntil t he fi nal st u d y visit a n d f or all seri o us or st u d y vacci ne -relate d a d verse e ve nts 
u ntil t hese are res ol ve d or u ntil partici pa nt  c o ntact disc o nti n ues.  Se vere a d verse e ve nts or S A Es 
t hat c o nti n ue at t he e n d of t he st u d y will be atte m pte d t o be f oll o we d u ntil res ol ve d or 
st a bilise d. 
8. 2. 5 
Re p orti n g Re q uire me nts a n d Pr oce d ures f or S A Es  
I n vesti gat ors m ust n ot wait t o c ollect a d diti o nal i nf or mati o n t o f ull y d oc u me nt t he e ve nt bef ore 
n otif yi n g t he l ocal Me dical M o nit or of a n S A E. T he i nitial n otificati o n s h o ul d i ncl u de t he 
f oll o wi n g (at mi ni m u m if a v ail a ble): 
8. 2. 6. 1 I nvesti g at or F oll o w- u p 
F oll o w u p f or S A Es m ust c o nti n ue u ntil res ol uti o n or st a bilis ati o n  a n d t he o utc o me re p orte d 
t o t he S p o ns or, e ve n if t his e xte n ds be y o n d t he S A E re p orti n g peri o d. 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 1 0 5  of 1 0 9  
1 0. 2. 3 I nteri m A n alyses  
T o hel p wit h t he pla n ni n g of f ut ure st u dies,  a n i nteri m a nal ysis of all a vaila ble data will be 
perf or me d i n J u ne w he n at least 2 0 partici pa nts ha ve bee n e nr olle d a n d after  t heir sec o n d 
d ose of st u d y vacci ne. 2 0 2 1. 
A p pe n di x  2  T o xicit y  M a n a ge me nt  G ui deli nes  f or  I m m u ne  Rel ate d  A d verse  E ve nts  
Ass oci ate d wit h Ni v ol u m a b  
D ose m o dific ati o n a n d t o xicit y m a n a ge me nt of i nf usi o n -re acti o ns rel ate d t o ni v ol u m a b 
A p pr o priate res uscitati o n e q ui p me nt s h o ul d be a vaila ble at t he be dsi de a n d a p h ysicia n rea dil y a vaila ble d uri n g 
t he peri o d of dr u g a d mi nistrati o n. 
F or  f urt her  i nf or mati o n,  please  refer  t o  t he  C o m m o n  Ter mi n ol o g y  Criteria  f or  A d verse  E ve nts  v 4. 0 3  v 5. 0  
( C T C A E) at htt p://cte p.ca ncer. g o v  
D ose M o dific ati o n Sc he m a a n d S u p p orti ve C are G ui deli nes f or Ni v ol u m a b  
N ote: T o xicit y gra des are i n acc or da nce wit h Nati o nal Ca ncer I nstit ute C o m m o n Ter mi n ol o g y Criteria f or 
A d verse E ve nts Versi o n 4 5 . 0 ( N CI-C T C A E v 5. 0).  
a D uri n g a d mi nistrati o n of t he sec o n d p hase of treat me nt ( ni v ol u ma b m o n ot hera p y) f oll o wi n g c o m bi nati o n 
treat me nt, per ma ne ntl y disc o nti n ue treat me nt if Gra de 3 diarr h oea or c olitis occ urs. 
A da pte d fr o m S u m mar y of Pr o d uct C haracteristics f or O P DI V O  1 0  m g/ m L  c o nce ntrate f or s ol uti o n f or i nf usi o n, 
2 4 Ja n uar y  2 0 2 0  3 0 N o ve m ber 2 0 2 0  
 
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 1 0 8  of 1 0 9  
If a partici pa nt has a 0. 5 l o g or greater dr o p i n he patitis B s urface a nti ge n at Da y 3 5, t he y ma y 
recei ve a b o oster d ose of M V A- H BV, at t he I n vesti gat or’s discreti o n a n d after disc ussi o n wit h 
t he S p o ns or ( U K partici pa nts o nl y). 
 
5. 7 
Met h o d of Assi g ni n g P artici p a nts t o Tre at me nt Gr o u ps  
Partici pa nts h a ve s o f ar bee n r a n d o mise d  will be  ra n d o mise d t o all o pe n gr o u ps o n a 1: 1: 1: 1 
all ocati o n as eac h gr o u p is i nitiate d. Pr ot oc ol Versi o n 6. 0 cl oses Gr o u ps 1 a n d 4 t o f urt her 
r a n d o mis ati o n a n d all re m ai ni n g p artici p a nts will be r a n d o mise d t o Gr o u ps 2 a n d 3 i n a 
1: 1 r ati o.  
A se nti nel partici pa nt will be d ose d i n c o h ort 1, a n d t he rest of t he c o h ort will o nl y be e nr olle d 
at least 4 8 h o urs later. 
 
5. 8. 2. 1 D osi n g Sc he d ule 
T he partici pa nts will be all ocate d t o d osi n g gr o u p de pe n di n g o n t he treat me nt sc he d ule a n d 
gr o u ps o pe n at t he ti me of r a n d o mis ati o n . Vacci nati o n will be perf or me d o n Da y 0, after 
eli gi bilit y has bee n rec o nfir me d, a n d o n Da y 2 8. 
 
T a ble  5 
O ver all Sc he d ule of Assess me nts at E ac h St u d y Visit  
Visit/ C all 
Scree n  V acci n ati o n 
Cli nic 
Tele p h o ne 
C all  
Cli nic 
V acci n ati o n 
Cli nic 
Tele p h o ne 
C all 
Cli nic  
E n d of St u d y  / 
E arl y 
Disc o nti n u ati o n  
Cli nic  
Ti me p oi nt ( wi n d o w) 
D a y 
M o nt h  
-4 2 t o - 1 
0 
1 ( + 1 d) 
7 ( ±1 d ) 
2 8  (+ 2 d ) 
2 9 ( + 1 d)  3 5 ( ±1 d ) 3 ( ±7 d )  6 ( ±7 d ) 
9 ( ± 7 d )  
I nf or me d c o nse nt 
X 
 
 
 
 
 
 
 
 
 
B aseli ne/eli gi bilit y v ari a bles  
 
 
 
 
 
 
 
 
 
 
De m o gra p hics 
X 
 
 
 
 
 
 
 
 
 
I ncl usi o n
 a n d
 e xcl usi o n
 
criteria 
X 
 
 
 
 
 
 
 
 
 
Hei g ht a n d wei g ht  
X 
 
 
 
 
 
 
 
 
 
Me dical a n d diseas e hist or y  
X 
 
 
 
 
 
 
 
 
 
HI V, H C V, H B V ( q ua ntitati ve 
H B V D N A a n d q ua ntitati ve 
H Bs A g) , H D V ser ol o g y 
X 
 
 
 
 
 
 
 
 
 
Uri nal ysis  
X 
 
 
 
 
 
 
 
 
 
Uri ne dr u g scree n  
X 
 
 
 
 
 
 
 
 
 
Uri ne pre g na nc y test ( β -h C G)  
X 
X [a ]  
 
 
X [a ]  
 
 
X [f] 
X [f] 
X 
L a b or at or y  eli gi bilit y  a n d  
s afet y tests  
 
 
 
 
 
 
 
 
 
 
Hae mat ol o g y 
X 
X [a ]  
 
X 
X [a ] 
 
X 
X 
X 
X 
Bi oc he mistr y 
X 
X [a ] 
 
X 
X [a ] 
 
X 
X 
X 
X 
Li ver f u ncti o n tests  
X 
X [a ] 
 
X 
X [a ] 
 
X 
X 
X 
X 
St u d y v acci n ati o n 
 
 
 
 
 
 
 
 
 
 
Vacci nati o n d ose  
 
X 
 
 
X 
 
 
X [g ] 
 
 
P ost- d ose o bser vati o n  
 
X 
 
 
X 
 
 
X [g ] 
 
 
Ni v ol u ma b d ose ( Gr o u p  3 
a n d 4  o nl y ) [b ] 
 
 
X 
 
X 
 
 
 
 
 
Ot her s afet y assess me nts  
 
 
 
 
 
 
 
 
 
 

 
Pr ot oc ol H B V 0 0 2  
Versi o n 6 . 0: 0 9  Dec  2 0 2 1  
 
V accitec h Lt d  
C O N FI D E N TI A L  
P a ge 1 0 9  of 1 0 9  
Visit/ C all 
Scree n  V acci n ati o n 
Cli nic 
Tele p h o ne 
C all  
Cli nic 
V acci n ati o n 
Cli nic 
Tele p h o ne 
C all 
Cli nic  
E n d of St u d y  / 
E arl y 
Disc o nti n u ati o n  
Cli nic  
Ti me p oi nt ( wi n d o w) 
D a y 
M o nt h  
-4 2 t o - 1 
0 
1 ( + 1 d) 
7 ( ±1 d ) 
2 8  (+ 2 d ) 
2 9 ( + 1 d)  3 5 ( ±1 d ) 3 ( ±7 d )  6 ( ±7 d ) 
9 ( ± 7 d )  
F ull p h ysical e xa mi nati o n  
X 
X [a ] 
 
 
X [a ] 
 
 
X [a ]  
 
X 
S y m pt o m - directe d p h ysical 
e xa mi nati o n 
 
 
 
X 
 
 
X 
X 
X 
 
Vital si g ns   
X 
X 
 
X 
X 
 
X 
X 
X 
X 
L ocal/s yste mic 
react o ge nicit y 
 
X [c ] 
X 
X 
X [c ] 
X 
X 
X [c ] 
 
 
U ns olicite d a d verse e ve nts [ d] 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Seri o us a d verse e v e nts a n d 
a d verse e ve nts of s pecial 
i nterest  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pri or a n d c o nc o mit a nt 
me dicati o ns 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Bl o o d f or H B V dise ase 
m ar kers [e ] 
 
X [a ] 
 
X 
X [a ] 
 
X 
X 
X 
X 
I m m u n o ge nicit y assess me nts 
 
 
 
 
 
 
 
 
 
 
Bl o o d f or cell ular 
i m m u n o ge nicit y assess me nts 
 
X [a ] 
 
X 
X [a ] 
 
X 
X [a ] 
X 
X 
[a] Pre -vacci nati o n o n Da y  0, Da y  2 8, a n d M o nt h  3 (f or U K partici pa nts ha vi n g a n M V A -H B V b o ost)  
[ b] 
Partici pa nts i n Gr o u p 3 will recei ve ni v ol u ma b o n Da y  2 8. Gr o u p 4 is n o w cl ose d  o nl y w hile Gr o u p 4 will recei ve ni v ol u ma b o n 
Da ys 1 a n d 2 8.  T he patie nts will be o bser ve d f or 3 0 mi n utes after vacci nati o n. If t here are n o safet y c o ncer ns ( vital si g ns a n d 
react o ge nicit y), ni v ol u ma b will be i nf use d o ver 3 0 mi n utes a n d t he patie nts will be o bser ve d i n t he st u d y ce ntre f or a f urt her 3 0 mi n utes 
p ost-i nf usi o n. 
[c] 
Ca pt ure d pre -vac ci nati o n a n d p ost -vacci nati o n o n Da ys 0 a n d 2 8, a n d M o nt h  3 (f or U K partici pa nts ha vi n g a n M V A - H BV b o ost ) , 
via e Diaries f or 7 da ys p ost -vacci nati o n a n d t he n at t he cli nic assess me nt 7 da ys p ost -vacci nati o n ( Da y 7 or 3 5)   
 
6. 3. 2 
Cli nic  Visits:  D a y  7,  D a y  3 5  a n d  M o nt h  3  +  7  D a ys  ( M V A -H B V  B o ost  [ U K  
p artici p a nts o nl y])  
 
• 
Bl o o d sa m ples will be ta ke n f or i m m u n o ge nicit y assess me nts a n d H B V disease mar kers  
T hese visits s h o ul d be a nc h ore d t o t he d ate of V acci n ati o n a n d sc he d ule d t o occ ur 7 ± 1 
d a y after v acci n ati o n. If v acci n ati o n is a d mi nistere d o n a n y d a y ot her t h a n D a y 2 8, t he 
f oll o w u p visit s h o ul d be sc he d ule d 6-8 d a ys after t he d ate of act u al v acci n ati o n.  All ot her 
st u d y visits after D a y 0 (e xce pt d a y 3 5) are a nc h ore d t o D a y 0. 
 
7. 1. 5 
Uri ne Pre g n a nc y Test  
A uri ne pre g na nc y test will be perf or me d i n fe male partici pa nts of c hil d beari n g p ote ntial at 
scree ni n g a n d c o nfir me d t o be ne gati ve pre-vacci nati o n o n Da y 0 a n d 2 8 a n d at M o nt h 3 if a 
b o oster d ose of M V A -H B V is gi ve n ( U K partici pa nts o nl y), a n d at M o nt h 3 a n d 6 f or t h ose 
i n Gr o u p 3 a n d 4,    as per l ocal sta n dar d pr oce d ures a n d at eac h of t he ti me p oi nts acc or di n g 
t o Ta ble 2.